September 3, 2006, 7:27 AM CT

Vaccine For Severe Form Of Malaria

Plasmodium falciparium, the most severe form of malaria hits pregnant women and children the hardest. A joint study between Karolinska Institutet in Sweden and Makerere University in Uganda has now produced some important findings on how the malaria parasite conceals itself in the placenta.

Plasmodium falciparium is the name of by far the most virulent of the four malaria parasites that infect man. It is especially dangerous in that it also infects the placenta of pregnant women, with fatal consequences for both her and the foetus. This, combined with the often feeble medical resources of malaria-stricken countries, can lead to such serous complications that the mother dies during delivery.

"For some reason, women in their first pregnancy lose the semi-immunity that is normally found in adults," explains Niloofar Rasti, a KI graduate student who has been working with the study. "The placenta seems to be an anatomically favourable environment for a subpopulation of the parasites".

The research group from Karolinska Institutet, under the leadership of Professor Mats Wahlgren, has been working with colleagues from KI's partner university in Uganda to study in detail how the parasite infects the placenta. Their results, which are reported in the American scientific journal PNAS, can enable the development of vaccines and therapies to combat severe malarial infections.........

Posted by: Mark      Permalink         Source

August 29, 2006, 9:19 PM CT

How Cancer Drug Aids An Anti-cancer Virus

Scientists here have discovered how a specific chemotherapy drug helps a cancer-killing virus. The virus is being tested in animals for the therapy of incurable human brain tumors.

The virus, a modified herpes simplex virus, is injected directly into the tumor, where it enters only the cancer cells and kills them. The study found, however, that within hours of the injection, infection-fighting immune cells are drawn into the tumor to attack the virus, reducing the therapy's effectiveness.

They also observed that a chemotherapeutic drug called cyclophosphamide briefly weakens those immune cells, giving the anti-cancer virus an opportunity to spread more completely through the tumor and kill more cancer cells.

Specifically, the drug slows the activity of immune cells called natural killer (NK) cells and macrophages, which are the body's first line of defense against infections.

The virus and drug cannot be used yet in humans because they require further study, as well as testing for safety and effectiveness through the clinical trials process.

The research, led by researchers with the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, is reported in the Aug. 22 issue of the Proceedings of the National Academy of Sciences.........

Posted by: Janet      Permalink         Source

August 27, 2006, 7:50 PM CT

Gut Tissue A Major Reservoir For HIV

FINDINGS: UCLA scientists have found the human gut to be a major reservoir harboring the HIV virus -- holding almost twice as much as a person's blood. In addition, the virus stored in the gut does not decay or reduce over time, as is also the case with blood-related reservoirs. It is well-known that peripheral blood mononuclear cells (PBMCs) and lymph nodes are principal reservoirs harboring the human immunodeficiency virus (HIV). The role of gut-associated lymphoid tissue (GALT) in this setting, however, had not been properly reviewed until now. Scientists from the Center for Prevention Research and the UCLA AIDS Institute at the David Geffen School of Medicine at UCLA, in collaboration with the AIDS Research Alliance in West Hollywood, Calif., collaborated on this research.



IMPACT: The findings further confirm that HIV remains persistent and elusive, and that eradicating the virus using current anti-retroviral treatment alone is not enough. Despite using fully suppressive treatment, patients in the study still had evidence of persistent, steady levels of HIV in gut tissue as well as in the blood.........

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August 24, 2006, 10:28 PM CT

Waterborne infectious diseases could soon be history

Waterborne infectious diseases, which bring death and illness to millions of people around the world, could largely be consigned to history by 2015 if global health partnerships integrate their programmes, as per Alan Fenwick writing in today's Science.

Professor Fenwick, from Imperial College London, argues that up to seven neglected tropical diseases including river blindness could be brought under control, with infection by some eliminated entirely, if existing programmes increase their coverage.

In Africa some 500 million people need therapy to control diseases such as disfiguring elephantiasis (lymphatic filariasis), river blindness (onchocerciasis), schistosomiasis, intestinal worms and the blinding eye infection trachoma.

