Nature Medicine

A drug recently approved to treat septic infections may help brain cells survive the effects of a stroke, University of Rochester neurologist Berislav Zlokovic and colleagues report in the 3 February online version of Nature Medicine. Activated protein C (APC) is known to have potent anticoagulant and anti-inflammatory properties. Now the researchers report that APC also directly prevents cell death and improves cell survival in a mouse model of stroke.

Stroke is the third leading cause of death and the most common cause of long-term disability. One type of stroke - called ischemic stroke—occurs when the blood supply to a part of the brain is suddenly interrupted. Deprived of oxygen and nutrients from the blood, brain cells begin to die, some within 2-3 hours, while others survive for several hours. To prevent the secondary damage, researchers have tried to develop neuroprotective drugs that can save the dying cells, but with little success—until now.

There are no approved neuroprotective drugs for stroke and the only drug available, tissue plasminogen activator (tPA), can itself damage cells if given after the first few hours. APC, in its FDA-approved form, is therefore an attractive option to treat not just stroke, but ischemic injury in the heart, lungs, kidneys and other organs, the researchers suggest.

Nature Medicine

RNA interference (RNAi) is a powerful technique for silencing the expression of genes and has been described as the most important scientific advance in recent years. But its potential to treat or prevent disease in live animals has thus far been unproven.

In the March issue of Nature Medicine, Judy Lieberman and her colleagues report for the first time that RNAi can successfully prevent liver injury and death in a mouse model of hepatitis.

The researchers used RNAi to silence Fas, which is implicated in a wide array of liver diseases, including autoimmune, viral and transplant rejection hepatitis. Intravenously injecting inhibitory RNAs against Fas, without the need for a delivery vector or virus, allowed mice to survive in two models of autoimmune hepatitis, the researchers report.

Nature Medicine

A microbicide can effectively block vaginal transmission of HIV in an animal model, researchers report in the March issue of Nature Medicine. The results are the first concrete evidence that microbicides can prevent virus attachment and entry into the vagina or rectum.

With an effective HIV vaccine still years away, there is a crucial need for effective ways to prevent the spread of the virus. Many scientists have pointed to microbicides as the solution. But most of the evidence for microbicide action has been empirical—until now.

In their report, John Moore and his colleagues present evidence that an antibody to the viral gp120 protein protects rhesus macaques from infection with the simian HIV virus. Because the antibody is expensive, the method is not yet a practical solution, the researchers point out. But the results provide a valuable proof-of-concept that should help pave the way for the testing and development of rationally designed microbicides.

Nature Medicine

A widely available derivative of vitamin B1 prevents the progression of diabetic complications such as retinal damage, Michael Brownlee and his colleagues report in the March issue of Nature Medicine. Diabetic retinopathy is one of the leading causes of blindness among adults.

Chronically high glucose levels in diabetics can, over time, damage the eyes, nerves, kidneys and other tissues. A group of glucose-derived compounds called "triosephosphates" accumulate to abnormally high levels in the cells of diabetics. The researchers show that benfotiamine acts by activating an enzyme called transketolase, which diverts the production of harmful triosephosphates to the more benign pentosephosphates.

The researchers fed diabetic rats benfotiamine, a fat-soluble synthetic analog of thiamine or vitamin B1, for 9 months. The compound prevents three major pathways of high-glucose damage and prevents diabetic retinopathy, the researchers found. Their results also shed mechanistic light on how elevated glucose levels damage tissues.