By David N. Leff

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Traditional or "typical" antipsychotic drugs, such as chlorpromazine (Thorazine) and haloperidol (Haldol) can control delusions and hallucinations in some schizophrenic patients, but may cause severely disabling symptoms, especially a Parkinsonian-like syndrome. The newer "atypical" drugs introduced in the last 10 years - notably risperidone (Risperdal) - rarely cause such side effects.

Risperidone reportedly reduces apathy and social withdrawal, and improves mental function, but until now there have been no clinical studies of how this atypical agent affects crucial areas of the brain in schizophrenic patients.

One such clinical trial is reported in the current Proceedings of the National Academy of Sciences (PNAS), dated Nov. 9, 1999. Its title: "Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia." Conducted by London's Institute of Psychiatry and the University of Cambridge in the UK, the study compared typical and atypical compounds in the functioning brains of awake schizophrenic subjects. It analyzed these cerebral activity changes by magnetic resonance imaging, which takes repeated "snapshots" of the brain at time intervals, revealing changes in blood flow and oxygen levels.

The co-authors' active subjects were 20 right-handed male patients, equally divided between the two drug classes, and 10 normal right-handed males recruited from the community. At onset of the trial, and again six weeks later, the co-authors measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task.

"Substitution of risperidone," their PNAS paper reported, "increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel [imaging element] and regional levels of analysis." It concluded, "This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs."

Alkermes Inc., of Cambridge, Mass, and Janssen Pharmaceutica, of Beerse, Belgium, are undertaking a Phase III trial of Risperdal in an intramuscular, injectable, sustained-release formulation. (See BioWorld Today, April 23, 1999, p. 1.)

Besides Weeds, Herbicide Kills Toxoplasma gondii, Protozoan Perpetrator Of Toxoplasmosis

A case of malaria popped up in New York City this month, leaving epidemiologists mystified as to how the tropical- disease parasite could have migrated to the Big Apple. That malarial pathogen, Plasmodium falciparum, belongs to a protozoan subtype called Sporozoea. So does another infectious Sporozoan, Toxoplasma gondii, which is not tropical but global. It causes toxoplasmosis, which can range from a wimpish infection, usually bested by a normal immune system, to a life-threatening disease that attacks eyes, brains and nervous systems. (See BioWorld Today, Jan. 10, 1996, p. 1.)

The current Proceedings of the National Academy of Sciences (PNAS), dated Nov. 9, 1999, carries an article titled: "Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase [ACC]."

The paper points out, "Several herbicides have already been shown to restrict apicomplexan parasite growth without toxicity to mammalian cells." (Apicomplexa is a subdivision of the Protozoan kingdom that includes Sporozoea.) The co-authors, at the University of Chicago, report that "Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70 percent at 10 mM in 2 days and effectively eliminates the parasite in 2 to 4 days at 10-100 mM." They added, "Clodinafop is not toxic to the host cell even at much higher concentrations."

One Vitamin E Subunit Promotes Arthritis; Another Curbs It, Suggests Biracial Study

Vitamin E is also known variously as tocopherol, antisterility factor and as an anti-oxidant. It sells briskly at health-food stores and pharmacies, largely because oxidants are reputed to promote aging. Last Monday, a component of vitamin E was indicted as somehow contributing to osteoarthritis. The study, reported to an American College of Rheumatology news conference in Boston, suggested that people who want to take vitamin E supplements should stick to the alpha form of tocopherol, and not buy products containing mixtures of vitamin E's four subunits - alpha, beta, gamma and delta.

The presentation by rheumatologist Joanne Jordan, an arthritis researcher at the University of North Carolina, Chapel Hill, stated: "We didn't find any protective effect for alpha-tocopherol, but we did find that gamma tocopherol was clearly associated with more arthritis." She noted, "This was very marked in African-Americans, and less so in Caucasians. We don't know why."

Jordan recalled, "The Framingham study [a large, decades-long ongoing population health survey] earlier suggested that higher vitamin E intake in the diet might help prevent progression of knee arthritis, but that study did not include African-Americans." Moreover, she pointed out that this North Carolina project, besides enrolling equal ethnic numbers of a 400-cohort population, did not rely on statements by subjects as to their eating habits, but assayed actual tocopherol blood levels.

Insulin-Like Growth Factor Abated Swollen Axons In Diabetic Rats, Presaging Human Therapy

Diabetic rats develop the same peripheral nervous system complications that afflict human diabetics. Some 60 percent of people with diabetes mellitus suffer some damage to these outlying nerves, which send messages to the body's limbs and other far-out sites. Diabetic neuropathy can also strike the sympathetic part of the autonomic nervous system, which controls involuntary reflexes. Such nerve injury adversely affects blood pressure and digestion.

The abnormally high levels of glucose in the blood - hallmark of diabetes - have harmful effects on nerve cells and their axons. Glucose makes the outer tips of sympathetic nerve axons swell into doorknob shapes, which mess up their communications.

An article in the American Journal of Pathology for November reports, "Insulin-like growth factor I reverses experimental diabetic autonomic neuropathy." At Washington University in St. Louis, the paper's co-authors injected insulin-like growth factor into diabetic rats with swollen axons. The treatment reduced the knob-like swellings by 80 percent.