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  <title>Journal Highlights</title>
  <link>http://www.aspet.org/Blog.aspx?blogid=219</link>
  <description>Pharmtalk</description>
  <dc:date>2013-06-18T22:56:29Z</dc:date>
  <dc:language>en-US</dc:language>
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 <item rdf:about="/Blog.aspx?id=4600&amp;blogid=219">
  <title>DMD Highlight: Differential expression of human cytochrome P450 enzymes from the CYP3A subfamily in the brains of alcoholic subjects and drug-free controls</title>
  <link>http://www.aspet.org/Blog.aspx?id=4600&amp;blogid=219</link>
  <description><![CDATA[<p>CYP3A4 and CYP3A5 proteins are expressed in human brains, but only CYP3A4 expression is increased in the frontal cortex microsomes of alcohol abusers. See article at Drug Metab Dispos 2013, 41 1187 1194. (DMD 051359)</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[CYP3A4 and CYP3A5 proteins are expressed in human brains, but only CYP3A4 expression is increased in the frontal cortex microsomes of alcohol abusers. See article at <em>Drug Metab Dispos</em> 2013, <strong>41:</strong><a title="1187-1194" href="http://dmd.aspetjournals.org/content/41/6/1187.abstract" target="_blank">1187-1194</a>. (DMD 051359)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4599&amp;blogid=219">
  <title>DMD Highlight: Application of target-mediated drug disposition model to small molecule heat shock protein 90 inhibitors</title>
  <link>http://www.aspet.org/Blog.aspx?id=4599&amp;blogid=219</link>
  <description><![CDATA[<p>High affinity inhibitors of heat shock proteins display high steady state volumes of distribution which is likely due to pharmacological target binding. See article at Drug Metab Dispos 2013, 41 1285 1294. (DMD 051490)</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[High affinity inhibitors of heat shock proteins display high steady-state volumes of distribution which is likely due to pharmacological target binding. See article at <em>Drug Metab Dispos</em> 2013, <strong>41:</strong><a title="1285-1294" href="http://dmd.aspetjournals.org/content/41/6/1285.abstract " target="_blank">1285-1294</a>. (DMD 051490)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4598&amp;blogid=219">
  <title>JPET Highlight: Behavioral effects and pharmacokinetics of MDMA (Ecstasy) in baboons</title>
  <link>http://www.aspet.org/Blog.aspx?id=4598&amp;blogid=219</link>
  <description><![CDATA[<p>This study characterized the behavioral effects of MDMA (Ecstasy) in a species closely related to humans. MDMA produced behavioral effects in baboons similar to humans and the blood levels of metabolites appear to be related to the changes. See article</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[This study characterized the behavioral effects of MDMA (Ecstasy) in a species closely related to humans. MDMA produced behavioral effects in baboons similar to humans and the blood levels of metabolites appear to be related to the changes. See article at <em>J Pharmacol Exp Ther </em>2013, <strong>345:</strong><a title="342–353" href="http://jpet.aspetjournals.org/content/345/3/342" target="_blank">342–353</a>. (JPET 203729)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4597&amp;blogid=219">
  <title>JPET Highlight: HCN1 channels as targets for amelioration of hyperalgesia in a mouse model of pain</title>
  <link>http://www.aspet.org/Blog.aspx?id=4597&amp;blogid=219</link>
  <description><![CDATA[<p>Analgesics targeting HCN1 must spare the cardiac pacemaker current which is carried mostly by HCN2 and HCN4. The general anesthetic propofol selectively inhibits HCN1 channels versus HCN2 4 and appears to be antihyperalgesic via the HCN1 channel. See article at</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Analgesics targeting HCN1 must spare the cardiac pacemaker current which is carried mostly by HCN2 and HCN4. The general anesthetic propofol selectively inhibits HCN1 channels versus HCN2-4 and appears to be antihyperalgesic via the HCN1 channel. See article at <em>J Pharmacol Exp Ther</em> 2013 <strong>345:</strong><a title="363–373" href="http://jpet.aspetjournals.org/content/345/3/363 " target="_blank">363–373</a>. (JPET 203620)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4596&amp;blogid=219">
  <title>JPET Highlight: Bioimaging real-time PXR-dependent mdr1a gene regulation</title>
  <link>http://www.aspet.org/Blog.aspx?id=4596&amp;blogid=219</link>
  <description><![CDATA[<p>A mouse containing firefly lucifrace (fLUC) knocked into the mdr1a genomic locus allows non invasive bioimaging of intestinal mdr1a gene expression in vivo. In the current study, we crossed mdr1a.fLUC mice into the pxr knockout (pxr ) genetic background and</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[A mouse containing firefly lucifrace (fLUC) knocked into the <em>mdr</em>1a genomic locus allows non-invasive bioimaging of intestinal <em>mdr</em>1a gene expression <em>in vivo</em>. In the current study, we crossed <em>mdr</em>1a.fLUC mice into the <em>pxr</em> knockout (<em>pxr</em>-/-) genetic background and studied the effects of a PXR ligand, and two taxanes. See article at <em>J Pharmacol Exp Ther </em>2013, <strong>345:</strong><a title="438–445" href="http://jpet.aspetjournals.org/content/345/3/438" target="_blank">438–445</a>. (JPET 203562)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4595&amp;blogid=219">
  <title>JPET Highlight: Effects of new SGLT2 inhibitor, Luseogliflozin, on diabetic nephropathy in T2DN rats</title>
  <link>http://www.aspet.org/Blog.aspx?id=4595&amp;blogid=219</link>
  <description><![CDATA[<p>The study examined the effect of hyperglycemia control with a new SGLT2 inhibitor, Luseogliflozin. Treatment with Luseogliflozin produced a sustained increase in glucose excretion and normalized blood glucose and HbA1c levels to the same level as seen in rats treated</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-05-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>The study examined the effect of hyperglycemia control with a new SGLT2 inhibitor, Luseogliflozin. Treatment with Luseogliflozin produced a sustained increase in glucose excretion and normalized blood glucose and HbA1c levels to the same level as seen in rats treated with insulin. Luseogliflozin also prevented the fall in GFR. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>345:</strong><a title="464–472" href="http://jpet.aspetjournals.org/content/345/3/464" target="_blank">464–472</a>. (JPET 203869)</p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4490&amp;blogid=219">
  <title>JPET Highlight: CB1 receptor signaling: A key interaction between EC-3 loop and TMH2</title>
  <link>http://www.aspet.org/Blog.aspx?id=4490&amp;blogid=219</link>
  <description><![CDATA[<p>Activation of the CB1 receptor is modulated by aspartate residue D2.63176 in transmembrane helix II. Modeling and mutation studies demonstrated that the ionic interactions between D2.63176 and K373 are important for CB1 signal transduction. See article at J Pharmacol Exp</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-04-18T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Activation of the CB1 receptor is modulated by aspartate residue D2.63176 in transmembrane helix II. Modeling and mutation studies demonstrated that the ionic interactions between D2.63176 and K373 are important for CB1 signal transduction. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>345:</strong><a title="189–197" href="http://jpet.aspetjournals.org/content/345/2/189" target="_blank">189–197</a>. (JPET 201046)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4489&amp;blogid=219">
  <title>JPET Highlight: Experimental models of disseminated scedosporiosis with cerebral involvement</title>
  <link>http://www.aspet.org/Blog.aspx?id=4489&amp;blogid=219</link>
  <description><![CDATA[<p>Scedosporium apiosperum is a fungus that can cause severe and often fatal cerebral infections. The study developed experimental models of disseminated scedosporiosis with cerebral involvement in immunocompetent and immunosuppressed rats. See article at J Pharmacol Exp Ther 2013 345 198–205.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-04-18T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Scedosporium apiosperum is a fungus that can cause severe and often fatal cerebral infections. The study developed experimental models of disseminated scedosporiosis with cerebral involvement in immunocompetent and immunosuppressed rats. See article at <em>J Pharmacol Exp Ther </em>2013 <strong>345:</strong><a title="198–205" href="http://jpet.aspetjournals.org/content/345/2/198" target="_blank">198–205</a>. (JPET 201541)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4488&amp;blogid=219">
  <title>JPET Highlight: Mechanism of LX4211 induced increases serum GLP-1 and PYY levels</title>
  <link>http://www.aspet.org/Blog.aspx?id=4488&amp;blogid=219</link>
  <description><![CDATA[<p>Clinically, LX4211 improves glycemic control while increasing levels of GLP 1 and PYY. Similar results were observed in mice treated with LX4211 and in SGLT2 mice, suggesting that part of the LX4211 pharmacology is through inhibition SGLT1. See article at</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-04-18T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Clinically, LX4211 improves glycemic control while increasing levels of GLP-1 and PYY. Similar results were observed in mice treated with LX4211 and in SGLT2-/- mice, suggesting that part of the LX4211 pharmacology is through inhibition SGLT1. See article at <em>J Pharmacol Exp Ther </em>2013, <strong>345:</strong><a title="250–259" href="http://jpet.aspetjournals.org/content/345/2/250" target="_blank">250–259</a>. (JPET 203364)</p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4487&amp;blogid=219">
  <title>JPET Highlight: UGT 1A polymorphism rs8330 is associated with liver acetaminophen glucuronidation</title>
  <link>http://www.aspet.org/Blog.aspx?id=4487&amp;blogid=219</link>
  <description><![CDATA[<p>Acetaminophen is cleared primarily by hepatic glucuronidation. Human liver bank samples were utilized to demonstrate that polymorphisms in genes encoding the acetaminophen UGT enzymes could explain interindividual variability in glucuronidation and risk for acetaminophen induced liver injury. See article at</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-04-18T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Acetaminophen is cleared primarily by hepatic glucuronidation. Human liver bank samples were utilized to demonstrate that polymorphisms in genes encoding the acetaminophen UGT enzymes could explain interindividual variability in glucuronidation and risk for acetaminophen induced liver injury. See article at <em>J Pharmacol Exp Ther </em>2013, <strong>345:</strong><a title="297–307" href="http://jpet.aspetjournals.org/content/345/2/297" target="_blank">297–307</a>. (JPET 202010)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4410&amp;blogid=219">
  <title>JPET Highlight: Paclitaxel ameliorates LPS-induced kidney injury by binding MD-2</title>
  <link>http://www.aspet.org/Blog.aspx?id=4410&amp;blogid=219</link>
  <description><![CDATA[<p>Paclitaxel protects against lipopolysaccharide (LPS) induced acute kidney injury (AKI) and improves animal survival. The present study suggests that paclitaxel binds MD 2 to block MD 2 TLR4 association during LPS treatment, resulting in the suppression of NF κB activation</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-03-21T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Paclitaxel protects against lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and improves animal survival. The present study suggests that paclitaxel binds MD-2 to block MD-2/TLR4 association during LPS treatment, resulting in the suppression of NF-κB activation and inhibition of pro-inflammatory cytokine production. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>345:</strong><a title="69–75" href="http://jpet.aspetjournals.org/content/345/1/69">69–75</a>. (JPET 202481)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4409&amp;blogid=219">
  <title>JPET Highlight: Quantifying the attenuation of the ketamine phMRI response in humans</title>
  <link>http://www.aspet.org/Blog.aspx?id=4409&amp;blogid=219</link>
  <description><![CDATA[<p>Ketamine evokes psychotomimetic symptoms resembling schizophrenia in healthy humans. Imaging markers of acute ketamine challenge have the potential to provide a powerful assay of novel therapies for psychiatric illness. The present study demonstrated a ketamine phMRI response that was attenuated</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-03-21T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Ketamine evokes psychotomimetic symptoms resembling schizophrenia in healthy humans. Imaging markers of acute ketamine challenge have the potential to provide a powerful assay of novel therapies for psychiatric illness. The present study demonstrated a ketamine phMRI response that was attenuated with both lamotrigine and risperidone. See article at <em>J Pharmacol Exp Ther </em>2013 <strong>345:</strong><a title="151–160" href="http://jpet.aspetjournals.org/content/345/1/151">151–160</a>. (JPET 201665)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4408&amp;blogid=219">
  <title>JPET Highlight: A novel macrolide solithromycin exerts superior anti-inflammatory effect</title>
  <link>http://www.aspet.org/Blog.aspx?id=4408&amp;blogid=219</link>
  <description><![CDATA[<p>Macrolides are reported to reduce exacerbation of COPD and also show anti inflammatory effects. However, the anti inflammatory efficacy of macrolides is weak. Here, we found that a novel macrolide fluoroketolide solithromycin (CEM 101) showed superior antiinflamatory effects in human</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-03-21T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Macrolides are reported to reduce exacerbation of COPD and also show anti-inflammatory effects. However, the anti-inflammatory efficacy of macrolides is weak. Here, we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior antiinflamatory effects in human cells obtained from COPD patients. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>345:</strong><a title="76–84" href="http://jpet.aspetjournals.org/content/345/1/76">76–84</a>. (JPET 200733)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4407&amp;blogid=219">
  <title>JPET Highlight: Refining the UGT1A haplotype associated with irinotecan-induced hematological toxicity in colorectal cancer patients</title>
  <link>http://www.aspet.org/Blog.aspx?id=4407&amp;blogid=219</link>
  <description><![CDATA[<p>The relationships between UGT1A candidate markers across the gene (n=21) and toxicity were prospectively evaluated. Haplotype analyses of markers with the 3'UTR SNP allowed the identification of a protective HI and two risk haplotypes HII and HIII, characterized by 2</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-03-21T14:54:00Z</dc:date>
  <content:encoded><![CDATA[The relationships between <em>UGT1A</em> candidate markers across the gene (n=21) and toxicity were prospectively evaluated. Haplotype analyses of markers with the 3'UTR SNP allowed the identification of a protective HI and two risk haplotypes HII and HIII, characterized by 2 and 3 unfavorable alleles respectively. See article at <em>J Pharmacol Exp Ther </em>2013, <strong>345:</strong><a title="95–101" href="http://jpet.aspetjournals.org/content/345/1/95">95–101</a>. (JPET 202242)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4303&amp;blogid=219">
  <title>JPET Highlight: A µ-opioid receptor ligand with reduced GI and respiratory dysfunction</title>
  <link>http://www.aspet.org/Blog.aspx?id=4303&amp;blogid=219</link>
  <description><![CDATA[<p>Morphine pharmacology in β arrestin2 knock out mice suggests that a ligand that promotes coupling of the &#181; opiod receptor&#160; to G proteins, but not β arrestins, will result in higher analgesic efficacy, less GI dysfunction, and less respiratory suppression</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-02-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Morphine pharmacology in β-arrestin2 knock out mice suggests that a ligand that promotes coupling of the µ-opiod receptor  to G proteins, but not β-arrestins, will result in higher analgesic efficacy, less GI dysfunction, and less respiratory suppression than morphine. This study tested the hypothesis TRV130. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/3/708" title="708–717">708–717</a>. (JPET 201616)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4302&amp;blogid=219">
  <title>JPET Highlight: The PK and PD relationships of an engineered human follistatin variant</title>
  <link>http://www.aspet.org/Blog.aspx?id=4302&amp;blogid=219</link>
  <description><![CDATA[<p>Human follistatin is a regulatory glycoprotein with widespread functions and promise for clinical applications. PK PD studies with the native follistatin 315 demonstrated that it was poorly suited for parenteral administration. In contrast, an engineered variant had ~100 and ~1600</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-02-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Human follistatin is a regulatory glycoprotein with widespread functions and promise for clinical applications. PK/PD studies with the native follistatin-315 demonstrated that it was poorly suited for parenteral administration. In contrast, an engineered variant had ~100 and ~1600-fold improvements in terminal half-life and exposure, respectively. See article at <em>J Pharmacol Exp Ther</em> 2013 <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/3/616" title="616–623">616–623</a>. (JPET 201491)<br /><br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4301&amp;blogid=219">
  <title>JPET Highlight: ADX71743, a negative allosteric modulator of metabotropic glutamate receptor 7 (mGlu7)</title>
  <link>http://www.aspet.org/Blog.aspx?id=4301&amp;blogid=219</link>
  <description><![CDATA[<p>ADX71743 is a negative modulator of mGlu7 which caused no impairment of locomotor activity in rodents but had an anxiolytic like profile in the marble burying and elevated plus maze tests. These in vivo data suggest that mGlu7 may be</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-02-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[ADX71743 is a negative modulator of mGlu7 which caused no impairment of locomotor activity in rodents but had an anxiolytic-like profile in the marble burying and elevated plus maze tests. These <em>in vivo</em> data suggest that mGlu7 may be a valid target for treating anxiety disorders and that ADX71743 may be an appropriate tool. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/3/624" title="624–636">624–636</a>. (JPET 200915)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4300&amp;blogid=219">
  <title>JPET Highlight: Puerarin ameliorates experimental alcoholic liver injury</title>
  <link>http://www.aspet.org/Blog.aspx?id=4300&amp;blogid=219</link>
  <description><![CDATA[<p>The purpose of this study was to examine if puerarin reduced alcoholic liver injury. In rats, chronic alcohol intake caused pathological changes in the liver, increased endotoxin level in portal vein and up regulated protein expression of hepatic CD68 and</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-02-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[The purpose of this study was to examine if puerarin reduced alcoholic liver injury. In rats, chronic alcohol intake caused pathological changes in the liver, increased endotoxin level in portal vein and up-regulated protein expression of hepatic CD68 and LPS receptors. These effects were reduced by administration of puerarin. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/3/646" title="646–654">646–654</a>. (JPET 201137)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4209&amp;blogid=219">
  <title>JPET Highlight: Chimeric Mice with Humanized Livers can Predict Human Drug Metabolism</title>
  <link>http://www.aspet.org/Blog.aspx?id=4209&amp;blogid=219</link>
  <description><![CDATA[<p>Preclinical studies have not always predicted human drug metabolism. The present study demonstrated that chimeric mice could provide a more predictive assessment of the predominant human metabolite formed by clemizole, a drug in clinical development for HCV infection. See article</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-01-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Preclinical studies have not always predicted human drug metabolism. The present study demonstrated that chimeric mice could provide a more predictive assessment of the predominant human metabolite formed by clemizole, a drug in clinical development for HCV infection. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/2/388" title="388–396">388–396</a>. (JPET 198697)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4208&amp;blogid=219">
  <title>JPET Highlight: Kv2.x Channels Regulate Insulin and Somatostatin Release from Pancreatic Islets</title>
  <link>http://www.aspet.org/Blog.aspx?id=4208&amp;blogid=219</link>
  <description><![CDATA[<p>Voltage gated potassium Kv2.1 and Kv2.2 channels are highly expressed in pancreatic islets. Pharmacologic inhibition of Kv2.x channels enhances glucose stimulated insulin secretion from isolated wilt type mice and human islets but not in islets from Kv2.1 mice, suggesting that</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-01-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Voltage-gated potassium Kv2.1 and Kv2.2 channels are highly expressed in pancreatic islets. Pharmacologic inhibition of Kv2.x channels enhances glucose stimulated insulin secretion from isolated wilt-type mice and human islets but not in islets from Kv2.1-/- mice, suggesting that inhibition of Kv2.1 may be a potential treatment of type 2 diabetes. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/2/407" title="407–416">407–416</a>. (JPET 199083)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4207&amp;blogid=219">
  <title>JPET Highlight: Suramin Improves Regeneration of Ethanol-Induced Steatotic Partial Liver Grafts</title>
  <link>http://www.aspet.org/Blog.aspx?id=4207&amp;blogid=219</link>
  <description><![CDATA[<p>Steatotic grafts are excluded for use in partial liver transplantation due to increased risk of primary non function. This study demonstrated that suramin improved liver function and outcome of partial liver transplants of steatotic livers taken from rats dosed acutely</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-01-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Steatotic grafts are excluded for use in partial liver transplantation due to increased risk of primary non-function. This study demonstrated that suramin improved liver function and outcome of partial liver transplants of steatotic livers taken from rats dosed acutely with ethanol. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/2/417" title="417–425">417–425</a>. (JPET 199919)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4206&amp;blogid=219">
  <title>JPET Highlight: Insight to Explain the Cardiac Safety of Pixantrone in Doxorubicin Treated Patients</title>
  <link>http://www.aspet.org/Blog.aspx?id=4206&amp;blogid=219</link>
  <description><![CDATA[<p>Doxorubicin cardiotoxicity correlates with cardiac drug levels, redox activation, and formation of the metabolite doxorubicinol. Cardiotoxicity may first be observed during salvage therapy with drugs such as mitoxantrone. In contrast, less cardiac toxicity has been observed in patients treated with</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2013-01-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Doxorubicin cardiotoxicity correlates with cardiac drug levels, redox activation, and formation of the metabolite doxorubicinol. Cardiotoxicity may first be observed during salvage therapy with drugs such as mitoxantrone. In contrast, less cardiac toxicity has been observed in patients treated with doxorubicin followed by pixantrone possibly due to minimal redox synergism with doxorubicin, and reduced formation of doxorubicinol. See article at<em>J Pharmacol Exp Ther </em>2013, <strong>344:</strong><a title="467–478" href="http://jpet.aspetjournals.org/content/344/2/467">467–478</a>. (JPET 200568)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4171&amp;blogid=219">
  <title>JPET Highlight: Hydrophobic Amino Acids in the Hinge Region of the 5A Apolipoprotein Mimetic Peptide are Essential for Promoting Cholesterol Efflux</title>
  <link>http://www.aspet.org/Blog.aspx?id=4171&amp;blogid=219</link>
  <description><![CDATA[<p>Apolipoprotein mimetic peptides are short amphipathic peptides that are being investigated as possible therapeutic agents for atherosclerosis. Studies using a series of 5A peptide analogues demonstrated that only peptides with hydrophobic amino acids in the hinge region were able to</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-12-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Apolipoprotein mimetic peptides are short amphipathic peptides that are being investigated as possible therapeutic agents for atherosclerosis. Studies using a series of 5A peptide analogues demonstrated that only peptides with hydrophobic amino acids in the hinge region were able to readily bind and solubilize phospholipid vesicles. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/1/50" title="50–58">50–58</a>. (JPET 198143)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4170&amp;blogid=219">
  <title>JPET Highlight: Phosphoinositide-Dependent Kinase-1 (PDK-1) Can Contribute to Hypertension</title>
  <link>http://www.aspet.org/Blog.aspx?id=4170&amp;blogid=219</link>
  <description><![CDATA[<p>Inhibition of PDK 1 blunted endothelin 1 constriction in arteries from rats that had hypoxia induced hypertension. In addition treatment of rats with a PDK 1 inhibitor lowered blood pressure in hypertensive rats but not in rats with normal blood</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-12-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Inhibition of PDK-1 blunted endothelin-1 constriction in arteries from rats that had hypoxia induced hypertension. In addition treatment of rats with a PDK-1 inhibitor lowered blood pressure in hypertensive rats but not in rats with normal blood pressure, suggesting that PDK-1 may be an effective target for some types of hypertension. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/1/68" title="68–76">68–76</a>. (JPET 195412)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4169&amp;blogid=219">
  <title>JPET Highlight: Screening for the Detection of G Protein-Coupled Receptor Heteromer Signaling</title>
  <link>http://www.aspet.org/Blog.aspx?id=4169&amp;blogid=219</link>
  <description><![CDATA[<p>Drugs targeting GPCRs make up more than 25% of all prescribed medicine. The ability of GPCRs to form heteromers with unique signaling properties may be a new drug target. The present study describes an approach to create an in vitro</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-12-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Drugs targeting GPCRs make up more than 25% of all prescribed medicine. The ability of GPCRs to form heteromers with unique signaling properties may be a new drug target. The present study describes an approach to create an <em>in vitro</em> assay in which large numbers of compounds can be screened and only activated heteromers are detectable. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/1/179" title="179–188">179–188</a>. (JPET 198655)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4168&amp;blogid=219">
  <title>JPET Highlight: A Cationic Analog of Ceramide Induces Pancreatic Cancer Cell Death</title>
  <link>http://www.aspet.org/Blog.aspx?id=4168&amp;blogid=219</link>
  <description><![CDATA[<p>Treatment of pancreatic cancer that cannot be surgically resected currently relies on cytotoxic chemotherapy with gemcitabine. LCL124 is a cationic ceramide that accumulated in and inhibited the growth of xenographs in vivo and gemcitabine resistant cells became more sensitive after</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-12-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Treatment of pancreatic cancer that cannot be surgically resected currently relies on cytotoxic chemotherapy with gemcitabine. LCL124 is a cationic ceramide that accumulated in and inhibited the growth of xenographs <em>in vivo</em> and gemcitabine resistant cells became more sensitive after treatment. See article at <em>J Pharmacol Exp Ther</em> 2013, <strong>344:</strong><a href="http://jpet.aspetjournals.org/content/344/1/167" title="167–178">167–178</a>. (JPET 199216)<br /><br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4080&amp;blogid=219">
  <title>JPET Highlight: Natriuretic Peptide-Induced Catecholamine Release From Cardiac Sympathetic Neurons</title>
  <link>http://www.aspet.org/Blog.aspx?id=4080&amp;blogid=219</link>
  <description><![CDATA[<p>   Heart failure does not appear to improve with the administration of recombinant BNP (nesiritide), despite the predicated beneficial effects of natriuretic peptides. Results from the present study suggest that the lack of improvement may be related to</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-11-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>Heart failure does not appear to improve with the administration of recombinant BNP (nesiritide), despite the predicated beneficial effects of natriuretic peptides. Results from the present study suggest that the lack of improvement may be related to a proadrenergic effect of natriuretic peptides. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/3/568 " title="568–577">568–577</a>. (JPET 198747)</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4079&amp;blogid=219">
  <title>JPET Highlight: GPR35 Antagonists Display High Species Ortholog Selectivity</title>
  <link>http://www.aspet.org/Blog.aspx?id=4079&amp;blogid=219</link>
  <description><![CDATA[<p>   Substantial selectivity in potency of a number of GPR35 agonists has previously been demonstrated between human and rat orthologs of this G protein coupled receptor. This study demonstrated that there is also species selectivity with GPR35 antagonists,</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-11-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>Substantial selectivity in potency of a number of GPR35 agonists has previously been demonstrated between human and rat orthologs of this G protein coupled receptor. This study demonstrated that there is also species selectivity with GPR35 antagonists, further demonstrating that care is required when exploring the function of GPR35 across species. See article at <em>J Pharmacol Exp Ther</em> 2012 <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/3/683 " title="683–695">683–695</a>. (JPET 198945) <br /><br /></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4078&amp;blogid=219">
  <title>JPET Highlight: Strontium is a Biased Agonist of the Calcium-Sensing Receptor</title>
  <link>http://www.aspet.org/Blog.aspx?id=4078&amp;blogid=219</link>
  <description><![CDATA[<p>   The calcium sensing receptor specific allosteric modulator, cinacalcet, is used to treat secondary hyperparathyroidism in patients with chronic kidney disease. Due to hypocalcemic side effects, clinical application is limited. The results of the present study suggest that</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-11-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>The calcium-sensing receptor specific allosteric modulator, cinacalcet, is used to treat secondary hyperparathyroidism in patients with chronic kidney disease. Due to hypocalcemic side effects, clinical application is limited. The results of the present study suggest that calcitonin secretion can be affected by CaSR-stimulated signaling bias. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/3/638" title="638–649">638–649</a>. (JPET 197210) </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=4077&amp;blogid=219">
  <title>JPET Highlight: Differential Effects of Selesipag and Prostacyclin Analogs in Rat Pulmonary Artery</title>
  <link>http://www.aspet.org/Blog.aspx?id=4077&amp;blogid=219</link>
  <description><![CDATA[<p>   ACT 333679 is the main metabolite of the selective prostacyclin (PGI2) receptor (IP receptor) agonist selexipag. This study demonstrated that the relaxant efficacy of the IP receptor agonist selexipag and its metabolite was not modified under conditions</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-11-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p><br />ACT-333679 is the main metabolite of the selective prostacyclin (PGI2) receptor (IP receptor) agonist selexipag. This study demonstrated that the relaxant efficacy of the IP receptor agonist selexipag and its metabolite was not modified under conditions associated with pulmonary arterial hypertension. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/3/547 " title="547–555">547–555</a>. (JPET 197152) <br /></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3976&amp;blogid=219">
  <title>JPET Highlight: Vascular Disrupting Agent, STA-9584, Targets Microvascular at the Center and Periphery of Tumor</title>
  <link>http://www.aspet.org/Blog.aspx?id=3976&amp;blogid=219</link>
  <description><![CDATA[<p>Vascular disrupting agents are an emerging class of therapeutics targeting the vascular network of solid tumors. However, clinical progression has been hampered, primarily due to the persistence of surviving cells in the well perfused areas of tumors. STA 9584 demonstrates</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-10-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Vascular disrupting agents are an emerging class of therapeutics targeting the vascular network of solid tumors. However, clinical progression has been hampered, primarily due to the persistence of surviving cells in the well perfused areas of tumors. STA-9584 demonstrates activity in well perfused areas of the tumor identifying it as a promising new therapeutic candidate. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/2/529" title="529–538">529–538</a>. (JPET 196873)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3975&amp;blogid=219">
  <title>JPET Highlight: Exacerbation of NSAIDS-Induced Small Intestinal Lesions by Anti-Secretory Drugs</title>
  <link>http://www.aspet.org/Blog.aspx?id=3975&amp;blogid=219</link>
  <description><![CDATA[<p>Antisecretory drugs are commonly used for the treatment of gastric and duodenal ulcers induced by NSAIDs. In rats, H2 receptor antagonists and proton pump inhibitors caused increases in NSAID induced small intestinal lesions leading to the conclusion that some antisecretory</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-10-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Antisecretory drugs are commonly used for the treatment of gastric and duodenal ulcers induced by NSAIDs. In rats, H2-receptor antagonists and proton pump inhibitors caused increases in NSAID induced small intestinal lesions leading to the conclusion that some antisecretory drugs may be inappropriate for the treatment of these ulcers. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/2/270" title="270–277">270–277</a>. (JPET 197475)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3974&amp;blogid=219">