The donation of drugs by pharmaceutical companies, together with financial donations from foundations, is already having a sizeable impact, with numbers given therapy for these diseases increasing from virtually zero in 1986 to between 20 and 80 million individuals annually in 2006.

More funding is mandatory to convince decision makers of the benefits of therapy, to improve health education material and to deliver the drugs to those who need them. The cost can be as low as 25 pence per person per year, and the impact would be rapid.........

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August 24, 2006, 10:12 PM CT

HIV Drug To Prevent Cervical Cancer

Scientists at the University of Manchester are in the process of developing a topical therapy against the human papilloma virus (HPV) which is responsible for pre-malignant and malignant disease of the cervix as well as other genital malignancies.

In the UK a number of thousands of women undergo surgery to remove premalignant lesions of every year. Instead they may be able to apply a simple cream or pessary to the affected area. The discovery may be even more significant in developing countries which lack surgical facilities and where HPV related cervical cancer is one of the most common forms of cancer in women.

Drs Ian and Lynne Hampson at the School of Medicine's Division of Human Development and Reproduction are in the process of developing the therapy from a type of drug that is given orally to treat HIV. This protease inhibitor can selectively kill cultured HPV infected cervical cancer cells and, since it is already available as a liquid formulation, it is possible it may work by direct application to the cervix.

The research, funded by the Humane Research Trust, is would be reported in the recent issue of the journal Anti-Viral Therapy (2006; 11(6): in press) and is also being presented at the International HPV meeting in Prague on 5 September.........

Posted by: Emily      Permalink         Source

August 21, 2006, 9:49 PM CT

Major Strategic Breakthrough In Controling The Aids Virus

A team of scientists from the Universit de Montral and the Centre hospitalier de l'Universit de Montral (CHUM) have announced an important breakthrough in fighting the human immunodeficiency virus (HIV). For the first time, researchers have identified a defect in the immune response to HIV and found a way to correct the flaw. Dr. Rafick-Pierre Skaly, an eminent researcher in cell biology, immunology, and virology, has confirmed the identification of a new therapeutic target (the PD-1 protein) that restores the function of the T cells whose role is to eliminate cells infected with the virus. This constitutes a major breakthrough, opening new prospects for the development of therapeutic strategies for controlling HIV infection. The research findings are published in today's issue of the journal Nature Medicine.

Dr. Skaly explained that "immune system cells made non-functional by HIV can be identified by the presence of a protein that is significantly overexpressed when infected by the virus." In fact, high levels of the protein are linked to a more serious dysfunction. "The most important discovery made in this study arises from the fact that by stimulating this protein, we succeeded in preventing the virus from making immune system cells dysfunctional," he added.

The findings were simultaneously reproduced by two other laboratories the labs headed by Dr. Bruce Walker at Harvard and Dr. Richard Koup at the NIH. "It's a rare occurrence for three teams to work together on attacking a major problem. Up until now, the virus has been more or less invincible. By combining our efforts, we found the missing link that may enable us to defeat the virus," noted Dr. Skaly. Discussions with partners are also underway to translate these research findings into clinical trials, which could start during the coming year.........

Posted by: Mark      Permalink         Source

August 21, 2006, 9:07 PM CT

Bulls-eye For Antibiotic Target

A Purdue University researcher has opened the door for possible antibiotic therapys for a variety of diseases by determining the structure of a protein that controls the starvation response of E. coli.

This research is applicable to the therapy of a number of diseases because that same protein is found in numerous harmful bacteria, including those that cause ulcers, leprosy, food poisoning, whooping cough, meningitis, sexually transmitted diseases, respiratory infections and stomach cancer, said David Sanders, an associate professor of biology. Sanders, who is part of the Markey Center for Structural Biology at Purdue, detailed his research in a paper reported in the Aug. 16 issue of the journal Structure.

"This is an important discovery for the field of antibiotics, which was greatly in need of something new," Sanders said. "The antibiotics available today face a challenge of increasing resistance and failure. This research suggests a whole new approach to combat bacterial infections. In addition, this protein is an excellent antibiotic target because it only exists in bacteria and some plants, which means the therapy will only affect the targeted bacterial cells and will be harmless to human cells".

