Editor's Note: Science Scan is a roundup of recently published, biotechnology-relevant research.
"Warfarin" has nothing to do with warfare. The word is an acronym for "Wisconsin Alumni Research Foundation," plus "arin." Warfarin, the drug, is an anticoagulant, also used as a rodenticide.
Results of the largest stroke-prevention trial ever conducted comparing AstraZeneca plc's investigational oral anticoagulant Exanta to warfarin in patients were published Nov. 20, 2003, in The Lancet. The article is titled "Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation [SPORTIF III]; randomized controlled trial."
SPORTIF III, (another acronym!), denotes "Stroke Prevention using an Oral Thrombin Inhibitor in Atrial Fibrillation" was an open-label, randomized, non-inferiority trial. Patients treated with Exanta suffered 29 ischemic strokes and systemic embolic events, compared to 52 events in patients treated with warfarin. That amounted to a statistically relative risk reduction of 41 percent. In the trial, there were 29 major bleeding events in the group receiving Exanta, compared to 41 in the warfarin arm.
SPORTIF III was conducted in 3,407 patients in 23 countries across Europe, Asia, Australia and New Zealand. The SPORTIF program enrolled both newly treated patients and patients already on warfarin therapy. Results of the North American part of the trial, which are part of the SPORTIF program and included 3,922 patients at 409 sites, were presented at the American Heart Association's 2003 Scientific Sessions on Nov. 11. Exanta is the first oral anticoagulant to reach late-stage clinical trials since the development of warfarin 50 years ago.
Atrial fibrillation (AF) occurs in about 2 million Americans, and is a major risk factor for ischemic stroke. AF increases that risk fivefold, and accounts for some 15 percent of all strokes nationally. The stroke rate among patients with AF averages about 5 percent per year, rising to almost 25 percent for those more than the age of 80. Older patients with risk factors such as hypertension or diabetes are at increased risk. The number of patients with AF is likely to increase by 2.5 times during the next 50 years, reflecting the growing elderly population.
In AF, the two small upper chambers of the heart, called the atria, quiver instead of beating effectively. Blood in those quivering chambers can pool and clot. If a section of the blood clot in the left atrium breaks off, travels to an artery in the brain and becomes lodged, a stroke may result.
The Lancet paper makes a final point: "We have shown that ximelagatran, administered in a fixed dose without coagulation monitoring, protects high-risk patients with atrial fibrillation against thromboembolism at least as effectively as well-controlled warfarin, and is associated with less bleeding. The continuing SPORTIF V trial will provide additional estimates of efficacy and safety in a similar population," it concluded.
Super-Hyper, High-Tech Breathalyzer' Measures Extent Ethanol Surpasses Social Drinking' Level
Researchers have identified receptors in the brain that are responsive to very low blood-alcohol levels achievable with moderate "social" drinking. Previously GABA (gamma-aminobutyric-acid) receptors have been thought to mediate some of the actions of alcohol, but only at concentrations exceeding 60 mM (60/1,000 of a gram-molecule. That's more than three times the legal blood-alcohol limit.)
To evaluate ethanol's effects on GABA receptors, scientists at the University of California at Los Angeles (UCLA), reported their research in the Proceedings of the National Academy of Sciences (PNAS), released online Nov. 17, 2003. Their paper's title is "Ethanol enhances alpha4beta3delta3 and alpha6beta3delta gamma-aminobutyric acid type A receptors at low concentrations known to affect humans."
To assay alcohol's effects on GABA receptors, the co-authors expressed rat GABA receptor genes in Xenopus laevis (African clawed frog) oocytes, and measured activity of the receptors in response to various concentrations of ethanol. Their paper reports that certain receptor types - those with a beta3 subunit and a delta subunit - responded to levels of alcohol as low as 3 millimolar. By comparison, GABA receptors with other types of subunits react to much higher levels of alcohol, not reached with social ethanol consumption.
Interestingly, the GABA receptors reacting to low alcohol levels are found in cellular locations and brain regions that mediate the effects of alcohol on behavior, such as the cerebellum (motor coordination), the hippocampal formation (memory loss) and the thalamus (sleep-promoting).
Ever-Faster Reaction, Higher Cost Effectiveness Outline Civilian Health Risk, Collateral Damage
Rapid advances in the detection, identification and decontamination of biological and chemical warfare agents in the civilian sector are under way. The announcement comes from a "Review" article in Science dated Nov. 20, 2003. Its title: "Technology challenges in responding to biological or chemical attacks in the civilian sector." The article's co-authors are at Lawrence Livermore National Laboratory in California.
For openers, the review notes that, "Increasingly sophisticated technologies are needed for counter-terrorism responses to biological and chemical warfare agents. Recently developed detection and identification systems are characterized by increased sensitivity, greater automation and fewer false alarms. Attempts are also under way to reduce the cost and complexity of field-deployable systems. A broad range of decontamination reagents for equipment and personnel is emerging, but decontamination of large buildings, inaccessible spaces and sensitive equipment remains problematic.
"Some techniques for detection, cleanup and restoration were put to the test in the United States after the letters containing anthrax were sent through the postal system in 2001. In this review we summarize - and often improved - detection, identification and decontamination technologies developed during the past few years, with a focus on field systems and emerging laboratory technologies. Military applications, forensics, law enforcement and medical aspects of incidents involving biological and chemical terrorism are beyond the scope of this review."