  <title>JPET Highlight: The Relationship Between in vitro Potency, Pharmacokinetics and Pharmacodynamics in a Series of  β-secretase Inhibitors</title>
  <link>http://www.aspet.org/Blog.aspx?id=3974&amp;blogid=219</link>
  <description><![CDATA[<p>The aspartyl protease BACE1 catalyzes the rate limiting step in the production of the peptide Aβ, and may be an important target for drug development in Alzheimer’s disease. This manuscript describes the combination of potency, high permeability, low P gp</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-10-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[The aspartyl protease BACE1 catalyzes the rate-limiting step in the production of the peptide Aβ, and may be an important target for drug development in Alzheimer’s disease. This manuscript describes the combination of potency, high permeability, low P-gp mediated efflux and low clearance required for robust <em>in vivo</em> efficacy after oral dosing. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/2/460" title="460–467">460–467</a>. (JPET 197954) <br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3973&amp;blogid=219">
  <title>JPET Highlight: Identification of the Plant Steroid a-Spinasterol as a Novel TRPV1 Antagonist</title>
  <link>http://www.aspet.org/Blog.aspx?id=3973&amp;blogid=219</link>
  <description><![CDATA[<p>The TRPV1 receptor is relevant to the perception of noxious stimuli and has been studied as a target for new analgesics. This study demonstrates the ability to identify a novel TRPV1 antagonist isolated from the leaves of the medicinal plant</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-10-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[The TRPV1 receptor is relevant to the perception of noxious stimuli and has been studied as a target for new analgesics. This study demonstrates the ability to identify a novel TRPV1 antagonist isolated from the leaves of the medicinal plant <em>Vernonia tweedieana</em> Baker. See article at <em>J Pharmacol Exp Ther </em>2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/2/258" title="258–269">258–269</a>. (JPET 195909)<br /><br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3924&amp;blogid=219">
  <title>JPET Highlight: Adenosine and Histamine Inhibit Ischemic Norepinephrine Release</title>
  <link>http://www.aspet.org/Blog.aspx?id=3924&amp;blogid=219</link>
  <description><![CDATA[<p>   During myocardial ischemia reperfusion, the formation of toxic aldehydes contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. This study suggests the existence in sympathetic neurons of</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-09-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>During myocardial ischemia/reperfusion, the formation of toxic aldehydes contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. This study suggests the existence in sympathetic neurons of a protective pathway that involves ALDH2 and can be activated by adenosine and histamine. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/1/97" title="97–105" target="_blank">97–105</a>. (JPET 196626)</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3923&amp;blogid=219">
  <title>JPET Highlight: Carvedilol Enhanced Mesenchymal Stem Cell Therapy for Myocardial Infarction</title>
  <link>http://www.aspet.org/Blog.aspx?id=3923&amp;blogid=219</link>
  <description><![CDATA[<p>   Mesenchymal stem cells (MSC) have been investigated for cardiac repair with encouraging results. However, one challenge is the survival of transplanted cells in the ischemic region. This study shows that treatment with Carvedilol can improve the response</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-09-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>Mesenchymal stem cells (MSC) have been investigated for cardiac repair with encouraging results. However, one challenge is the survival of transplanted cells in the ischemic region. This study shows that treatment with Carvedilol can improve the response of transplanted MSCs during myocardial infarction. See article at <em>J Pharmacol Exp Ther</em> 2012 <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/1/62" title="62–71" target="_blank">62–71</a>. (JPET 196915)  <br /></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3922&amp;blogid=219">
  <title>JPET Highlight: Sepantronium Bromide (YM155) Enhances Response of Human B-cell non-Hodgkin Lymphoma to Rituximab</title>
  <link>http://www.aspet.org/Blog.aspx?id=3922&amp;blogid=219</link>
  <description><![CDATA[<p>   In the treatment of B cell non Hodgkin lymphoma, rituximab along with chemotherapy improves long term survival. However, the majority of patients eventually relapse, requiring the development of more effective therapies. This study demonstrated the antitumor effects</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-09-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>In the treatment of B-cell non-Hodgkin lymphoma, rituximab along with chemotherapy improves long-term survival. However, the majority of patients eventually relapse, requiring the development of more effective therapies. This study demonstrated the antitumor effects in mice of a treatment involving a survivin suppressant and rituximab. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>343:</strong><a href="http://jpet.aspetjournals.org/content/343/1/178 " title="178–183" target="_blank">178–183</a>. (JPET 195925) <br /></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3921&amp;blogid=219">
  <title>JPET Highlight: Modification of Glucorticoids Dissociate NF-kB Inhibitory Efficacy from GRE-associated Side Effects</title>
  <link>http://www.aspet.org/Blog.aspx?id=3921&amp;blogid=219</link>
  <description><![CDATA[<p>   Glucocorticoids are standard of care for many inflammatory. However, the side effect profiles of pharmacological glucocorticoids are significant. These results demonstrate that a Δ 9,11analogue dissociates the GR mediated transcriptional activities from anti inflammatory activities. See article</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-09-20T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>&#160;</p>
<p>Glucocorticoids are standard of care for many inflammatory. However, the side effect profiles of pharmacological glucocorticoids are significant. These results demonstrate that a Δ-9,11analogue dissociates the GR-mediated transcriptional activities from anti-inflammatory activities. See article at <em>J Pharmacol Exp Ther </em>2012, <strong>343:</strong><a target="_blank" title="225–232" href="http://jpet.aspetjournals.org/content/343/1/225">225–232</a>. (JPET 194340)</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3838&amp;blogid=219">
  <title>JPET Highlight: Inverse relationship between in vitro cannabinoid efficacy and decreased sensitivity after multiple days of dosing</title>
  <link>http://www.aspet.org/Blog.aspx?id=3838&amp;blogid=219</link>
  <description><![CDATA[<p>Synthetic cannabinoids are marketed and used as alternatives to cannabis. However, some synthetic cannabonoids have been shown to have higher CB1 receptor agonist efficacy. This difference might partially explain differences in dependence liability and adverse effects of the synthetic cannabinoids.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-08-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Synthetic cannabinoids are marketed and used as alternatives to cannabis. However, some synthetic cannabonoids have been shown to have higher CB1 receptor agonist efficacy. This difference might partially explain differences in dependence liability and adverse effects of the synthetic cannabinoids. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/3/843" title="843–849">843–849</a>. (JPET 196444)<br /><br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3837&amp;blogid=219">
  <title>JPET Highlight: Impact of Glucocorticosteroids and ß2-adrenoceptor agonists on airway smooth muscle</title>
  <link>http://www.aspet.org/Blog.aspx?id=3837&amp;blogid=219</link>
  <description><![CDATA[<p>Increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. In this study, glucocorticosteroids and &#223;2 adrenoceptor agonists synergistically inhibited ASM phenotype switching, potentially contributing to the increased effectiveness of combined treatment in asthma. See</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-08-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Increased airway smooth muscle (ASM) mass and contractility, contributes to increased airway narrowing in asthma. In this study, glucocorticosteroids and ß2-adrenoceptor agonists synergistically inhibited ASM phenotype switching, potentially contributing to the increased effectiveness of combined treatment in asthma. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/3/780" title="780–787">780–787</a>. (JPET 195867)<br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3836&amp;blogid=219">
  <title>JPET Highlight: Vivofludimus Improves Colitis in Rats by a Dual Mode of Action</title>
  <link>http://www.aspet.org/Blog.aspx?id=3836&amp;blogid=219</link>
  <description><![CDATA[<p>Vidofludimus (Vido) is a novel immunomodulatory drug that inhibits lymphocyte proliferation and IL 17 secretion and has been shown to improve colitis in rodents. The present study demonstrates that both inhibition of lymphocyte proliferation and IL 17 play important roles</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-08-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Vidofludimus (Vido) is a novel immunomodulatory drug that inhibits lymphocyte proliferation and IL-17 secretion and has been shown to improve colitis in rodents. The present study demonstrates that both inhibition of lymphocyte proliferation and IL-17 play important roles in the effect of Vido on colitis. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/3/850 " title="850–860">850–860</a>. (JPET 192203)<br /><br />]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3835&amp;blogid=219">
  <title>JPET Highlight: Antinociceptive Effects of Nicotinic Partial agonists in Acute and Tonic Pain Models</title>
  <link>http://www.aspet.org/Blog.aspx?id=3835&amp;blogid=219</link>
  <description><![CDATA[<p>Full agonists of nicotinic receptors have demonstrated antinociceptive effects in a wide range of acute, tonic and chronic pain models. However, their effectiveness is limited by side effects. This study shows that partial agonists of different nicotinic subtypes are also</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-08-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Full agonists of nicotinic receptors have demonstrated antinociceptive effects in a wide range of acute, tonic and chronic pain models. However, their effectiveness is limited by side effects. This study shows that partial agonists of different nicotinic subtypes are also potential targets for the treatment of pain. See article at <em>J Pharmacol Exp Ther </em>2012, <strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/3/742" title="742–749">742–749</a>. (JPET 194506)]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3683&amp;blogid=219">
  <title>JPET Highlight: Compartmentized regulation of adenylyl cyclases provides opportunity for selective bronchodilatory modalities</title>
  <link>http://www.aspet.org/Blog.aspx?id=3683&amp;blogid=219</link>
  <description><![CDATA[<p>   Investigators have found that ß adrenergic receptor agonists induce relaxation of airway smooth muscle via both cAMP dependent and  independent mechanisms. Therapies that take advantage of the distinct signaling complexes in order to more specifically alter</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-07-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p>Investigators have found that ß-adrenergic receptor agonists induce relaxation of airway smooth muscle via both cAMP-dependent and -independent mechanisms. Therapies that take advantage of the distinct signaling complexes in order to more specifically alter bronchodilation would represent exciting new treatment modalities. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a target="_blank" title="586–595" href="http://jpet.aspetjournals.org/content/342/2/586">586–595</a>. (JPET 193425)<br /><br />Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3682&amp;blogid=219">
  <title>JPET Highlight: Regulating hypoxia-inducible factor-1α with apolipoprotein A-I mimetic peptides</title>
  <link>http://www.aspet.org/Blog.aspx?id=3682&amp;blogid=219</link>
  <description><![CDATA[<p>   This study demonstrates that apoA I mimetic peptide L 4F treatment dramatically decreased HIF 1α expression in mouse ovarian tumor demonstrating that apoA I mimetic peptides inhibit expression and activity of HIF 1α and that inhibition of</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-07-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p></p>
<p>This study demonstrates that apoA-I mimetic peptide L-4F treatment dramatically decreased HIF-1α expression in mouse ovarian tumor demonstrating that apoA-I mimetic peptides inhibit expression and activity of HIF-1α and that inhibition of HIF-1α may be a critical mechanism responsible for suppression of tumor progression. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/2/255" title="255–262" target="_blank">255–262</a>. (JPET 191544)<br /><br />Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics<br /></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3681&amp;blogid=219">
  <title>JPET Highlight: Treating Parkinson’s disease with selective dopamine D4 antagonists</title>
  <link>http://www.aspet.org/Blog.aspx?id=3681&amp;blogid=219</link>
  <description><![CDATA[<p>   Oral administration of the dopamine D4 antagonist, L 745,870 in combination with L DOPA significantly alleviates dyskinesia. Importantly, the anti dyskinetic efficacy was achieved without compromising L DOPA anti parkinsonian benefit, thereby identifying D4 receptors as a</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-07-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p>Oral administration of the dopamine D4 antagonist, L-745,870 in combination with L-DOPA significantly alleviates dyskinesia. Importantly, the anti-dyskinetic efficacy was achieved without compromising L-DOPA anti-parkinsonian benefit, thereby identifying D4 receptors as a promising target for dyskinesia. See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>342:</strong><a target="_blank" href="http://jpet.aspetjournals.org/content/342/2/576" title="576–585">576–585</a>. (JPET 195693)<br /><br />Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3680&amp;blogid=219">
  <title>JPET Highlight: Modulating stress through ß adrenergic receptors as pharmacotherapy for relapse prevention</title>
  <link>http://www.aspet.org/Blog.aspx?id=3680&amp;blogid=219</link>
  <description><![CDATA[<p>   Data in beta receptor deficient KO mice suggest that activation of beta 2 adrenergic receptors is necessary for stress induced cocaine seeking. These findings suggest that targeting beta adrenergic receptors may represent a promising pharmacotherapeutic strategy for</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-07-17T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p>Data in beta receptor-deficient KO mice suggest that activation of beta-2 adrenergic receptors is necessary for stress-induced cocaine seeking. These findings suggest that targeting beta adrenergic receptors may represent a promising pharmacotherapeutic strategy for preventing drug relapse. See article at <em>J Pharmacol Exp Ther </em>2012, <strong>342:</strong><a target="_blank" title="541–551" href="http://jpet.aspetjournals.org/content/342/2/541"><span class="design_selected_field">541–551</span></a>. (JPET 193615)<br /><br />Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3561&amp;blogid=219">
  <title>&#39;How To&#39; Tips for Twitter</title>
  <link>http://www.aspet.org/Blog.aspx?id=3561&amp;blogid=219</link>
  <description><![CDATA[<p>For ASPET members who want to learn the basics of Twitter, including how to sign up for an account and get started, <a href="/uploadedFiles/Blog/ASPET/How-Tos for Twitter.pdf" title="click here" target="_blank">click here</a> to view a cheat sheet have created for you as a follow-up on our original "<a href="http://www.aspet.org/Blog.aspx?id=3272&amp;blogid=219" title="Twitter Tips for 'N00bs'" target="_blank">Twitter Tips for 'N00bs'</a>" article.</p>
<p> </p>
<p> </p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-06-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>For ASPET members who want to learn the basics of Twitter, including how to sign up for an account and get started, <a href="http://www.aspet.org/uploadedFiles/Blog/ASPET/How-Tos%20for%20Twitter.pdf" title="click here" target="_blank">click here</a> to view a cheat sheet we have created for you as a follow-up on our original "<a href="http://www.aspet.org/Blog.aspx?id=3272&amp;blogid=219" title="Twitter Tips for 'N00bs'" target="_blank">Twitter Tips for 'N00bs'</a>" article.</p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3535&amp;blogid=219">
  <title>JPET Highlight: Attenuation of chemotherapy-induced peripheral neuropathy by etodolac</title>
  <link>http://www.aspet.org/Blog.aspx?id=3535&amp;blogid=219</link>
  <description><![CDATA[<p>The antiallodynic effect of etodolac increases upon repeated administration therefore, along with safer long term use it may also attenuate the adverse neurological effects of paclitaxel chemotherapy. See article at J Pharmacol Exp Ther 2012, 342 53 60. (JPET 187401)Copyright</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-06-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>The antiallodynic effect of etodolac increases upon repeated administration; therefore, along with safer long-term use it may also attenuate the adverse neurological effects of paclitaxel chemotherapy. See article at<em>J Pharmacol Exp Ther 2012, </em><strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/1/53" title="53-60" target="_blank">53-60</a>. </p>
<p>Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3534&amp;blogid=219">
  <title>JPET Highlight: Regulation of vemurafenib exposure in the brain by ABC transporters</title>
  <link>http://www.aspet.org/Blog.aspx?id=3534&amp;blogid=219</link>
  <description><![CDATA[<p>Intracellular accumulation and brain exposure of vemurafenib was significantly restricted by P gp and BCRP and may significantly impact ongoing trials in brain metastases of melanoma.  See article at J Pharmacol Exp Ther 2012, 342 33 40.  (JPET 192195)Copyright ©</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-06-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Intracellular accumulation and brain exposure of vemurafenib was significantly restricted by P-gp and BCRP and may significantly impact ongoing trials in brain metastases of melanoma. See article at<em>J Pharmacol Exp Ther 2012, </em><strong>342:</strong><a href="http://jpet.aspetjournals.org/content/342/1/33" title="33-40" target="_blank">33-40</a>. (JPET 192195)</p>
<p>Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3533&amp;blogid=219">
  <title>JPET Highlight: Lyn kinase activator MLR-1023 potentiates insulin and improves glucose homeostasis</title>
  <link>http://www.aspet.org/Blog.aspx?id=3533&amp;blogid=219</link>
  <description><![CDATA[<p>MLR 1023 lowered blood glucose similar to metformin without eliciting a hypoglycemic response, with a faster onset of action than roziglitazone and without causing weight gain. See article at J Pharmacol Exp Ther 2012, 342 23 32. (JPET 192187)Copyright ©</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-06-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>MLR-1023 lowered blood glucose similar to metformin without eliciting a hypoglycemic response, with a faster onset of action than roziglitazone and without causing weight gain. See article at<em>J Pharmacol Exp Ther 2012, </em><strong>342:</strong><a target="_blank" title="23-32" href="http://jpet.aspetjournals.org/content/342/1/23">23-32</a>. (JPET 192187) </p>
<p>Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3532&amp;blogid=219">
  <title>JPET Highlight: Lyn activation and restoring glucose tolerance</title>
  <link>http://www.aspet.org/Blog.aspx?id=3532&amp;blogid=219</link>
  <description><![CDATA[<p>MLR 1023 reduced blood glucose levels without increasing insulin secretion in vivo by allosterically activating the non receptor linked kinase Lyn suggesting a new treatment modality for type 2 diabetes. See article at J Pharmacol Exp Ther 2012, 342 15</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-06-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>MLR-1023 reduced blood glucose levels without increasing insulin secretion in vivo by allosterically activating the non-receptor linked kinase Lyn suggesting a new treatment modality for type 2 diabetes. See article at<em>J Pharmacol Exp Ther 2012, </em><strong>342:</strong><a target="_blank" title="15-22" href="http://jpet.aspetjournals.org/content/342/1/15">15-22</a>. (JPET 192096)</p>
<p>Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3272&amp;blogid=219">
  <title>Twitter Tips for &#39;N00bs&#39;</title>
  <link>http://www.aspet.org/Blog.aspx?id=3272&amp;blogid=219</link>
  <description><![CDATA[<p>In reference to my first blog entry, “An Introduction to Social Media” (http www.aspet.org Blog.aspx?id=3245&amp;blogid=219), our aim is to try to reach members who have not yet joined the fray in social media and get them involved in the conversation.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-05-01T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>In reference to my first blog entry, “<a target="_blank" title="An Introduction to Social Media" href="http://www.aspet.org/Blog.aspx?id=3245&amp;blogid=219">An Introduction to Social Media</a>,” our aim is to try to reach members who have not yet joined the fray in social media and get them involved in the conversation. To those of you who are more experienced in social media, please feel free to share ideas and to help us reach the demographic of those who have not yet put forth a strong effort in social media.<br /><br />Those of you who attended ASPET programs at EB 2012 in San Diego, we hope you had a very thought-provoking meeting experience. <a target="_blank" title="Scicurious blogged about the ASPET Experimental Biology programming in detail" href="http://blogs.scientificamerican.com/scicurious-brain/">Scicurious blogged about the ASPET Experimental Biology programming in detail</a>, while we focused on live tweeting on Twitter to keep you abreast of our programs and activities throughout the day (<a target="_blank" title="http://www.twitter.com/aspet" href="http://www.twitter.com/aspet">http://www.twitter.com/aspet</a>). You may have also noticed tweets about our furry friend, the ASPET Donkey, making appearances at certain ASPET events at EB.<br /><br />Over the past few years, Twitter has become a go-to source to send out and receive breaking news. The often quirky snippets of information, also known as “tweets” give you details and often a link to click on within a span of 140 characters. As you are only allotted 140 characters per tweet, learning the abbreviated lingo for Twitter is a key element of getting this social network to work for you. I learned the term “n00b” (yes, those are zeros), short for neophyte, when I read some of the feedback on my initial blog post in April. I learned the term from following conversations about ASPET on Twitter, as the feedback portion of our PharmTalk blogs was not working at the time. Twitter is a useful tool to engage in dialog in that manner, and many associations use it to supplement their customer service efforts.<br /><br />A few other keys to Twitter are as follows: shortened URLs, hashtags, referencing others’ Twitter handles (a handle is what a Twitter account name is called), retweets, and modified tweets. The practice of shortening URLs—a URL is another name for a Web address—allows one to write more text in a given tweet as the Web address won’t take up as many spaces of your tweet after being shortened. Two of the most prominent URL shorteners are <a target="_blank" title="ow.ly" href="http://ow.ly">ow.ly</a> and <a target="_blank" title="bit.ly" href="https://bitly.com/">bit.ly</a>. To shorten your URL, go to one of these websites, type in the full URL, and click the button that says “shorten” or “shrink it.” Then, once you have logged into your Twitter account, all you have to do is click the blue “compose new tweet” button in the upper right-hand corner of the screen and copy and paste the shortened URL into your tweet along with a message that fits within the 140 character limit.<br /><br />The two most commonly used symbols on Twitter are “#” and “@.” Any Twitter text that follows a “#” is referred to as a “hashtag.” Following the pound sign, you must start with a letter (numbers but not symbols can follow the first letter). The idea of a Twitter hashtag is to create searchable topics on Twitter. This also allows Twitter to see what particular topics are trending at any given moment. If you wanted to see recent comments about ASPET, you could type “#ASPET” into the search feature at the top of the page. You can start topics by creating your own hashtag or add to topics that already exist by using the hashtag for that topic. Over the past few weeks, the #eb2012 hashtag was used in many tweets in preparation for and during Experimental Biology in San Diego in late April.<br /><br />The “@” is used to reference another person’s (or group’s) Twitter handle when you want to refer to them in any manner, reply to, or retweet one of their messages. As such, the “@” symbol should be followed by the name of the Twitter handle you are referencing in your tweet. If you want to reply to someone’s tweet, simply move your mouse so that the little hand icon on the screen is on the tweet to which you want to reply, click the link that says “open,” and once you have opened that tweet, click “reply” and type your message. In your reply, “@(TwitterHandleYouAreReplyingTo)” will show up and the beginning of your tweet.<br /><br />When you “retweet” a message, you are sharing another’s tweet with your list of followers on Twitter. ASPET shares important and interesting information generated from other groups or people in the scientific community by retweeting a handful of tweets of those whom we follow. There are three common ways to retweet a message. You can find a tweet that you would like to spread to your followers, and whether or not you are following that particular Twitter handle or they are following you, you can just hit the retweet button and the post shows up in your tweets as a retweet with the original tweeter’s Twitter handle above it. You can also retweet a message by typing “RT @(TwitterHandle)” plus the content of message. Or if you want to send a retweet but are modifying the text of the original tweet, you should, out of common courtesy, write “MT @(TwitterHandle)” plus the content of the modified message to signal that you are posting a modification of someone else’s tweet. When you type the “@” symbol plus a Twitter handle into the site’s search feature, you can track recent tweets in which that particular Twitter handle is mentioned.<br /><br />The above tips are in no way a comprehensive set of instructions and social mores on Twitter. This is merely an overview of the basics to help you get started. If you are still confused, we will soon be putting together a basic guide on how to use Twitter. So join us in the Twitter-verse and happy tweeting!</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3245&amp;blogid=219">
  <title>An Introduction to Social Media</title>
  <link>http://www.aspet.org/Blog.aspx?id=3245&amp;blogid=219</link>
  <description><![CDATA[<p>Hello everyone. Let me take a moment to introduce myself. My name is Gary Axelrod. I am the new Web and Social Media Manager at ASPET. We recently came up with the idea to do a monthly blog article about</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-04-02T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Hello everyone. Let me take a moment to introduce myself. My name is Gary Axelrod. I am the new Web and Social Media Manager at ASPET. We recently came up with the idea to do a monthly blog article about social media which aims to present both general ideas and some specifics as related to medical and research professionals, and of course pharmacology. So, without further ado, I thought I would start off with the basics for column number one.</p>
<p>Social media (also known as Web 2.0) is everywhere these days. Web 2.0 expertise is a great tool for subject matter experts to have. Of the vast array of social networks, each has their own niche market, audience, and followers. ASPET is currently active on Facebook, Twitter, and LinkedIn. We aim to use Facebook and Twitter to promote ASPET events, public policy issues, and current pharmacology news. We currently use LinkedIn to connect with our members and share information on ASPET public policy updates and careers in pharmacology.</p>
<p>We encourage you to get involved on your own with social media and connect with us. That way, you can establish a presence on social media and promote your own causes. By connecting with and engaging ASPET, there exists the potential for mutually beneficial opportunities, as we could each post or tweet back and forth in public view. Once you experiment and find the right social network avenues for yourself, this allows you to spread your knowledge and ideas far beyond the reach of traditional research and traditional media outlets. Social media outlets are great for sharing everything from quick updates to major discoveries. And of course, who doesn’t appreciate those tongue-in-cheek one-liners that we all see while scrolling through updates on our computer or mobile device?</p>
<p>As social media is still in its infancy—Twitter just recently turned six, and Facebook is the eight-year-old ball of energy in the house—there are no set ways to do things. This is both a blessing in that social media promotes originality and a curse in that one person’s social media boon could spell disaster for another person or organization. The main idea of social media is to serve as a platform by which one can easily share information. Ultimately, it’s up to you how helpful the information you share is. Social media is so popular that traditional media such as major magazines and TV outlets use it as a way to connect with readers and viewers and receive feedback from them. Subjectively speaking, the benefits of connecting with a broad reach of users on various social media networks are what make it all worthwhile.</p>
<p>As mentioned above, social media works both ways. If you have suggestions for us on how we can improve our social media outreach and engagement, consider this your invitation to submit feedback to us.</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3213&amp;blogid=219">
  <title>JPET Highlight: Nrf2 Pathway in the CNS</title>
  <link>http://www.aspet.org/Blog.aspx?id=3213&amp;blogid=219</link>
  <description><![CDATA[<p>Free radicals exert significant oxidative stress on tissues and cells and are implicated in the pathogenesis of neurodegenerative disorders such as multiple sclerosis (MS). The study by Scannevin et al. characterized the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and explored the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Using multiple assay formats, these studies indicate that both DMF and MMF are able to promote cytoprotective responses in cells by activating the Nrf2 pathway, enabling them to better withstand oxidative stress. The attenuation of H2O2-induced calcium accumulation, along with potential mitigation of other cellular events related to toxic oxidative challenge, resulted in MMF or DMF-dependent increase in viability in astrocytes and neurons in an Nrf2-dependent manner. The oxidative injury and challenge paradigms explored are highly relevant to the mechanistic damage that occurs in MS, and these preclinical studies using DMF and MMF collectively provide a compelling rationale for the use of DMF as a therapeutic agent in the treatment of MS.<br />See article at <em>J Pharmacol Exp Ther </em>2012, <strong>341:</strong><a title="274-284" href="http://jpet.aspetjournals.org/content/341/1/274" target="_blank">274-284</a>.  (JPET 190132)<br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-03-16T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Free radicals exert significant oxidative stress on tissues and cells and are implicated in the pathogenesis of neurodegenerative disorders such as multiple sclerosis (MS). The study by Scannevin et al. characterized the potential direct neuroprotective effects of dimethyl fumarate (DMF) and its primary metabolite monomethyl fumarate (MMF) on cellular resistance to oxidative damage in primary cultures of central nervous system (CNS) cells and explored the dependence and function of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway in this process. Using multiple assay formats, these studies indicate that both DMF and MMF are able to promote cytoprotective responses in cells by activating the Nrf2 pathway, enabling them to better withstand oxidative stress. The attenuation of H2O2-induced calcium accumulation, along with potential mitigation of other cellular events related to toxic oxidative challenge, resulted in MMF or DMF-dependent increase in viability in astrocytes and neurons in an Nrf2-dependent manner. The oxidative injury and challenge paradigms explored are highly relevant to the mechanistic damage that occurs in MS, and these preclinical studies using DMF and MMF collectively provide a compelling rationale for the use of DMF as a therapeutic agent in the treatment of MS.<br />See article at <em>J Pharmacol Exp Ther </em>2012, <strong>341:</strong><a title="274-284" href="http://jpet.aspetjournals.org/content/341/1/274" target="_blank">274-284</a>.  (JPET 190132)<br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3212&amp;blogid=219">
  <title>JPET Highlight: Treating Arthritis Through BTK Inhibition</title>
  <link>http://www.aspet.org/Blog.aspx?id=3212&amp;blogid=219</link>
