Agglutination of platelets by a serum factor in the presence of EDTA

The platelets of a patient with reticulum-cell sarcoma were found to exhibit agglutination and cytopathic changes when her blood was treated with EDTA but not with other anticoagulants. Investigation showed that the phenomenon was caused by a serum factor that was probably an antibody.     

Prodrugs to Improve the Oral Bioavailability of a Diacidic Nonpeptide Angiotensin II Antagonist

DMP 811 is a diacidic angiotensin II antagonist. It has relatively low oral bioavailability in rats. A prodrug approach to improving oral bioavailability was tested. Five esters were synthesized and their stability in rat plasma in vitro was determined. The hydrolysis rates of these five esters ranged from almost immediate to negligible. A simple n-propyl ester was hydrolyzed very slowly (< 10% in 24 hr) in rat plasma in vitro, and after oral dosing in rats plasma prodrug concentrations were much greater than DMP 811 concentrations. A pivaloyloxymethyl ester (1) was hydrolyzed relatively rapidly in rat plasma in vitro. Prodrug 1 was rapidly hydrolyzed by the intestine in vitro, and the intestinal permeation of DMP 811 was increased. DMP 811 oral bioavailability was 47% in rats dosed with 10 mg/kg 1, compared to 11% for rats dosed with 10 mg/kg DMP 811. However, DMP 811 bioavailability was only 27% after a 2 mg/kg dose of 1. In vitro plasma hydrolysis of 1 was highly species-dependent, with a half-life of 13 hr in human plasma but only 1 min in rat plasma. The prodrug approach has potential for improving the oral bioavailability of DMP 811, but selection of the optimal prodrug must be done in humans or in a species, such as dogs, with hydrolysis characteristics closer to humans.     

Sindbis virus induced fusion of tissue cultured Aedes albopictus ( mosquito) cells

The alphavirus Sindbis was tested for its ability to mediate cell fusion of tissue cultured invertebrate cells. It was found that Sindbis virus grown in BHK-21 cells produced optimal fusion of BHK-21 cell monolayers after brief exposure to pH 5.3. Fusion of mosquito cells by the same virus occurred optimally at pH 4.6 (a pH which results in the destruction of the virus particle) if the cells were cultured in Eagle MEM. Mosquito cells cultured in insect cell medium could not be fused at any pH tested (as low as 4.0). The differences in the response to pH were not due to an inhibitory component in the media and cells cultured in alternate media required several days to weeks to assume the fusion characteristics of cells maintained in that media. All cells in all media were infected by Sindbis with equal efficiency, as determined by infectious center assay. These data suggest that the pH requirement for initiating the virus mediated fusion event does not reside with the virus alone.     

Sindbis virus maturation in cultured mosquito cells is sensitive to actinomycin D

In contrast to its effects on Sindbis virus production in vertebrate cell cultures, actinomycin D was found to inhibit the production of virus in cultured Aedes albopictus cells and Bombyx mori cells. One to two hours of incubation in the presence of actinomycin D was required for the inhibition to be observed. Synthesis and processing of virus structural polypeptides were found to be normal during the period of arrest of virus production. These data are interpreted as indicating the presence of a labile host function involved in the assembly of Sindbis virus components into mature virus in invertebrate host cells.     

The impact of a brief tobacco-use cessation intervention in public health dental clinics

BACKGROUND: Public health dental clinic patients use tobacco at disproportionately high rates. The purpose of this study was to evaluate a tobacco-use cessation program delivered via public health dental practitioners. METHODS: Two public health dental clinics participated in this quasiexperimental design study. First, all patients in one clinic who used tobacco (n = 178) received usual care. Next, the authors trained all practitioners to conduct a tobacco-use assessment and provide a brief cessation intervention. Subsequently, all patients in both clinics who used tobacco (N = 190) received the intervention. All enrolled patients had an income at or below the federal poverty level. The authors conducted follow-up assessments at six weeks and three and six months after enrollment. RESULTS: Differences in self-reported quitting by condition between participants in the two groups were significant across all endpoints. Patients in the intervention group were more likely to quit than those receiving usual care (15.5 versus 4.3 percent) and after 12 months (18.8 versus 4.6 percent). Controlling for enrollment differences between patients in the two groups (age, race/ethnicity, time to first cigarette after waking), the authors found that differences between groups were significant for quitting at three months (P < .05; odds ratio [OR] = 4.85; 95 percent confidence interval [CI] = 1.20, 19.60), and six months (P < . 01; OR = 5.25; 95 percent CI = 1.35, 20.36). CONCLUSIONS: The results of this study suggest the viability and effectiveness of delivering a tobacco intervention to low-income smokers via public dental practitioners. A randomized clinical trial is warranted. CLINICAL IMPLICATIONS: The potential reach of public health dental clinics is great. Because of the high percentage of tobacco-using patients in these clinics, the public health impact of a program such as the one reported here would be significant.