glycogen and Hymenolepiasis

The transport of [14C]glucose by Hymenolepis microstoma in vitro following in vivo treatment with cyclosporin A (CsA) was determined over a range of concentrations. For untreated (control) worms glucose uptake showed saturation kinetics with a small diffusion component. Estimates of the maximum velocity of glucose uptake (Vmax) and the affinity of substrate for the glucose transporter (Kt) revealed that untreated 8-day-old worms had a Vmax twice that of 15-day-old worms and that younger worms had a lower Kt. An inverse relationship was demonstrated between log10 worm weight and the rate of uptake of [14C]glucose, reflecting the relatively greater number of glucose transporters due to the larger surface area:volume ratio of smaller worms. Treatment of H. microstoma with CsA in vivo significantly increased the diffusion component of glucose uptake in vitro. Parasites from drug-treated mice had a significantly lower Vmax for glucose uptake than size-matched controls. The affinity of glucose for its transporter in CsA-treated worms (Kt) was not significantly different from size-matched controls. Both juvenile and adult worms underwent transient depletion in total glycogen content after CsA treatment in vivo. The data confirm that CsA treatment in vivo disrupts the functional integrity of the worm tegument, one facet of which is impaired acquisition of glucose.

Topics: Analysis of Variance; Animals; Biological Transport, Active; Cyclosporine; Diffusion; Female; Glycogen; Hymenolepiasis; Hymenolepis; Linear Models; Male; Mice

Amoscanate possesses chemotherapeutic activity against schistosomes, and in higher doses against many other helminths including filariids and Hymenolepis diminuta. The primary mode of action of this compound is unknown. Effects of the drug on the carbohydrate metabolism as well as on the tegumental and nephridial epithelia of H. diminuta were examined. At various time intervals after administration of the drug to rats infected with H. diminuta, the parasites were recovered and incubated in glucose-salts medium for 90 min. Chemotherapy resulted in decreases in succinate, lactate, and acetate recoveries, while ATP levels dropped. In addition, glycogen levels were depressed in drug-treated worms which were homogenized immediately upon isolation. Glycogen synthase I activity was inhibited 16-61% in cestodes obtained from Amoscanate-treated animals and homogenized immediately, but returned to normal levels after incubation for 90 min in glucose-salts medium prior to homogenization and assay. Phosphorylase a activity was found to be 25-30% higher in preparations of worms from drug-treated rats, which correlates with the rapid depletion of glycogen in parasites exposed to the drug. However, in contrast with glycogen synthase activity, the elevation of phosphorylase a activity in H. diminuta exposed to the drug was not readily reversible. Attempts to demonstrate activity of the drug in vitro by incubating intact cestodes directly with Amoscanate were unsuccessful. Thin sections of parasites obtained from Amoscanate-treated rats and examined by transmission electron microscopy revealed surface alterations of the tegument and nephridial canals. Alterations included bleb formation and erosion of microtriches from the tegument, as well as disappearance of microvilli from nephridial canals. However, these effects became manifest only after 4 or more hr exposure of the rat to the drug. Biochemical effects, on the other hand, were significant after 3 hr exposure.

Topics: Adenosine Triphosphate; Aniline Compounds; Animals; Anthelmintics; Diphenylamine; Energy Metabolism; Glucose; Glycogen; Glycogen Synthase; Hymenolepiasis; Hymenolepis; Isothiocyanates; Male; Microscopy, Electron; Microvilli; Phosphorylases; Rats; Thiocyanates

An investigation of the chemotherapeutic and biochemical effects of two benzimidazole anthelmintics, thiabendazole (TBZ) and cambendazole (CBZ), on Hymenolepis diminuta in experimentally infected rats is reported. Thiabendazole was active against H. diminuta at a relatively high dosage. A single oral dose of TBZ at 250 mg/kg body weight on day 15 of infection eliminated 100% of the tapeworms as determined at necropsy 5 days after treatment. The chemotherapeutic actions of TBZ on H. diminuta were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TBZ 24 hr earlier were significantly smaller and contained much less glycogen (as a percent of the wet weight) than worms from unmedicated controls. Protein concentrations increased in TBZ-treated worms and at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TBZ-treated worms were significantly lower than the corresponding control values. Cambendazole proved to be five times more potent than TBZ against H. diminuta and produced the same basic changes in worm weight and chemical composition within 18 hr of treatment of the host. Administration of a single oral dose of TBZ or CBZ to the host produced in H. diminuta another change, the onset of which coincided with, or preceded, the gross alterations in worm weight and chemical composition. That change, observed in in vitro studies carried out 14 hr after treatment, revealed that tapeworms from drug-treated rats absorbed and metabolized much smaller quantities of exogenous glucose than did the controls, and the ability of the worm to accumulate glucose against a concentration difference was significantly depressed.

Topics: Animals; Benzimidazoles; Cambendazole; Glucose; Glycogen; Hymenolepiasis; Hymenolepis; Male; Proteins; Rats; Rats, Inbred Strains; Thiabendazole

Topics: Animals; Benzimidazoles; Fenbendazole; Glucose; Glycogen; Hymenolepiasis; Hymenolepis; Male; Proteins; Rats; Rats, Inbred Strains

Topics: Animals; Bile Ducts; DNA; Female; Glucose; Glycogen; Hymenolepiasis; Intestine, Small; Liver; Liver Glycogen; Mice; Proteins; RNA; Spleen

Topics: Animals; Bile Acids and Salts; Cestoda; Culture Media; Glycogen; Glycosaminoglycans; Histocytochemistry; Hydrogen-Ion Concentration; Hymenolepiasis; Larva; Lipoproteins; Mice; Microbial Collagenase; Microscopy, Electron; Pancreatin; Pepsin A; Tribolium

Topics: Acetates; Acids; Anaerobiosis; Animals; Cestoda; Circadian Rhythm; Fermentation; Glycogen; Hymenolepiasis; Lactates; Male; Pyruvate Dehydrogenase Complex; Rats; Succinates; Time Factors