  <description><![CDATA[<p>Nonreceptor tyrosine kinases, such as Bruton's tyrosine kinase (Btk), regulate the signal transduction of the B-cell antigen (BCR) and Fc (FcR) receptors that are critical in the development of rheumatoid arthritis (RA); therefore, pharmacological inhibition may affect multiple steps in the pathogenesis of RA and represent a useful therapeutic approach. The study by Xu et al. characterized the role of Btk using the novel, selective Btk inhibitor RN486 [6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one] in rodent and in vitro models of immune hypersensitivity and arthritis. The selective Btk inhibitor RN486 blocked BCR- and FcR-mediated biological and immune responses in both human cellular assays (tumor necrosis factor αproduction and CD69 expression) and rodent models (type I and III hypersensitivity), providing evidence for mechanism-based actions relevant to human diseases. RN486 produced robust efficacy in two standard rodent models of RA at concentrations that effectively block immunoreceptor-mediated pharmacodynamic responses, expression of CD69 in mice and PCA in rats. Together, these data show that Btk is a key regulator of immunoreceptor-mediated responses in both rodents and humans. Because these immunoreceptor-mediated responses are conserved between rodents and humans, and are essential for the development of immune arthritis in both species, they suggest clinical relevance and support the development of selective Btk inhibitors as RA therapeutics.<br />See article at <em>J Pharmacol Exp Ther </em>2012, <strong>341:</strong><a title="90-103" href="http://jpet.aspetjournals.org/content/341/1/90" target="_blank">90-103</a>.  (JPET 187740) <br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-03-16T14:54:00Z</dc:date>
  <content:encoded><![CDATA[Nonreceptor tyrosine kinases, such as Bruton's tyrosine kinase (Btk), regulate the signal transduction of the B-cell antigen (BCR) and Fc (FcR) receptors that are critical in the development of rheumatoid arthritis (RA); therefore, pharmacological inhibition may affect multiple steps in the pathogenesis of RA and represent a useful therapeutic approach. The study by Xu et al. characterized the role of Btk using the novel, selective Btk inhibitor RN486 [6-cyclopropyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-5-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-2H-isoquinolin-1-one] in rodent and in vitro models of immune hypersensitivity and arthritis. The selective Btk inhibitor RN486 blocked BCR- and FcR-mediated biological and immune responses in both human cellular assays (tumor necrosis factor αproduction and CD69 expression) and rodent models (type I and III hypersensitivity), providing evidence for mechanism-based actions relevant to human diseases. RN486 produced robust efficacy in two standard rodent models of RA at concentrations that effectively block immunoreceptor-mediated pharmacodynamic responses, expression of CD69 in mice and PCA in rats. Together, these data show that Btk is a key regulator of immunoreceptor-mediated responses in both rodents and humans. Because these immunoreceptor-mediated responses are conserved between rodents and humans, and are essential for the development of immune arthritis in both species, they suggest clinical relevance and support the development of selective Btk inhibitors as RA therapeutics.<br />See article at <em>J Pharmacol Exp Ther </em>2012, <strong>341:</strong><a title="90-103" href="http://jpet.aspetjournals.org/content/341/1/90" target="_blank">90-103</a>.  (JPET 187740) <br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3211&amp;blogid=219">
  <title>JPET Highlight: Epigenetic Regulation of Angiomyogenesis</title>
  <link>http://www.aspet.org/Blog.aspx?id=3211&amp;blogid=219</link>
  <description><![CDATA[<p>Inhibition of histone deacetylases (HDACs) by trichostatin A (TSA) has previously been shown to induce a pharmacological preconditioning effect against acute myocardial ischemia and reperfusion injury; however, it is not clear whether the mechanism of TSA promotes endogenous angiomyogenesis in infarcted mouse hearts. In the present study, Zhang et al. investigated whether in vivo inhibition of HDAC preserves cardiac performance and prevents cardiac remodeling in mouse myocardial infarction (MI) through stimulation of endogenous regeneration. These studies demonstrate that in vivo inhibition of HDAC improved cardiac functional recovery and antagonized myocardial remodeling in chronic MI. Notably, HDAC inhibition significantly improved animal survival rate after MI, which is associated with the mitigation of both myocardial and serum tumor necrosis factor α levels in MI heart. HDAC inhibition stimulated the self-renewal of cardiac stem cells and resulted in robust increases in proliferation and cytokinesis in the MI hearts, which are associated with the enhancement of the newly formed myocytes and angiogenic responses. HDAC inhibition-induced cardioprotection also involves the activation of Akt-1 and inhibition of apoptosis. This study provides novel evidence that a new therapeutic strategy could be developed based upon HDAC inhibition, eliciting the stimulation of cardiac endogenous regeneration and angiogenesis in the infarcted heart.</p>
<p>See article at <em>J Pharmacol Exp Ther </em>2012 <strong>341:</strong><a title="285-293" href="http://jpet.aspetjournals.org/content/341/1/285" target="_blank">285-293</a>.  (JPET 189910) </p>
<p>•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-03-16T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Inhibition of histone deacetylases (HDACs) by trichostatin A (TSA) has previously been shown to induce a pharmacological preconditioning effect against acute myocardial ischemia and reperfusion injury; however, it is not clear whether the mechanism of TSA promotes endogenous angiomyogenesis in infarcted mouse hearts. In the present study, Zhang et al. investigated whether in vivo inhibition of HDAC preserves cardiac performance and prevents cardiac remodeling in mouse myocardial infarction (MI) through stimulation of endogenous regeneration. These studies demonstrate that in vivo inhibition of HDAC improved cardiac functional recovery and antagonized myocardial remodeling in chronic MI. Notably, HDAC inhibition significantly improved animal survival rate after MI, which is associated with the mitigation of both myocardial and serum tumor necrosis factor α levels in MI heart. HDAC inhibition stimulated the self-renewal of cardiac stem cells and resulted in robust increases in proliferation and cytokinesis in the MI hearts, which are associated with the enhancement of the newly formed myocytes and angiogenic responses. HDAC inhibition-induced cardioprotection also involves the activation of Akt-1 and inhibition of apoptosis. This study provides novel evidence that a new therapeutic strategy could be developed based upon HDAC inhibition, eliciting the stimulation of cardiac endogenous regeneration and angiogenesis in the infarcted heart.</p>
<p>See article at <em>J Pharmacol Exp Ther </em>2012 <strong>341:</strong><a title="285-293" href="http://jpet.aspetjournals.org/content/341/1/285" target="_blank">285-293</a>.  (JPET 189910) </p>
<p>•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=3210&amp;blogid=219">
  <title>JPET Highlight: Humanized Glycoprotein VI Mouse Models</title>
  <link>http://www.aspet.org/Blog.aspx?id=3210&amp;blogid=219</link>
  <description><![CDATA[<p>The search for better antiplatelet drugs that efficiently prevent platelet thrombus formation while having a minimal effect on general hemostasis remains a competitive challenge. Glycoprotein VI (GPVI) is considered to be an attractive target for the development of new antithrombotic agents. Mangin et al. developed a genetically modified mouse expressing human GPVI (hGPVI) as a preclinical tool to evaluate the role of human GPVI in various models of thrombosis and to screen anti-GPVI compounds. The mice were viable, fertile, and without hematological defects; platelet aggregation, fibrinogen binding, and P-selectin exposures were normal in response to various agonists. The blocking antibody Fab fragment 9O12.2 (anti-GPVI) inhibited collagen-induced platelet aggregation in vitro and ex vivo. In hGPVI mice, 9O12.2 did not prolong tail bleeding time or increase blood loss. The hGPVI model therefore offers the possibility of establishing the bleeding tendency of anti-GPVI compounds alone or associated in dual or tri-therapy with other antiplatelet agents. This unique animal model may permit evaluation of agents targeting human GPVI in terms of efficacy and safety and enable one to determine more relevant human doses and therapeutic combinations, which may help design future clinical studies.</p>
<p>See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>341:</strong><a title="156-163" href="http://jpet.aspetjournals.org/content/341/1/156" target="_blank">156-163</a>.  (JPET 189050)  <br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>
<p> </p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-03-16T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>The search for better antiplatelet drugs that efficiently prevent platelet thrombus formation while having a minimal effect on general hemostasis remains a competitive challenge. Glycoprotein VI (GPVI) is considered to be an attractive target for the development of new antithrombotic agents. Mangin et al. developed a genetically modified mouse expressing human GPVI (hGPVI) as a preclinical tool to evaluate the role of human GPVI in various models of thrombosis and to screen anti-GPVI compounds. The mice were viable, fertile, and without hematological defects; platelet aggregation, fibrinogen binding, and P-selectin exposures were normal in response to various agonists. The blocking antibody Fab fragment 9O12.2 (anti-GPVI) inhibited collagen-induced platelet aggregation in vitro and ex vivo. In hGPVI mice, 9O12.2 did not prolong tail bleeding time or increase blood loss. The hGPVI model therefore offers the possibility of establishing the bleeding tendency of anti-GPVI compounds alone or associated in dual or tri-therapy with other antiplatelet agents. This unique animal model may permit evaluation of agents targeting human GPVI in terms of efficacy and safety and enable one to determine more relevant human doses and therapeutic combinations, which may help design future clinical studies.</p>
<p>See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>341:</strong><a title="156-163" href="http://jpet.aspetjournals.org/content/341/1/156" target="_blank">156-163</a>.  (JPET 189050)  <br />•Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2441&amp;blogid=219">
  <title>JPET Highlight: Spleen Tyrosine Kinase Selective Inhibitor and Treatment of Rheumatoid Arthritis</title>
  <link>http://www.aspet.org/Blog.aspx?id=2441&amp;blogid=219</link>
  <description><![CDATA[<p> Spleen tyrosine kinase (Syk) is broadly involved in regulating leukocyte immune function, principally by facilitating cellular activation in response to receptor engagement of antigen or of immune complex. Coffey et al. report on the discovery and characterization of (4-(3-(2<em>H</em>-1,2,3-triazol-2-yl)phenylamino)-2-((1<em>R</em>, 2<em>S</em>)-2-aminocyclohexylamino) pyrimidine-5-carboxamide acetate (P505-15), a novel, highly specific and potent orally available small-molecule inhibitor of Syk; they test the hypothesis that specific pharmacological inhibition of Syk kinase activity is sufficient to modulate leukocyte immune function and ameliorate inflammation in vivo. P505-15 potently and specifically inhibited Syk kinase activity in vitro (including whole blood assays), and ex vivo after oral dosing of P505-15, without inhibiting Syk-independent signaling. Submicromolar concentrations in blood, predicted to result in 67% inhibition of Syk, led to statistically significant anti-inflammatory effects in the mouse collagen antibody-induced arthritis (CAIA) and the rat collagen-induced arthritis (CIA) models. Syk kinase inhibition by P505-15 mimics the immunomodulatory phenotype of Syk knockout observed in other rodent models of rheumatoid arthritis. These data suggest that the specific inhibition of Syk may be a sufficient and safe strategy to control immune function in inflammatory diseases. P505-15 is currently in clinical development for the treatment of inflammatory diseases.</p>
<p id="p-2" style="font-size: 13px; ">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/350" class="design_selected_field">350–359</a>.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-01-24T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1">Spleen tyrosine kinase (Syk) is broadly 
involved in regulating leukocyte immune function, principally by 
facilitating cellular
                  activation in response to receptor engagement of 
antigen or of immune complex. Coffey et al. report on the discovery and 
characterization
                  of (4-(3-(2<em>H</em>-1,2,3-triazol-2-yl)phenylamino)-2-((1<em>R</em>, 2<em>S</em>)-2-aminocyclohexylamino)
 pyrimidine-5-carboxamide acetate (P505-15), a novel, highly specific 
and potent orally available
                  small-molecule inhibitor of Syk; they test the 
hypothesis that specific pharmacological inhibition of Syk kinase 
activity
                  is sufficient to modulate leukocyte immune function 
and ameliorate inflammation in vivo. P505-15 potently and specifically
                  inhibited Syk kinase activity in vitro (including 
whole blood assays), and ex vivo after oral dosing of P505-15, without 
inhibiting
                  Syk-independent signaling. Submicromolar 
concentrations in blood, predicted to result in 67% inhibition of Syk, 
led to statistically
                  significant anti-inflammatory effects in the mouse 
collagen antibody-induced arthritis (CAIA) and the rat collagen-induced
                  arthritis (CIA) models. Syk kinase inhibition by 
P505-15 mimics the immunomodulatory phenotype of Syk knockout observed 
in
                  other rodent models of rheumatoid arthritis. These 
data suggest that the specific inhibition of Syk may be a sufficient and
                  safe strategy to control immune function in 
inflammatory diseases. P505-15 is currently in clinical development for 
the treatment
                  of inflammatory diseases.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/350">350–359</a>.
               </p>
<ul class="copyright-statement">
<li id="copyright-statement-1" class="fn">Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</li>
</ul>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2440&amp;blogid=219">
  <title>JPET Highlight: Knockin of Mutated α1 Glycine Receptor Subunits Alters Sensitivity to GABAergic Drugs</title>
  <link>http://www.aspet.org/Blog.aspx?id=2440&amp;blogid=219</link>
  <description><![CDATA[<p>Alcohol actions on recombinant glycine receptors (GlyRs) showed that mutations M287L and Q266I of the α1 subunit lead to a reduction in ethanol potentiation of glycine-induced current. Blednov et al. constructed knockin mice with each of these mutations, allowing the use of behavioral testing to determine the influence of these changes on behavioral effects of ethanol and other drugs. Rotarod ataxia was one behavioral effect of ethanol reduced more in the Q266I mutant than the M287L mutant. Mutant mice also differed in ethanol consumption, ethanol-stimulated startle response, signs of acute physical dependence, and duration of loss of righting response produced by ethanol, butanol, ketamine, pentobarbital, and flurazepam. Some of these behavioral changes were mimicked in wild-type mice by acute injections of low, subconvulsive doses of strychnine. Both mutants showed increased acoustic startle response and increased sensitivity to strychnine seizures. In addition to reducing ethanol action on the GlyRs, these mutations reduced glycinergic inhibition, which may also alter sensitivity to GABAergic drugs. These results show the ability of a single amino acid change in the GlyR α1 subunit to decrease specific behavioral actions of ethanol and to alter other nonethanol behaviors, demonstrating the importance of GlyR function in diverse neuronal systems.</p>
<p id="p-2" style="font-size: 13px; ">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/317">317–329</a>.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-01-24T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1">Alcohol actions on recombinant glycine 
receptors (GlyRs) showed that mutations M287L and Q266I of the α1 
subunit lead to a
                  reduction in ethanol potentiation of glycine-induced 
current. Blednov et al. constructed knockin mice with each of these 
mutations,
                  allowing the use of behavioral testing to determine 
the influence of these changes on behavioral effects of ethanol and 
other
                  drugs. Rotarod ataxia was one behavioral effect of 
ethanol reduced more in the Q266I mutant than the M287L mutant. Mutant
                  mice also differed in ethanol consumption, 
ethanol-stimulated startle response, signs of acute physical dependence,
 and duration
                  of loss of righting response produced by ethanol, 
butanol, ketamine, pentobarbital, and flurazepam. Some of these 
behavioral
                  changes were mimicked in wild-type mice by acute 
injections of low, subconvulsive doses of strychnine. Both mutants 
showed
                  increased acoustic startle response and increased 
sensitivity to strychnine seizures. In addition to reducing ethanol 
action
                  on the GlyRs, these mutations reduced glycinergic 
inhibition, which may also alter sensitivity to GABAergic drugs. These 
results
                  show the ability of a single amino acid change in the 
GlyR α1 subunit to decrease specific behavioral actions of ethanol and
                  to alter other nonethanol behaviors, demonstrating the
 importance of GlyR function in diverse neuronal systems.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/317">317–329</a>.
               </p>
<ul class="copyright-statement">
<li id="copyright-statement-1" class="fn">Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</li>
</ul>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2439&amp;blogid=219">
  <title>JPET Highlight: Mutations of the α1 Glycine Receptor Subunit Regulate Sensitivity to Alcohols</title>
  <link>http://www.aspet.org/Blog.aspx?id=2439&amp;blogid=219</link>
  <description><![CDATA[<p> Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels, and ethanol has the ability to potentiate glycine activation of the GlyR. Borghese et al. investigated the putative binding sites for alcohol (alteration of ethanol sensitivity) by introducing two mutations in the GlyR α1 subunit, M287L [transmembrane domain (TM) 3] and Q266I (TM2). Both mutants showed a reduction in glycine sensitivity and glycine-induced maximal currents. Activation by taurine, another endogenous agonist, was almost abolished in the M287L GlyR. Zinc enhancement of ethanol potentiation of glycine responses was absent in M287L GlyRs. Survival of homozygous knockin mice was impaired, and electrophysiological features of isolated neurons in the brain stem showed decreased glycine-mediated currents and decreased ethanol potentiation. This study suggests that many of the basic characteristics, such as channel properties, present in mutated GlyRs expressed in <em>Xenopus laevis</em> oocytes and human embryonic kidney 293 cells were similar to those observed in isolated neurons and membrane preparations from the corresponding knockin mice: 1) a small but general impairment of glycine action, most evident in the glycine-induced maximal currents, and 2) lack of sensitivity to ethanol.</p>
<p id="p-2" style="font-size: 13px; ">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/304">304–316</a>.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-01-24T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1">Glycine receptors (GlyRs) are inhibitory 
ligand-gated ion channels, and ethanol has the ability to potentiate 
glycine activation
                  of the GlyR. Borghese et al. investigated the putative
 binding sites for alcohol (alteration of ethanol sensitivity) by 
introducing
                  two mutations in the GlyR α1 subunit, M287L 
[transmembrane domain (TM) 3] and Q266I (TM2). Both mutants showed a 
reduction
                  in glycine sensitivity and glycine-induced maximal 
currents. Activation by taurine, another endogenous agonist, was almost
                  abolished in the M287L GlyR. Zinc enhancement of 
ethanol potentiation of glycine responses was absent in M287L GlyRs. 
Survival
                  of homozygous knockin mice was impaired, and 
electrophysiological features of isolated neurons in the brain stem 
showed decreased
                  glycine-mediated currents and decreased ethanol 
potentiation. This study suggests that many of the basic 
characteristics,
                  such as channel properties, present in mutated GlyRs 
expressed in <em>Xenopus laevis</em> oocytes and human embryonic kidney 
293 cells were similar to those observed in isolated neurons and 
membrane preparations
                  from the corresponding knockin mice: 1) a small but 
general impairment of glycine action, most evident in the 
glycine-induced
                  maximal currents, and 2) lack of sensitivity to 
ethanol.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/304">304–316</a>.
               </p>
<ul class="copyright-statement">
<li id="copyright-statement-1" class="fn">Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</li>
</ul>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2438&amp;blogid=219">
  <title>JPET Highlight: Treating Asthma with Prostaglandin D2 Receptor Antagonists</title>
  <link>http://www.aspet.org/Blog.aspx?id=2438&amp;blogid=219</link>
  <description><![CDATA[<p> On mast cells, prostaglandin D 2  (PGD 2 ) and its receptor D prostanoid receptor 2 (DP 2 )
 have been linked to the development of allergic inflammation, which has
 spurred interest in identifying more potent and
                  selective antagonists of this receptor to treat asthma
 and related disorders.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-01-24T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1">On mast cells, prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) and its receptor D prostanoid receptor 2 (DP<sub>2</sub>)
 have been linked to the development of allergic inflammation, which has
 spurred interest in identifying more potent and
                  selective antagonists of this receptor to treat asthma
 and related disorders. Pettipher et al. describe the pharmacological
                  profile of 
(5-fluoro-2-methyl-3-quinolin-2-ylmethylindo-1-yl)-acetic acid 
(OC000459), an indole-1-acetic acid derivative and
                  a potent and selective DP<sub>2</sub> antagonist. OC000459 potently displaces PGD<sub>2</sub> from DP<sub>2</sub> but does not interfere with the ligand-binding properties or functional activities of other prostanoid receptors. OC000459
                  competitively antagonized eosinophil shape-change responses induced by PGD<sub>2</sub>.
 OC000459 inhibited activation of T helper 2 (Th2) cells and eosinophils
 in response to supernatants from IgE/anti-IgE activated
                  human mast cells. OC000459 was orally bioavailable in 
rats and inhibited blood eosinophilia and airway eosinophilia in 
response
                  to 13,14-dihydro-15-keto-PGD<sub>2</sub>. OC000459 is a highly potent, selective, and orally active DP<sub>2</sub>
 antagonist that inhibits mast cell-dependent activation of Th2 cells 
and eosinophils. This compound is proving to be an excellent
                  tool in defining the role of DP<sub>2</sub> in asthma and related allergic disorders. It is currently being evaluated in phase IIb trials and has the potential to be
                  one of a new class of oral anti-inflammatory agents to treat allergic disorders.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/473">473–482</a>.
               </p>
<ul class="copyright-statement">
<li class="fn" id="copyright-statement-1">Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics</li>
</ul>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2436&amp;blogid=219">
  <title>How do we prepare pharmacology students for the world outside of academia?</title>
  <link>http://www.aspet.org/Blog.aspx?id=2436&amp;blogid=219</link>
  <description><![CDATA[<p>&#160; Remy L. Brim, PhD Bioethics Fellow National Institutes of Health &#160; Since finishing my pharmacology Ph.D. in February, I have been thinking about the experiences I had during graduate school, and which ones really have prepared me for my</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2012-01-13T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p align="center"> </p>
<p align="center">Remy L. Brim, PhD</p>
<p align="center">Bioethics Fellow</p>
<p align="center">National Institutes of Health</p>
<p align="center"><strong> </strong></p>
<p>Since finishing
my pharmacology Ph.D. in February, I have been thinking about the experiences I
had during graduate school, and which ones really have prepared me for my life
outside of the lab. Although pharmacologists as a whole are doing well in the <a href="http://news.yahoo.com/blogs/lookout/10-college-majors-lowest-unemployment-rates-163049193.html">job
market</a>, I don’t believe that this reflects they are <em>all</em> employed in the positions they want to be in, or in positions
that will help them achieve their career goals. 
I know that after graduation, some students who do not want to be on an
academic track will accept post-doctoral fellowships that will prepare them for
little else than academia.  We can better
prepare students who aim for careers away from the bench for what they will
face after graduation. </p>
<p>Students
that attend graduate school in other fields (such as medicine, law, business, mathematics
or philosophy) either have a structured system for finding a position after
graduation or are taught career development skills as part of their curriculum.  Pharmacology and other basic science PhDs are
very different in this regard.  What to
do after graduation seems to most students like a vague notion of “getting a
post-doc” and one day “finding a real job”. 
Furthermore, it’s very difficult as a student to find opportunities
outside of academia that align to ones strengths and interests while working in
an academic setting, sometimes in a geographical location without many other
scientific professionals.</p>
<p>I am currently a
Bioethics Fellow in the Clinical Center at the National Institutes of Health
where I work in a multidisciplinary department made up of doctors,
philosophers, lawyers, nurses, and post-bachelor’s degree fellows.  I’d like to give you my perspective, as a <em>very</em> recent graduate who is away from
the bench, on the three most useful educational opportunities and professional
development skills that can help students. 
 </p>
<p><strong>Refine scientific writing skills and develop writing skills for broader
audiences:</strong> I credit much of my success in and after graduate school to my thesis
advisors and graduate department demanding a lot of writing.  We were required to take a grant writing
course and complete a grant on our thesis research, followed by Preliminary
Exams which included writing an additional grant on a topic <em>not</em> related to our thesis work.  I wrote and published several first-author
papers.  I also had the opportunity to
collaborate with the pharmaceutical industry and wrote industrial research
protocols and study reports.  Through
ASPET, I was able to write a press release about some of my work.  </p>
<p>Being forced to
learn different styles and grow as a writer has been the single most helpful
thing I did. The breadth of writing I did is more than what many graduate
students have the opportunity to do. Because of my experiences, I’m now more
flexible with my style, more open to critiques, and have more confidence to try
new things. It also helped during interviews to have tangible proof of my experience.  As faculty mentors, providing more
opportunities for students to gain science writing experience, besides basic publications
and grants (whether that be through courses, lab activities, mock job
applications etc), would really benefit them. 
For students, be proactive and seek out these opportunities from your
mentor and the people around you if they aren’t built into your curriculum.</p>
<p><strong>Learn to orally convey research, arguments, and knowledge effectively:  </strong>My graduate department trained us to effectively
communicate by requiring one formal seminar presentation per year until
graduation. It was always practiced with at least one course director before it
was given, and received a post-seminar critique.  By the time my thesis defense came and I was
interviewing, I had the skills to prepare and deliver effective
presentations.  I’ve also become much
more skilled at non-formalized public speaking through this experience.  </p>
<p>Though
not every program has a system of “speaker training,” the difference between
those who are practiced and those who are not is astounding.  Oral communication is such a critical skill
and is highlighted when competing for jobs with people who may have an MBA or a
JD; whose degrees required a high level of proficiency in oral communication.  Students need to be pushed to (and themselves
look for opportunities to) communicate in public forums about what they do in
order to be competitive in the job market (either academic or non-academic!).  The only way to get better at this skill is
to do it, however nerve-racking it may be.</p>
<p><strong>Develop a career strategy: </strong>Much of my knowledge and success so far
is attributable to my mentor who successfully made the transition from academia
and has worked with me closely for the last couple of years.  A lot of what I’m going to share I learned
through this relationship, and from career sessions at Experimental Biology
meetings. Students can help themselves with these tools and mentors can help
their students by encouraging them to use these tools: </p>
<p><em>Start thinking about what to do next, well
before you have to do it</em>- The job search takes a long time, as does
figuring out which path one wants to take.  This needs to be done alongside thesis work,
not after it’s complete.  Experimental
Biology has career sessions to help gain a broad understanding of the job
search process.  Browsing job postings
from the <a href="http://www.usajobs.gov/">federal government</a> and
pharmaceutical companies is a good way to see what types of positions exist,
and identify the skills and experiences they require.  This creates a workable pathway for
developing a skill set that qualifies you for positions of interest.  Communication between students and thesis
advisors and/or committees about career interests is essential, as senior
members in the field have a board network that they can access to help
students.</p>
<p><em>Conduct informational interviews- </em>This is a great way to learn about what other people (like
the ones in a committee members network) are doing, whether it’s a lab for a
post-doc, work life at a specific company, or details on a type of career.  The <a href="http://career.ucsf.edu/lifesci/options.learn.html">UCSF Office of Career and Professional Development </a>has great resources for scientists on how to request
an interview, questions to ask, goals to achieve in the interview, etc (their
site also has great advice on application cover letters, resumes, CVs and job
interviewing). Talking with many people will develop a breadth of knowledge for
the kinds of opportunities that are available.  Although people are very busy, they are, in my
experience, very willing to talk with young people that are interested in their
achievements. </p>
<p><em>Develop a professional image and attitude</em>-
The biggest difference I have seen between science PhD students and post-docs and
the other advanced degree holders is their attitude when introducing themselves
and their work when networking.  Introducing
yourself as “I’m just a post-doc, working in a lab” does not give credence to the
skills, abilities and knowledge you’ve obtained.  If you state confidently:  “I’m a Pharmacologist, currently working on
how cancer cells interact with new chemotherapeutic drugs and am gaining a
greater knowledge of drug regulation by leading an interest group of my
colleagues once a month,” people’s interest will be piqued, especially people
in those “alternative” fields.  Develop
an “elevator pitch” so that what you do can be conveyed in a quick and easy-to-understand
way.  Order some business cards to take
to scientific conferences (or informational interviews) so contact information
can be easily exchanged.  </p>
<p><em>Take on volunteer work</em>- Remember the “dream
job” posting that required a skill or experience that was lacking? Find a way
to get it! If that’s more writing experience, volunteer to write things for a
PI, for the university’s press office, for a professional society, or for a
local paper.  If it’s speaking skills,
volunteer to give a seminar in another department or at a local high school.  Leadership experience can be gained by organizing
a session at a conference, starting and running a journal club or interest
group, or helping to organize departmental events. It’s more work, but it
demonstrates initiative and gives tangible proof of abilities.  </p>
<p>What I needed as
a student was to have someone give me a little push of confidence and some
tasks I could do to help myself.  If you’re
a mentor, sit down with your students, let them know that you are there to help
and give them some of these small things to do if they are struggling with choosing
a career path, or how to get down the path they’ve chosen.  If you’re a student, you’ve already done the
hardest work in the lab, so gain some of the extra skills needed<a name="_GoBack"></a> to succeed and work on building your image! It’s the best
thing you can do.</p>
<p> </p>
<p><em>These views and
opinions are my own and do not reflect the views of the National Institutes of
Health, the Department of Health and Human Services or the United States Federal
Government.</em></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2414&amp;blogid=219">
  <title>JPET Highlight: Glycogen Synthase Kinase 3β/β-Catenin Signaling but Not Hypoxia-Inducible Factor-1α Contributes to Defective Renal Wound Healing during Hypoxia</title>
  <link>http://www.aspet.org/Blog.aspx?id=2414&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
 During wound healing, hypoxia, partly as a result of 
vascular damage and decreased blood supply along with increased oxygen
                  consumption of wounded cells, induces angiogenesis and
 tissue remodeling but may also affect the healing response of 
parenchymal
                  cells. Peng et</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-12-29T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1"> </p>
<p id="p-1">During wound healing, hypoxia, partly as a result of 
vascular damage and decreased blood supply along with increased oxygen
                  consumption of wounded cells, induces angiogenesis and
 tissue remodeling but may also affect the healing response of 
parenchymal
                  cells. Peng et al. investigated whether and how 
hypoxia affects wound healing in parenchymal cells in injured organs, 
such
                  as the kidneys. When renal proximal tubular cells 
(RPTC) are exposed to hypoxic conditions (1% oxygen), wound healing 
(scratch
                  model) and migration are significantly slower. 
Hypoxia-inducible factor-1α (HIF-1α) was induced by wounding under 
normoxic
                  and enhanced under hypoxic conditions; however, 
scratch-wound healing was not significantly affected by either 
pharmacological
                  activation of HIF or genetic deletion of HIF-1. The 
induction of β-catenin during hypoxia is accompanied by glycogen 
synthase
                  kinase 3β (GSK3β) inactivation (possibly by Akt 
activation) and can be mimicked by pharmacological inhibition of GSK3β. 
Significantly
                  higher Akt activation was observed during wound 
healing under hypoxia. These results suggest that hyperactivation of Akt
 by
                  wound healing in hypoxic cells may inactivate GSK3β, 
resulting in the induction of β-catenin to prevent wound healing in 
renal
                  tubular cells under hypoxia.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/176">176–184</a></p>
<p id="p-2"><a href="http://jpet.aspetjournals.org/lookup/volpage/340/176"></a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2413&amp;blogid=219">
  <title>JPET Highlight: Role of Neuronal Nitric-Oxide Synthase in Acetaminophen-Induced Hepatotoxicity</title>
  <link>http://www.aspet.org/Blog.aspx?id=2413&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
 Acetaminophen (APAP;  N -acetyl- p -aminophenol),
 a commonly used analgesic/antipyretic drug, when overdosed, produces a 
centrilobular hepatic necrosis and hepatotoxicity
                  driven predominantly by oxidative stress. Agarwal et 
al. studied the role of neuronal nitric-oxide synthase (nNOS) in</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-12-29T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1"> </p>
<p id="p-1">Acetaminophen (APAP; <em>N</em>-acetyl-<em>p</em>-aminophenol),
 a commonly used analgesic/antipyretic drug, when overdosed, produces a 
centrilobular hepatic necrosis and hepatotoxicity
                  driven predominantly by oxidative stress. Agarwal et 
al. studied the role of neuronal nitric-oxide synthase (nNOS) in 
APAP-induced
                  hepatotoxicity in nNOS knockout (KO) and wild-type 
(WT) mice. APAP toxicity induced significant increases in alanine 
aminotransferase
                  (ALT) and aspartate aminotransferase (AST) in WT mice 
as early as 4 h after dosing, whereas in nNOS KO mice, the increases
                  were significantly delayed, occurring 8 h after 
dosing. However, there was no difference between WT and nNOS KO mice in 
terms
                  of the ultimate histopathology of APAP hepatotoxicity.
 Because oxidative stress is regulated by manganese superoxide dismutase
                  (MnSOD), it is interesting that MnSOD is the only 
nitrated protein in nNOS KO mice, which suggests that nitration of MnSOD
                  is dependent on other NOS forms in the liver. 
Decreased MnSOD activity coincides with increased nitration of MnSOD and
 increased
                  ALT release, suggesting that inhibition of MnSOD 
activity in APAP toxicity contributes to toxicity. These results 
indicate
                  that the delay in the onset of hepatotoxicity in the 
nNOS KO mice compared with the WT mice suggests that nNOS plays an 
important
                  role in initiation of APAP hepatotoxicity.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/134">134–142</a></p>
<p id="p-2"><a href="http://jpet.aspetjournals.org/lookup/volpage/340/134"></a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2412&amp;blogid=219">
  <title>JPET Highlight: Targeting the Arthritic Joint with Small Interfering RNA-Encapsulated Liposomes</title>
  <link>http://www.aspet.org/Blog.aspx?id=2412&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
 Rheumatoid arthritis (RA) is characterized by chronic 
synovitis affecting multiple joints. Some forms of RA can be effectively
                  treated with anti-TNF-α therapies. However, systemic 
treatment with anti-tumor necrosis factor-α (TNF-α) therapies can result
                  in an impaired</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-12-29T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1"> </p>
<p id="p-1">Rheumatoid arthritis (RA) is characterized by chronic 
synovitis affecting multiple joints. Some forms of RA can be effectively
                  treated with anti-TNF-α therapies. However, systemic 
treatment with anti-tumor necrosis factor-α (TNF-α) therapies can result
                  in an impaired immune system and opportunistic 
infection; therefore, targeting therapies to the inflamed joints could 
avoid
                  some of these systemic toxicities. Komano et al. 
evaluated the accumulation of small interfering RNA (siRNA)-encapsulated
                  liposomes in inflamed joints and the therapeutic 
potential of these siRNA-encapsulated liposomes targeting TNF-α. Using a
                  complex of the encapsulated liposome wrapsome (WS) and
 Cy5-labeled siRNA (siRNA/WS), higher fluorescence was observed in the
                  inflamed joints versus normal tissues and in 
synoviocytes versus splenocytes/bone marrow/peripheral blood leukocytes.
 The
                  majority of Cy5-positive synoviocytes were CD11b<sup>+</sup>, primarily macrophages and neutrophils. With the TNF-α targeting siRNA/WS, significant reductions in TNF-α mRNA and severity
                  of the arthritis in the joints were observed. The siRNA/WS was mainly incorporated into CD11b<sup>+</sup>
 cells, including macrophages and neutrophils, in the inflamed synovium,
 suggesting its potential therapeutic effects in RA
                  by silencing the expression of inflammatory molecules 
produced by these cells in the joint and not systemically.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/109">109–113</a></p>
<p id="p-2"><a href="http://jpet.aspetjournals.org/lookup/volpage/340/109"></a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2411&amp;blogid=219">
  <title>JPET Highlight: Histamine 3 Receptor and Angiotensin II Receptor Balance Regulates Cardiac Arrythmias</title>
  <link>http://www.aspet.org/Blog.aspx?id=2411&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
 In severe myocardial ischemia, norepinephrine (NE) is 
abundantly carried out of sympathetic nerve terminals by the NE 
transporter,
                  neuronal NA + /H +  exchanger (NHE), and is a key arrhythmogenic determinant. Hashikawa-Hobara et al. investigated whether enhanced ischemic
                 </p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-12-29T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p id="p-1"> </p>
<p id="p-1">In severe myocardial ischemia, norepinephrine (NE) is 
abundantly carried out of sympathetic nerve terminals by the NE 
transporter,
                  neuronal NA<sup>+</sup>/H<sup>+</sup> exchanger (NHE), and is a key arrhythmogenic determinant. Hashikawa-Hobara et al. investigated whether enhanced ischemic
                  cardiac dysfunction, which is manifest when histamine H3 receptors (H<sub>3</sub>R) are blocked or deleted, results from an unimpeded angiotensin II receptor (AT<sub>1</sub>R)-NHE activation. These studies have uncovered a novel cardioprotective action resulting from activation of neuronal H<sub>3</sub>R in mammalian heart. Binding of an endogenous ligand to H<sub>3</sub>R,
 most likely histamine, released by action of reactive oxygen species 
produced during ischemia/reperfusion, reduces the
                  formation of diacylglycerol, diminishing protein 
kinase C activity. This in turn decreases NHE activity, causing 
intracellular
                  acidification, and stimulates the production of nitric
 oxide (NO), which suppresses AT<sub>1</sub>R expression. H<sub>3</sub>R-induced decrease in NHE activity and increased NO synthesis may be responsible for decreased AT<sub>1</sub>R protein abundance. These findings suggest that down-regulation of AT<sub>1</sub>R signaling and attenuation of NE release by activation of neuronal H<sub>3</sub>R are plausible mechanisms of cardioprotection, not only in myocardial ischemia but also in other cardiac dysfunctions in
                  which ANG II plays a major role, such as heart failure.
               </p>
<p id="p-2">See article at <em>J Pharmacol Exp Ther</em> 2012, <strong>340:</strong><a href="http://jpet.aspetjournals.org/lookup/volpage/340/185">185–191</a></p>
<p id="p-2"><a href="http://jpet.aspetjournals.org/lookup/volpage/340/185"></a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2372&amp;blogid=219">
  <title>Translating Pharmacology into Career Choices in the Pharmaceutical and  Biotechnology Industry</title>
  <link>http://www.aspet.org/Blog.aspx?id=2372&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
 James E. Barrett, Ph.D. Professor and Chair Director, Drug Discovery and Development Program Department of Pharmacology and Physiology Drexel University College of Medicine Philadelphia, PA 19102    Students frequently have many concerns and face many decisions about starting a career whether that career is in</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-10-28T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<div align="center">James E. Barrett, Ph.D.<br />Professor and Chair<br />Director, Drug Discovery and Development Program<br />Department of Pharmacology and Physiology<br />Drexel University College of Medicine<br />Philadelphia, PA 19102<br /></div><p><br />Students frequently have many concerns and face many decisions about starting a career whether that career is in pharmacology or any other scientific discipline.  All too often, choices are made on the basis of insufficient information or predisposed viewpoints about what a particular career entails.  Despite the concerns surrounding research funding, diminished academic positions and the consolidation of the pharmaceutical industry, the landscape of science remains broad and provides many opportunities for informed students.  Science is dynamic, is continually evolving and provides many challenging opportunities, particularly for those interested in pharmacological sciences.  <br /><br />It is not always the case that career paths are linear.  Indeed, the traditional ‘model’ whereby students enter graduate school, obtain their Ph.D., take a postdoctoral position to gain additional experience for a number of years and then move to an academic position to repeat the process seems to be diminishing.  In my case, I followed this pattern for the first fifteen years of my career prior to making a decision to move into the pharmaceutical industry.  This was an “awakening” in many respects and I remained in industry for the next 15 years before moving recently back to academia.  Indeed, a great part of the enlightenment discovered in industry was the realization of the fundamental importance of pharmacology in the drug discovery and development process.  Pharmacological principles were critical from the very first compound assay, to in vitro evaluation, in vivo activity, through to metabolism, and then into clinical development, just to name a few of the points of intersection where pharmacological oversight and guidance were important.  The integration of pharmacology into the complex fabric of drug discovery and development emphasized just how critical the discipline was to evaluating a compound, assessing its therapeutic potential, evaluating liabilities and then integrating all this and further information into making a decision about progression into humans.<br /><br />These processes are complex, not always straightforward, are time consuming and, to some extent, are mysterious to many.  It has been estimated that it takes anywhere between 10-15 years and approximately $1 billion to bring a drug to the point where it has been approved by the FDA and can be prescribed by physicians.  Although this information is generally known, the details that are involved in bringing a drug to market are not readily available to students pursuing their graduate degrees and is also true of many faculty.  The decision to return to an academic position on my part was based on the realization that there were no formal academic programs wherein the details of drug discovery and development were taught.  A major impetus for the decision to develop a program in drug discovery that would be embedded within a pharmacology department actually came from graduate students at a number of universities.  In particular, I attended a joint program in behavioral pharmacology between Wake Forest University School of Medicine and the University of North Carolina that was organized by Linda Dykstra and Mike Nader where there was a great deal of interest from the students about what it was like to work in industry.  The many questions that followed showed a keen interest in knowing more about the pharmaceutical industry and also a realization that the industry had a great deal of options for students with sound scientific training in pharmacology.<br /><br />The solution to this uncertainty and lack of formal training in drug discovery and development within an academic setting has led to the creation of a Master of Science Degree Program in Drug Discovery and Development at Drexel University College of Medicine in Philadelphia, PA.  (<a target="_blank" title="www.drexelmed.edu/drug-discovery-development" href="http://www.drexelmed.edu/drug-discovery-development">www.drexelmed.edu/drug-discovery-development</a>).  This program starts with basic principles of target identification, validation, high throughput screening, chemical and biological space, animal model systems, and toxicology and moves through the many different and integrated steps in the drug discovery and development process that lead eventually to regulatory interactions, FDA approval and post marketing surveillance.  We have been fortunate to incorporate course offerings and lectures from the LeBow School of Business and the School of Public Health as well as Biomedical Engineering to provide a breadth of opportunities for students enrolled in the program.   Because the Philadelphia area is located in the midst of many pharmaceutical and biotechnology companies, we are fortunate in being able to attract many individuals within the industry to participate in the program.  Students are exposed to a range of topics specifically related to the pharmaceutical industry but also must take a number of other courses, including graduate pharmacology.  We have also incorporated other evolving topics into the program that include pharmacogenetics and pharmacovigilence, translational medicine and bioinformatics.  As the industry changes so will the program, moving into exciting new areas such as systems pharmacology and computational approaches to drug discovery.  Indeed, our future plans are to provide opportunities for students enrolled in the program to do research rotations or internships at many of the nearby pharmaceutical and biotechnology companies.<br /><br />The Drexel University College of Medicine Program in Drug Discovery and Development joins a number of other relatively new and exciting directions within academia where drug discovery research centers have been established.  These include, for example, those at Vanderbilt University and the University of North Carolina at Chapel Hill where there are sizeable commitments and considerable expertise in drug discovery and development.  As the larger pharmaceutical industry continues to move in rather unpredictable directions, academic research centers have a great deal to offer in terms of research and educational opportunities for students interested in the many options provided within the industry.  Indeed, the integration of both research and educational drug discovery programs within an academic setting provides enhanced and we hope enlightened career opportunities for students interested in pursuing a career in pharmacology within the pharmaceutical sector.</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2297&amp;blogid=219">
  <title>Debt Ceiling Debate Offers No Relief for Funding</title>
  <link>http://www.aspet.org/Blog.aspx?id=2297&amp;blogid=219</link>
  <description><![CDATA[<p> Prepared by Jim Bernstein,&#160; Director of Government &amp;amp; Public Affairs  
  “All of us who are concerned for peace and triumph of reason and justice must be keenly aware of how small an influence reason and honest good will exert upon events in the political field“  –  Albert Einstein   “There are always too many</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-07-13T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Prepared by Jim Bernstein,  Director of Government &amp; Public Affairs </p>
<p><em>“All of us who are concerned for peace and triumph of reason and justice must be keenly aware of how small an influence reason and honest good will exert upon events in the political field“</em> –  Albert Einstein<br /><br /><em>“There are always too many Democratic congressmen, too many Republican congressmen, and never enough U.S. congressmen”</em> - unknown <br /><br />Just when it seemed Congress might finally stop bumbling its way to a deal that addresses the deficit and debt crisis averting a government default on August 2, Washington manages to outdo itself and prove Einstein’s theory correct.   While all the political machinations provide a peculiar form of comedy relief to some individuals and new material for the Comedy Channel, the implications for future funding of biomedical research could be significant, not to mention prospects for the nation’s prosperity.  <br /><br />The latest plan thrown out there (as of July 13) to solve the nation’s twin deficit and debt problem was offered by Senator Mitch McConnell (R-KY).   McConnell’s plan would permit the President to raise the debt ceiling by $2.5 trillion in three increments by the end of 2012.  Congress would have a chance to reject each increment but Obama would certainly veto this effort and the debt ceiling would rise.   The caveat is that the President would have to identify spending cuts that would be equal to each of the incremental rises in debt.   Presumably Congress would want a say in what programs get cut or not through its annual appropriations process and that will be a problem for NIH and other federal science programs.   In any event, this plan is in doubt as Tea Party members would not agree to raise the debt ceiling for any reason, particularly one that allows the President to make unspecified spending cuts.  <br /><br />Other plans considered just in the past couple of weeks included proposals that would have cut anywhere from $2 to $4 trillion dollars in federal spending.   The President and House Speaker John Boehner (R-OH) then rolled out a comprehensive $4 trillion reduction plan that would have included cuts in discretionary, entitlement, and defense spending as well as tax revenue increases was rejected by Republicans who object to raising revenue anyway and anywhere.  This plan also raised the ire of liberal Democrats who do not want to see any changes in Medicare or Social Security.   This plan was comparable to what the President’s own bipartisan commission detailed last year, but was ignored by Obama until last week.     However, Rep. Boehner, under pressure from anti-tax Tea Party members and fearing a challenge to his Speaker’s position, pulled his support from this plan saying the votes to pass it were not there in the House.  Boehner may or may not be correct about that.  It is true that the overwhelming majority of House Republicans won’t vote for any package containing any type of tax increase.  However, the bill could pass with a strong majority of Democrats and just some Republicans.   It could happen but Boehner really can’t allow that or Tea Party members would try to remove him from the Speaker’s position.<br /><br />Instead, Rep. Boehner and Sen. McConnell fell back to a plan that looked at $2.4 trillion in spending cuts with no tax increases.  Until, that is, they apparently abandoned that position too for McConnell’s most recent plan to provide the President with the authority to incrementally raise the debt ceiling limit.   <br /><br />Whenever, if ever, there is some deficit and debt agreement to avoid default on August 2, it will certainly entail significant cuts to domestic discretionary programs.  These programs comprise less than 20% of all federal spending yet will bear the brunt of spending cuts.  Defense spending seems once again to be spared.  The House recently passed the Department of Defense FY’12 appropriations bill.   This bill grows Pentagon spending by $17 billion in FY’12.  As for an indication of how hard it is to make cuts to Pentagon spending, look no further than failed attempts to modestly reduce funding to military bands or the Pentagon’s sponsorship of NASCAR races to promote recruitment.   Politico quoted a frustrated Rep. Barney Frank (D-MA), “The military budget is not on the table.  The military is at the table and it is eating everybody else’s lunch.”  Politico further reported that data compiled by Senate Appropriations Committee Chairman Daniel Inouye (D-HI) staff show that over the past decade, the annual Pentagon appropriations bill has grown five times the rate of domestic non-security spending bills (i.e. NIH, FDA, etc); when additional emergency war funding related to Iraq and Afghanistan is counted the disparity grows to 9-1. <br /><br />All these swirling events do not make for an optimistic forecast for future funding levels for the NIH and other federal science agencies.  But it is imperative that ASPET members continue to contact their elected officials to make our case.    NIH is viewed very favorably on Capitol Hill.  It is certainly difficult to reconcile how such favor does not translate into more favorable funding outcomes.  But our case for sustained funding for NIH is a compelling one and it is a case that must be told repeatedly to legislators.   For tips on how to do this view the following pages or contact me at <a href="mailto:jbernstein@aspet.org">jbernstein@aspet.org</a>, tel: 301-634-7062.<br /><a target="_blank" title="http://www.aspet.org/Advocacy/Grassroots/" href="http://www.aspet.org/Advocacy/Grassroots/">http://www.aspet.org/Advocacy/Grassroots/</a><br /><a target="_blank" title="http://www.aspet.org/Page.aspx?id=2086" href="http://www.aspet.org/Page.aspx?id=2086">http://www.aspet.org/Page.aspx?id=2086</a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2184&amp;blogid=219">
  <title>The Future of Pharmacology and ASPET</title>
  <link>http://www.aspet.org/Blog.aspx?id=2184&amp;blogid=219</link>
  <description><![CDATA[<p> &#160;By:&#160; Lynn Wecker, Brian Cox, Jim Halpert, John Lazo 
 &#160; 
 The role of professional societies has changed dramatically since the founding of ASPET just over 100 years ago.  We are practicing our profession in a rapidly changing environment with major technological advances.  Council believes that the time is right</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-05-25T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> By:  Lynn Wecker, Brian Cox, Jim Halpert, John Lazo</p>
<p> </p>
<p>The role of professional societies has changed dramatically since the founding of ASPET just over 100 years ago.  We are practicing our profession in a rapidly changing environment with major technological advances.  Council believes that the time is right to conduct a SWOT (Strengths, Weaknesses, Threats and Opportunities) analysis of ASPET, to ensure that our society provides the best support over the next decade for its members, our profession, and perhaps even others in an ever-changing global society. <br /><br />Why a SWOT analysis?  What might be accomplished?  Although we have moved forward consistently, and have taken advantage of technological and social media opportunities to reach out to a wider range of members and potential members, many questions still remain.  <br /><br />What is our vision for the future?   How should ASPET position itself to serve the future needs of pharmacologists, our discipline, and the world?  What is unique about pharmacology?  Do we have an identity crisis? <br /><br />We have invited ASPET Divisions and Chapters to provide Council their views on the roles and responsibilities of ASPET. We are also inviting comments and suggestions from individual members. You may comment directly to this blog or send your comments to <a href="mailto:ccarrico@aspet.org">Christie Carrico</a>, Executive Officer.  Comments sent in response to this blog will be posted for further suggestions and ideas.<br /><br />We welcome a vigorous debate on the critical roles and responsibilities of the society.   We want to hear from everyone with an interest in the future success of pharmacology and pharmacologists.  After all, you are our future.</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2125&amp;blogid=219">
  <title>NIH Advocacy in Need of Critical Care</title>
  <link>http://www.aspet.org/Blog.aspx?id=2125&amp;blogid=219</link>
  <description><![CDATA[<p> &#160; 
  Better
late than never. &#160;  Congress, unable to
reach agreement on the FY’11 budget that began October 1, finally completed
legislation that funds programs for the remaining 6 months of the fiscal
year. &#160;  NIH will receive $30.7 billion, a
1% reduction from its FY’10 spending level. &#160;
 We won’t torment you</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-04-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">Better
late than never.<span style="">  </span>Congress, unable to
reach agreement on the FY’11 budget that began October 1, finally completed
legislation that funds programs for the remaining 6 months of the fiscal
year.<span style="">  </span>NIH will receive $30.7 billion, a
1% reduction from its FY’10 spending level.<span style=""> 
</span>We won’t torment you by rehashing how that happened or why because you
are probably tired of hearing about it.<span style=""> 
</span>And in any event, you can expect more of the same as Congress reconvenes
early May to hash out a FY’12 budget and deal with raising the federal debt
limit ceiling. <span style=""> </span>How these two issues are
addressed and ultimately resolved has profound funding implications for the
NIH.<span style="">  </span></span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">It
is a measure of how significantly the expectations of the biomedical research
community have been reset that a 1% cut from the previous year’s budget is
viewed by some with relief that NIH was not cut more.<span style="">  </span><span style="">  </span></span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><strong style=""><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">Déjà vu</span></strong></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">So,
for better or worse, the FY 2012 budget season has begun.<span style="">  </span>Almost certainly, any agreement, whenever we
ultimately arrive at one, will entail additional cuts to domestic discretionary
programs.<span style="">  </span>The Republican-led House has
passed its FY 2012 budget resolution that calls for significant cuts to
discretionary spending, tax cuts for the wealthiest Americans, and changes to
Medicare and Medicaid. The Democrat controlled Senate will almost certainly
resist this plan, but will have to agree on many spending cuts.<span style="">  </span>So you can expect more of the same debate and
rhetoric emanating from Washington in the weeks and months ahead. </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">To
compound an already difficult FY 2012 funding situation, the above scenario is
also influenced by Congressional debate over raising the federal debt level
ceiling, which currently stands at $14.3 trillion. To lift the debt ceiling
sometime this summer, Republicans and some Democrats will use additional cuts
in spending as a bargaining chip to increase the debt ceiling limit.<span style="">  </span>Polls show that the public is against raising
the debt ceiling limit so many in Congress will vote against raising the limit
at least once before they vote for it to avoid the country going into default. </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">None
of this means that NIH will be cut.<span style="">  </span>But
in this economic and political environment, it becomes difficult to imagine any
scenario where the funding situation for NIH moves modestly forward from its
current FY’11 level.<span style="">  </span>As the recently
completed fiscal year spending bill revealed, NIH may “succeed” only relative
to other programs.<span style="">   </span></span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">NIH
and other domestic discretionary spending programs total about $450 billion of
federal spending, about one-eighth of total spending.<span style="">  </span>Interest payments alone totaled $197 billion
in FY 2010.<span style="">  </span>Interest debt payments in
2021 are estimated to total over $790 billion.<span style=""> 
</span>So unless this country gets it deficit and federal debt under control,
the U.S. will pay more money to foreign governments than it pays collectively
for biomedical research, repairing bridges, improving food safety, etc.<span style="">  </span>Here is another way to view it:<span style="">  </span>NIH currently supports approximately 50,000
research grants across the country, at an average of about $400,000 per
grant.<span style="">  </span>If the U.S. did not need to make
those interest payments in 2010, those interest payments could instead have
funded about 490,000 grants; and in 2021 NIH would be able to fund 1,980,000
grants.</span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><span style="">  </span></span></p>
<p class="MsoNormal"><strong style=""><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">New Paradigm</span></strong></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">It
is not just Republicans but Democrats too who have embraced austerity and
deficit reduction measures.<span style="">  </span>The Obama
Administration has called for increases in investments in science and
technology and yet NIH funding is going backwards. What are others saying about
NIH? <span style=""> </span>Early this spring, the
Congressional Budget Office (CBO) issued a report, Reducing the Deficit:
Spending and Revenue Options. (<a href="http://www.cbo.gov/ftpdocs/120xx/doc12085/03-10-ReducingTheDeficit.pdf">http://www.cbo.gov/ftpdocs/120xx/doc12085/03-10-ReducingTheDeficit.pdf</a>)
that outlines 100 options and policy implications lawmakers could consider as
they look to address deficits and debt.<span style=""> 
</span>The CBO report is only intended to provide options and makes no
recommendations.<span style="">  </span>Yet it is instructive
to look at what options the CBO lists to “Reduce or Constrain Funding for the
National Institutes of Health (see page 121 of chapter three: Discretionary
Spending Options).”</span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"><br />
CBO offers two options and you won’t like any of them.<span style="">  </span>One is to restrict the rate of growth at the
NIH to 1% per year and option two is to cut funding for NIH to its FY 2003
level and only then allow it to grow with inflation.<span style="">  </span>CBO notes that these options would force NIH
to focus on research that would provide the most significant benefits.<span style="">  </span>CBO does acknowledge that cuts to the
extramural research programs would disrupt funding for programs already under
way and discourage innovation that would improve people’s health. </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;">All
this means is that for the remainder of the year, it is more critical than ever
that ASPET members make the case to Congress that investing in the NIH should
be a national priority.<span style="">  </span>If you think
that your Representative or Senator is especially difficult, that is even more
reason to speak to them and their staff on what NIH does and what it means to
your community and the nation. A collective effort by all in the biomedical
research community can make a difference in preventing cuts, and possibly
seeing the NIH budget move forward. <span style=""> </span>We
can’t predict what will happen or where help may come from.<span style="">  </span>In 1995, NIH faced cuts and prolonged freezes
in its budget.<span style="">  </span>Yet, it was Republican
leadership that ultimately increased the NIH budget and was the catalyst behind
the doubling effort that ended in 2003.<span style="">  </span>If
you would like more information on how to meet with your Congressional
delegation, how to prepare for a meeting, and the many advocacy resources
available to scientists, contact me at <a href="mailto:jbernstein@aspet.org">jbernstein@aspet.org</a>.<span style="">   </span></span></p>
<p class="MsoNormal"><span style="font-size: 12pt; font-family: &quot;Times New Roman&quot;,&quot;serif&quot;;"> </span></p>
<p class="MsoNormal"><span style=""> </span></p>
<p class="MsoNormal"><span style=""> </span></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2101&amp;blogid=219">
  <title>New Guide for the Care and Use of Laboratory Animals</title>
  <link>http://www.aspet.org/Blog.aspx?id=2101&amp;blogid=219</link>
  <description><![CDATA[<p> Dear ASPET Member: 
 &#160; 
 Although a 2005-2006 public comment period yielded the conclusion that no substantive revision to the existing Guide for the Care and Use of Laboratory Animals was needed, the new Guide that has been released for public comment is twice as long as the 1996 version and contains a great deal</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-04-14T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Dear ASPET Member:</p>
<p> </p>
<p>Although a 2005-2006 public comment period yielded the conclusion that no substantive revision to the existing Guide for the Care and Use of Laboratory Animals was needed, the new Guide that has been released for public comment is twice as long as the 1996 version and contains a great deal of new “policy”. </p>
<p>   </p>
<p>The final opportunity to provide comments for the NEW Guide for the Care and Use of Laboratory Animals (8<sup>th</sup> ed.) expires <strong><u>midnight April 24</u></strong>.  </p>
<p> </p>
<p>Specifically, you are being asked to say whether or not the 8<sup>th</sup> edition of the Guide should supplant the 1996 version of the Guide as PHS Policy governing federally funded researchers, and to provide supporting comments.  </p>
<p><u></u></p>
<p><u>General concerns</u>:</p>
<p> </p>
<ul>
<li>Increased expense (e.g., new cage sizes for rodent breeding; larger cages for newly mandated social housing) </li>
<li>Increased paperwork burden.  For example, all deviations from “should” statements contained in the new Guide will need to be in an approved protocol </li>
<li>Increased power of local IACUCs to restrict already peer-reviewed research </li>
</ul>
<p><u></u></p>
<p><u>Specific Concerns</u>: </p>
<p> </p>
<ul>
<li>Constraints on multiple procedures in animals </li>
<li>Constraints on multiple surgeries (not just multiple major survival surgeries) </li>
<li>Increased intra- and post-operative surgical monitoring for <u>all </u>species</li>
<li>Increased constraints governing food- or fluid-restriction </li>
<li>Poorly conceived instruction dictating the use of “chemicals and other substances” in laboratory animals (**see below for explanation) </li>
<li>New specific guidance on “post-approval” monitoring (e.g., direct observation of laboratory procedures) </li>
</ul>
<p> </p>
<p>This is <strong>YOUR FINAL CHANCE</strong> to provide input. It is critical for scientific organizations and individual scientists to weigh in.  Vote either “Adopt or  Not” at the site below. The numbers of comments on specific issues will be catalogued, and <strong>YOUR VOTE COUNTS!</strong><strong><em>Researchers who use drugs in their work should use their expertise, in particular, to comment on the non-pharmaceutical drug policy that is reprinted below.  Share your views and help other members who want to comment.</em></strong>  (Note that names of those submitting comments will not be published.  Affiliations only will be listed if you are commenting on behalf of the organization or institution.)</p>
<p><strong><em></em></strong></p>
<p>The link to the Federal Register comment site is: <a href="http://grants.nih.gov/grants/olaw/2011guidecomments/add.htm">http://grants.nih.gov/grants/olaw/2011guidecomments/add.htm</a></p>
<p> </p>
<p>You will be given the opportunity to download a pdf of the entire new Guide on that site.  </p>
<p><strong></strong></p>
<p><strong>The possible outcomes of the comment period include:</strong></p>
<p><strong></strong></p>
<ol>
<li><strong>OLAW will adopt as PHS Policy “as is”; </strong></li>
<li><strong>OLAW will adopt but with published guidance on “exceptions” to PHS Policy; or</strong></li>
<li><strong>OLAW will retain 1996 Guide as PHS Policy</strong>.  </li>
</ol>
<p> </p>
<p>A second question to be answered via the Federal Register mechanism regards the time frame in which PHS-Assured institutions and NIH intramural programs would be required to comply if the 2011 Guide is adopted as PHS Policy.  The deadline for full compliance that is proposed in the Federal Register <strong>is March, 2012</strong>.  </p>
<p> </p>
<p>In your comments, we suggest you <strong>recommend at least 4 years (e.g., 2015) given the expense of a variety of cage size and housing requirements that are being required at a time of great financial difficulty for research institutions.</strong></p>
<p><strong>  </strong></p>
<p><strong>**Of special interest is the following paragraph on p. 31 of the 2011 Guide.  If you comment on nothing else, please comment on this.  </strong></p>
<p><strong></strong></p>
<p> “Use of Non-Pharmaceutical-Grade Chemicals and Other Substances The use of pharmaceutical-grade chemicals and other substances ensures that toxic or unwanted side effects are not introduced into studies conducted with experimental animals. They should therefore be used, when available, for all animal-related procedures (USDA 1997b). The use of non-pharmaceutical-grade chemicals or substances should be described and justified in the animal use protocol and be approved by the IACUC (Wolff et al. 2003); for example, the use of a non-pharmaceutical-grade chemical or substance may be necessary to meet the scientific goals of a project or when a veterinary or human pharmaceutical-grade product is unavailable. In such instances, consideration should be given to the grade, purity, sterility, pH, pyrogenicity, osmolality, stability, site and route of administration, formulation, compatibility, and pharmacokinetics of the chemical or substance to be administered, as well as animal welfare and scientific issues relating to </p>
<p>its use (NIH 2008).”<a name="_GoBack"></a></p>
<p> </p>
<p>Please visit the Federal Register link provided above to provide your input.  And we appreciate all thoughtful comments below.</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2060&amp;blogid=219">
  <title>ASPET Members Views Welcome on NCRR/NCATS Proposed Reorganization</title>
  <link>http://www.aspet.org/Blog.aspx?id=2060&amp;blogid=219</link>
  <description><![CDATA[ASPET
Council would be interested in hearing your views about the proposed creation
of the National Center for Advancing Translational Sciences (NCATS).]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-02-25T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p>ASPET
Council would be interested in hearing your views about the proposed creation
of the National Center for Advancing Translational Sciences (NCATS).  As you may be aware, The National Center for
Research Resources (NCRR) Task Force has prepared a set of final interim
recommendations NIH Director Francis Collins concerning placement of NCRR
programs within NIH and the establishment of NCATS.  The recommendations (which can be read in
full at: <a href="http://lists.aamc.org/t/111020/491575/10195/0/">http://feedback.nih.gov/index.php/ncats/task-force-recs/</a>),
conclude that many NCRR programs would benefit from their transfer to other
entities at NIH:</p>
<p> </p>
<p>1.    
