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    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.004"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265739410460"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_217"
                     title="Herpes Therapy Doesn&apos;t Bar HIV Transmission (CME/CE)"
                     score="-0.003"
                     href="http://www.medpagetoday.com/HIVAIDS/HIVAIDS/tb/18071?impressionId=1265739410460"
                     
      &lt;p&gt;Treating herpes has no effect on the transmission of HIV among discordant couples, researchers said.&lt;/p&gt;
&lt;p&gt;The lack of efficacy was found in a large, randomized clinical trial despite significant reductions in HIV viral load among those treated for herpes simplex-2 (HSV-2), according to Connie Celum, MD, of the University of Washington, and colleagues.&lt;/p&gt;
&lt;p&gt;Researchers will have to look for new ways to prevent transmission among discordant couples (in which one partner has HIV and the other does not), Celum and colleagues concluded online in the&lt;em&gt; New England Journal of Medicine.&lt;/em&gt;&lt;/p&gt;
&lt;p&gt;The study comes after earlier trials also showed that treating HSV-2 with the antiviral acyclovir (Zovirax) did not lower the risk of getting HIV. (See &lt;a href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; mce_href=&quot;http://www.medpagetoday.com/HIVAIDS/HIVAIDS/9884&quot; target=&quot;_blank&quot;&gt;Herpes Treatment No Help in Preventing HIV&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The trials  --  and the current study  --  had their origins in epidemiological and laboratory observations that having an HSV-2 infection increased the risk of contracting HIV.&lt;/p&gt;
&lt;p&gt;Researchers reasoned that a converse effect might also be true  --  treating HSV-2 in HIV-negative people might reduce their risk of infection.&lt;/p&gt;
&lt;p&gt;The reasoning was bolstered by clinical trials showing that treating HSV-2 in HIV-positive people lowered their viral load.&lt;/p&gt;
&lt;p&gt;In the current study, that effect also occurred. HIV-positive volunteers treated with acyclovir saw, on average, a reduction in plasma concentration of HIV by 0.25 log&lt;sub&gt;10&lt;/sub&gt; copies per milliliter compared with members of the placebo group. The difference was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;But transmission among the couples was not affected, implying that a greater reduction in viral load is needed, the researchers said.&lt;/p&gt;
&lt;p&gt;The study, randomized and placebo-controlled, included 3,408 couples in Africa in which only one of the partners had HIV (but was not taking antiretroviral therapy) and also had an HSV-2 infection.&lt;/p&gt;
&lt;p&gt;The outcome was first reported at the Cape Town meeting of the International AIDS Society last year (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/IAS/15242&quot; target=&quot;_blank&quot;&gt;IAS: Acyclovir Flops in Preventing HIV Transmission&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The primary outcome was transmission between partners, verified by genetic sequencing of the virus.&lt;/p&gt;
&lt;p&gt;Transmission between partners was verified in 84 of the 132 recorded cases of transmission, the researchers said, and they were evenly divided  --  41 among those getting the drug and 43 in the placebo group.&lt;/p&gt;
&lt;p&gt;On the other hand, the use of the drug reduced the occurrence of herpes lesions by 73%, which was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001.&lt;/p&gt;
&lt;p&gt;The reduction of herpes lesions suggests that the drug was being used, the researchers said, and therefore that the lack of efficacy against HIV was not a result of nonadherence to acyclovir.&lt;/p&gt;
&lt;p&gt;Overall, the rate of HIV transmission in the study was 2.7 cases per 100 person-years, markedly lower than earlier observations. The researchers attributed that to such interventions as monthly counseling on risk reduction and free condoms.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study had support from the Bill and Melinda Gates Foundation, as well as the University of Washington, the National Institute of Allergy and Infectious Diseases, Gen-Probe, and the National Institute of Mental Health.&lt;/p&gt;&lt;p&gt;Celum reported financial links with GlaxoSmithKline and several other authors reported links with various pharamceutical companies.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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                     title="Livers Under Wrap: AASLD 2005"
                     score="-0.005"
                     href="