Systematic review of topical treatments for fungal infections of the skin and nails of the feet. (1/66)

OBJECTIVE: To identify and synthesise the evidence for efficacy and cost effectiveness of topical treatments for superficial fungal infections of the skin and nails of the feet. DESIGN: Systematic review. INTERVENTIONS: Topical treatments for superficial fungal infections. MAIN OUTCOME MEASURES: Cure confirmed by culture and microscopy for skin and by culture for nails in patients with clinically diagnosed fungal infections. RESULTS: Of 126 trials identified in 121 papers, 72 (57.1%) met the inclusion criteria. Placebo controlled trials yielded pooled relative risks of failure to cure skin infections: allylamines (0.30, 95% confidence interval 0.24 to 0.38); azoles (0.54, 0.42 to 0.68); undecenoic acid (0.28, 0. 11 to 0.74); and tolnaftate (0.46, 0.17 to 1.22). Although meta-analysis of 11 trials comparing allylamines and azoles showed a relative risk of failure to cure of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven reports in English favoured allylamines (0.79, 0.69 to 0.91), but four reports in foreign languages showed no difference between the two drugs (1. 01, 0.90 to 1.13). Neither trial of nail infections showed significant differences between alternative topical treatments. CONCLUSIONS: Allylamines, azoles, and undecenoic acid were efficacious in placebo controlled trials. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive than azoles. The most cost effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails.  (+info)

Opposite effects of GABA(A) and GABA(C) receptor antagonists on the b-wave of ERG recorded from the isolated rat retina. (2/66)

The largest component in the fully dark-adapted ERG is a corneal-positive response, known as the b-wave, and believed to originate from depolarizing (ON-type) bipolar cells. The two types of GABA receptors, GABA(A) and GABA(C) have been reported to exist on bipolar cells in rat retina. The goal of these experiments was to find whether these GABA receptors participate in the generation of the b-wave of electroretinogram (ERG). ERGs were recorded from the isolated rat retinas. The P(2)(t) component, obtained by subtracting the ERGs measured before the application of 50 micrograms APB from those measured after the application of 50 micrograms APB, was used as an indicator of depolarizing bipolar cell activity. Photovoltages, the fast P(3)(t) component of ERG, were registered between the two microelectrodes across the rod outer segments. Bicuculline and 3-aminopropylphosphonic acid (3-APA) were used as selective antagonists of GABA(A) and GABA(C) receptors, respectively. It was found that the GABA(A) and GABA(C) receptors antagonists have opposite effects on the b-wave: bicuculline increased the b-wave amplitude, while 3-APA reduced the amplitude of the b-wave. Neither bicuculline nor 3-APA affect photoreceptors.  (+info)

New therapies on the horizon. (3/66)

Statins have proved to be potent drugs for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, because the response to current statin therapy regimens is not always sufficient to reach defined goal levels, additional drugs to lower LDL-C are needed. New drugs may soon be available to lower LDL-C levels by mechanisms that differ from those of the statins. Among these new agents are a bile acid binding resin, inhibitors of bile acid transport, inhibitors of cholesterol transport, inhibitors of cholesterol esterification, and triglyceride-lowering agents.  (+info)

The development of an in-vitro perfusion system for studies on cultured cells. (4/66)

The design and use of a perfusion system, using a modified flow chamber for studies on cultured animal cells, is described. Rat thoracic aorta smooth muscle cells were isolated by an explant method and grown on Thermanox coverslips. These were introduced into the flow chamber. A flow rate of 25ml/min and a shear stress of 14.6 dynes/cm2 (12 dyne = 10 microN) (both within physiological limits) were maintained. Cells remained attached to the coverslips after 8h of perfusion with culture medium. The effect of exposing rat smooth muscle cells to the cardiovascular toxin, allylamine, is also described. The components of the system are routinely available, simple to clean, easy to assemble and sterilize. The incorporation of an in-line sensor that monitors pH, PO2, PCO2 and temperature ensures that the perfusion conditions remain within physiological limits. Automation means that minimal supervision is required. This system provides a potential mechanism in which cultured vascular cells may be perfused under controlled haemodynamic conditions, and their response to a cytotoxin may be evaluated.  (+info)

Overview of pharmacologic therapy for the treatment of dyslipidemia. (5/66)

Although the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines stress the importance of nonpharmacologic lipid modification interventions such as diet and exercise, the guidelines also recognize that many patients will require drug therapy to achieve low-density lipoprotein cholesterol (LDL-C) target goals. Currently available lipid-modifying drugs include bile acid sequestrants (or resins), fibrates, nicotinic acid, and statins, with each class exerting different effects on the lipid profile. In addition, nonprescription agents such as plant stanols and sterols have been shown to be effective in modifying plasma lipids. Of these agents, the statins are the most effective, most widely prescribed, and best-tolerated form of lipid-lowering drug therapy. New formulations of other drugs, such as niacin and bile acid sequestrants, can also improve treatment regimes and reduce side effects, thereby improving patient compliance with these therapies. In patients who have high levels of LDL-C and triglycerides together with low concentrations of high-density lipoprotein cholesterol (HDL-C), combination therapy may be required. Ezetimibe, a selective cholesterol absorption inhibitor, is the first of a new class of lipid-lowering agents and provides a new agent for the management of patients with dyslipidemia. Data from the ezetimibe clinical development program suggests that this agent can be used alone or in combination with statins to reduce LDL-C, improve compliance, and bring more patients to ATP III target goal.  (+info)