Transfer
of CTSA program into a new NIH Center, the National Center for Advancing
Translational Sciences;</p>
<p>2.    
Placing
the Research Centers in Minority Institutions program in the National Institute
of Minority Health and Health Disparities;</p>
<p>3.    
Placing
the Science Education Partnership Awards program in the Office of the Director
(OD) of the NIH and be combined with the Office of Science of Education
currently within the Office of Science Policy in the OD;</p>
<p>4.    
Placing
the Institutional Development Award (IDeA) program in the NIGMS;</p>
<p>5.    
Transfer
Biomedical Technology Research Centers (BTRC) to either NIGMS or the national
Institute of Biomedical Imaging and Bioengineering; grants related to
biomedical imaging and point of care diagnostics to NIBIB and all other BTRCs
to NIGMS; and</p>
<p>6.    
Placing
several NCRR programs in a new Infrastructure Entity devoted to trans-NIH
infrastructure and capacity building, including extramural construction;
research and animal facilities improvement; comparative medicine programs
(including non-human primate research resources, other disease model resources,
training and career development for animal medicine, and clinical research
resources – exception is Pancreatic Islet Cell Resource Center proposed
transfer to NIDDK; and shared and high end instrumentation .</p>
<p>You
can read FASEB’s comments on the NCATS/NCRR Working Group proposal to create
NCATS and dissolve NCRR here: <a href="http://www.faseb.org/Portals/0/PDFs/opa/2.2.11%20FASEB%20NCATS%20Letter.pdf" title="http://www.faseb.org/Portals/0/PDFs/opa/2.2.11%20FASEB%20NCATS%20Letter.pdf" target="_blank">http://www.faseb.org/Portals/0/PDFs/opa/2.2.11%20FASEB%20NCATS%20Letter.pdf</a></p>
<p> </p>
<p>We
would be interested in hearing your thoughts and perspective and anonymous
replies are welcome too.   </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=2017&amp;blogid=219">
  <title>The Irresistible Force vs. the Immovable Object</title>
  <link>http://www.aspet.org/Blog.aspx?id=2017&amp;blogid=219</link>
  <description><![CDATA[<p>The President’s State of the Union address on January 25 provided some relative optimism that funding levels for NIH may be alright; the Congressional Budget Office’s (CBO) latest projected FY’11 budget deficit at a record $1.5 trillion suggests that such optimism may be misplaced </p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2011-02-01T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<div align="left"><h3> By:  Jim Bernstein, ASPET Director of Public Affairs</h3>
<p> </p>
</div><p align="center"> Loggerheads:
<em>in or into a state of quarrelsome
disagreement – Webster’s Dictionary</em></p>
<p> The President’s
State of the Union address on January 25 provided some relative optimism that
funding levels for NIH may be alright; the Congressional Budget Office’s (CBO)
latest projected FY’11 budget deficit at a record $1.5 trillion suggests that
such optimism may be misplaced (<a href="http://www.cbo.gov/doc.cfm?index=12039">http://www.cbo.gov/doc.cfm?index=12039</a>).</p>
<p>President
Obama proposed a five-year budget freeze for all domestic discretionary
spending programs.  But the freeze is an
aggregate number and the president was clear that some programs, like NIH, will
do better than others in his budget to be released next week: “In a few weeks, I will be sending a
budget to Congress that helps us meet that goal. We’ll invest in biomedical
research, information technology, and especially clean energy technology - an
investment that will strengthen our security, protect our planet, and create
countless new jobs for our people.”</p>
<p> The
opposition party’s response to the President’s address predictably opposed any
new spending increases.  And then the CBO
report rippled through Congress.  While
the CBO report was not surprising, the timing was not the best.  In any event, the message coming from the
Administration and Congress is that big cuts are unavoidable to many programs
and even favored programs won’t be happy with what they get.  </p>
<p>As
if to underscore that point and to show how fluid and troubling the situation
is, I attended a meeting the day after the State of the Union held by
Congressional staff from the Senate Majority (Democrat) Labor, Health and Human
Services, and Education Subcommittee. 
The Labor/HHS Subcommittee funds the NIH among many programs under its
jurisdiction.  The meeting was for
advocates to hear the Subcommittee’s political perspective and discuss what can
be done to preserve funding for the Subcommittee’s programs.  They made the following points to consider: </p>
<p>·        
They are not certain how many programs under their
jurisdiction may have to be cut but some cuts will be deep;</p>
<p>·        
The Senate Subcommittee will fight any attempts to
move for cuts back to FY’2008 or 2006 spending levels and will fight against
anticipated House spending cuts; </p>
<p>·        
It is critical that constituents in home district
reach out, particularly to new members, and even to Tea Party elected officials
to illustrate what significant cuts in spending means in the home district;</p>
<p>·        
Grassroots support by constituents and meeting with
their Representatives can influence the debate in the Senate and within the
Administration in a positive way, even if the spending cuts coming out of the
House are not in our favor; </p>
<p>·        
Need to dispel the idea that anything the government
does is not good or is job killing and can be done solely by private sector;</p>
<p>·        
Important for individuals and their institutions to
articulate what cuts would mean to biomedical research and their institutions.</p>
<p>House Republicans may or may not include cuts to defense spending.  The Pentagon consumes almost one quarter of
all federal spending and taking potential DoD cuts off the table puts greater
pressure on the domestic discretionary side, which accounts for less than
one-fifth of all spending.  For its part,
the Pentagon has identified $78 billion in cuts. There are a number of
Republican-inspired efforts that purport to cut the deficit but typically do
not address defense or entitlement spending. 
Some House Republicans want to cut $100 billion this year alone.  The Washington Post estimates that this would
mean a 30% cut in spending over the remainder of the fiscal year. The
Republican Study Group which consists of the most conservative bloc of House
Republicans wants to reduce spending by non-defense agencies by more than 40%
over a decade.  No medical research
programs are included among the specific program cuts mentioned by the group. </p>
<blockquote></blockquote>
<p>Even more peculiar is freshman Sen. Rand Paul’s legislation that would cut $500
billion from government spending, including funding for NIH.  Rep. Michelle Bachman (R-MN) has introduced a
bill to cut the budget by $425 billion, by among other things, freezing VA
health spending, eliminating the National Health Service Corps, reducing NSF
funding to 2008 levels and eliminating NSF spending on elementary and secondary
education. House Budget Chair Paul Ryan (R-WI) wants to set the new FY 2011
spending cap at the FY’2008 spending level when the House returns from its
recess on February 7. In this scenario, Ryan would leave it to appropriators to
determine how those cuts are made.  </p>
<p>No matter
what is proposed, something will have to be done before March 4, the day when
the Continuing Resolution that funds the government expires and the debt
ceiling debates begin.  So you are likely
to see even more spending bills introduced that call for draconian cuts to the
domestic discretionary spending side of the ledger.  At the moment, FY’11 CR funding levels are
stuck at FY’10 spending levels.  </p>
<p>What happens next, nobody knows. </p>
<p> </p>
<p> </p>
<p> </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1978&amp;blogid=219">
  <title>NIH Funding Still in Flux; But ASPET Members Can Help</title>
  <link>http://www.aspet.org/Blog.aspx?id=1978&amp;blogid=219</link>
  <description><![CDATA[With
NIH supported once more by a Continuing Resolution, a new majority in the House
of Representatives, and bipartisan agreement that the federal budget deficit
must be reduced, biomedical scientists are justifiably concerned about future
federal funding.  In his blog of November
3 entitled No (Tea) Party in Store for Biomedical Research Funding, Jim
Bernstein, ASPET’s Director of Government 
Relations and Public Affairs, has initiated a very timely
discussion.  Rather than reiterate the
many cogent points made by Jim and those who have responded to his blog, I
would like to emphasize some of the activities in which ASPET is engaged and
how individual members may contribute to a strong voice for federal research
funding.]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-11-30T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<h4>By:  Jim Halpert, ASPET President
</h4>
<p>With
NIH supported once more by a Continuing Resolution, a new majority in the House
of Representatives, and bipartisan agreement that the federal budget deficit
must be reduced, biomedical scientists are justifiably concerned about future
federal funding.  In his blog of November
3 entitled No (Tea) Party in Store for Biomedical Research Funding, Jim
Bernstein, ASPET’s Director of Government 
Relations and Public Affairs, has initiated a very timely
discussion.  Rather than reiterate the
many cogent points made by Jim and those who have responded to his blog, I
would like to emphasize some of the activities in which ASPET is engaged and
how individual members may contribute to a strong voice for federal research
funding.</p>
<p>At
a minimum, members should take action when ASPET or FASEB sends out an alert to
contact members of Congress.   This only
takes moments and usually involves a simple point and click.  The points you need to make are
provided.  If asked to contact
Congressional members by phone, then you will again be given the relevant
talking points along with your Representatives’ phone number.  This typically should not take more than five
minutes of your time. We frequently hear from Congressional staff and leaders
that biomedical researchers often do not make their voice heard in numbers to
be effective.  .
But there has also been clear evidence of success over the years where
individual Members of Congress contacted their leadership regarding an
issue raised by their scientists-constituents. 
Also, ASPET has been asked by some Congressional Offices to enlist the
support of its membership in support of specific legislation.  Your individual response is part of a larger
collective effort that can make a difference. </p>
<p>This
is an especially critical year for ASPET members to consider becoming more
actively involved and visit their members of Congress.  There has been significant turnover in
Congress, and that presents an opportunity for those individuals with new
Representatives and Senators.  It is
important to remember that Congress and their staff are not universally
informed about how NIH works and how successful our federal investment has been
over the years.  They are looking for
expertise and need scientists to explain that to them reliably.  Scientists are expert on the subject matter,
and every ASPET member should feel confident in meeting their elected officials
to discuss these matters.</p>
<p>ASPET’s
Public Affairs Office can facilitate such visits in a number of ways.   First, members are encouraged to visit the
ASPET advocacy page/grassroots education at <a href="Advocacy/Grassroots">http://www.aspet.org/Advocacy/Grassroots</a>
for information on how to meet with Members of Congress and reach out to the media
and to obtain other advocacy resources to help make the case for strong federal
funding for research.  Second, the Public
Affairs Office (<strong>jbernstein@aspet.org)</strong> can answer questions on how to do
this.  ASPET will coordinate
Congressional visits as part of the Graduate Student Colloquium at the
Experimental Biology 2011 Meeting in Washington,
 DC this April.  Specific talking points will be provided to
participants. However, all ASPET members can seek advice through the ASPET
Advocacy page on how to arrange a  Congressional visit in Washington, how to meet with  Congressional representatives in your local
district, and how to write a timely and effective opinion piece in support of
biomedical research .  Members should
also consider including a visit to Congress when in town for study section or
other business.   Again, the Public Affairs Office can help with
talking points.</p>
<p>In
addition, ASPET’s Advocacy Outreach Program will be happy to visit individual departments.  This program is intended to inform graduate
students, post-docs (younger faculty is target but all welcome) and other
interested faculty about how and why they need to become proactive in advocacy
activities in support of federal funding of biomedical research.  Presentations include an overview of the
political and legislative factors influencing the debate and how scientists can
help to influence Congress, media and the public. Jim Bernstein will be at the University of Louisville
early next year and has visited to date, Emory, UTSW
Medical Center,
the Michigan Pharmacology Colloquium at Wayne State,
and Vanderbilt.</p>
<p>In
conclusion, amidst all the concern about future federal research funding,
active involvement by scientific societies and their individual members becomes
more crucial than ever.     </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1976&amp;blogid=219">
  <title>New IC for Substance Use, Abuse and Addiction Research</title>
  <link>http://www.aspet.org/Blog.aspx?id=1976&amp;blogid=219</link>
  <description><![CDATA[<p>As many of you are aware, NIH Director Francis Collins has recommended that a new, single institute for substance use, abuse, and addiction research.  Since a significant number of ASPET
members may be directly affected by this possible reorganization, we invite you
to post your views on this potential reorganization.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-11-22T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>As many of you are aware, NIH
Director Francis Collins has recommended that a new, single institute for substance
use, abuse, and addiction research.  This
new Institute proposed by Dr. Collins follows the NIH Scientific Management
Review Board recommendation that a new Institute form that would integrate the
relevant substance abuse research portfolios from NIDA, NIAAA, and other NIH
Institutes and Centers.  The statement by
Dr. Collins is below.</p>
<div><p>A task force of experts, led by NIH
Principal Deputy Director Lawrence A. Tabak and NIAMS Director Stephen I. Katz,
will review all of NIH's 27 Institutes and Centers to determine where substance
use, abuse, and addiction research programs currently exist and to make
recommendations about what programs should be moved into the proposed new
Institute. The task force hopes to provide a detailed plan in the summer of
2011. </p>
<p>Since a significant number of ASPET
members may be directly affected by this possible reorganization, we invite you
to post your views on this potential reorganization.</p>
<p></p>
<p>Read the NIH Scientific Management Review Board (November
2010): Report on Substance Use, Abuse and Addiction Research at NIH.</p>
<p><a href="http://smrb.od.nih.gov/announcements/SUAA-Report-Final-Nov15.pdf">http://smrb.od.nih.gov/announcements/SUAA-Report-Final-Nov15.pdf</a></p>
<br /><p>≈  ≈  ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈   ≈  </p>
</div><h1><font style="font-size: 12pt;">Statement
of NIH Director Francis S. Collins, M.D., Ph.D., on Recommendation to Create a
Single Institute for Substance Use, Abuse, and Addiction Research</font> </h1>
<p>On Nov. 15, 2010, I received the formal recommendation from the National
Institutes of Health (NIH) Scientific Management Review Board that NIH create a
new Institute focusing on substance use, abuse, and addiction research and
related public health initiatives. This Institute would integrate the relevant
research portfolios from the National Institute on Drug Abuse (NIDA), the
National Institute on Alcohol Abuse and Alcoholism (NIAAA), and other NIH
Institutes and Centers. The formation of a single, new Institute devoted to
such research makes scientific sense and would enhance NIH's efforts to address
the substance abuse and addiction problems that take such a terrible toll on
our society.</p>
<p>Substance use, abuse, and addiction research is carried out by many NIH
entities besides NIDA and NIAAA. Consequently, I have asked NIH Principal
Deputy Director Lawrence A. Tabak, D.D.S., Ph.D., and National Institute of
Arthritis and Musculoskeletal and Skin Diseases Director Stephen I. Katz, M.D.,
Ph.D., to pull together a task force of experts from within NIH to look
carefully across all of NIH’s 27 Institutes and Centers to determine where
substance use, abuse, and addiction research programs currently exist and make
recommendations about what programs should be moved into the proposed new
Institute. In addition, the task force will survey NIDA and NIAAA for programs
that are not related to substance use, abuse, and addiction research and make
recommendations about where such programs will go. Final recommendations to the
NIH Director will be informed by consultation with relevant stakeholders.</p>
<p>Clearly, it will take some time to carry out this assessment in a
thoughtful, systematic manner. I anticipate that the task force will produce a
detailed reorganization plan for my consideration sometime in the summer of
2011.</p>
<p>In the interim, all existing substance use, abuse, and addiction research
programs at NIH will continue <em>status quo</em>. It is imperative we keep
these important lines of research moving forward with all due speed for the
benefit of the nation's health. </p>
<p> </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1975&amp;blogid=219">
  <title>ABRCMS Meeting a Big Success</title>
  <link>http://www.aspet.org/Blog.aspx?id=1975&amp;blogid=219</link>
  <description><![CDATA[<p>I just got back from the Annual Biomedical Research Conference for Minority Students, held in Charlotte, NC.  Nearly 2000 bright, energetic, enthusiastic minority undergraduate science students were in attendance and ASPET, along with many of our sister societies, had a booth where we had the opportunity to interact with these amazing students.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-11-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>I just got back from a really fantastic meeting.  The Annual Biomedical Research Conference for
Minority Students, held in Charlotte, NC, attracted nearly 2000 bright,
energetic, enthusiastic minority undergraduate science students.  For most of the students, it was their first
scientific meeting.  For many, it was
their first time away from their home state or territory.  The students attended mentoring sessions,
career enrichment sessions, scientific lectures, poster sessions and networking
sessions.   Because this was the 10<sup>th</sup>
anniversary of the ABRCMS meeting, there were some extra-special plenary
speakers – Maya Angelou, Neil DeGrasse Tyson (he was so entertaining I am
almost ready to forgive him for demoting Pluto from planetary rank), Jeremy
Berg, and Francis Collins, to name just a few. 
 The convention center oozed
inspiration!</p>
<p> </p>
<p>ASPET had a booth in the exhibit hall, along with a dozen
or so other scientific societies and nearly a hundred academic
institutions.  Why do we go?  Since pharmacology isn’t an undergraduate
discipline, most of the students don’t know that it is a field they can go into
as a graduate student.  So we go to talk
about pharmacology research and careers. 
A few students are familiar with pharmacology.  More often, however, they think it is some
type of pharmacy.  So at a minimum we can
clear up some misconceptions about pharmacology.  At this meeting, we (Marcus DeLatte of the
Diversity Committee, and I) talked to several particularly dynamic students who
came back to the booth several times to talk more with us, who signed up for
student memberships, who asked thoughtful and intelligent questions about
pharmacology research and research opportunities, who stopped by the booth yet
again to remind us that they were now members and looked forward to getting
emails from us.  </p>
<p> </p>
<p>But the meeting provides much better opportunities than
that.  All you need to do is hear one or
two students talk about how excited they are that they have gotten to do
research to know that this group of students is our future.  If we can get some of them tuned into
pharmacology, through our summer internships, through just talking with them
about pharmacology, through directing them to the appropriate institutions to
pursue an area that interests them, we have made an investment in not only the
future of ASPET but the future of pharmacology. 
</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1969&amp;blogid=219">
  <title>No (Tea) Party in Store for Biomedical Research Funding</title>
  <link>http://www.aspet.org/Blog.aspx?id=1969&amp;blogid=219</link>
  <description><![CDATA[More than
half a century ago, American Humorist Will Rogers observed, “Ancient Rome
declined because it had a Senate, now what’s going to happen to us with both a
House and Senate?”  We are about to find
out.<br />]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-11-03T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Jim Bernstein, Director of Government Relations and Public Affairs </p>
<p>More than
half a century ago, American Humorist Will Rogers observed, “Ancient Rome
declined because it had a Senate, now what’s going to happen to us with both a
House and Senate?”  We are about to find
out.    </p>
<p>With the
Republicans and Tea Party candidates making huge gains in winning a significant
majority in the House and making additional gains in the Senate, the entire
political class in Washington, including the Obama administration, realizes that
the deficit and debt must be addressed.  How
to do it is the problem, and leaving aside taxes for the moment, on the
spending side the issue now becomes clear: what gets cut and who makes do with
less.  So what are the practical
implications for biomedical research funding when the new 112<sup>th</sup>
Congress convenes in January?  </p>
<p>Lawmakers
quit work on legislation early October and left Washington to allow them more
time to campaign for re-election.   The
“lame duck” Congress will return mid-November and try to complete some
unfinished business, including work on FY’2011 spending bill that include
funding for the NIH.   Since Congress
could not agree on funding levels before they recessed, they passed a
Continuing Resolution (CR) that currently funds federal programs at the FY’2010
level.  The CR is current through
December 3 at which time Congress will extend the CR – possibly through
mid-March, or work out an omnibus spending bill that includes all
appropriations bills.</p>
<p>For the NIH, the most optimistic terms of the
next CR or omnibus would allow for a $1 billion or 3.2% increase above the
FY’10 level.  It is possible the terms
could be a continuation of the current CR (funding at the FY’10 level) or even
worse.  Well before mid-term election
there was already growing pressure to cut discretionary spending.   Legislating across the board cuts on the
NIH, FDA and other federal agencies will certainly create chaos but do little
to address rising deficit and national debt concerns since non-defense domestic
discretionary spending only accounts for about 20% of the federal budget.  One of the more radical proposals with some
support in Congress would roll back spending levels to FY 2008.  If that spending level were enacted, FDA
alone would see a 25% reduction in the agency’s budget ($2.345 billion in FY’10
to FY’08 level of $1.713 billion).  Another proposal that failed to pass would
have cut discretionary funding levels by 5%. 
 The large gains made by many
conservative candidates will only embolden the new Republican House majority
and Senate Republicans, as well as the “blue dog” moderate Democrats, who now
see little incentive to work with an even more liberal Democrat caucus to adequately
fund discretionary programs. There is now no reason for Republicans to act on
the budget until the new Congress takes power in January and exercises their
new muscle. </p>
<p>But the
bottom line is that with the new Republican majority in the House and the
Democrats narrower majority in the Senate, there would seem little chance of NIH
or other federal science agencies seeing any real growth. Obama will have no
political power to really improve the funding situation for biomedical
research, but if Congress passed a spending bill making draconian cuts to
biomedical research it would draw a presidential veto.   So despite the rhetoric about reigning in
government spending, when the rubber hits the road, there almost certainly
won’t be dramatic cuts in biomedical research funding.  But no one will be happy and there will be
real pain with no growth in the enterprise. </p>
<p>Sometime in
December, the national deficit commission appointed by President Obama will
issue recommendations to presumably help Congress make tough decisions on a
roadmap to address crushing deficit and debt burdens.  The goal is to reduce the deficit by
one-third by 2015.  It is not certain
what if any impact this bipartisan commission will really have.  Presumably the commission has all deficit
reduction options on the table but Republicans won’t accept anything on the
revenue (i.e., tax increase) side.   So
while you will hear a lot of noise about this in a few weeks, it is not likely
anything will really materialize.</p>
<p>But the
biggest influence on the fortunes of biomedical research funding might not even
originate in this country.  In the United
Kingdom, the government has proposed raising taxes and almost a 20% reduction
in most programs except for the Medical Research Council and some other health
programs.  The goal is to eliminate the
deficit in five years.  The plan involves
a mix of spending cuts (77%) and tax increases (23%) Setting aside whatever
thoughts you may have about the severity of the cuts proposed, or whether it
does not adequately address the revenue side, it is impossible to imagine that
any politician in this country would have the courage to even suggest a similar
option.  The exception for the MRC is
important and does provide hope for NIH. 
If scientists-advocates for NIH can make a compelling case – and you can
- in this country that funding for NIH and other federal science agencies needs
to be enhanced, we can point to the U.K. model as a country that is serious
about deficit reduction but also recognizes that funding for biomedical
research is deserving of an exception.  <em>Science</em> recently quoted the former head
of the MRC, Colin Blakemore who noted advocacy efforts done by scientists, “It
is wonderful to learn that Government has listened to the scientific
community.  Collectively we have made the
case that funding science is not a cost but a way to invest in creating a
stronger economy, which is the best way to guarantee the recovery that will
benefit everyone.” </p>
<p>One thing is
clear, the President, the 112<sup>th</sup> Congress, and those that follow, will
need to address the deficit and debt in a substantial way.  A variety of budget analysts say that if
these two issues are not addressed this decade the federal government will be
spending more than $1 trillion (not a typo – One Trillion Dollars) a year in
interest payments on the national debt. 
That is more than one-fourth of the FY 2010 budget.  $1 trillion could help pay for more police,
better roads, and more school teachers. 
It certainly might even fund a few more RO1s, P30s, RPGs, fellowships
and training grants.  It has been said
that wealthy nations depend on strong, effective political systems and that
these healthy political systems can only function with a strong center.  It remains to be seen what, if any, level of
bipartisan cooperation can be made that would preserve yet alone grow funding
for biomedical research. . And so I’ll conclude as I began with another wise
quote from Will Rogers, “I don’t make jokes, I just watch the government and
report the facts.” </p>
<p> </p>
<p> </p>
<p> </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1909&amp;blogid=219">
  <title>Message from President James Halpert</title>
  <link>http://www.aspet.org/Blog.aspx?id=1909&amp;blogid=219</link>
  <description><![CDATA[It is a great honor to have been
elected President of ASPET.  The Society
and its Council exist to serve the needs of the members, to advance the
discipline of pharmacology, and to advocate for the pivotal role of biomedical
science in health care and in society in general.  A strong ASPET is especially important at a
time when senior as well as entering pharmacologists in academia, industry, and
government are facing tremendous challenges and heightened expectations from
the public.  In this climate, forging new
partnerships and alliances among pharmacologists working in the various sectors
is crucial.  Training the next
generations of pharmacologists and ensuring that they have multiple career opportunities
is also a major responsibility of ASPET and its members.]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-09-07T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Dear ASPET Members,</p>
<p>It is a great honor to have been
elected President of ASPET.  The Society
and its Council exist to serve the needs of the members, to advance the
discipline of pharmacology, and to advocate for the pivotal role of biomedical
science in health care and in society in general.  A strong ASPET is especially important at a
time when senior as well as entering pharmacologists in academia, industry, and
government are facing tremendous challenges and heightened expectations from
the public.  In this climate, forging new
partnerships and alliances among pharmacologists working in the various sectors
is crucial.  Training the next
generations of pharmacologists and ensuring that they have multiple career opportunities
is also a major responsibility of ASPET and its members. </p>
<p>Specifically, what can ASPET,
Council, and the President do at this time to strengthen the discipline of
pharmacology?  Clearly we must maintain
our core mission of publishing leading journals in the field, holding high
quality meetings, and providing value to our members.  Under the oversight of the Board of
Publications Trustees Chaired by Jim Barrett, the dedicated work and rigorous
standards of ASPET’s editors and editorial boards, and the management of
Journals Director Rich Dodenhoff, the five ASPET journals continue to
thrive.  They represent a major means by
which new scientific breakthroughs and timely reviews in our field are
disseminated, as well as the major source of revenue to ASPET.  I especially welcome our two new editors
David R. Sibley of <em>Pharmacological Reviews</em> and Michael F. Jarvis of the <em>Journal
of Pharmacology and Experimental Therapeutics.</em> 
They join Eric Johnson of <em>Drug Metabolism and Disposition</em>, Jeff Conn of
<em>Molecular Pharmacolog</em>y, and Harry Smith of <em>Molecular Interventions</em>. </p>
<p>Jack Bergman will continue to chair
the Program Committee.  Its success is
due in large measure to the creative and enthusiastic input from ASPET’s nine
Divisions, which ensures an annual meeting that reflects existing strengths as
well as new directions in pharmacology. 
