Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers

Tolcapone (Ro 40-7592) is a novel inhibitor of catechol-O-methyltransferase that is being developed for clinical use in the treatment of Parkinson's disease as add-on therapy to a combination of levodopa and a peripheral amino acid decarboxylase inhibitor (benserazide or carbidopa). The current single-blind, randomized study was designed to evaluate the effect of tolcapone compared with placebo on plasma levodopa concentrations in healthy volunteers concomitantly receiving 25 mg of carbidopa and 100 mg of levodopa (Sinemet 25-100) and to assess the tolerability and safety of this combination. Placebo or tolcapone at doses of 5, 10, 25, 50, 100, 200, 400, and 800 mg was coadministered orally with Sinemet 25-100. Each dose was tested in a crossover fashion in a new group of six participants who each received active drug on one occasion and placebo on the other. Tolcapone increased the area under the plasma concentration-time curve and half-life of levodopa approximately twofold, without appreciably increasing the peak concentration. The maximum effect on levodopa half-life was observed with the 200-mg dose. Adverse effects were minor at all doses.     

Biochemical studies on combined effects of garlic (Allium sativum Linn) and ginger (Zingiber officinale Rosc) in albino rats

Adult male rats of wistar strain were fed diets containing (w/w) 2% garlic (group II), 0.5% ginger (group III) and a combination of garlic plus ginger (group IV) for 4 weeks to study their effects on serum biochemical parameters. A significant increase in body weight was observed in all groups except that fed ginger (group III). A significant decrease in blood glucose, serum total cholesterol and serum alkaline phosphatase were found in all groups, whereas serum triglycerides were decreased significantly only in group IV. Serum HDL-cholesterol was significantly increased only in groups III and IV. However, HDL-cholesterol, VLDL-cholesterol and atherogenic index were significantly decreased in animals fed with combination of the two, compared to garlic/ginger alone. Hence, a combination of garlic and ginger is much more effective in reducing blood glucose and serum lipids.     

Association between hyperadrenocorticism and development of calcium-containing uroliths in dogs with urolithiasis

OBJECTIVE: To determine, among dogs with urolithiasis, whether dogs that had hyperadrenocorticism would be more likely to have calcium-containing uroliths than would dogs that did not have clinical evidence of hyperadrenocorticism. DESIGN: Retrospective case-control study. ANIMALS: 20 dogs that had urolithiasis and hyperadrenocorticism and 42 breed-matched dogs that had urolithiasis but did not have clinical evidence of hyper-adrenocorticism. PROCEDURE: Signalment, urolith composition, results of bacterial culture of urine, and results of adrenal axis tests were recorded. A multivariate logistic regression model was created, including terms for age, sex, and hyperadrenocorticism. The outcome variable was presence or absence of calcium-containing uroliths. RESULTS: Among dogs with urolithiasis, those that had hyperadrenocorticism were 10 times as likely to have calcium-containing uroliths as were dogs that did not have clinical evidence of hyperadrenocorticism (odds ratio, 10.5; 95% confidence interval, 1.5 to 23.4). Neutered and sexually intact females were less likely to have calcium-containing uroliths than were neutered males (odds ratios, 0.041 [95% confidence interval, 0.0057 to 0.29] and 0.024 [95% confidence interval, 0.0012 to 0.51, respectively). CLINICAL IMPLICATIONS: Prompt diagnosis and treatment of hyperadrenocorticism may decrease prevalence of calcium-containing uroliths in dogs.     

Molecular mechanisms for the regulation of the expression and function of muscarinic acetylcholine receptors

The regulation of muscarinic acetylcholine receptor expression and function was investigated in cultured cells and in knockout mice. Muscarinic agonist exposure causes m2 receptor desensitization and sequestration and decreases the expression of cardiac potassium channels. The expression of m2 receptors in chick retina is regulated by a developmentally regulated secreted factor. Mice lacking the m1 receptor exhibit a loss of muscarinic regulation of M-current potassium channel activity and pilocarpine-induced seizures.     

Role of fever in infection: has induced fever any therapeutic potential in HIV infection?

Ancient societies had no rational understanding of fever. The Greeks were the first to recognise that it may be part of nature's method of effecting cure in some diseases. How best to assist nature went through many trials and errors. Appreciation of the prognostic value of fever and how it may be controlled was slow to appear. That there was a place in the therapeutic arsenal for induced fever came only with the 20th century. Finding a suitable, safe, and satisfactory means came slowly. The curative power of well controlled and reproducible levels of fever was proved by the arrest of one deadly and incurable complication of a sexually transmitted disease in the first half of this century. The purpose of this review is to promote discussion and, hopefully, well ordered laboratory and clinical trials aimed at learning whether or not induced fevers have a place in the care of patients with HIV/AIDS.