Parasite escape through trophic specialization in a species flock.

Adaptive radiation occurs when species diversify rapidly to occupy an array of ecological niches. As opportunities for parasite infection and transmission may greatly vary among these niches, adaptive radiation is expected to be associated with a turnover of the parasite community. As major agents of natural and sexual selection, parasites may play a central role in host diversification. The study of parasite turnover may thus be of general relevance and could significantly improve our understanding of adaptive radiation. In this study, we examined the parasite faunas of eleven species belonging to the tribe Tropheini, one of several adaptive radiations of cichlid fishes in Lake Tanganyika. The most parsimonious ancestral foraging strategy among the Tropheini is relatively unselective substrate browsing of aufwuchs. Several lineages evolved more specialized foraging strategies, such as selective combing of microscopic diatoms or picking of macro-invertebrates. We found that representatives of these specialized lineages bear reduced infection with food-web-transmitted acanthocephalan helminths, but not with parasites with a direct life cycle. Possibly, the evolution of selective foraging strategies entailed reduced ingestion of intermediate invertebrate hosts of acanthocephalans. We conclude that some species belonging to the Tropheini virtually escape acanthocephalan infection as a by-product of trophic specialization.

Relationship between nonphenacetin combined analgesics and nephropathy: a review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy.

BACKGROUND: The debate on the association between nonphenacetin-containing combined analgesics and renal disease has lasted for several years. METHOD: A peer review committee of scientists, selected jointly by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry was asked to critically review data on the relationship between nonphenacetin combined analgesics and nephropathy. RESULTS: The committee regarded epidemiologic evidence on nonphenacetin combined analgesics as inconclusive because of sparse information and substantial methodological problems. The committee also noted that a diagnosis of analgesic-associated nephropathy (AAN) in clinical practice usually depends on information about exposure before or in the early stages of the disease and is seldom accompanied by specific histologic evidence. The morphologic finding of papillary calcification can arise from other conditions and is not specific for AAN. For these reasons, the identification criteria for AAN should be reappraised with scientific methods to validate the diagnostic procedure. In the limited amount of experimental pharmacological data in humans and animals, the committee found no convincing evidence to confirm or refute the hypothesis that nonphenacetin combined analgesics are more nephrotoxic than single formulations. For caffeine taken with combined analgesics, the currently available information is not sufficient to postulate a harmful toxicological effect. CONCLUSION: The committee's two main conclusions were that sufficient evidence is absent to associate nonphenacetin combined analgesics with nephropathy and that new studies should be done to provide appropriate data for resolving the question.

Biochemical activity, pharmacokinetics, and tolerability of MK-886, a leukotriene biosynthesis inhibitor, in humans.

MK-886, a leukotriene biosynthesis inhibitor, was evaluated in double-blind, placebo-controlled, randomized single- and multiple-dose studies in 12 and 24 healthy male subjects, respectively. The effects of a single dose (250, 500, and 750 mg) and multiple doses (100 mg and 250 mg every 8 hours) of MK-886 on calcium ionophore stimulated leukotriene B4 synthesis ex vivo in whole blood were evaluated. Inhibition of leukotriene B4 biosynthesis ex vivo occurred in a dose-related manner up to a 500 mg single dose, and 250 mg every 8 hours. A single dose of 500 mg MK-886 significantly inhibited leukotriene B4 biosynthesis by a maximum of 60% at 2 hours after the dose (p < 0.05). Multiple doses of 250 mg significantly inhibited leukotriene B4 biosynthesis by a maximum of 52% at 2 hours after the dose (p < 0.05). The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-886 concentrations (r = 0.78). In conclusion, the single and multiple doses of MK-886 evaluated in this study were well tolerated overall and partially inhibited leukotriene B4 biosynthesis ex vivo in whole blood.

Effect of antacids on the bioavailability of diflunisal in the fasting and postprandial states.

Diflunisal is long-acting salicylate derivative. We examined the effect of single concomitant doses of three antacids on diflunisal bioavailability under fasting or fed conditions (30 min after finishing a standard meal). With the use of an open, randomized, and balanced design, one 250-mg diflunisal tablet was given to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area under the time curve (AUC), peak plasma concentrations, and 0-to 96-hr urinary excretion were determined. Food (alone) decreased peak plasma concentrations by 16% (P less than 0.05) but did not affect AUC or urinary excretion. Under fasting conditions, aluminum hydroxide reduced AUC by 26% (P less than 0.01), peak plasma concentrations by 46% (P less than 0.01), and urinary excretion by 14% (P less than 0.05). Magenisuum hydroxide suspension (in the fasting state) increased the early plasma concentrations (by 130% at 0.5 hr and 64% at 1 hr, P less than 0.05) and increased AUC by 10% (P less than 0.05) but had no effect on urinary excretion. In the fed state neither aluminum hydroxide nor the aluminum hydroxide/magnesium hydroxide mixture had any detectable effect.

Gastrointestinal blood loss after diflunisal and after aspirin: effect of ethanol.

Fecal blood loss was evaluated in normal subjects with 51Cr-labeled red cells. In a double-blind parallel study in 10 subjects, 250 mg diflunisal twice daily did not significantly increase blood loss in two consecutive treatment periods, while 750 mg acetylsalicylic acid (ASA) 4 times daily did so. In a double-blind crossover study in 2 subjects, diflunisal, 250 mg twice daily again did not significantly affect fecal blood loss during a 4-day treatment period, and there also was no significant effth diflunisal during two additional treatment days. ASA, 600 mg 4 times daily, induced an increase in blood loss and this effect was significantly enhanced by the addition of alcohol. The difference between treatments in the way they interact with alcohol was also statistically significant.

Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.

It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis.