Johns Hopkins Gazette: June 23 1997

In Brief
Medical News

Effects of clozapine breakdown studied

Breakdown products, or metabolites, of the drug clozapine, a common anti-psychotic drug, have been found to stop the replication of HIV in human cell cultures. Four clozapine metabolites inhibited the replication of three different strains of HIV at non-toxic concentrations, said Hopkins researcher Lorraine V. Jones-Brando of the Hopkins Children's Center's Stanley Laboratory for the Study of Schizophrenia and Bipolar Disease.

"Though the clozapine metabolites are unlikely to be useful for the treatment of HIV infection," Jones-Brando said, "it is possible they may inhibit the replication of other viruses at much lower concentrations."

Hopkins researchers found that effective concentrations of the clozapine metabolites were 6,000 times higher than an effective dose of AZT, an anti-retroviral drug commonly used to slow the progression to AIDS. A lack of knowledge about high concentrations of clozapine breakdown products in humans and the high concentrations necessary for promoting anti-viral activity make it an unlikely candidate for fighting HIV, Jones-Brando said.

Jones-Brando added that the anti-viral activity of clozapine metabolites is consistent with the possibility that viral infections may play a role in schizophrenia and other serious neuropsychiatric diseases.

The study was published in a recent issue of Schizophrenia Research.

Measuring viral load adds a valuable prognostic tool

Because the progression to AIDS differs among people infected with HIV, it has been difficult for clinicians to determine which markers might offer the best indications of disease progression. While declining CD-4 lymphocyte counts have been used in the past, a new study suggests that using CD-4 counts along with measures of viral load (the amount of genetic material in circulating virus) gives the most accurate prediction of when those infected with HIV might develop AIDS. According to researchers, this information is critical to decisions about when to start anti-retroviral therapy.

"Not only does the amount of virus in the blood provide great prognostic information in combination with the level of immune deficiency, but it also precisely predicts how fast the immune system declines in HIV-infected individuals," said Alvaro Munoz, professor of epidemiology at the School of Public Health and co-author of a study published in the June 15 issue of Annals of Internal Medicine.

In the study, carried out at four university-based MACS (Multicenter AIDS Cohort Study) sites, of the 1,604 HIV-infected men followed, only 1.7 percent of those with the lowest viral load measurements and the highest CD-4 counts had developed AIDS at the six-year mark. In contrast, 97.9 percent of those with the highest levels of viral load and lowest CD-4 counts had developed AIDS over the same period.

Lung cells squirt antimicrobial spray

Hopkins scientists recently found that lung cells have a unique defense against bacteria. It comes in the form of a natural compound spray that lung cells squirt on attacking bacteria. Researchers call the compound hTAP, or human tracheal antimicrobial peptide.

"People have always thought that the lungs only attacked infections via the classical immune system--B cells, T cells and other immune cells," said Pete Pedersen, a professor of biological chemistry at the School of Medicine. "But lung cells apparently have their own line first line defense mechanism_they shoot out one or more peptides that kill bacteria."

Researchers in Pedersen's lab discovered hTAP while studying lung damage caused by cystic fibrosis. The spray mechanism appears to be disabled in CF patients, increasing their vulnerability for lung infections and diseases like tuberculosis. Researchers hope they can mass-produce hTAP or similar compounds to help fight lung infections in CF patients and in the general population.

Pedersen speculated that cells in other areas of the body at high risk for infection, such as the eyes, the gut or mouth, may also secrete similar germ-fighting compounds.

Other News

JHU Vision provides information on activities

If your campus organization wants to get the word out about an event, don't neglect JHU Vision, said Damien Newton, the student coordinator of Target Vision, an information service on the Homewood campus. "I don't think there is any group that doesn't want to use JHU Vision, but there may be some that, as of yet, are unaware of our existence and potential," Newton said.

JHU Vision, a free service of the university, posts event-related and other information on television sets in Levering Market, the Levering lobby, next to the Gilman bookstore, the Athletic Center lobby and in the Terrace Court Caf‚. "All someone needs to do is fill out the forms, and we make the slide that will go onto the system," Newton said. "We have limited staff right now, so you need to make an appointment."

Any event that is open to students can be posted on JHU Vision. Target Vision will soon be reachable by e-mail at Call Damien Newton at 410-516-7077.

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