Repetitive administration of acetylcholine receptor agonist rescues brain inflammation and brain damage after hypoxia-ischemia in newborn rat.

OBJECTIVE: We examined the effect of repetitive administration of acetylcholine receptor agonist (carbachol) on brain damage and microglial accumulation in three brain regions after hypoxia-ischemia (HI) in newborn rat. STUDY DESIGN: Seven-day-old Wistar rats were divided into two groups, one receiving a 0.1 mg/kg dose of carbachol on days 7, 8 and 9 to examine the attenuating effect on brain damage with decreasing accumulation of microglia, and the other group receiving saline as a control. Rats were subjected to left carotid artery ligation followed by hypoxia. We evaluated brain damage and the number of microglias in three regions on days 10 and 14. RESULTS: Brain tissue was better preserved in the carbachol group on days 10 and 14. Microglial accumulation in the cortex was strong and persisted from day 10s to 14 in the control. Conversely, the accumulation of microglias was attenuated in the hippocampus and white matter on day 14. Carbachol significantly reduced the number of microglias in the hippocampus and white matter on day 10 and in the cortex on days 10 and 14. CONCLUSION: The main area of late inflammation was the cortex. Repetitive administration of carbachol reduces early and late inflammation after HI in the developing brain.

Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats.

The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg/kg and depressed with fasudil at 10 mg/kg. Fasudil at 10 mg/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced by 5 min coronary artery occlusion and 5 min reperfusion, decreased the incidence of ventricular tachycardia and abolished the occurrence of ventricular fibrillation. The incidences of ventricular tachycardia and ventricular fibrillation in the fasudil (10 mg/kg) + ischemic preconditioning group were found to be similar to the ischemic preconditioning group. However, low doses of fasudil (0.3 and 1 mg/kg) appeared to prevent the antiarrhythmic effects of ischemic preconditioning. Carbachol (4 microg/kg/min for 5 min) induced marked reductions in mean arterial blood pressure, heart rate and abolished ventricular tachycardia. Marked reductions in ventricular ectopic beats and ventricular tachycardia were noted in the fasudil (10 mg/kg) + carbachol preconditioning group. Lactate levels were markedly reduced in the ischemic preconditioning group and this reduction was prominently inhibited with fasudil at 1 mg/kg. Ischemic preconditioning caused a marked decrease in plasma malondialdehyde levels. Fasudil (10 mg/kg), ischemic preconditioning and carbachol preconditioning each generated marked reductions in ischemic myocardial malondialdehyde levels. Decreases in infarct size were observed with fasudil (10 mg/kg) treatment, ischemic preconditioning and carbachol preconditioning when compared to control. These results suggest that low doses of fasudil (0.3 and 1 mg/kg) appeared to prevents the effects of ischemic preconditioning and carbachol preconditioning, but a high dose of fasudil (10 mg/kg) was able to produce cardioprotective effects on myocardium against arrhythmias, infarct size or biochemical parameters and mimic the effects of ischemic preconditioning in anesthetized rats.

Pharmacological advancements in the treatment of chronic anal fissure.

Chronic anal fissure is a tear in the lining of the anal canal that, if not treated appropriately at an early stage, causes considerable anal pain during defaecation. Surgery is no longer considered the first-line treatment of this common condition, as recent advancements in medical treatment has produced promising results in the healing of fissures, thus avoiding the unwanted complications that frequently occur following operative treatment. This review looks at those pharmacological agents used commonly in the treatment of chronic anal fissures and explores alternative therapies that may be of benefit in the future.

[The effect of timolol and parasympathicomimetica in the treatment of the elevated intraocular pressure (author's transl)]. / Timolol und Parasympathicomimetica bei der Behandlung des erhöhten intraocularen Druckes.

45 patients with ocular hypertension or open-angle glaucoma were tested to see if, and to what extent timolol and three other different parasympathicomimetics (pilocarpine 2%, carbachol 1.5%, aceclydine 2%) produced an supplementary reduction of the intraocular pressure. An equally marked, additional drop in eye pressure was achieved when patients who had been given timolol over an extended period of time, were additionally treated with one dose of pilocarpine 2% or carbachol 1.5%. Aceclydine 2% produced no statistically significant additional effect. Patients who had only been treated with pilocarpine 2% over an extended period of time and then were given one dose of timolol 0.25% produced a drop in eye presure more than double that of those patients who had been primarily treated with timolol and then received pilocarpine or carbachol. These results will be discussed on the basis of the mode of action of the applied medications.