Regulation of alpha7-integrin expression in vascular smooth muscle by injury-induced atherosclerosis. (6/66)

Injury of vascular smooth muscle cells (VSMCs) by allylamine (AAM) leads to phenotypic changes associated with atherogenic progression including increased proliferation, migration, and alterations in cell adhesion. In the present study, the relationship between AAM-induced vascular injury and expression of the alpha(7)-integrin subunit was investigated. The alpha(7)-mRNA and protein expression were examined using real-time RT-PCR, fluorescence-activated cell sorting analysis (FACS), immunohistochemistry, and immunoblotting. In cultured VSMCs from aortas of AAM-treated rats (70 mg/kg for 20 days), alpha(7)-mRNA levels were increased more than twofold compared with control cells. No change was seen in beta(1)-integrin expression. FACS analysis revealed increased cell surface expression of alpha(7)-protein (25 +/- 9%; *P < 0.05). AAM treatment of naive VSMCs enhanced alpha(7)-mRNA expression (2.4 +/- 0.7-fold, mean +/- SE; *P < 0.05). The increased alpha(7)-mRNA expression was attenuated by the amine oxidase inhibitor semicarbazide and the antioxidant pyrrolidine dithiocarbamate, which confirms a role for oxidative stress in modulating alpha(7)-expression. In vivo alpha(7)-mRNA and protein expression were enhanced in the aortas of AAM-treated rats. In addition, increased alpha(7)-integrin expression facilitated AAM VSMC adhesion to laminin more efficiently compared with control (51 +/- 2%; *P < 0.05). Chemical injury induced by AAM significantly enhances alpha(7)-integrin expression in VSMCs. These findings implicate for the first time the expression of alpha(7)-integrin during the response of VSMCs to vascular injury.  (+info)

Ketogenic diet decreases circulating concentrations of neuroactive steroids of female rats. (7/66)

Ketogenic diet (KD) is used to manage intractable epilepsy; however, the mechanisms underlying its therapeutic effects are not known. Steroid hormones, such as progesterone and testosterone, are derived from cholesterol, and are readily 5alpha-reduced to dihydroprogesterone and dihydrotestosterone, which are subsequently converted to 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) and 3alpha-androstanediol, neuroactive steroids that can influence seizures. The present study examined the effects of the KD on circulating concentrations of these neuroactive steroids, and their precursors, in intact female rats. Thirty-six, 22-day-old female Sprague-Dawley rats (weaned at 21 days) were fasted for 8 hours prior to placement on one of three dietary regimens for 6 weeks: ad libitum chow, calorie-restricted chow, or KD. After 6 weeks of the diet, when six rats in each dietary condition were in diestrus and six were in behavioral estrus, all rats were administered pentylenetetrazole (PTZ, 70 mg/kg, i.p.). The latency and incidence of seizures were recorded by an observer who was uninformed of the estrous cycle and dietary treatment conditions of the rats. Immediately after each test, trunk blood was obtained for later measurement of pregnane (progesterone, dihydroprogesterone, 3alpha,5alpha-THP) and androstane (testosterone, dihydrotestosterone, 3alpha-androstanediol) neuroactive steroid concentrations in plasma by radioimmunoassay. KD tended to lengthen the latency to, and significantly reduced the number of, PTZ-induced barrel roll seizures. KD also significantly reduced plasma levels of the pregnane (dihydroprogesterone, 3alpha,5alpha-THP) and androstane (dihydrotestosterone, 3alpha-androstanediol) 5alpha-reduced metabolites. These data suggest that levels of pregnane and androstane neuroactive steroids, or their precursors, may underlie some of the antiseizure effects of KD.  (+info)

Asymmetric synthesis of 4,5,6- and 3,4,5,6-substituted azepanes by a highly diastereoselective and enantioselective lithiation-conjugate addition sequence. (8/66)

Asymmetric syntheses of 4,5,6- and 3,4,5,6-substituted azepanes have been achieved by highly diastereoselective and enantioselective (-)-sparteine-mediated asymmetric lithiation-conjugate additions of N-Boc-N-(p-methoxyphenyl)-2,3-substituted allylamines to a beta-aryl alpha,beta-unsaturated ester followed by hydrolysis, cyclization, and reduction. Access to the enantiomeric adduct is provided by an invertive lithiation-stannylation-lithiation sequence.  (+info)

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