Nifedipine in rat liver cirrhosis.

Rat liver cirrhosis induced by CCl4+ethanol was employed to assess the effectiveness of nifedipine in reducing liver injury. Nifedipine reduced the severity of hepatocellular necrosis, significantly decreased Mallory bodies (p < 0.01), decreased polymorphonuclear inflammatory infiltrate (p < 0.05) and reduced perivenular fibrosis. Plasma lactic acid levels were significantly increased in the CCl4+ethanol group (p < 0.01). Lactacidaemia remained at normal values when the calcium antagonist blocker was employed. Nifedipine did not significantly alter the incidence of cirrhosis in this experimental model.

In vitro cultivation of cells from larval Schistosoma mansoni.

With the intent of providing a useful tool for studies on the cellular and molecular biology of Schistosoma mansoni, we have attempted to establish indefinitely proliferating cell lines. Primary (mother) sporocysts have served as sources of tissue fragments for initiation of primary cultures in complex media containing fetal bovine serum. Viability is maintained for several months, during which time there is differential survival of individual cell types. Cells that ultrastructurally resemble germinal cells are among the most persistent. Contractile responsiveness to serotonin and flagellar movement of flame cells are sustained for several weeks. Exposure to epidermal growth factor failed to induce tyrosine phosphorylation as detectable by western blot analysis. Incorporation of 5-bromo-2'-deoxyuridine into nucleic acid has been used as an indicator of the merit of experimental variables tested for their growth-promoting potential. Continuous proliferation remains an elusive goal, but coculture with host snail ganglia has yielded promising results. These primary cultures can be used to obtain useful information on parasite physiology. In light of our results, and of the varied lines of investigation that would be facilitated by such tools, further efforts to immortalize cell lines are warranted.

Culture of cells from juvenile worms of Schistosoma mansoni.

Tissue disruption methods were developed and serum-free cell culture media formulated for the maintenance in vitro of cells from juvenile worms (day 18 after infection) of Schistosoma mansoni. Cultures maintained viability for up to 6 mo when plated on a feeder layer of irradiated rat liver cells and survived primarily as clusters of small (2.5-4 microns diameter) cells with a high nuclear-to-cytoplasmic ratio and relatively few organelles identified by electron microscopy. Cultures synthesized a protein profile similar to that of intact worms, and the cell clusters maintained a time- and concentration-dependent contractile response to serotonin. Cells synthesizing DNA were detected by precursor incorporation and flow cytometry in cultures initially and also after several weeks in vitro, although the percentage of cells synthesizing DNA decreased with time. Efforts to identify peptide growth factor-responsive tyrosine phosphorylation were negative, and the overall amount of S. mansoni phosphotyrosine-containing proteins identified by western blot with anti-phosphotyrosine monoclonal antibody was much less than that found in a peptide growth factor-responsive mouse cell line.