Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Hospital contacts for injuries and musculoskeletal diseases among seamen and fishermen: A population-based cohort study

<p>Abstract</p> <p>Background</p> <p>We studied musculoskeletal diseases (MSD) and injuries among fishermen and seamen with focus on low back disorders, carpal tunnel syndrome (CTS), rotator cuff syndrome and arthrosis.</p> <p>Methods</p> <p>Cohorts of all male Danish seamen (officers and non-officers) and fishermen employed 1994 and 1999 with at least six months employment history were linked to the Occupational Hospitalisation Register. We calculated standardised incidence ratios (SIR) for the two time periods, using rates for the entire Danish workforce as a reference.</p> <p>Results</p> <p>Among fishermen, we found high SIRs for knee arthrosis, thoraco-lumbar disc disorders, injuries and statistically significant SIRs above 200 were seen for both rotator cuff syndrome and CTS. The SIR was augmented for injuries and reduced for hip arthrosis between the two time periods. The SIRs for injuries and CTS were high for non-officers. A sub-analysis revealed that the highest risk for CTS was found among male non-officers working as deck crew, SIR 233 (95% CI: 166–317) based on 40 cases. Among officers, the SIRs for injuries and MSDs were low. The number of employed Danish fishermen declined with 25% 1994–1999 to 3470. Short-term employments were common. None of the SIRs increased with increasing length of employment.</p> <p>Conclusion</p> <p>Both fishermen and non-officers have high SIRs for injuries and fishermen also for MSD. Only the SIR for injuries among fishermen was augmented between 1994 and 1999. Our findings suggest an association between the incidence of rotator cuff syndrome and CTS and work within fishery. Long-term cumulative effects of employment were not shown for any of the disease outcomes. Other conditions may play a role.</p

Evidence for inhibition of cholinesterases in insect and mammalian nervous systems by the insect repellent deet

<p>Abstract</p> <p>Background</p> <p>N,N-Diethyl-3-methylbenzamide (deet) remains the gold standard for insect repellents. About 200 million people use it every year and over 8 billion doses have been applied over the past 50 years. Despite the widespread and increased interest in the use of deet in public health programmes, controversies remain concerning both the identification of its target sites at the olfactory system and its mechanism of toxicity in insects, mammals and humans. Here, we investigated the molecular target site for deet and the consequences of its interactions with carbamate insecticides on the cholinergic system.</p> <p>Results</p> <p>By using toxicological, biochemical and electrophysiological techniques, we show that deet is not simply a behaviour-modifying chemical but that it also inhibits cholinesterase activity, in both insect and mammalian neuronal preparations. Deet is commonly used in combination with insecticides and we show that deet has the capacity to strengthen the toxicity of carbamates, a class of insecticides known to block acetylcholinesterase.</p> <p>Conclusion</p> <p>These findings question the safety of deet, particularly in combination with other chemicals, and they highlight the importance of a multidisciplinary approach to the development of safer insect repellents for use in public health.</p

Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder

Workshop Enhances Clinical Faculty Development

Enhanced clinical faculty teaching strategies and skills. Consistent approaches to clinical education. Increased faculty and student satisfaction. Positive student outcomes. Strengthened alliance with clinical affiliates

Ipsilateral Arthrodesis of the Metatarsophalangeal and Interphalangeal Joints of the Hallux

BACKGROUNDArthrodesis of the metatarsophalangeal joint of the hallux is frequently used for treatment of a variety of disorders. However, occasionally patients who have complex deformities or degenerative changes of the hallux require reconstruction of both the metatarsophalangeal and interphalangeal joints. There is concern that arthrodesis of both the metatarsophalangeal and ipsilateral interphalangeal joints could be problematic, interfering with the toe-off phase of gait or with shoewear.METHODSA retrospective evaluation of seven feet in five patients who had simultaneous arthrodesis of the metatarsophalangeal and ipsilateral interphalangeal joints of the hallux was undertaken. These cases represented all the patients who had this procedure within the practice of three orthopaedic foot and ankle specialists, totaling over 50 surgeon-years of experience. The indication for surgery in all patients was moderate to severe pain with ambulation with severe fixed deformity of both the interphalangeal and metatarsophalangeal joints of the hallux. All patients had pain that limited their ambulation and interfered with their daily activities. All patients required modified shoewear to accommodate their foot deformity. The mean age of patients was 53 years. The patients were evaluated by questionnaire and radiographic examination.RESULTSAt an average of 46 months followup, all patients had resolution of their pain and were able to wear nonprescription shoes. All had limitations that interfered with full athletic activities but had no limitation of daily activities. Three patients who were employed returned to their occupations and two who were not employed were able to continue housework.CONCLUSIONArthrodesis of the metatarsophalangeal and ipsilateral interphalangeal joints of the hallux results in painless function in patients with moderate demands

Health care costing: data, methods, current applications. Med Care

H ealth care costs continue to grow rapidly, straining budgets and raising questions about whether consumers are getting good value for the money spent. There has never been a more pressing need for conceptually sound and empirically accurate estimates of health care costs, for a variety of applications. For example, cost estimates are pivotal in the setting of public and private health care budgets at all levels and establishing reimbursement rates; in cost-effectiveness analyses and other economic evaluations; and in assessing the impact of investments in research to prevent, detect, and treat disease. Yet, the development of valid, reliable, feasible, and comparable (across studies) measures of health care cost has proved to be challenging, both in the United States and elsewhere. Substantial variation exists across studies in data and methods, even for cost studies with seemingly a similar intent. One major source of difficulty lies with the data. In most health cost analyses, the data for measuring and valuing resource use were created for purposes other than health care costing (primarily reimbursement) and hence are imperfectly designed for the task at hand. The alternative approach, to collect the cost data de novo, is often expensive, and there is not yet consensus on how best to do it. Health care costs are inherently difficult to measure, whatever the choice of data source(s). For multiple reasons, the posted prices of health care goods and services often do not convey accurate or useful information about economic cost. The health care system produces literally thousands of heterogeneous products, whose individual &quot;prices&quot; are often not observed in the complex maze of pricing for bundled services. Moreover, observed prices may reflect differences in market power between buyers and sellers (as reflected, for example, in negotiated price discounts), efforts to cross-subsidize unprofitable services, and other market imperfections and idiosyncrasies. A second source of difficulties in health care costing is the absence of professional consensus on some data and methods issues. At a general level, there is universal agreement that the cost of any health care activity should be defined in terms of the &quot;economic opportunity costs&quot; of the component resources, with each resource valued in its next best use. In reality, there are substantial variations in how this textbook definition is applied because it provides little specific guidance on a number of practical issues. These include the components (or types) of cost to be included in the analysis, the assignment of opportunity cost values to these components, when and how to combine multiple data sources, key conceptual and study design issues (eg, identifying the cost attributable to a specific disease or activity), statistical challenges (eg, how best to handle heavily right-skewed cost data), and effective approaches for reporting findings. Similarly, within specific arenas of application (eg, cost-effectiveness analysis ͓CEA͔), there may be broad consensus regarding certain operating principles (eg, emphasis on the societal perspective), but little guidance on how best to bring data and From th