slo K(+) channel gene regulation mediates rapid drug tolerance

Changes in neural activity caused by exposure to drugs may trigger homeostatic mechanisms that attempt to restore normal neural excitability. In Drosophila, a single sedation with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage between these two phenomena by using a mutation and a transgene. A mutation that eliminates slo expression prevents tolerance, whereas expression from an inducible slo transgene mimics tolerance in naive animals. The behavioral response to benzyl alcohol can be separated into an initial phase of hyperkinesis and a subsequent phase of sedation. The hyperkinetic phase causes a drop in slo gene expression and makes animals more sensitive to benzyl alcohol. It is the sedative phase that stimulates slo gene expression and induces tolerance. We demonstrate that the expression level of slo is a predictor of drug sensitivity.     

Evidence-based burn care—An assessment of the methodological quality of research published in burn care journals from 1982 to 2008

Introduction

The quantity and quality of research evidence in peer-reviewed burn care journals have never been evaluated. The aim of this study was to empirically assess the evidence available in this literature.

Methods

All studies published in Burns and Journal of Burn Care and Research between 1st January 1982 and 31st December 2008 were reviewed. Articles were tabulated according to their study design into the following groups: meta-analyses; randomised controlled trials; controlled trials; comparative studies and case series/reports.

Results

A total of 2215 original articles were evaluated, of which 67.0% were from Burns and 33.0% were from Journal of Burn Care and Research. There were 3 meta-analyses (0.1%), 179 (8.1%) randomised controlled trials, 56 (2.5%) controlled clinical trials, 715 (32.3%) comparative studies and 1262 (57.1%) case series/reports. Journal of Burn Care and Research published a higher proportion of randomised controlled trials than Burns (11.9% vs. 6.2%; p < 0.001). There was no significant difference in the proportion of published controlled trials between the two journals (3.0% vs. 2.3%; p = 0.333). Journal of Burn Care and Research published a higher proportion of comparative studies than Burns (27.9% vs. 41.4%; p < 0.001). Case series/reports made up the highest proportion of articles in both Burns (63.6%) and Journal of Burn Care and Research (43.7%), with Burns publishing a higher proportion of these than Journal of Burn Care and Research (p < 0.001). From 1982 to 2008, when articles from both journals were considered together there were significant increases in the proportion of randomised controlled trials (0 (0%) to 10 (9%); p < 0.001) and controlled clinical trials (0 (0%) to 1 (1%); p < 0.001). There were no significant changes in the proportion of comparative studies (11 (44%) to 28 (16%); p = 0.846) or case series/reports (14 (56%) to 71 (65%); p = 0.448).

Discussion

The burn care literature suffers from a relative shortage of high-quality evidence. More randomised controlled trials are warranted.     

Ocular application of chitosan

INTRODUCTION: A major problem in ocular therapeutics with classical formulations is the maintenance of an effective drug concentration at the site of action for a long period of time. Enhancement of ocular bioavailability with increased dose penetration and longer retention time at desired sites can be achieved by recent formulations. Chitosan stands out with its unique structural advantageous characteristics for different types of formulations like in situ gelling systems, micro- and nanoparticles, inserts, etc. AREAS COVERED: In this review, the authors focus on ocular therapeutics and the characteristics that make chitosan more acceptable in ocular applications. EXPERT OPINION: Chitosan seems to be one of the most promising polymeric carriers for both hydrophilic and lipophilic drugs for ocular application.     

Tolerance to Anesthesia Depends on Synaptic Proteins

The hypnotic effects of anesthetics are caused by their interactions with neuronal components vital for proper signaling. An understanding of the adaptive mechanisms that lead to the development of anesthetic tolerance can offer insight into the regulation of neuroexcitability and plasticity that alter behavioral output. Here we use genetic and pharmacological manipulation of Drosophila to investigate the mechanisms of tolerance to benzyl alcohol. The mutants tested were temperature-sensitive paralytics that interfere with neuronal signaling: two mutations in dynamin that affect vesicle recycling, shi ^ts1 and shi ^ts2, and one that affects the voltage-activated Na⁺ channel, para ^ts1. We also used N-ethylmaleimide (NEM) to pharmacologically interfere with synaptic function. We found that blocking the generation of action potentials using a temperature-sensitive paralytic mutation does not induce nor prevent the development of functional tolerance to benzyl alcohol, but that disruption of synaptic signaling using mutations in the dynamin gene or by NEM treatment inhibits the induction of tolerance.     

Perineuritis in acute lyme neuroborreliosis

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56‐year‐old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis. Muscle Nerve, 2009