Biomedical subjects
Publications and source records attributed to B Ellenberger.
By providing everything from electronic mail to "virtual patients," computer technology and the Internet have made enormous resources available to physicians. Science writer Beth Ellenberger gives an overview of the different levels of Internet access, as well as the e-mail addresses of some medical resources that will be useful to physicians.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
The ability to prevent schistosomiasis by using an oral chemoprophylactic agent, which acts by preventing cercarial penetration, has been unexplored. We initially examined the effect of praziquantel (PZQ) as such an agent and found that it was moderately effective in blocking cercarial penetration, but that this effect was dependent on the vehicle used to administer the drug. ICR mice were given a total of 200 mg/kg PZQ per os over an 8-hr period in a divided dose of 50 mg/kg/2 hr. At time periods ranging from 0 to 92 hr after the last dose, mice were exposed to approximately 75 75Se-labeled cercariae via the tail. Twenty-four hours later, mice were sacrificed, their tails were removed and subjected to autoradiography, and the percentage of penetration was calculated. Cremophor El, 50% PEG 200, 50% propylene glycol, vegetable oil, and cod liver oil were used as PZQ vehicles. When Cremophor El (ethoxylated castor oil) was used to administer PZQ, a 93% reduction in cercarial penetration was seen at 0 hr and a 98%+ reduction rate was seen from 4 to 24 hr postexposure. However, Cremophor El alone had an essentially equivalent effect on cercarial penetration from 8 to 92 hr after administration. These unexpected results led us to investigate both castor oil and ricinoleic acid (castor oil is 87% ricinoleate as triglyceride) as oral anti-penetration agents. Mice were given the lipids orally by gavage for 7 days. On Day 8, each group of 12 mice was exposed to approximately 75 75Se-radiolabeled cercariae. Castor oil gave protection rate ranging from 90 to almost 100% at an optimal concentration of 0.3 ml/day x 3 or 7 days (approximately 9.8 g/kg/day). These observations suggest that chemoprophylaxis may be possible by dietary supplementation with lipids having anti-penetration activity or by molecules that resemble these lipids.
A simple method for the collection of third-stage larvae of Necator americanus has been described. This technique provides repeated recovery of very clean larvae from cultures in moderate numbers.
Four methods of transforming cercariae to schistosomulae in vitro in ELAC buffer (pH 7.2, 37 C, 0-6 hr incubation) were compared in relation to biochemical and ultrastructural characteristics. The transformation methods used were chemical (3 mM linoleate), mechanical (centrifuge/vortex), mechanical/chemical, and heat (incubation at 37 C). Ultrastructural characteristics examined were based on the presence or absence of glycocalyx, heptalaminate membrane, cyton granules, and nuclear condition. Two EM fixation methods were used. Biochemical parameters assayed were loss of water tolerance (uptake of trypan blue dye), eicosanoid biosynthesis (PGE, LTB4, and 5-HETE), protein synthesis (leucine uptake), RNA synthesis (uracil and orotic acid uptake), and DNA synthesis (thymidine uptake). EM characteristics were remarkably similar for all transformation methods except heat incubation, with transformed cercariae evidencing the characteristics of schistosomulae (cyton granule migration, absence of glycocalyx and heptalaminate membrane); however, euchromatic nuclei could not be demonstrated using in vivo or in vitro transformation methods. Despite the ultrastructural similarities between transformation methods, biochemical data demonstrated that the resultant organisms were quite different. The chemical transformation method gave the highest rate of loss of water tolerance and eicosanoid production. RNA and protein synthesis were not correlated to ultrastructural changes and were highest in those organisms undergoing mechanical transformation methods, significantly higher than in those cercariae transformed by the chemical method. DNA synthesis was not demonstrated using any transformation method, although thymidine uptake did occur. Our data indicate substantial biochemical differences exist between morphologically similar organisms. Thus, experiments using any type of artificially transformed schistosomule must be interpreted with caution until additional biochemical and physiological studies on cercarial transformation are undertaken.
We have previously reported that cercarial penetration is highly correlated with cercarial production of leukotrienes (LT's) and hydroxyeicosatetraenoic acids (HETE's). Because skin also produces various eicosanoids, we undertook an investigation of skin eicosanoids in various strains of mice and 1 strain of rat in order to ascertain if skin eicosanoids could be correlated to cercarial penetration. SENCAR, ICR, NMRI, A/J, C3H/HeJ, C57Bl/6, ASEBIC, and BALB/c mouse strains were used in this study as well as the SD-Rat strain. The ability of cercariae to penetrate skin was strain specific. A/J and SENCAR mice had the highest penetration rates (approximately 98%), whereas the SD-Rat strain had the lowest (43%). These penetration rates we linearly correlated with tail skin HETE production at 10 min (R = 0.826), whereas HETE production at 60 min had a parabola-shaped relationship (R = 0.793). The primary infection of mice with Schistosoma mansoni cercariae may therefore be directly correlated with both the skin's innate ability to synthesize HETE, as well as with cercarial eicosanoid production, especially HETE levels. However, we believe that skin eicosanoid production is just one of many factors affecting cercarial skin penetration. Other factors discussed are: skin surface fatty acid levels, cercarial eicosanoid production, epidermal vs. dermal eicosanoid production, and the immunocompetence of the host.