Sanders and his collaborator, Miriam Hasson, studied the structure of exopolyphosphatase, a protein in E. coli bacteria that functions as an enzyme and catalyzes chemical reactions within the bacteria. This enzyme provides the signal for bacteria to enter starvation mode and limit.........

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August 20, 2006, 9:26 PM CT

How HIV 'exhausts' killer T cells

American and South African researchers working at the epicenter of the AIDS epidemic in South Africa have discovered how the human immunodeficiency virus (HIV) "exhausts" killer T cells that would otherwise attack the virus. The scientists observed that HIV can simply "turn off" fully functional T cells by flipping a molecular switch on the cells. In test tube studies, however, the researchers showed that they could reinvigorate the killer T cells by blocking that inhibitory switch, which is called programmed death-1 (PD-1).

The study's senior author, Bruce Walker, a Howard Hughes Medical Institute researcher at Massachusetts General Hospital, said that clinical testing of drugs that block the PD-1 switch could begin very soon, since such drugs exist already. However, he cautioned that these kinds of drugs could cause serious side effects, including autoimmune reactions that trigger the immune system to attack the body. Walker added that the researchers' findings will also likely have application in understanding other chronic viral diseases.

The findings by Walker and colleagues were published in an advance online publication on August 20, 2006, by the journal Nature. Walker is also at the Partners AIDS Research Center and Harvard Medical School. Other co-authors were from the University of KwaZulu Natal in South Africa, Oxford University, Dana-Farber Cancer Institute of Harvard Medical School, Emory University School of Medicine, and The Wistar Institute.........

Posted by: Mark      Permalink         Source

August 19, 2006, 9:24 PM CT

New Treatment For Dangerous Staph Infections

Duke University Medical Center scientists have demonstrated in an international clinical trial the effectiveness and safety of a new drug for treating bloodstream and heart infections caused by Staphylococcus aureus bacteria, a major cause of sickness and death worldwide.

Based on the trial, the Food and Drug Administration already has approved the drug -- daptomycin -- for treating heart infections and bacteremia, also known as bloodstream infection or blood poisoning, caused by S. aureus, as per Vance G. Fowler Jr., M.D., an associate professor of infectious diseases who took part in the study.

"This is the first new drug the FDA has approved in two decades for treating these types of potentially life-threatening infections," Fowler said. "This advance adds a new weapon to our dwindling arsenal of antibiotics against these difficult-to-treat infections."

Daptomycin had been approved by the FDA in 2003 for treating skin infections caused by S. aureus. But until now, Fowler said, no one knew definitively whether the drug would be effective against the more serious bloodstream and heart infections.

The scientists published their findings in the August 17, 2006, issue of the New England Journal of Medicine. Cubist Pharmaceuticals, which manufactures daptomycin, funded the study.........

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August 17, 2006, 11:07 PM CT

Structure of key enzyme in plague bacterium

Scientists at the National Institute of Standards and Technology (NIST) have solved the structure of a key enzyme from the bacterium responsible for plague, finding that it has a highly unusual configuration. The results may shed light both on how the bacterium kills and on fundamental cell signaling processes.

The NIST team determined the three-dimensional shape of class IV adenylyl cyclase (AC), an enzyme found in plague bacteria -- Yersinia pestis -- by purifying and crystallizing the protein and using X-ray crystallography at the Center for Advanced Research in Biotechnology to resolve its configuration. Adenylyl cyclase is a fundamental enzyme found in one form or another in organisms ranging from bacteria to mammals. It synthesizes cyclic AMP (cAMP*), an important signaling molecule that in turn triggers a variety of cellular processes. Six distinct classes of AC are known, playing a wide variety of roles. AC-II is part of the anthrax bacterium's killing mechanism, for example, while AC-III triggers adrenaline release in humans.

Shape plays an essential role in determining the biological function ery difficult to determine for such large molecules. Three-dimensional structures are known for only two other forms of AC. The NIST experiments revealed that AC-IV has a shape completely different from the other two known shapes. AC-IV folds into a rare form of a barrel-like shape previously seen in only three other unrelated proteins.........

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