Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w. ) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated wa ter. In the alendronate group significant reductions of choleste rol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system., Ľ. Cibičková, R. Hyšpler, N. Cibiček, E. Čermáková, V. Palička., and Obsahuje bibliografii
During shock, prognosis of a patient depends largely on intestinal barrier function. The potency of gut epithelium to represent an obstacle to toxins is determined by the blood supply. All established methods of mucosal function determination necessitate the functional involvement of bloodstream. Microdialysis allows monitoring of extracellular substances in the gut submucosa, but its potential use for gut barrier integrity assessment is unknown. Twelve rats underwent perfusion of the descending colon either with 20 % ethanol or control medium (vehicle). Both media contained equal amounts of a radioactive tracer substance (51Cr-EDTA). Mucosal permeability for 51Cr-EDTA was assessed by microdialysate to luminal perfusate activity ratios. Sampling was performed using the colon submucosal microdialysis technique. The group subjected to ethanol treatment had profound macro- and microscopical alterations in perfused colonic segment associated with a significant increase in tracer permeability during ethanol exposure (2.354±0.298 % for ethanol as opposed to 0.209±0.102 % for control group, p<0.01), which remained elevated for 60 min after cessation of ethanol administration (3.352±0.188 % for ethanol compared to 0.140± 0.0838 % for the control group, p<0.001). Submucosal microdialysis with radioactive tracer substance can be considered a feasible and advantageous alternative of gut barrier function estimation. Parallel monitoring of local tissue chemistry with this method remains a challenge in the future., N. Cibiček, H. Živná, Z. Zadák, J. Kulíř, E. Čermáková, V. Palička., and Obsahuje bibliografii a bibliografické odkazy
Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer´s disease. Cholesterol plays an important role in Alzheimer´s disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug., Ľ. Cibičková, V. Palička, N. Cibiček, E. Čermáková, S. Mičuda, L. Bartošová, D. Jun., and Obsahuje bibliografii a bibliografické odkazy