January 22, 2011, 6:32 AM CT

Defense mechanism against bacteria

Under standard laboratory conditions, the human beta-defensin 1 (hBD-1), a human antibiotic naturally produced in the body, had always shown only little activity against microbes. Nevertheless the human body produces it in remarkable quantities. The solution to the puzzle was the investigation process itself, as the research group led by Dr. Jan Wehkamp at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology of the Stuttgart-based Robert Bosch Hospital found out.

Before the research group took a new approach to this research, defensins were commonly tested in the presence of oxygen, eventhough little oxygen is present, for example, in the human intestine. Starting out from the discovery that a special antibiotic-activating protein of the human body is diminished in patients with inflammatory bowel diseases, Crohn's Disease and Ulcerative Colitis, the working group investigated how defensins act under low-oxygen conditions. During their investigations the researchers found out that under these conditions hBD-1 unfolds a strong antibiotic activity against lactic acid bacteria and yeast.

Furthermore the scientists discovered that another human protein, thioredoxin, is able to activate beta-defensin 1 even in the presence of oxygen. Moritz Marcinowski and Professor Johannes Buchner from the Department of Chemistry at the Techch, used circular dichroism spectroscopy to elucidate the differences between the folded inactive and the unfolded active form of the protein......... Posted by: Mark      Read more         Source

January 18, 2011, 7:14 AM CT

Outcomes following primary HIV infection

Women, nonwhites, and people in the southern United States who were newly infected with HIV and followed for an average of four years experienced greater HIV/AIDS-related morbidity in comparison to men and people of other races living in other regions of the country. The findings, reported in the February 15 issue of The Journal of Infectious Diseases, underscore the urgent need to improve the health of these populations in order to reduce HIV-related morbidity and mortality in the U.S. (Please see below for a link to the embargoed study online.).

The scientists did not expect women to show the worst health outcomes because their viral loads were lower and CD4+ T cell counts were higher than men's following diagnosis, reported study author Amie L. Meditz, MD, of the University of Colorado- Denver. (The study was part of the Acute Infection and Early Disease Research Program, a multicenter study network funded by the National Institute of Allergy and Infectious Diseases.) However, during the course of the study (1997-2007), the frequency of HIV-related illnesses in women was more than double that of men, with nonwhite women having the most negative outcomes. After eight years of infection, HIV-related events affected 64 percent of nonwhite women, and AIDS-defining events occurred in 22 percent of nonwhite women. In comparison, HIV-related and AIDS-defining events occurred in 21 percent and 6 percent of individuals in other combined race and sex groups, respectively......... Posted by: Mark      Read more         Source

January 16, 2011, 9:28 PM CT

Development of anti-HIV neutralizing antibodies

New findings are bringing researchers closer to an effective HIV vaccine. Scientists from Seattle Biomedical Research Institute (Seattle BioMed), Vanderbilt University and the Ragon Institute of MGH, MIT and Harvard report findings showing new evidence about broadly-reactive neutralizing antibodies, which block HIV infection. Details are published January 13 in the open-access journal PLoS Pathogens

As per author Leo Stamatatos, Ph.D., director of the Viral Vaccines Program at Seattle BioMed and a major stumbling block in the development of an effective vaccine against HIV is the inability to elicit, by immunization, broadly reactive neutralizing antibodies (NAbs). These antibodies bind to the surface of HIV and prevent it from attaching itself to a cell and infecting it. However, a fraction of people infected with HIV develop broadly neutralizing antibodies (bNAbs) capable of preventing cell-infection by diverse HIV isolates, which are the type of antibodies scientists wish to elicit by vaccination.

"We've observed thanbsp;   Read more         Source

January 5, 2011, 6:38 AM CT

Double doses of chicken pox vaccine most effective

When vaccinating children against varicella (chicken pox), scientists at Yale School of Medicine have found, two doses are better than one. In fact, the odds of developing chicken pox were 95 percent lower in children who had received two doses of the vaccine compared with those who had received only one dose.

Reported in the February 1 issue of Journal of Infectious Diseases, the study was led by Eugene D. Shapiro, M.D., professor in the Department of Pediatrics at Yale and colleagues at Yale and Columbia universities.

The Centers for Disease Control and Prevention (CDC) began recommending a single dose of chicken pox vaccine for children ages 1 to 13 in 1995. The chicken pox rate fell drastically and studies showed that the effectiveness of one dose was 86 percent. But there was still a high rate of breakthrough illness in immunized children. The CDC changed the immunization policy for chicken pox in 2006, adding a second dose for children ages 4 to 6. In this study, Shapiro and his team showed that the effectiveness of two doses is 98.3 percent.

Past studies have suggested that two doses of varicella vaccine are associated with higher antibody levels than one dose, but this is the first study to assess the clinical effectiveness of two doses of the vaccine in the general population. In a survey of Connecticut children, Shapiro and his team discovered 71 cases of chicken pox in children ages 4 and older. None of these children had received two doses of vaccine; 66 (93 percent) had received one dose and five (7 percent) had received no vaccine......... Posted by: Mark      Read more         Source

December 29, 2010, 6:24 AM CT

Key interaction in hepatitis C virus

Researchers from the Florida campus of The Scripps Research Institute have identified a molecular interaction between a structural hepatitis C virus protein (HCV) and a protein critical to viral replication. This new finding strongly suggests a novel method of inhibiting the production of the virus and a potential new therapeutic target for hepatitis C drug development.

The study was reported in the January 2010 issue (Volume 92, Part 1) of the Journal of General Virology

These new data underline the essential role of the viral protein known as "core" as a primary organizer of the infectious HCV particle assembly and support a new molecular understanding of the formation of the viral particle itself.

"While our finding that the HCV core interacts with the non-structural helicase protein was not totally unexpected, this had not really been confirmed until this study," said Scripps Florida Professor Donny Strosberg, who led the study. "But the most exciting part is that small molecule inhibitors of dimerization [the joining of two identical subunits] of core actually inhibit interaction between core and helicase, thus possibly preventing production of an infectious viral particle".



A Viral Plague

Hepatitis C virus infects between 130 and 170 million people worldwide and is the cause of an epidemic of liver cirrhosis and cancer. Because current HCV therapys are only partially effective, many alternative molecular mechanisms are actively being pursued as possible drug targets......... Posted by: Mark      Read more         Source

December 21, 2010, 6:23 AM CT

Malaria-infected cells stiffen, block blood flow

Eventhough the occurence rate of malaria has declined in all but a few countries worldwide, as per a World Health Organization report earlier this month, malaria remains a global threat. Nearly 800,000 people succumbed to the mosquito-borne disease in 2009, nearly all of them in the developing world.

Physicians do not have reliable therapy for the virus at various stages, largely because no one has been able to document the malaria parasite's journeys in the body.

Now scientists at Brown University and the Massachusetts Institute of Technology have used advanced computer modeling and laboratory experiments to show how malaria parasites change red blood cells and how the infected cells impede blood flow to the brain and other critical organs.

Their findings, reported in the early online edition of the Proceedings of the National Academy of Sciences, could help doctors chart, in real time, the buildup in the body of cells infected with malaria or other diseases (such as sickle-cell anemia) and to prescribe therapy accordingly.

"The idea is to predict the evolution of these diseases, just like we predict the weather," said George Karniadakis, professor of applied mathematics at Brown and corresponding author on the paper.