The annual meeting is also a major forum for new scientists to become
familiar with and participate in the discipline.  In that regard, I laud the recent creation of
a new category of Postdoctoral Member, which will provide an attractive and
affordable transition from Graduate Student Member to Regular Member.   Reaching out to undergraduate and graduate
students as well as postdoctoral fellows and providing them with networking and
career development opportunities must be one of the highest priorities of
ASPET. </p>
<p>Under the leadership of our
Executive Officer, Christie Carrico, Past-Presidents Joe Beavo and Brian Cox,
and Web Editor Jon Maybaum, ASPET has made a major investment in re-designing
and expanding our web site.  The new site
offers streamlined access to vital information on the discipline of
pharmacology, ASPET, training programs, career opportunities, and research
highlights.  The site also offers
opportunities for interactive columns that are designed to facilitate
communication among members.  Comments
from members are welcomed, and we hope you will share your ideas as to how to
make the web site more valuable to you and your colleagues.  The web site should also enhance our public
advocacy efforts driven by the Public Affairs Committee and the Public Affairs
Office under Jim Bernstein.  Clearly,
together with other societies we must intensify our efforts to educate the
public and political leaders about the benefits and future promise of
biomedical research.  This will become
increasingly important as healthcare costs continue to skyrocket and federal
budgets remain under intense pressure.  </p>
<p>Fortunately, thanks to prudent
financial management, careful oversight by the Investment Subcommittee chaired
by Chip Rutledge, and a major new donation, ASPET’s reserves have bounced back
and now exceed the levels in August 2008. 
Council and the Finance Committee chaired by Bryan Cox will continue to
monitor the finances carefully to make sure that funds from members in the form
of dues, journal page charges, and other contributions are used wisely. Through
ongoing and new initiatives ASPET will ensure a strong scientific foundation
for future drug discovery and drug therapy, help train new pharmacologists, and
educate the public and our political representatives. </p>
<p>Sincerely yours,</p>
<p>James R. Halpert</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1692&amp;blogid=219">
  <title>NIH and the Drug Discovery Pipeline</title>
  <link>http://www.aspet.org/Blog.aspx?id=1692&amp;blogid=219</link>
  <description><![CDATA[A recent article in Newsweek by Sharon Begley and Mary
Carmichael calls attention to the decline over recent years in the number of new drugs
introduced into medical practice. They suggest that NIH funding priorities
should be targeted more directly towards the support of the pre-clinical and
clinical studies required for the introduction of promising drug candidates
into the clinic, arguing that the return on investment in NIH has been
‘approximately as satisfying’ for taxpayers and patients as the return on
public investment in the AIG bailout.]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-06-01T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>NIH and the Drug Discovery Pipeline</p>
<p>Brian Cox, ASPET President</p>

<p>A recent article in Newsweek by Sharon Begley and Mary
Carmichael (Deperately Seeking Cures, Newsweek, 31 May 2010;&#160; <a href="http://www.newsweek.com/id/238078">http://www.newsweek.com/id/238078</a>)
calls attention to the decline over recent years in the number of new drugs
introduced into medical practice. They suggest that NIH funding priorities
should be targeted more directly towards the support of the pre-clinical and
clinical studies required for the introduction of promising drug candidates
into the clinic, arguing that the return on investment in NIH has been
‘approximately as satisfying’ for taxpayers and patients as the return on
public investment in the AIG bailout.&#160; This
particular argument trivializes complex issues in both cases; here I will not
comment on the value of the support of the AIG baillout but would argue that
public investment in NIH over many years has indeed provided a very handsome
return on investment. NIH-supported research has been fundamental to the
development and passage to the clinic of many new drugs that are now reducing
deaths from many kinds of cancers, reducing heart attacks and stroke, relieving
the symptoms and slowing the progress of arthritis, Alzheimer’s disease and
other neurodegenerative diseases, improving the treatment of glaucoma – the
list can go on and on.&#160; Without continued
funding of fundamental research by NIH at levels comparable to the support
provided in recent years there will in the future be no novel drug candidates
to be directed into the translational pipeline.</p>
<p>Despite this success, Begley and Carmichael were correct in
noting that the number of new drugs making the transition from laboratory into
clinical has been fewer in the last few years that in previous decades. The
reasons are complex. In the past many of the supposedly new agents introduced
each year were designed to mimic the actions of drugs already in use, offering
only modest improvements in therapy over existing drugs.&#160; In recent years it has been less
cost-effective for drug companies to introduce new forms of old drugs, and it
has not been necessary. NIH investment in research on, for example, the human
genome and parallel investment in public databases making genomic information
available to all, has transformed the identification of novel potential drug
targets, and new high throughput screening methods (also developed in part with
NIH support) have markedly facilitated the discovery of totally new agents that
can attack the newly identified biologic targets. While some of these new
agents have indeed made it into the clinic with significant clinical benefit
(e.g., Gleevac<sup>R</sup>), other novel targets have proved to be associated
with unacceptable toxicity as well as potential clinical benefit. Fortunately
the toxic effects that result from actions at some novel targets are also being
identified earlier in the drug development pathway, resulting in their removal
from the drug pipeline earlier and reducing toxicity in initial clinical
trials.&#160; Early identification of
unacceptable toxicity reduces the fraction of initially tested novel agents
that eventually join the ranks of therapeutic drugs of choice, but this is
beneficial in reducing the numbers of patients who experience drug-induced
side-effects. Increasingly, this type of very basic drug discovery and
characterization is being conducted in academic settings and in research
institutes supported in part by NIH, rather than in the laboratories of big
pharma – another fundamental shift in the drug-discovery process taking place
over recent years.</p>
<p>Begley and Carmicheal also argue correctly that the
processes required to move a novel agent from laboratory to clinic are not well
supported by current funding mechanisms.&#160;
ASPET has for many years encouraged the support of training programs for
integrative bioscientists who can conduct the pre-clinical studies in animals
that are essential to reduce the risk to human volunteers in the initial
testing of a totally novel agent in human subjects,. NIH, through NIGMS and
working with ASPET, has recently supported the development of training courses
in integrated organ systems pharmacology to increase the pool of investigators
trained to conduct these studies, but more needs to be done to provide training
resources for such individuals, and to develop secure career pathways for them
in the future. Another critical shortage is in the training of clinical
pharmacologists to conduct the expansion in clinical trial activities that is
implicit in the proposals of Begley and Carmichael.&#160; Clinical pharmacology training programs have
not been well supported in recent years, yet an increased cadre of trained
clinical pharmacologists with experience in designing and implementing efficient
clinical trials would not only assist the drug pipeline, but also assist in the
better evaluation of existing medications so that only the most effective and
safest medications remain in use. </p>
<p>Improved training and support mechanisms in these critical
drug evaluation arenas, is becoming critical if we are to exploit effectively
the increase in knowledge of genetic and environmental differences between
individual patients.&#160; The potential
benefits of personalized medicine can only be achieved if novel methods of
evaluating drugs effects efficiently in very small numbers of individuals can
be achieved. Improved methods for identifying individual differences in
responses to drugs are sorely needed.&#160;
Such developments will also require a greater flexibility and
sophistication by the FDA in its evaluation of requests for drug approvals. </p>
<p>Improving the throughput of the drug pipeline from
laboratory to clinical by enhancements along the lines of those proposed here
may require the development of new business models for drug development.&#160; It is not clear that big pharma is set up
appropriately to take on these tasks, although large drug companies have proved
very adaptable to circumstances in the past and may be able to reinvent
themselves again in an era of personalized medicine and required comparative
effectiveness evaluation.&#160; As noted
above, there has already been a trend to move drug discovery to research units
in academic settings, such as the Vanderbilt Program in Drug Discovery lead by
Jeff Conn (http://www.connlab.com/jobs.html), the Drug Discovery Institute at
the University of Pittsburgh lead by John Lazo&#160;
(http://www.upddi.pitt.edu/). Such entities may be better placed than
freestanding small biotech companies to withstand the uncertainties inherent in
drug discovery and the volatility in the availability of essential venture
capital. We can also expect that new entities will emerge to conduct
pre-clinical testing and clinical trials in the near future.&#160; The optimum model for the bench-to-bedside
pipeline remains to be determined; several variants may emerge.&#160; </p>
<p>NIH has served the nation very well for more than 60 years;
its record in supporting basic discoveries in biomedical science that have been
critical for the identification of novel drug targets has been unrivaled
anywhere in the world. &#160;The drug
discovery process now faces many new challenges. These will best be met if
support for NIH remains strong and consistent. Basic science, largely funded by
NIH, is the foundation on which all future developments must rest.&#160;&#160; </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1686&amp;blogid=219">
  <title>Making Molecules Into Medicines—The Critical Role of Integrative and Organ Systems Pharmacology Training</title>
  <link>http://www.aspet.org/Blog.aspx?id=1686&amp;blogid=219</link>
  <description><![CDATA[Pharmacology is a key integrative medical science
discipline.  In the following article, Myron Toews discusses educational
opportunities offered through ASPET and NIGMS in integrated organ systems
approaches to drug development.  All graduate students and others
interested in careers relating to drug development should consider these
opportunities.]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-05-18T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Pharmacology is a key integrative medical science
discipline.  In the following article, Myron Toews discusses educational
opportunities offered through ASPET and NIGMS in integrated organ systems
approaches to drug development.  All graduate students and others
interested in careers relating to drug development should consider these
opportunities.</p>
<p><strong></strong></p>
<p><strong>"Making
Molecules Into Medicines—The Critical Role of Integrative and Organ Systems
Pharmacology Training"</strong></p>
<p><strong>Myron Toews</strong>, University of Nebraska Medical Center IOSP Summer
Short Course Director</p>
<p><strong></strong></p>
<p>Making molecules into medicines is a major goal of the
discipline of pharmacology. However, making molecules into medicines cannot
occur until those molecules have been studied in the "integrative"
environment of multiple cell types working together as isolated organ systems
and of multiple organ systems working together in the intact animal. Providing
a strong introduction to the principles and the laboratory methods for studying
drug action in isolated organs and intact animal systems is the goal of the four
NIH-funded Integrative and Organ Systems Pharmacology (IOSP) Short Courses
being offered again this summer.  The
leadership of ASPET strongly encourages all pharmacology students, postdocs,
and faculty to consider these short courses, in particular their importance for
enhancing career opportunities and advancement.</p>
<p>The major advances in molecular biology, cellular biology,
and genetics over the last 30 years have greatly advanced the potential as well
as the popularity of "cellular and molecular pharmacology", changing
the focus for many training programs from "medicines" to
"molecules". An unfortunate consequence of the exciting advances at
the molecular end of the pharmacology spectrum is that the more traditional
components of pharmacology that can only be studied in intact animals, isolated
organs, or multi-cellular tissue preparations have received short shrift in
many pharmacology graduate and post-doctoral training programs. As a result,
the pharmaceutical industry now finds it very hard to identify and recruit
pharmacologists who have the expertise needed to move their molecules into
medicines. Industry leaders have commented that "gene jocks and screeners
are a dime a dozen" but that "integrative pharmacologists are hard to
find and are paid premium salaries" as a result. Even for those who are
not "skilled" in any particular aspect of IOSP, having sufficient
exposure to the general concepts to be able to effectively communicate with
their more integrative counterparts in industry is viewed as a major strength,
helping to translate molecular knowledge into the appropriate organ system or
intact animal studies to test efficacy, potency, and safety prior to moving
drugs toward human studies.</p>
<p>It was because of a strong push from ASPET and a strong push
from the pharmaceutical industry that the National Institutes of General
Medical Sciences began funding a set of IOSP Short Courses to help
pharmacologists begin their move into more integrative and translational
directions.   Four IOSP Short Courses are available this
summer at Michigan State University, University of Nebraska, University of
North Carolina, and Vanderbilt University. 
Details on each can be found at:  
<a href="../../../../../../../../../../../Page.aspx?id=312">http://www.aspet.org/Page.aspx?id=312</a></p>
<p> All four courses
include a similar introduction to the basics of using animals and tissues in
pharmacology research, but each course offers unique aspects in terms of
emphasis on specific organ systems or disease entities , variations in the
specific animal and tissue model systems used, and other differences in terms
of industry involvement, individually tailored components, and campus
environments. All of the courses have received strongly positive feedback from
previous students, so potential students can pick the course that is best for
them based on content, location, or whether the course is early, middle, or
late summer.  The IOSP summer short
courses draw faculty from many different institutions to provide the needed
expertise, which also provides students a broad exposure to IOSP research and
policies in both industry and academia.</p>
<p> The ASPET web site
also has information about the  ASPET-Integrative
and Organ Systems Sciences (ASPET-IOSS)  fellowships that are available for those who
want to take advantage of more advanced training opportunities to pursue this
type of research training directly in an industry setting:  <a href="../../../../../../../../../../../uploadedFiles/Advocacy/Support_for_Integrative_and_Organ_Systems_Sciences/ASPET-IOSS%20FUND%20Guidelines.pdf?n=5996">http://www.aspet.org/uploadedFiles/Advocacy/Support_for_Integrative_and_Organ_Systems_Sciences/ASPET-IOSS%20FUND%20Guidelines.pdf?n=5996</a>).
</p>
<p> </p>
<p>DO NOT take the risk of leaving your molecules "in the
bottle or on the bench". Register for one of the IOSP Short Courses this
summer and start working on "making your molecules into medicines!!"</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1634&amp;blogid=219">
  <title>Hope and Glory:  Forecasting NIH&#39;s Difficult Future in 2011</title>
  <link>http://www.aspet.org/Blog.aspx?id=1634&amp;blogid=219</link>
  <description><![CDATA[This week ASPET has offered written testimony in support of a $37
billion FY 2011 NIH budget to the House Labor/Health and Human Services
Appropriations Subcommittee. The following article by Jim Bernstein
provides the background to this testimony, clearly depicting the
difficult political and economic environment under which we will be
operating in the near future.]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-04-14T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p> This week ASPET has offered written testimony in support of a $37 billion FY 2011 NIH budget to the House Labor/Health and Human Services Appropriations Subcommittee.  The following article by Jim Bernstein provides the background to this testimony, clearly depicting the difficult political and economic environment under which we will be operating in the near future.  It makes for interesting if sometimes depressing reading.  Now, more than ever, it is important for ASPET members to make themselves heard by their Congressional Representatives.  Please take the time to read this piece and consider what action you can take.<br /><br />Brian Cox<br />President  </p>
<h3><p> </p>
</h3>
<h2>Hope and Glory: Forecasting NIH’s Difficult Future in FY 2011</h2>
<p><br />Jim Bernstein<br />ASPET Director of Government &amp; Public Affairs</p>
<p><br />ASPET members have received from many national media sources what seems to be a relentless barrage of bad and pessimistic news concerning the nation’s economic plight, a partisan political process seemingly at an impasse over a variety of important policy issues, and little optimism that federal funding for biomedical research will see any real growth.  Given this state of affairs, it might be a good time to look at how economics and politics can be the difference between being awarded that grant you spent so much time writing – or not.  How did the NIH go from doubling its budget over a five year growth period (1998-2003) to losing roughly 15% of it purchasing power in the latter part of the past decade?  This is not intended to be a class in civics or economics that you might have founded so tedious in high school or college.  But hopefully it will inform some and cause others in our community who never cared to look up from the bench at the issues impacting their laboratories to become not just scientists but scientist-advocates for biomedical research.   </p>
<p><br />For the moment, the $10.4 billion appropriated in 2009-2010 to the NIH through the American Recovery and Reinvestment Act (AARA) as part of the economic stimulus package passed by Congress helped to restore much of the purchasing power that NIH had lost.   Sen. Arlen Specter (D-PA) was the originator and prime advocate for NIH ARRA funds.  At the time, there was considerable debate and concern within the biomedical research community over how NIH would manage such a huge increase in funding.  Perhaps the more critical issue was what would happen in FY 2011 without continued support to maintain the infrastructure that ARRA would build?  The Administration seemingly recognized this “falling off the cliff” scenario.  Kathleen Sebelius, Secretary of the Department of Health and Human Services initially acknowledged that researchers would be in trouble, “We certainly need to begin working on what happens in 2011 and 2012.”   However, her additional comments were troubling.  She stated that because of ARRA funding, NIH “didn’t need additional resources.”    Shortly thereafter, President Obama released his proposed FY 2011 budget recommendations for federal programs and recommended a 3.2% increase for NIH above its FY 2010 budget.  This increase will not even account for inflation, effectively extending more than half dozen years of relative decline in the NIH budget’s purchasing power.   FASEB has recently completed models showing that if President Obama’s NIH budget proposal were adopted, the purchasing power of the NIH would decrease from $36.4 billion in FY 2010 (taking into account ARRA funding) to $32.2 billion, a 14.3% decline and research capacity would shrink by 11%.  View: <a href="http://www.aspet.org/WorkArea/linkit.aspx?LinkIdentifier=id&amp;ItemID=1631&amp;libID=1653" title="FASEB Research Trends Data Shows Need for Sustained Funding In FY'11">http://www.aspet.org/PolicyUpdatesNews.aspx?id=1631</a></p>
<p><br />However, all President’s budgets are only recommendations and almost always declared “dead on arrival.”  While President Obama’s proposed budget disappoints, keep in mind that all President’s recommendations for NIH always disappoint.  The doubling began under the Clinton Administration, who, like all presidents offered similar anemic budget increases for NIH.  What is sometimes overlooked and often forgotten is that the origins and push for the doubling came not from the White House or Congressional Democrats, but from fiscally conservative Republican leadership.  Former Representatives Newt Gingrich (R-GA) and John Porter (R-IL) - who chaired the appropriations subcommittee that makes the programmatic funding decision for NIH, were instrumental in helping NIH achieve the doubling.  In the other chamber, former Senators Mark Hatfield (R-OR) and Connie Mack (R-FL) were prime movers, along with current Senator Arlen Specter who was a Republican at that time (Specter switched party affiliation last year).  Why is this important?  Well, notice that all but one of the above mentioned are retired.  Sen. Specter remains but finds himself in a tough political fight to keep his seat.  In fact, the reason he switched from Republican to Democrat was that he concluded he would not be able to win the Republican primary in Pennsylvania.  Senator Specter aside, the fact is that the NIH’s most vocal, supportive, informed and passionate supporters in Congress are not there anymore.  And no one has replaced them.  Yes, every one is in favor of biomedical research and all rational people want cures for diseases that touch everyone.  But that does not mean that the current Congressional makeup has anyone who has taken up NIH as their own cause.   With no true congressional “champion” NIH will have a harder time making satisfactory gains. </p>
<h3>Deficit Politics</h3>
<p>Congress has a “deadline” of April 15 to finish the FY 2011 budget resolution.  But that obviously was not met and in any event it is nonbinding.  Congress has failed to adopt a budget four times in the past 35 years: 1999, 2003, 2005, and 2007.   But Congress does not need to pass a budget resolution anymore than you need to adopt a budget for yourself.  You can spend as much as you want but maybe a budget would give you some much needed discipline.  Same with Congress.   So what is the big deal if Congress does not get its act together for FY 2011?  This is an election year and all House seats are up for reelection as are many Senate seats.   With a record $1.4 billion deficit and soaring national debt, the Republican minority in Congress is sure to make the majority party pay politically for not passing a responsible budget that will address these twin problems.   The Democrats also are not in any rush to pass a budget that will have to contain some cuts to key programs and/or raise taxes, neither of which is appealing to the public.  In fact, a recently released Economist poll indicated that 62% of respondents said they wanted to reduce the budget deficit via budget cuts instead of raising taxes.  However, when asked what area of federal spending they would be willing to cut, only foreign aid received a majority at 71%.  Cuts to Social Security and Medicare – which have by far the largest impact on the federal spending – were opposed by 93%.   Take a look at the pie below.  It shows where all federal spending went in FY 2008.  Social Security, Medicare, Medicaid are all entitlement programs with growing costs and account for approximately 40% of the budget.  Throw in defense spending (20%) and the interest we pay on the national debt (8.5%) and almost 70% of our federal spending is consumed.  Now look at all the remaining 30% that get funded.  Funding for NIH and other life science research is embedded among these areas.  This also would include spending for dozens of other programs that people care about, provide critical support to individuals or otherwise provide valuable services to our country.  This would include funds for programs like mine safety, school lunch or milk programs for underserved populations, FBI, bridge and road repair, etc.   </p>
<p><br /><img height="269" width="421" title="Federal Deficit" alt="Federal Deficit" src="http://www.aspet.org/uploadedImages/Blog/ASPET/Blog-OMB-Pie-Chart.gif" /></p>
<p><br />NIH must compete with other labor, health and education programs within the Appropriations Labor/HHS Subcommittee’s jurisdiction.  There are 12 Appropriation Subcommittees and each has a finite amount of money to spend. The NIH is already the largest program under the Labor/HHS Subcommittee purview.   Somebody always gains at someone else’s expense.  Any significant increase in the NIH budget will likely have to come from another program.  And any increase in other programs would mean less for NIH.      <br />Recently, Ben Bernanke, the Chairman of the Federal Reserve, stated that the federal government will have to get serious about reducing debt either through increased taxes, cuts in spending, or combination of both.  There is a general consensus to begin to bring the budget deficit and federal debt down.  How to do this is the problem, and the tired maxim of the “devil is in the details” certainly applies here.     </p>
<p><br />Many ASPET members might recall the Republican led “Contract with America” in the mid 1990s that would restrain the growth of programs.  There was even a failed Congressional effort to cut – not limit - the NIH budget.  And yet, it was during this time that the move to double the NIH budget began.   As mentioned above, it was because of the Republican leadership that the doubling came about.  Republicans viewed NIH as an entrepreneurial and successful federal agency worthy of being well funded.  So, in FY 2011, could NIH fortunes take a similar and favorable turn?  There are two significant differences however between the mid-1990s and present day events.  One is that the current economic environment is more difficult than the mid-1990s.   Budget deficit and debt projections in future years are dismal without major tax and spend policy changes.  Several economic studies have indicated that the interest we will pay on the debt will more than double by the end of the decade (creating greater pressure to reduce domestic discretionary spending).   Politically, the environment is much more polarized than in the Contract with America days.  It is not clear how many, if any, of the Tea Party movement’s followers would view NIH as a federal program that works and is an important asset.  Whatever the movement’s long-term impact and outlook is, it will likely have some influence on spending decisions in FY 2011. </p>
<h3>Our FY 2011 “Ask”</h3>
<p>ASPET has submitted testimony to the House Labor/HHS Appropriations Subcommittee that recommends a FY 2011 NIH budget of $37 billion [link to testimony].   The $37 billion recommendation is consistent with the NIH’s own program justification and consistent with the recommendations of other societies in the FASEB community.  View ASPET’s testimony here: View:<a href="http://www.aspet.org/WorkArea/linkit.aspx?LinkIdentifier=id&amp;ItemID=1633&amp;libID=1655" title="ASPET Congressional Testimony Supports $37b NIH FY 2011 Budget">http://www.aspet.org/PolicyUpdatesNews.aspx?id=1633</a><br /><br />The FY 2011 mark was determined by taking the FY 2010 budget ($30.7 billion) and adding half of the ARRA funding -$4.2 billion.  ($8.4 billion of $10.4 billion was for research).  We then added 6.3% -$2.2 billion, accounting for half of that amount as an inflation adjustment.      
</p>
<p><br />$37 billion is an ambitious mark for NIH.   It will be difficult to achieve.  Congressional Appropriators are looking at the FY 2010 NIH budget of $30.7 billion as the base in determining the FY 2011 budget.  They are viewing the ARRA funds as supplemental appropriations.  Our community must take into account that ARRA funding was significant, has helped to build up infrastructure and manpower, and needs to be added to the FY 2010 base when making final FY 2011 funding decisions.  We hope each ASPET member will take the time in the coming months to contact their Members of Congress and educate them about NIH’s needs.  It is critical that ASPET members leave the message that we need a new national commitment to the NIH for sustained and predictable growth over the long term.  We need to sustain momentum for medical progress and build and expand the capacity of NIH to improve health, power economic growth and innovation, and advance science.  Make the case by pointing to how ARRA money has contributed to your institution or provided grant money for your own research.  The AAMC has surveyed institutions on their ARRA success stories: <a title="AAMC Report Details ARRA (Stimulus) Funding at Medical Institutions" href="http://www.aspet.org/WorkArea/linkit.aspx?LinkIdentifier=id&amp;ItemID=1480&amp;libID=1502">http://www.aspet.org/PolicyUpdatesNews.aspx?id=1480.</a>  <br />For information on how to contact your Member of Congress, as well as ASPET’s Advocacy Outreach Program, view ASPET’s Grassroots Congressional Education web page at: <a href="http://www.aspet.org/WorkArea/linkit.aspx?LinkIdentifier=id&amp;ItemID=172&amp;libID=193" title="Grassroots Congressional Education">http://www.aspet.org/Page.aspx?id=172</a>.  </p>
<p><br />There likely has never been a more difficult time for NIH.  The pressures on Congress to limit growth in the NIH will be extreme.    In response to this difficult economic and political climate we have already seen several bipartisan proposals to cap discretionary spending by Members of Congress.  While none have been successful, future attempts could be.  Scientists have an obligation as stewards of public monies to speak out about how your research is conducted and the reasons why a robustly funded federally funded biomedical research enterprise makes sense.  Everyone in Congress is supportive of biomedical research and many do understand what NIH has contributed to public health and local economies.  The public is overwhelmingly supportive of biomedical research.  But focus groups conducted in the past year indicate that the public really does not have any idea what the NIH is nor what it does.  To the extent they have heard of the NIH, they tend to think of it as a mouthpiece for public health messages, similar to the Surgeon General’s Office.  So the bottom line is that we really cannot do enough to educate the public about what NIH is and what it does.  And we need to continually make the case to Congress relentlessly.  </p>
<p><br />Despite what you have just read here, our intention was not to be morbidly pessimistic, but we must be realistic.  These are tough times but the many forecasts predicting a dire economic future might not be realized either.  The environment won’t turn suddenly for the better but it might improve slowly enough and that is still another reason to become actively involved in advocacy for NIH.  If our community of scientist-advocates is not making its case in tough times, it won’t have credibility when the funding environment starts to improve. </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1567&amp;blogid=219">
  <title>How to Stifle Innovaton and Creativity:  New Requirements for the VAS Section of NIH Grants</title>
  <link>http://www.aspet.org/Blog.aspx?id=1567&amp;blogid=219</link>
  <description><![CDATA[<p>Over the last month of two I seem to have been particularly burdened with mandatory training courses and other regulatory requirements related to the conduct of research in my laboratory -- annual radiation safety training, prevention of sexual harassment training, whistleblower protection training, human research protection training, animal research protocol submissions and modifications.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-03-24T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>&#160;</p>
<p>Over the last month or two I seem to have been particularly
burdened with mandatory training courses and other regulatory requirements
related to the conduct of research in my laboratory – annual radiation safety
training, prevention of sexual harassment training, whistleblower protection
training, human research protection training, animal research protocol
submissions and modifications, radiation safety training. Next month will bring
additional mandated training, and more reporting requirements.&#160; None of this is unusual – all faculty in
research-oriented universities and colleges have similar requirements. And I do
not wish to imply that these activities serve no useful function; most of them
do. Nevertheless the collective burden is cumulative; the ability of research
professionals to conduct innovative and productive research programs is in
danger of significant impairment by the excessive regulatory burden that is now
imposed on investigators in research institutions of all kinds. </p>
<p>Just over a year ago, I was privileged to hear a talk given
by Dr. Sara Rockwell at the annual meeting the Association of Medical School
Pharmacology Chairs.&#160; Dr. Rockwell is a
Professor of Therapeutic Radiology and Pharmacology at Yale University, where
she conducts cell culture and animal research related to the treatment of
cancers, and where she also teaches courses in ethics and career development in
addition to her teaching roles in radiation biology and pharmacology.&#160; Dr. Rockwell’s talk last year was on the
ever-increasing regulatory burden on faculty and the negative impact this
burden has on their productivity and innovation.&#160; Dr. Rockwell is also Yale’s representative on
the Federal Demonstration Project (FDP), where she recently served as Vice-chair
of the FDP and Chair of the FDP faculty committee.&#160; The FDP, a partnership of federal agencies
and academic institutions that receive federal research funding, was created a
decade ago with sponsorship by the National Academies to consider the problem
of the increasing impact of expanding federal regulations on research.</p>
<p>The results of a recent FDP survey have been published (1)
and have also been summarized by Dr. Rockwell (2). More than six thousand
faculty at many universities responded. A major finding is that 42% of the time
spent by an average PI on a federally funded research project was expended on
administrative tasks related to that project rather than on the research
itself. Not surprisingly, many scientists have complained that their research
productivity is being adversely affected. For scientists in biomedical and life
sciences research, mandated requirements relating to animal care and use issues
were very high on the list of most time-consuming burdens. For research
clinicians, IRB issues figured prominently. Many institutions also impose
additional administrative and reporting requirements that do not directly
relate to funded research projects, and thus are not included in this time
estimate.&#160; This very substantial
expenditure of time and effort on purely regulatory and administrative
functions is not a very cost-effective way of conducting business.&#160;&#160; However, the establishment of the FDP and
the publication of its survey results last year suggested that the problem had
been recognized, and raised the possibility that any proposed additional
administrative tasks would be scrutinized very carefully before imposition,
with opportunities provided for public discussion of the costs and the benefits
of any new requirements.&#160; Optimists were
encouraged to think that ways would be found to reduce the cumulative federal
administrative burden. </p>
<p>It was therefore particularly disturbing to learn that the
NIH Office of Scientific Review has altered its interpretation of the minimal
information required for completion of the Vertebrate Animal Section (VAS) of
the standard NIH grant submission form to require now much more complete
information relating to the animal use. &#160;Institutes began circulating draft versions of
the regulations in January and a formal Notice (NOT-OD-10-027) has been issued
this week (3). The new information now explicitly required in the VAS section
includes details of the veterinary staff caring for the animals, the schedule
of monitoring, indications for veterinary intervention to alleviate discomfort,
distress or pain, treatments to be used to alleviate these conditions,
descriptions of restraint devices, indicators for humane experimental endpoints,
and method(s) for euthanasia with rationale for selection.&#160; IRG members, in addition to their requirement
to review the scientific merits of the proposal, are also required to evaluate
these detailed technical issues relating to animal use and welfare. </p>
<p>The Animal Welfare Act (AWA), revised in 2002, is explicit
in placing the burden of ensuring that research on laboratory animals is
conducted according to the requirements of the Act upon the institution
sponsoring the research.&#160; Institutions
are required to establish Institutional Animal Care and Use Committees (IACUCs)
to address the justification for the proposed use of the animals and review and
approve proposed procedures as well as the standards of veterinary care and
facility maintenance. They must also appoint an Institutional Official
personally responsible for ensuring that requirements of the AWA are followed.