The scientists worked with Plasmodium falciparum, a parasite that can cause cerebral malaria by lodging in capillaries of the brain, particularly among children. The parasite is found globally but is most common in Africa......... Posted by: Mark      Read more         Source

December 7, 2010, 7:19 AM CT

A flu vaccine that lasts

The costly, time-consuming process of making, distributing and administering millions of seasonal flu vaccines would become obsolete if scientists could design a vaccine that confers decades-long protection from any flu virus strain. Making such a universal influenza vaccine is feasible but licensing it may require innovation on several fronts, including finding new ways to evaluate the efficacy of vaccine candidates in clinical trials, conclude researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

In a Nature Medicine commentary, authors Anthony S. Fauci, M.D., NIAID director, and Gary J. Nabel, M.D., Ph.D., director of the NIAID Vaccine Research Center, contrast the envisioned universal influenza vaccine with today's seasonal influenza vaccines. Current seasonal flu vaccines prompt immune responses that mimic those made following natural exposure to the flu virus. Both exposure and vaccination elicit antibodies directed at the roundish head portion of a lollypop-shaped flu protein called hemagglutinin (HA). But the composition of HA's head changes from year to year, gradually becoming unrecognizable to previously made antibodies. Thus, vaccinationwhich induces antibodies tailored to that year's HA head regionmust be repeated annually to maintain immunity to the virus......... Posted by: Mark      Read more         Source

December 7, 2010, 7:04 AM CT

Influenza virus strains show increasing drug resistance

Two new studies raise public health concerns about increasing antiviral resistance among certain influenza viruses, their ability to spread, and a lack of alternative antiviral therapy options. The findings appear in the January 1 issue of The Journal of Infectious Diseases (Please see below for links to these articles online.).

Influenza viruses are treated with two classes of drugs: M2 blockers (adamantanes) and neuraminidase inhibitors (NAIs), including oseltamivir and zanamivir. While the spread of influenza strains with resistance to one class of drugs has been well documented in recent years, a new report from Larisa Gubareva, MD, PhD and his colleagues at the Centers for Disease Control and Prevention (CDC) and at health agencies in West Virginia, Texas, and Canada, confirms that dual resistance can emerge in several ways and has been on the rise during the past three years.

The study analyzed 28 seasonal H1N1 viruses with dual resistance from 2008 to 2010 from five countries, revealing that additional antiviral resistance could rapidly develop in a previously single-resistant strain as a result of mutation, drug response, or gene exchange with another virus.

Eventhough dual resistant viruses are still rare, the researchers noted an increase in the number of tested viruses with this resistance, from 0.06 percent (2007-2008) to 1.5 percent (2008-2009) to 28 percent (2009-2010); however, during the 2009-2010 season the number of circulating seasonal H1N1 viruses was low, and only 25 viruses were tested. "Because only two classes of antiviral agents are approved, the detection of viruses with resistance to drugs in both classes is concerning," said Dr. Gubareva. "If circulation of viruses with dual resistance becomes more widespread among any of the predominant circulating influenza A viruses, therapy options will be extremely limited. New antiviral agents and strategies for antiviral treatment are likely to be necessary in the future"......... Posted by: Mark      Read more         Source

November 23, 2010, 8:03 AM CT

HIV drugs interfere with blood sugar

The same powerful drugs that have extended the lives of countless people with HIV come with a price - insulin resistance that can lead to diabetes and cardiovascular disease.

Now, scientists at Washington University School of Medicine in St. Louis have determined why that happens. Their research shows that HIV protease inhibitors directly interfere with the way blood sugar levels are controlled in the body. This leads to insulin resistance, a condition that occurs when the body produces enough insulin but doesn't use it properly.

This confirmation provides the potential to develop safer antiviral drugs.

Paul Hruz, MD, PhD, assistant professor of pediatrics and of cell biology and physiology at the School of Medicine, and his team observed that first-generation protease inhibitors, including the drug ritonavir, block GLUT4, a protein that transports glucose from the blood into the cells where it is needed. This raises blood sugar levels - a hallmark of diabetes.

"Our lab has established that one of the effects of these drugs is blocking glucose transport, one of most important steps in how insulin works," says Hruz, senior author of the study reported in the Nov. 19 Journal of Biological Chemistry. "Now that we've identified the main mechanism, we will look to develop new drugs that treat HIV but don't cause diabetes"......... Posted by: Mark      Read more         Source