Institutional laboratory animal research programs are also subject to regular
accreditation review and most are subject to oversight by USDA inspectors.&#160; All of the information now required by NIH
for inclusion in the VAS section of the 398 form is a necessary and accepted
part of the information that has always been required for review by the local IACUC,
and the local committees are much better placed than IRG members to determine
if the local animal welfare programs are adequate and appropriate.&#160; The revised approach to review of animal use
for NIH research applications thus alters the balance between central and local
oversight of animal welfare issues, and makes a mockery of the “just-in-time”
provision that requires detailed review of technical compliance issues only
when grant funding is approved and available.&#160;
With the percentage success-rate for obtaining funding for each
individual NIH submission now in the single digits for some institutes, the
revised approach will require that faculty members submitting research
proposals may now have to develop this detailed information on their proposed
animal studies and on veterinary care procedures for every submission, not just
for every funded grant, a substantial increase in workload. </p>
<p>The impetus for this change in approach by the Office of
Scientific Review is not clear; some have argued that the more detailed
information has always been required in the 398 NIH grant application form, but
in practice over many years a simple description of the proposed animal models
with a clear statement of the justification(s) for their use has been deemed
sufficient for the IRG to determine that the proposed animal model is the most
appropriate and legitimate way to address the research goals. The benefits that
are expected to accrue with respect to animal welfare from this additional
burden on both submitting investigators and on their colleagues who serve on
the NIH IRGs have not been defined.&#160;
Despite recent modifications to the grant application process to reduce
the length of applications, and to focus on innovation and creativity, one
group of federal research administrators appears determined to expand, not
limit, the regulatory demands required for each and every application.&#160; The FDP should take a careful look at this
additional regulatory burden on those seeking to advance the public health
through research; perhaps it needs to grow some teeth.</p>
<p>References:&#160; </p>
<p>1. Decker, R.
S., Wimsatt, L., Trice, A. G., &amp; Konstan, J. A. (2007). <em>A profile of
federal-grant administrative burden among Federal Demonstration Partnership
faculty: A report of the faculty standing committee of the Federal Demonstration
Partnership</em>. Federal Demonstration Partnership Web site: <u><a target="_blank" title="http://thefdp.org/Faculty%20burden%20survey%20report.pdf" href="http://thefdp.org/Faculty%20burden%20survey%20report.pdf">http://thefdp.org/Faculty%20burden%20survey%20report.pdf</a></u><u></u></p>
<p>2. Rockwell S., The FDP Faculty Burden Survey, Res
Management Rev 16(2): 28-41, 2009. (This paper is available on the FDP website
at&#160; <a target="_blank" title="http://sites.nationalacademies.org/PGA/fdp/index.htm" href="http://sites.nationalacademies.org/PGA/fdp/index.htm">http://sites.nationalacademies.org/PGA/fdp/index.htm</a>
)</p>
<p>3. Instructions for Completion and Peer Review of the
Vertebrate Animal Section (VAS) in NIH Grant Applications and Cooperative
Agreements, downloaded 18 Mar 2010,&#160; <a target="_blank" title="http://grants.nih.gov/grants/guide/notice-files/NOT-OD-10-027.html" href="http://grants.nih.gov/grants/guide/notice-files/NOT-OD-10-027.html">http://grants.nih.gov/grants/guide/notice-files/NOT-OD-10-027.html</a></p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=1072&amp;blogid=219">
  <title>Ion Channelopathies at the IUPHAR 2010 World Congress of Pharmacology</title>
  <link>http://www.aspet.org/Blog.aspx?id=1072&amp;blogid=219</link>
  <description><![CDATA[<p> The 2010 World Congress in Pharmacology to be held in
Copenhagen in July is organized around a series of focused conferences each
integrating recent basic and clinical research on a discrete topic in 2 or 3
day program within the main Congress schedule. The topics for all the
conferences look very interesting, but one that caught my eye is on ion
channelopathies (FC12: Ion channelopathies: new windows on complex disease and
therapy).</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2010-01-04T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Brian M. Cox

</p>
<p> </p>
<p><img hspace="5" height="137" align="left" width="100" style="width: 100px; height: 137px;" src="http://www.aspet.org/uploadedImages/Meeting/Other_Meetings_of_Interest/logo.gif?n=4326" alt="WorldPharma2010 logo" title="WorldPharma2010 logo" />The 2010 World Congress in Pharmacology to be held in
Copenhagen in July is organized around a series of focused conferences each
integrating recent basic and clinical research on a discrete topic in 2 or 3
day program within the main Congress schedule. The topics for all the
conferences look very interesting, but one that caught my eye is on ion
channelopathies (FC12: Ion channelopathies: new windows on complex disease and
therapy). </p>
<p>It is approaching 60 years since Hodgkin, Huxley,  Katz and co-workers provided the initial
foundations for understanding of the roles of ion channels in the contraction
of muscle. These observations, and the demonstration in a series of papers
published between 1949 and 1952 by Hodgkin and Huxley of the role of sodium and
potassium conductances in the propagation of the action potential in the axon
of the giant squid, have led to five decades of research on the large number of
ligand-regulated ion channels that are now known to exist, a number that could
not have been anticipated in the early 1950s. 
(I am indebted to the brief review by Colquhoun &amp; Sakmann, 1998, for
a concise summary of the initial studies on ligand-regulated ion
channels).  Since these early years,
improved techniques for analysis of channel properties, molecular cloning
approaches, and channel protein sequence comparisons across species and between
individuals have revealed the subunit complexity of the major ion channels and
some insights into the molecular mechanisms involved in ion conductance.  These studies are now beginning to provide
additionally a basis for understanding of the role of polymorphisms in the
structure of critical subunits in inherited disorders of ion channel
function.  A research area that for many
years was mainly of interest to the basic scientist focused on understanding
membrane protein properties and receptor signal-transduction mechanisms is now
expanding to provide insights into clinical conditions and to the development
of novel therapeutic approaches. </p>
<p>Under the Chairmanship of Bill Catterall of the University
of Washington, an exciting program has been developed for each session in the
channelopathies conference, each with presentations from experts from several
countries.  Some sessions will consider
the role of impaired channel function in disorders of nerve or muscle in
inherited epilepsy, migraine, pain conditions, periodic paralyses, cardiac
arrythmias and hypertension.   Others
will address the roles of ion channels in what used to be described as
non-excitable tissues, including components of the endocrine and immune
systems.  This multidisciplinary
approach, including presentations on both laboratory and clinical studies, will
draw attention to commonalities of channel function across tissue types as well
as pointing to features unique to specific tissues. The conference epitomizes
the objectives of the Congress as a whole, the “remarriage” (to quote the
Congress Chairs, Kim Brosen and Michael Mulvany) of basic and clinical
pharmacology.</p>
<p>This is just one of eighteen focused conferences at the
Copenhagen World Congress; the others are on equally interesting topics.  Check out the full program at <a target="_blank" title="www.worldpharma2010.org" href="http://www.worldpharma2010.org"><u>www.worldpharma2010.org</u></a> /
.   Young scientists and graduate
students in the USA should check to see if they might be eligible for a travel
award from ASPET providing partial support towards the costs of attending the
conference (details at <a href="http://www.aspet.org/awards/travel/" title="Travel Awards"> www.aspet.org/awards/travel</a>).  Note that the <span style="font-weight: bold;">deadline for abstract
submission for the Congress is 15 January 2010</span>. </p>
<p>Refs:</p>
<p>Colquhoun
D, &amp; Sakmann B. (1998) From muscle endplate to brain synapses: a short
history of synapses and agonist-activated ion channels. <span style="text-decoration: underline;">Neuron</span> 20: 381-87.</p>
<p> </p>
<p>Fatt P &amp; Katz B. (1951).
An analysis of the end-plate
potential recorded with an intra-cellular electrode.<span style="text-decoration: underline;">
J. Physiol (Lond)</span> 115, 320-370.</p>
<p> </p>
<p>Hodgkin
AL, &amp; Huxley AF (1952) A quantitative description of membrane current and
its application to conduction and excitation in nerve, <span style="text-decoration: underline;">J. Physiol (Lond)</span>, 117:
500-554. </p>
<p> </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=969&amp;blogid=219">
  <title>2010 World Congress of Pharmacology</title>
  <link>http://www.aspet.org/Blog.aspx?id=969&amp;blogid=219</link>
  <description><![CDATA[<p>The date for submission of abstracts for the International Union of
Pharmacology (IUPHAR) 2010 World Congress in Pharmacology is fast
approaching (the last date for abstract submission is 15 January 2010);
now is the time to start planning to attend what promises to be a very
interesting meeting. A message from Sam Enna, former ASPET
President and current IUPHAR Secretary-General, outlines plans for the
meeting, which will be held in Copenhagen in July.</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-12-09T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p><img hspace="5" height="137" border="1" align="left" width="100" title="WorldPharmaLogo" alt="WorldPharmaLogo" src="http://www.aspet.org/uploadedImages/Awards_and_Fellowships/Travel_Awards/logo.gif?n=8570" style="border-color: rgb(128, 128, 128); width: 100px; height: 137px;" />The date for submission of abstracts for the International Union of Pharmacology (IUPHAR) 2010 World Congress in Pharmacology is fast approaching (the last date for abstract submission is 15 January 2010); now is the time to start planning to attend what promises to be a very interesting meeting.  A message (see below) from Sam Enna, former ASPET President and current IUPHAR Secretary-General, outlines plans for the meeting, which will be held in Copenhagen in July.<br /><br />Two new features of the program caught my attention. For several decades basic and clinical pharmacologists have held separate world congresses; in 2010 these two meetings will be merged in a single congress giving equal programming weight to both fields.   For pharmacologists based in the United States, where pre-clinical and clinical pharmacologists often do not attend the same meetings, this is a welcome return to the roots of the discipline of pharmacology. At a time when many funding agencies are emphasizing translational research, the increased exposure of basic scientists to the clinical applications of their discoveries will be of benefit to ASPET members, and clinical pharmacologists should find the sessions on the identification of novel drug targets and on drug discovery to be useful. The other innovation, described in more detail by Dr. Enna, is the use of focused conferences on discrete topics within the overall program, so that attendees should be able to find consecutive programming specifically in their fields of interest throughout the meeting.<br /><br />ASPET members should note that the society has, as for previous IUPHAR World Congresses, set aside funds to provide travel support for graduate students and young scientists to attend the 2010 World Congress. Check the ASPET web site for details and how to apply for travel support from ASPET (  <a title="Travel Awards" href="http://www.aspet.org/awards/travel/">www.aspet.org/awards/travel/</a>  ).  This is a great opportunity to attend what promises to be a fascinating conference in a very interesting city, as well as to meet pharmacologists from around the world.<br /><br />Brian Cox<img height="74" align="right" width="407" title="beach" alt="beach" src="http://www.aspet.org/uploadedImages/Blog/ASPET/The Islands Brygge Harbour Bath(1).jpg?n=4106" style="width: 407px; height: 74px;" /><br />President, ASPET</p>
<p><br /><br /><img hspace="5" height="141" align="left" width="217" title="Congress Ctr" alt="Congress Ctr" src="http://www.aspet.org/uploadedImages/Blog/ASPET/Bella-Center-ny.jpg?n=4503" style="width: 217px; height: 141px;" />The International Union of Basic and Clinical Pharmacology (IUPHAR) will hold its 16th World Congress in Copenhagen, Denmark, July 17-23, 2010.  Designated WorldPharma2010 (www.WorldPharma2010.org), the meeting is organized and hosted by the Danish Society for Pharmacology.  This is the first IUPHAR Congress to cover both the basic and clinical aspects of the discipline.  Highlights of the meeting include 18 focused conferences, each of which lasts from 2 to 2 &#189; days.  Focused conference topics include ion channels in analgesia and anesthesia, transmembrane transport, simulation and data modeling in drug development, pediatric clinical pharmacology, and G protein-coupled 7TM receptors, to name a few.  In most cases, the focused conferences emphasize the translational nature of the work, illustrating how information gleaned from basic laboratory research can be exploited clinically.  Among the focused conference speakers are Randy Blakely, Jane Mitchell, Jean Philippe Pin, Michelle Bouvier, Marc Caron, William Catterall, Frank Gonzalez, Peter Kalivas, George Koob, and Paul Vanhoutte.  Another feature of the meeting includes two dozen plenary lectures.  Speakers in this group include Salvador Moncada, Trevor Sharp, Brian Kobilka, Sue Duckles, Shizou Akira, Peter Barnes, and Olavi Pelkoknen.  Poster sessions, workshops, satellite meetings, and sponsored symposia round out the meeting.  <br /><br /><img hspace="5" height="230" align="left" width="152" title="Round Tower" alt="Round Tower" src="http://www.aspet.org/uploadedImages/Blog/ASPET/RoundTower.jpg?n=3385" />Scheduled social events are an opening reception, a reception at Copenhagen City Hall, and a dinner at Tivoli Gardens.  Beyond this, Copenhagen and the<img height="150" align="right" width="225" title="Tivoli Gardens" alt="Tivoli Gardens" src="http://www.aspet.org/uploadedImages/Blog/ASPET/800px-Tivoligardens2.jpg?n=2197" style="width: 225px; height: 150px;" /> surrounding Danish countryside offer a wide range of activities from castle tours, to cycling, to art museums, and seaside activities.<br /><br />The abstract submission deadline for WorldPharma2010 is January 15, 2010.  The deadline for advanced, and therefore reduced, registration is March 15, 2010.<br /><br />The meeting venue will be the new congress center in Copenhagen (www.worldpharma2010.org/information).  The Star Alliance Airline Network is offering Congress participants a 20% discount on airfare (http://www.worldpharma2010.org/officialcarrier.php).  Questions about the meeting should be directed to Dr. Kim Brøsen (kbrosen@health.sdu.dk), Congress President, or Dr. Mike Mulvany (mm@farm.au.dk), the Congress Secretary-General.</p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=966&amp;blogid=219">
  <title>The Economic Impact of Medical Research</title>
  <link>http://www.aspet.org/Blog.aspx?id=966&amp;blogid=219</link>
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--></style><span style="font-size: 12pt; font-family: &quot;Cambria&quot;,&quot;serif&quot;;">Most
biomedical scientists welcomed the availability of ARRA stimulus funding for
medical research although the mechanisms proposed for its distribution and the
need for rapid spending by those lucky enough to receive the funds were viewed
by some with a fair degree of skepticism. The doubling of NIH funding during
the period 1998-2003 had already indicated that a rapid injection of funds into
medical research without provision for a longer-term continuation of the
increased levels of support can distort the growth and development of the most
cost-effective research programs.<span style="">  </span></span><meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
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--></style><span style="font-size: 12pt; font-family: &quot;Cambria&quot;,&quot;serif&quot;;">Economists
are now arguing that the use of ARRA stimulus funds to support medical research
has not had the desired effects of providing a rapid stimulus to economic
activity, and thus should be considered a wasteful use of funding that was
designed to restore economic growth.<span style="">  </span></span></p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-11-30T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Brian Cox<br />President, ASPET</p>
<p> </p>
<p>Most biomedical scientists welcomed the availability of ARRA
stimulus funding for medical research although the mechanisms proposed for its
distribution and the need for rapid spending by those lucky enough to receive
the funds were viewed by some with a fair degree of skepticism. The doubling of
NIH funding during the period 1998-2003 had already indicated that a rapid
injection of funds into medical research without provision for a longer-term
continuation of the increased levels of support can distort the growth and
development of the most cost-effective research programs.<span>  </span>While increasing employment opportunities for
young scientists in the short term, transient surges in research funding
followed by a period of reduced funding (when the rate of inflation in the
costs of scientific research is taken into account) may eventually result in
the abandonment of the profession by scientists who have been trained over many
years at significant cost.<span>  </span>Nevertheless,
most scientists have concluded that when the total pool of funding for medical
research is inadequate, any additional funds, including those provided by ARRA,
are better than nothing.<span>  </span></p>
<p>Economists are now arguing that the use of ARRA stimulus
funds to support medical research has not had the desired effects of providing
a rapid stimulus to economic activity (1), and thus should be considered a
wasteful use of funding that was designed to restore economic growth.<span>  </span>The implied lesson might be that increased
support of medical research is not in itself a useful stimulus to the economy. </p>
<p>However, this is not a legitimate conclusion.<span>  </span>The American Association of Medical Colleges
(AAMC) has recently published a report of a study evaluating the economic
impact of academic medical centers (including the economic effects of
education, research and clinical services) on the local economy of every state
in the Union (2). This study was conducted by the consulting firm, Tripp
Umbach, an organization that has performed more than 150 economic impact
studies for academic and health care delivery organizations.<span>   </span>Since this report covers the calendar year
2008, the impact of the additional ARRA funding of medical research (which was
not distributed in any significant amount until 2009) was not covered.<span>   </span>Nevertheless, the report demonstrates the
very powerful economic impact of academic medical centers on the local economy
in almost every state.<span>  </span>The combined
impact of all academic medical centers for 2008 is estimated at $512 billion,
supporting 3.3 million jobs.<span> 
</span>Approximately 1 in 43 of the wage earners in the US has a job because
they work either directly for an academic medical center or they provide
indirect services that arise from the activities of these centers.<span>  </span></p>
<p>Of course not all of these jobs and this economic activity
are directly related to medical research expenditure – education and clinical
services provide a large part of this total sum – but the unique feature of an
academic medical center is that basic as well as translational research is a
critical and fundamental component of the mix of activities that comprise the
center’s activities. Without the medical research component - the activity that
defines an academic center, the magnitude of the stimulus to the local economy
is much reduced.<span>  </span>There is a tremendous
leverage effect of medical research expenditures, attracting many other related
activities that provide a powerful stimulus to the local economy.</p>
<p>While the economic benefit of academic medical centers is
concentrated in states with several large centers, the report shows that states
with fewer and smaller academic health centers also benefit.<span>  </span>New York leads the way in economic benefit,
with academic health centers in the state providing a stimulus of about $69
billion in 2008. Pennsylvania, California and Massachusetts follow, but even
states with many fewer centers get significant benefit from their academic
health centers.<span>  </span>In many regions the
local medical university is one of the major employers in the region. </p>
<p>The solid evidence from the AAMC of the value to local
economies of activities that are driven by the research and research-related
activities of academic medical centers provides strong support for the argument
that development of a more stable economic base for medical research is not
only effective in developing innovative and effective therapies, but also
offers strong support to the local economy.</p>
<p>When you talk with your neighbors, with opinion leaders in
your community, and with local politicians and their staffers, do not forget to
emphasize that in addition to helping to advance medial care and improve
community health, the biomedical research that is conducted in your local
universities and medical centers contributes significantly to the creation of
well-paying jobs as it provides a powerful stimulus to the local economy.<span>  </span>And don’t forget to drive home the importance
of steady long-term growth in research funding rather than episodic booms
followed by periods of financial starvation.<span> 
</span>The quality jobs that are created by biomedical research can only be
maintained if the funding for research is sustained over the long-term. </p>
<p>References: </p>
<ol type="1" start="1">
<li>Editorial:<span>  </span>Without forward planning, the billions
     of dollars in the US stimulus package will go to long-term waste.<span>  </span>Nature, 461: 847-8, 2009.</li>
<li>AAMC
     Report:<span>  </span>The economic impact of
     AAMC-Member Medical Schools and Teaching Hospitals, 2008.<span>   </span>AAMC, Washington DC, September 2009. </li>
</ol>
<p> </p>
<p> </p>
<p> </p>
<p> </p>]]></content:encoded>
 </item>
 <item rdf:about="/Blog.aspx?id=873&amp;blogid=219">
  <title>It&#39;s not your father&#39;s Anaheim!</title>
  <link>http://www.aspet.org/Blog.aspx?id=873&amp;blogid=219</link>
  <description><![CDATA[<p>Experimental
Biology 2010 in Anaheim - It's
already time to start making plans for the ASPET's Annual Meeting - the
deadline for Abstract Submission is 4 November!   The 2010 meeting will be
in Anaheim, California.  I invited Christie Carrico to give us a preview
of plans for the meeting and the venue.  It is going to be a great
meeting;  I look forward to seeing all of you there.   Brian
Cox</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-10-26T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Experimental
Biology 2010 in Anaheim - It's
already time to start making plans for the ASPET's Annual Meeting - the
deadline for Abstract Submission is 4 November!   The 2010 meeting will be
in Anaheim, California.  I invited Christie Carrico to give us a preview
of plans for the meeting and the venue.  It is going to be a great
meeting;  I look forward to seeing all of you there.</p>
<p>Brian
Cox</p>
<p><strong></strong></p>
<p align="center"><strong>It’s not your
father’s Anaheim!</strong></p>
<p align="center"><strong></strong>Christie Carrico<strong><br /></strong></p>
<p> </p>
<p>Many of us remember one of the last of the old Federation
Meetings held in Anaheim in 1992. 
And  not fondly.  The convention center was ugly and dark, the
headquarters hotel (Disneyland Hotel) wasn’t even close to the center and the
other hotels, while cheap, were incredibly tacky and not very modern.  I always stayed at the Alpine Motel, partly
because of cost, but also because of the fake icicles that hung from the eaves
which appealed to my sense of whimsy, it being Southern California.  Of course, there was Disneyland.  Flash forward 18 years to April 2010 where EB
will once again be meeting in Anaheim. 
But it’s not the Anaheim you may remember.</p>
<p> </p>
<p><img height="151" border="1" align="left" width="195" title="Convention Center" alt="Convention Center" src="http://www.aspet.org/uploadedImages/Meeting/Annual_Meeting/Convention Blue Tone.gif?n=3395" />First, the Convention Center has been completely
redone—as in adding a whole new front and two stories up.  What was the old center is now just the
exhibit hall and the new foyer with a full glass front is light and
welcoming.  The meeting rooms, part of
the addition, are convenient and modern. 
Each of the Societies meeting at EB has its own mini-corridor
perpendicular to the foyer where its session rooms are located.  These are wide enough to provide seating and
space for people to congregate and network in between (yes and even during) sessions
but short enough to still let in the light from the foyer.  The Anaheim Convention Center is now one of
the nicest and best laid out convention centers we will have met in.</p>
<p> </p>
<p>The two headquarters hotels, Marriott and Hilton, are
next door... literally.  ASPET will be in
the Hilton and it is a very short walk across a pedestrian mall to the
Convention Center.  You can literally
roll out of bed at 8 and make an 8:30 lecture with time to stop at the Hilton
food court to grab a bagel on the way to the convention center.  In addition, all of the hotels in Anaheim are
giving our meeting attendees terrific incentives to attend this meeting.  The Hilton Hotel is discounting its daily
internet access fee by 50%, its daily buffets by 20%, its exercise facility to
$ 9 per day, and double HHonors points for meeting attendees.  Many other hotels are offering complimentary
continental breakfasts, discounts in their restaurants and discounted or free
Internet access in the guest rooms in addition to the special meeting room
rates.  All of the hotels are on the ART
(Anaheim Resort Transit) bus route, otherwise known as the Disneyland bus.   Most of the cutesy motels along Katella
Avenue close to the Convention Center are gone, but I was pleased to see that
the Alpine Hotel remains.  It has been
upgraded to look more like an upscale Alpine Lodge than a motel, but the
icicles are still there.  Even in April.</p>
<p> </p>
<p>ASPET ‘s Scientific Program Committee has planned an
outstanding scientific program for EB2010. 
Palmer Taylor will be giving the Axelrod lecture.  Eric Nestler will give the Ray Fuller Lecture
on “Transcriptional and epigenetic mechanisms of drug addiction,” followed by a
symposium that further explores the epigenetic mechanisms of learning and
memory.  There are exciting symposia on
“Regenerative pharmacology and stem cell research for tissue and organ repair,”
“Accessory proteins for G-proteins: Partners in signaling,””Integrating
genetics, genomics, and pharmacology: How the Pharmacogenomics Knowledge Base
catalyzed pharmacogenomic research and translational medicine,” Protein-protein
interactions and modulation of drug metabolism,” “Redos regulation and stress
response proteins,”” A new era in industrial/academic partnerships,” “Applying
Web 2.0 technologies in teaching pharmacology,” “Orphan cytochrome P450s,” “
New therapeutic approaches to combat arterial thrombosis” and much much
more.  To view the full program, go to <a href="../../../../meetings/EB2010/">http://www.aspet.org/meetings/EB2010/</a>.   </p>
<p> </p>
<p>As always, the ASPET meeting at EB2010 will be one of the
premier pharmacology networking events, with the Opening Reception, Division
mixers, Student-Mentor Mixer, and Diversity <img height="72" align="right" width="108" style="width: 108px; height: 72px;" src="http://www.aspet.org/uploadedImages/Blog/ASPET/WIP logo_red.jpg?n=6565" alt="WIP Into Shape" title="WIP Into Shape" />Mentoring Breakfast.  Don’t miss the annual WIP Into Shape
Networking Walk on Sunday morning, an informal opportunity to network and walk
in the beautiful Southern California weather.</p>
<p> </p>
<p><img height="106" align="left" width="164" style="width: 164px; height: 106px;" src="http://www.aspet.org/uploadedImages/Meeting/Annual_Meeting/Disney by Micky Jones.gif?n=1913" alt="Mickey Mouse" title="Mickey Mouse" />As for all the other things that you would like to do in
Anaheim if you weren’t going to be at the meeting the whole  time, the perennial favorites are still
there—Knott’s Berry Farm, the Crystal Cathedral, and of course,
Disneyland.  Only now it is Disneyland,
Downtown Disney, and Disney’s California Adventure.  Disneyland is directly across the street from
the Convention Center so there is no need even to ride the bus.  Because Anaheim is, above all else, a family
vacation destination, the prices are much more reasonable than in many of our
other meeting cities.  In addition, the
service people are pleasant and glad to have you there.  Anaheim has recently completed building the
Garden Walk.  A short walk from the
Convention Center, this is a lovely pedestrian mall with lots of outdoor shops
and restaurants and entertainment.  The
winning Los Angeles Angels of Anaheim baseball team and stadium can also be
found in Anaheim.  In nearby Santa Ana is
the Discovery Science Center housed in a building shaped like a cube poised on
one corner.  The Honda Center in Anaheim
is home to the 2007 Stanley Cup winning Anaheim Ducks.  There are lots of beaches within easy driving
distance (let’s not forget whence came the inspiration for The O.C.)!   </p>
<p> </p>
<p>Anaheim is easy to get to.  There are three airports in addition to Los
Angeles International (LAX): Orange County/ John Wayne (SNA), Long Beach (LGB),
and LA/Ontario (ONT).  The latter three
are serviced by some of the less expensive airlines and do not require
traversing the length and breadth of the city of Los Angeles to get to
Anaheim.  Long Beach and John Wayne
airports are a matter of only 20-30 minutes from the convention center area. </p>
<p> </p>
<p>Make your plans now to attend EB2010 April 24-28, 2010 in
Anaheim.  The deadline to submit an
abstract is <strong>November 4, 2009</strong>.  The deadline for ASPET Division Best Abstract
Awards is November 17, 2009, and the deadline for ASPET Travel Awards is
December 1, 2009.  The deadline to make
hotel reservations at the discounted meeting rate is March 19, 2010. </p>
<p> </p>
<p> </p>
<p>Web Sites to Visit to Find out More</p>
<p>Garden Walk   <a href="http://www.anaheimgardenwalk.com/">http://www.anaheimgardenwalk.com/</a></p>
<p>Los Angeles Angels of Anaheim <a href="http://losangeles.angels.mlb.com/index.jsp?c_id=ana">http://losangeles.angels.mlb.com/index.jsp?c_id=ana</a></p>
<p>Discovery Science Center <a href="http://www.discoverycube.org/">http://www.discoverycube.org/</a></p>
<p>Honda Center <a target="_none" href="http://www.hondacenter.com/">http://www.hondacenter.com</a></p>
<p>Disneyland <a target="_none" href="http://www.disneyland.com/">http://www.disneyland.com</a></p>
<p>Knott’s Berry Farm 
<a target="_none" href="http://www.knotts.com/">http://www.knotts.com</a></p>
<p>Photos courtesy of Anaheim/OC Convention and Visitors' Bureau and Mickey Jones (Mickey Mouse photo).<br /></p>
<p> </p>
<p> </p>
<p> </p>]]></content:encoded>
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 <item rdf:about="/Blog.aspx?id=858&amp;blogid=219">
  <title>Licensing examinations and scientific preparation of future physicians: Views of an ASPET participant</title>
  <link>http://www.aspet.org/Blog.aspx?id=858&amp;blogid=219</link>
  <description><![CDATA[<p align="left">Licensing
examinations and scientific preparation of future physicians: Views of an ASPET
participant</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-10-14T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p> </p>
<p>Guest Article on Medical Education Issues<br /> <br />I am delighted to present the first guest contribution to the Pharm Talk blog,  a very interesting paper from Paul Insel from the University of California San Diego on recent developments in the world of medical education, specifically changes in the USMLE and a recent report from the AAMC on the scientific foundations for future physicians.  Paul is ideally qualified to discuss these issues since he has served for many years on USMLE test development committees and was also a member of the AAMC-HHMI committee that authored their new report.   Paul's article points to a number of potential implications of these changes for the teaching of pharmacology to medical students, and therefore their significance for departments of pharmacology in medical schools.    I look forward to seeing member comments on these issues.  <br /> <br />Brian Cox<br /></p>
<p> </p>
<p align="center">Licensing
examinations and scientific preparation of future physicians: Views of an ASPET
participant</p>
<p align="center">Paul
A. Insel</p>
<p> ASPET members who are involved in the teaching of medical
students are probably aware of and may have participated in recent discussion
(and in some institutions, turmoil) regarding curriculum content and the role
of pharmacology in revised curricula. It has been said that “the only constant
is change”; this is certainly the case for medical school curricula. For the
past 30+ years, most institutions have modified their curricula   to
accommodate new didactic approaches  (e.g., “active learning” methods, small group
sessions, electronic instructional materials, self-directed learning, etc.) and
in parallel, have developed courses that integrate knowledge among the basic
medical sciences and between the basic and clinical sciences.  As a discipline with substantial efforts in
the science that underlies the practice of medicine, pharmacology provides
critical knowledge for health science students but at the same time there are
numerous challenges in the teaching of pharmacology, not the least of which is
that pharmacology departments increasingly hire faculty members who have not
been trained as pharmacologists.</p>
<p> In recent months, two important events have occurred that
may change the educational landscape of medical training and more specifically,
the efforts of pharmacologists, in such training. These potential changes
involve the: 1) licensing of physicians and 2) training of physicians. I will
briefly discuss each but will start with the former since such efforts antedate
the latter and because the impact of changes in the licensing process could
prove to be more immediate and perhaps have a greater impact on pharmacologists.
</p>
<p> </p>
<p>As someone who has helped develop the licensing examination
(through activities that have included membership and Chairmanship of the
Pharmacology Test Committee, Chair of Step 1 of the United States Medical
Licensing Examination (USMLE)) and as a participant in meetings held to discuss
changes in the licensing examination,  my
experience and knowledge regarding the USMLE 
may be of interest to ASPET members. In addition, I was the only
pharmacologist who served on the American Association of Medical
Colleges-Howard Hughes Medical Institute (AAMC-HHMI) task force that developed
the recent recommendations regarding the training of physicians (1;
downloadable at <a href="http://www.aamc.org/scientificfoundations">www.aamc.org/scientificfoundations</a>).
Nevertheless, the opinions I express below are only my own.</p>
<p> The USMLE, commonly referred to as “the Boards”, is the
series of 3 examinations (“Steps”) required for an individual to obtain a
license to practice medicine in the United States and that are typically taken
after preclinical coursework (Step 1) and clinical activities (Step 2) in
medical school (or schools of osteopathy) and during post-MD/DO clinical
training (Step 3). Each Step has a “gatekeeper” function: Step 1 seeks to
assess whether an examinee has sufficient knowledge of the sciences that
underlie the practice of medicine to begin clinical training, Step 2 assesses
if an examinee’s knowledge and ability are sufficient to undertake the
supervised practice of medicine (typically in the first post-MD/DO year) and
Step 3 evaluates if an examinee is prepared for the unsupervised practice of
medicine. The examinations define a minimal standard and are designed for
licensure decisions (i.e., protection of the public), although performance of
examinees is also used for secondary purposes, such as to aid in selection of
trainees for post-MD residency positions based on performance on Step 1 and/or
Step 2. In addition, portions of the Step 1 and Step 2 examination questions in
individual disciplines are assembled together and commonly used as “shelf
exams” to evaluate medical student knowledge in  basic science courses or clinical rotations.
The USMLE represents a joint effort of the National Board of Medical Examiners
(NBME, which is responsible for test preparation), the Federation of State
Medical Boards (FSMB) and the Educational Council for Foreign Medical Graduates
(ECFMG). Importantly, the 3 Steps are “high stakes” because examinees must pass
all of them as part of the single path for licensure to practice medicine in
the United States.  The three portions of
the licensing examination have existed for &gt;30 years although some evolution
has occurred, with inclusion of new material and testing formats, for example
the use of standardized patients (i.e., actors and actresses) to assess certain
clinical skills as part of Step 2. </p>
<p> In
recent years discussions held by members of the NBME/USMLE and certain other
stake holders in the licensing community led to a plan (Comprehensive review of
the USMLE, available at <a href="http://www.usmle.org/General_Information/CEUP-Summary-Report-June2008">www.usmle.org/General_Information/CEUP-Summary-Report-June2008</a>)
that would eliminate Step 1 and create two “Gateway examinations”, whose focus
would be to assure that examinees were prepared, respectively, for the
supervised (Gateway A) and unsupervised (Gateway B) practice of medicine. Key
to the rationale for this proposed revision of the USMLE was the notion that
the assessments that lead to licensure are primarily designed to assure the
public that practitioners have appropriate knowledge and skills for medical
practice and that other uses, for example, to assist in the evaluation of
trainees for post-MD/DO training, are of secondary importance. </p>
<p> This proposed revision in the USMLE struck a “raw nerve” for
many, especially pharmacologists and others primarily involved in teaching the
basic sciences in medical schools. Although the intent of those involved in
revising the USMLE was to improve the assessment of physicians and their skills
for medical practice, the proposed elimination of Step 1 was perceived by many
as counterintuitive to these goals, especially with respect to the role of the
basic sciences, such as pharmacology, that underlie the practice of medicine.
An excellent recent article by Olaf Andersen summarizes the efforts related to
the proposed changes in the licensing exams and the response to these proposed
changes by members of the academic community (2).</p>
<p> From discussions that I had with NBME staff, I was surprised
to learn that those who advocated for revision of the USMLE with elimination of
Step 1 had largely ignored one important aspect:  preparation for the Step 1 examination is an important
educational experience because students review-- and sometimes learn
anew--important aspects of the basic medical sciences and in addition,
consolidate and integrate knowledge, including basic science material taught in
different courses.  Such integration is
critical for optimal performance of medical students in the clinical years and
for their careers as physicians, especially in the training of scientifically
literate, inquisitive physicians (3). </p>
<p> It was initially planned that the changes in USMLE,
including the elimination of Step 1, would be implemented within the next few
years but it now appears that substantial further discussion will occur prior
to such implementation. Efforts by a large number of those involved in basic
science education in medical schools (including several ASPET members)
contributed to a re-evaluation of the plan to eliminate Step 1. To the extent
that the focus remains on the role of basic science in the practice of medicine
and the optimal way to assure that physicians are appropriately knowledgeable
and have skills for life-long learning related to the science that underlies
medical practice, I believe that those involved in basic science training,
including pharmacologists, have little to fear by changes in the USMLE. Those
interested in reading other viewpoints regarding the proposed changes in USMLE
may wish to consult other recent articles (4,5).</p>
<p> In part in response to the discussions that have arisen with
respect to proposed changes in the USMLE, one can foresee that the potential
role of pharmacologists as educators may expand beyond the current focus--the
teaching of pharmacology in the preclinical years of medical school-- to a
greater didactic role in the clinical years of medical school training. Such
teaching efforts would likely relate to clinically relevant aspects of
pharmacokinetics, pharmacodynamics, pharmacogenetics, new therapeutic agents
and perhaps topics such as pharmacoeconomics, assessment of efficacy and
toxicity, and the relative effectiveness of different therapeutic approaches,
including use of placebos.  Such efforts
will be challenging to many pharmacologists since teaching in the clinical
years of medical school (and even more so, in later phases of clinical training)
is likely to benefit from prior personal observation of patient responses to
drugs developed during active involvement in clinical care.  Faculty in schools of pharmacy who have Pharm
D degrees (Doctors of Pharmacy) and who are clinically active may be more
effective educators for this type of teaching. To the extent that Pharmacology
department faculty members with other advanced degrees are not knowledgeable
about clinically relevant topics and/or shun involvement in such teaching
efforts, they—and perhaps entire departments-- run the risk of being
marginalized in the teaching of pharmacology and therapeutics in medical
schools in the future.</p>
<p> As I
noted above, I first discussed the changes related to USMLE because I believe
that they are of  immediate importance to
ASPET members, especially those who are actively involved in teaching medical
students. However, over the long-term, the recent efforts related to the
Scientific Foundations for Future Physicians, as discussed in detail by the
report issued by the committee involved in these efforts (1), are likely to
have major impact on members of ASPET. 
The AAMC-HHMI committee spent considerable effort in defining scientific
competencies, including in pharmacology and therapeutic-related areas. “Competencies”
emphasize “learner performance” and thus refer to action-oriented skills and
learned abilities that are a consequence of education (1, 6).  The overarching principles of the committee’s
report emphasize how scientific knowledge is obtained and evolved; the roles of
biological complexity, genetic diversity and interactions between systems
within the body, development and influence of the environment on health and
disease; the need to permeate the curriculum with curiosity, skepticism,
objectivity and scientific reasoning; and the requirement in modern medicine and
its practitioners to synthesize information and collaborate across disciplines.
A key aspect of the committee’s report is the recognition of changes in the
content of undergraduate science courses and how greater integration might
occur among such courses. Changes recommended in requirements for medical
school admission and in scientific concepts that future physicians need to
acquire, with a focus on competencies and not courses, are an important feature
of the AAMC-HHMI committee’s report. </p>
<p> Pharmacologists will likely appreciate that the AAMC-HHMI
committee urges increased emphasis on principles of physical chemistry and
mathematics, which are fundamental to understanding of pharmacokinetics and
pharmacodynamics. The committee’s report stresses the importance of
understanding therapeutic goals and principles. In addition the Scientific
Foundations for Future Physicians report emphasizes the need to integrate the
traditional basic science disciplines in both undergraduate and medical schools
and to prepare students to be life-long learners, who are able to incorporate
new discoveries into understanding of principles, especially as related to the
basic science disciplines. Of note, the committee’s report proposes changes in
pre-medical education in chemistry, including a decrease in certain aspects of
organic chemistry but with greater emphasis on aspects of biochemistry. As Greg
Petsko (an AAMC-HHMI committee member and current President of the American
Society of Biochemistry and Molecular Biology) has noted, biochemists who teach
in medical school biochemistry courses should see this as an important
challenge to what they have traditionally taught in those courses (7).</p>
<p> Akin to what I described above regarding the proposed
changes in the USMLE, the ultimate impact of the proposals contained in the
Scientific Foundations for Future Physicians is difficult to discern. Perhaps
the greatest challenge involves implementation, especially of the changes
proposed for undergraduate, pre-medical education and in particular, the need
for those involved in teaching undergraduates to create integrated educational
materials and to provide classroom and laboratory experiences that incorporate
multiple disciplines (e.g., chemistry, biology and physics). This will likely
require new interactions and efforts among undergraduate faculty; medical
school faculty members in multiple disciplines have worked together for many
years to create pre-clinical courses. Thus, faculty in pharmacology and other
medical school disciplines may be able to offer useful guidance to
undergraduate colleagues regarding the development of teaching materials that
incorporate concepts from multiple disciplines and as importantly, how decreased
autonomy in curricular design may help provide students with integrative
educational experiences that are well-suited for life-long learning. </p>
<p> Pharmacologists have the potential to provide considerable
assistance in the design and execution of curricula envisaged by
recommendations in the Scientific Foundations for Future Physicians report. I
thus urge ASPET members and faculty in undergraduate, medical school and other
health-related professional schools to examine the report (1). It not only will
provoke discussion but also may be a catalyst for changes in pre-professional
and professional education in the health sciences. There are challenges in
obtaining broad acceptance and even more so in their implementation. The roles
of pharmacologists as educators in the future may be quite different than at
present but based on efforts related to the AAMC-HHMI report and in addition,
as noted above in the discussion of the USMLE, such educational efforts will
almost certainly increase. </p>
<p> <u>References</u></p>
<ol type="1" start="1">
<li> Scientific Foundations for Future
     Physicians. Report of the AAMC-HHMI Committee. 2009.</li>
<li>Andersen OS. Changing the
     USMLE. Challenges and opportunities for physiology and other medical
     school basic science departments. <em>The
     Physiologist</em>. 52, number 2. April, 2009.</li>
<li> Ausiello D. Science education and
     communication: AAP Presidential Address. <em>J. Clin Invest.</em> 117:3128-3130, 2007.</li>
<li> Brass, E. Basic biomedical sciences and
     the future of medical education: implications for internal medicine. <em>J. Gen. Internal Med </em>, in press,
     2009.</li>
<li> Fincher RE, Wallach PM and Richardson WS.
     Basic science right, not basic science lite: Medical education at a
     crossroad. <em>J Gen Internal Med</em> ,
     in press, 2009. </li>
<li>Epstein
     R and Hundbert E. Defining and assessing professional competence. <em>JAMA </em>287:
     226-35, 2002.</li>
<li> Petsko G. What doctors know. <em>ASBMB Toda</em>y. Aug, 2009, pp3-5.</li>
</ol>




 <br /><p> <span> </span></p>]]></content:encoded>
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 <item rdf:about="/Blog.aspx?id=763&amp;blogid=219">
  <title>The Critical Role of Animal Research in Public Health</title>
  <link>http://www.aspet.org/Blog.aspx?id=763&amp;blogid=219</link>
  <description><![CDATA[<p>The juxtaposition of two items in the news over the last week or two caught my eye. The Foundation for Biomedical Research (FBR), a non profit foundation supporting the use of animals in biomedical research, announced</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-09-15T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>Brian M. Cox, President, ASPET<br /><br />The juxtaposition of two items in the news over the last week or two caught my eye. The Foundation for Biomedical Research (FBR), a non-profit foundation supporting the use of animals in biomedical research, announced the results of a national poll conducted at the end of last year that found, when compared with a similar poll conducted in 2006, that public support for the use of animals in biomedical research is declining. If the decline continues at the same rate, FBR calculated that by August of 2010 less than 50% of the public would be supportive of animal research. The reasons for this shift are unclear, but the result is potentially very damaging for biomedical research in the future. FBR has launched a public outreach campaign under the name “8twenty10” (i.e., Aug of 2010; see the FBR web site), and has created another web site, “Research Saves.org” for public comment on this issue, with the goal of educating the public about the critical role of animal research in past advances in medical health and the continuing importance of studies conducted in animals for the development of new therapies for diseases and disorders that are currently not effectively treated (for more discussion of this, see the ASPET Public Affairs Web Page Policy Updates). <br />The FBR campaign has several features. They are asking biomedical scientists to send to FBR “previously printed and cleared human interest stories about scientists working with animals to discover breakthroughs for diseases and conditions”, and to visit the Research Saves Lives web site regularly to post personal comments in response to the comments they are receiving from opponents of animal research. FBR has also developed a provocative “advance animal directive” card that they suggest should be signed and carried by opponents of the use of animals in medical research. This card indicates that the holder is an opponent of the research use of animals and therefore declines to accept the current treatments of choice for a long list of common and not-so-common conditions; treatments that were all developed on the basis of animal studies critical to the demonstration of their safety and effectiveness. <br />I suspect that almost all professional pharmacologists strongly believe that animal research must continue to play a significant role in our continuing efforts to understand the processes of disease and aging, to develop new and safe treatments to cure or ameliorate health problems, and to test the safety of chemical in our environment. It is therefore in our interests to support the FBR campaign, and to take advantage of our professional roles to press the point whenever possible that elimination of animal research would have a profoundly negative impact on future improvements in health care and public health. <br />The second news item originated in Europe three years ago, with the passage by the European Commission of a program entitled the “Registration, Evaluation, Authorization and Restriction of Chemicals (REACH)” requiring that all chemical products introduced before 1981 that are produced in an amount greater that 1000 tons per year be registered now, and subjected to rigorous animal testing for potential toxicity by 2018. (Chemicals introduced since 1981 are already subject to such testing in both Europe and the United States). This issue is back in the news because a toxicologist currently based at Johns Hopkins University and a private consultant have recently published an opinion paper in Nature indicating that by their calculations up to 54 million laboratory animals will be needed to conduct all the mandated tests (Hartnung &amp; Rovida, 2009). Hartnung &amp; Rovida suggest that the “legacy” chemicals requiring testing represent about 97% of the independent chemical entities in use today and about 99% of the production volume. They report that by the end of 2008, the number of substances pre-registered for testing with the European Chemical Agency (ECHA) had reached about140,000 (posted by roughly 65,000 companies), with the required testing estimated to cost about US$13.6 billion. Initial estimates of the numbers of compounds that would require testing and the numbers of required animals, developed during the preparation of the legislation on the basis of production figures from the period 1991-94, were much lower; about 2.6 million animals at an estimated upper range cost of about US$5.5 billion. Part of the increase is due to the REACH requirement that reproductive toxicity be tested over two generations. Additionally, the European Union has increased in size from 12 to 27 countries over this period, accompanied by a substantial growth of the chemical industry.<br />The estimate of Hartung &amp; Rovida (2009) is challenged by ECHA (see Gilbert, 2009), who believe that alternative testing methods will become available and that results from initial testing including one-generation reproductive toxicity tests, will result in the withdrawal of many of the compounds prior to more extensive testing, thus substantially reducing the required numbers of animals. Nevertheless, all concede that the initial ECHA estimates of the required numbers and costs for safety testing were too low. <br />I cannot comment usefully on the reliability of either estimate, but it is clear from this interesting discussion that it is taken for granted within the European Community that a very substantial increase in animal testing will be required to protect public health in an environment with an increasing chemical burden. It is interesting that the European Union, an arena that has become very restrictive in its approach to regulation of the use of animals in biomedical research, recognizes that it is necessary to conduct a very large number of tests in animals, even as many of the older in vivo safety tests in animals are being eliminated by newly developed high-throughput in vitro tests. There are also plans for increased testing of pre-1981 chemicals in public use in the United States, Canada, and Japan. The proposed regulations in these countries are not yet finalized, but it is highly likely that a significant increase in animals testing will be required in these countries also. These proposed tests are for evaluation of chemical safety; there will also be a continuing and probably increasing need for additional animal testing in the development of novel drugs and biologics. At some point the conflict between public perception of animal testing and the requirements for improved public health will have to be reconciled. I wish the new campaign by the Foundation for Biomedical Research every success. Visit the “8twenty10” page at FBR to lend your support. <br /><br />References: <br />ASPET Public Affairs Policy Updates; <a title="http://www.aspet.org/PolicyUpdatesNews.aspx?id=550" href="http://www.aspet.org/PolicyUpdatesNews.aspx?id=550" target="_blank">http://www.aspet.org/PolicyUpdatesNews.aspx?id=550</a> .<br />Foundation for Biomedical Research (FBR), <a title="http://www.fbresearch.org/" href="http://www.fbresearch.org/" target="_blank">http://www.fbresearch.org/</a> <br />Gilbert N, (2009) Chemical safety costs uncertain. Nature 460: 1065.<br />Hartnung T &amp; Rovida C, (2009) Chemical regulators have overreached, Nature 460: 1080-1081.<br /></p>]]></content:encoded>
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 <item rdf:about="/Blog.aspx?id=608&amp;blogid=219">
  <title>Comparative Effectiveness Research (CER): Career Opportunities for Pharmacology Graduates</title>
  <link>http://www.aspet.org/Blog.aspx?id=608&amp;blogid=219</link>
  <description><![CDATA[<p> Comparative Effectiveness Research (CER) has been much in the news lately. The American Recovery and Reinvestment Act of 2009 (ARRA) has set aside over $1 billion for the “development and dissemination” of research comparing the effectiveness and outcomes of different health care treatments and strategies (Iglehart, 2009). As part of this effort, the Institute of Medicine was commissioned to recommend national priorities for CER. Their report in June (IOM, 2009) presents a definition of CER, along with a list of 100 priority questions relating to health care delivery that should be addressed quickly, and an outline strategy to facilitate an ongoing and robust CER enterprise. Should pharmacologists be following these developments?</p>]]></description>
  <dc:creator></dc:creator>
  <dc:date>2009-08-12T14:54:00Z</dc:date>
  <content:encoded><![CDATA[<p>We plan to use this blog as a forum for the discussion of critical issues that may have significant impact of the professional lives of pharmacologists over the next decade. Initial postings may be generated by the President and/or other society officers or staff, but we will also invite others to contribute.  We hope to generate feedback in the form of Comments from members and anyone else who chooses to respond. </p>
<p>Note that all entries in this blog reflect the personal opinions of the author(s), not the “official” position of the American Society for Pharmacology and Experimental Therapeutics. There are other locations on the new web page for “official” society statements. In the blog we hope to stimulate interest and encourage debate.  </p>
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<p><strong>Comparative Effectiveness Research (CER):  Career Opportunities for Pharmacology Graduates?</strong></p>
<p>Brian M. Cox, President ASPET</p>
<p>Comparative Effectiveness Research (CER) has been much in the news lately. The American Recovery and Reinvestment Act of 2009 (ARRA) has set aside over $1 billion for the “development and dissemination” of research comparing the effectiveness and outcomes of different health care treatments and strategies (Iglehart, 2009). As part of this effort, the Institute of Medicine was commissioned to recommend national priorities for CER. Their report in June (IOM, 2009) presents a definition of CER, along with a list of 100 priority questions relating to health care delivery that should be addressed quickly, and an outline strategy to facilitate an ongoing and robust CER enterprise. Should pharmacologists be following these developments?</p>
<p>The IOM’s list of 100 priority questions is interesting; about one third of the listed topics explicitly involve evaluations of the comparative effectiveness of pharmacologic therapies, and others address undefined treatment strategies that in many cases also include drugs or biologic agents.  In some instances the critical questions relate to the relative cost-effectiveness of different drug treatments; in others comparisons of drug treatments with non-pharmacologic treatments are proposed. The emphasis is often on comparative effectiveness of selected treatments in vulnerable human populations. The IOM suggests that new randomized controlled trials will be required to address 49 of its 100 priority question, although other approaches including prospective observational studies, database reviews and systematic literature reviews are all expected to have their place.  Achievement of these goals will require a marked expansion of support for new clinical trials that will compare different agents and other treatments in the defined populations, and improved meta-analyses of previously published trials. Financing many of these trials will be difficult. How will the costs of trials comparing different proprietary agents be apportioned when one agent is likely to emerge as the preferred treatment?  Public financial support will be required in addition to continued private sector funding. ARRA funding, with its goal of achieving a rapid expenditure of funds to stimulate the economy, might be a good vehicle for initiating this endeavor but other funding sources will have to be found for the stable long-term investment in CER.  The goal must be the development of an infrastructure that can support the enhanced research activities and have the credibility required for the results of the comparative testing to become etsbalished medical practice. While some savings should eventually emerge from the more efficient use of current health delivery resources, these savings will also have to support expanded coverage of health care delivery for the uninsured. </p>
<p>Politicians have noted the need for continued public support. Senators Baucus (D-Mont) and Conrad (D-ND) have introduced the Patient-Centered Outcomes Research Act of 2009 (Senate Finance Committee, 2009), which would establish a private, non-profit corporation (the Patient-Centered Outcomes Research Institute) “to generate scientific evidence and new information on how diseases, disorders and other health conditions can be treated to achieve the best clinical outcome for patients,” with a proposal for funding to be provided by contributions from both public and private payers through a designated trust fund. Part of the income would be derived from small annual fees imposed on individual health insurance plans. The bill is currently still in committee and its future is uncertain. The House has yet to address this issue, but recently David Broder of the Washington Post reported in an editorial column that two House representatives (Ron Kind, D-WI; Bruce Braley, D-IA) have added provisions to the draft House bill on health care reform that would take advantage of the IOM’s intellectual resources and experience in this area to deliver “high-quality evidence-based, patient-centered care” (Broder, 2009). Again the future of this provision is uncertain, but it clearly reflects recognition that CER will have a major role to play in improved health care delivery in the future.  Other countries, including Australia, France, Germany and the United Kingdom, have already moved someway down this road, with established agencies charged with implementation of evidence-based treatment choices in health care delivery. (I hope to discuss experiences with CER outside the USA in a future Pharm Talk). </p>
<p>With an increased emphasis on CER in the future, evidence-based medicine will become an important determinant of the treatment options that will be available under most health delivery plans. It is not clear that there are enough trained scientists to support the expansion of CER. While clinicians must play an important role in evaluating clinical effectiveness, the most effective research teams will also employ other scientists in the design and implementation of CER projects. Oversight agencies will need appropriately trained scientists as well as physicians to regulate and evaluate these studies, and to disseminate evidence-based treatment guidelines. </p>
<p>Back to the question - should pharmacologists be following these developments?  My answer is “Yes” (with a capital Y).   Most ASPET members are predominantly involved in pre-clinical research, but many play an important role in the education of physicians where understanding evidence-based medicine and CER is an increasingly important part of the curriculum. A strong training in pharmacology can provide a very well balanced view of the critical issues associated with comparisons of the clinical effectiveness of different medications. If pharmacology departments wish to continue to be relevant to the ongoing discussions on optimal cost-effective health care they need to adapt their training programs to expand the career options for which their graduates are qualified, including training for careers supporting CER. ASPET still includes “Experimental Therapeutics” as part of its name; it appears that as the society moves into its second century, it would make a lot of sense for members to place increased emphasis on this aspect of its mission.</p>
<p>Do others agree?  I look forward to seeing your comments (See the link for posting comments below the references). </p>
<p>References:</p>
<p>Broder D (2009) One healthy competition, Washington Post,  2 Aug 2009. <a href="http://www.washingtonpost.com/wp-dyn/content/article/2009/07/31/AR2009073102614.html">http://www.washingtonpost.com/wp-dyn/content/article/2009/07/31/AR2009073102614.html</a>, accessed 8/6/09.</p>
<p>Iglehart JK (2009) Prioritizing comparative-effectiveness research – IOM recommendations. New Eng J Med 361: 325-328.</p>
<p>Institute of Medicine Report (2009) Initial national priorities for comparative effectiveness research, June 2009, <a href="http://www.iom.edu/cerpriorities">http://www.iom.edu/cerpriorities</a>, accessed on 8/6/09.</p>
<p>Senate Finance Committee News Release, June 2009  Baucus, Conrad introduce bill to invest in research on best practices in health care, <a href="http://finance.senate.gov/press/Bpress/2009press/prb060909.pdf">http://finance.senate.gov/press/Bpress/2009press/prb060909.pdf</a>, accessed 8/6/09.</p>
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