Endogenous methyl palmitate modulates nicotinic receptor-mediated transmission in the superior cervical ganglion

Nitric oxide (NO) is identified as the endothelium-derived relaxing factor and a neurotransmitter with a superfusion bioassay cascade technique. By using a similar technique with rat superior cervical ganglion (SCG) as donor tissue and rabbit endothelium-denuded aortic ring as detector tissue, we report here that a vasodilator, which is more potent than NO, is released in the SCG upon field electrical stimulation (FES) or addition of nicotine. Release of this vasodilator was enhanced by arginine analogs, including N^ω-nitro-l-arginine (a NO synthase inhibitor), suggesting that it is not NO. Analysis by gas chromatography/mass spectrometry identified 2 saturated fatty acids, palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME), being released from the SCG upon FES in the presence of arginine analogs. Exogenous PAME but not SAME induced significant aortic dilation (EC₅₀ = 0.19 nM), indicating that PAME is the potent vasodilator. Release of PAME and SAME was significantly diminished in chronically decentralized SCG but not denervated SCG, suggesting the preganglionic origin. Furthermore, release of both fatty acids was calcium- and myosin light chain kinase-dependent, suggesting that both were released from axoplasmic vesicular stores. Electrophysiological studies further demonstrated that PAME but not SAME inhibited nicotine-induced inward currents in cultured SCG and the α7-nicotinic acetylcholine receptor-expressing Xenopus oocytes. Endogenous PAME appears to play a role in modulation of the autonomic ganglionic transmission and to complement the vasodilator effect of NO.     

''MYNI''s orthosis'': a self-adjustable, dynamic knee extension orthosis for quadriceps weakness in haemophilia rehabilitation

In developing countries like India, where walking is the primary, preferred and feasible mode of transport, the implications following quadriceps weakness poses a serious threat to ones functional independence. This has been a challenge for professionals while ambulating individuals with haemophilia, where quadriceps weakness is very common. Although external splinting has been understood for many years, as a means of support in haemophilia, there is still a dearth of knowledge in making an appropriate splint to assist or to take over the weak quadriceps during ambulation. This newly designed 'MYNI's orthosis' helps in versatile ways in addition to assisting the weak quadriceps. It provides prolonged stretch to contracted tissue, allows for being used as a serial cast in improving the knee range and is cosmetically acceptable. Above all, it is user-friendly, thus enhancing compliance and superior outcome in haemophilic knee rehabilitation.     

Adjunctive quetiapine for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: a meta-analysis of randomized controlled treatment trials

Small studies have shown positive effects from adding a variety of antipsychotic agents in patients with obsessive-compulsive disorder who are unresponsive to treatment with serotonin reuptake inhibitors. The evidence, however, is contradictory. This paper reports a meta-analysis of existing double-blind randomized placebo-controlled studies looking at the addition of the second-generation antipsychotic quetiapine in such cases. Three studies fulfilled the inclusion criteria. Altogether 102 individuals were subjected to analysis using Review Manager (4.2.7). The results showed evidence of efficacy for adjunctive quetiapine (<400 mg/day) on the primary efficacy criterion, measured as changes from baseline in total Yale-Brown Obsessive Compulsive Scale scores (P=0.008), the clinical significance of which was limited by between-study heterogeneity. The mechanism underlying the effect may involve serotonin and/or dopamine neurotransmission.     

Prevalence of anaemia among adolescent girls in the urban slums of Vellore, south India

A community-based, cross-sectional study was conducted to determine the prevalence of anaemia among unmarried, adolescent south Indian girls in an urban slum setting. A total of 100 apparently healthy girls between the ages of 11 and 18 years were recruited. Their socioeconomic, dietary and anthropometric information was collected, and blood haemoglobin (Hb) was estimated. The prevalence of anaemia (Hb < 12 g%) was 29%. Most had mild anaemia; severe anaemia was not seen. Two-thirds of those with anaemia had low serum ferritin (<12 microg/L). Significant associations were observed between anaemia and low socioeconomic status, religion and reporting infrequent/non-consumption of meat (heme iron). Only meat consumption was related to haemoglobin by multiple regression analysis. Anaemia is a common problem among adolescent girls in this setting, though severe anaemia is rare. There is a need to improve their haemoglobin status through dietary modification along with preventive supplementation and nutrition education.     

Evidence for an Alzheimer Disease Susceptibility Locus on Chromosome 12 and for Further Locus Heterogeneity

Context.— Alzheimer disease (AD) susceptibility genes have been identified on chromosomes 1, 14, 19, and 21, and a recent study has suggested a locus on chromosome 12. Objective.— To confirm or refute the existence of a familial AD susceptibility locus on chromosome 12 in an independent sample of familial AD cases. Design.— Retrospective cohort study. DNA data for 6 chromosome 12 genetic markers were evaluated using parametric lod score and nonparametric linkage methods and linkage heterogeneity tests. The latter include the admixture test of homogeneity in the total group of families and the predivided sample test in families stratified by the presence or absence of an apolipoprotein E (APOE) 4 allele among affected members. Parametric analyses were repeated assuming autosomal dominant inheritance of AD and either age- and sex-dependent penetrance or zero penetrance for the analysis of unaffected relatives. Setting.— Clinical populations in the continental United States, Canada, Argentina, and Italy. Patients.— Fifty-three white families composed of multiple members affected with AD, from whom DNA samples were obtained from 173 patients with AD whose conditions were diagnosed using established criteria and from 146 nondemented relatives. Main Outcome Measure.— Presence of an APOE 4 allele among affected family members. Results.— Using parametric methods, no evidence for linkage to the region spanned by the chromosome 12 markers could be detected if familial AD is assumed to arise from the same genetic locus in all 53 families. However, significant evidence for linkage was detected in the presence of locus heterogeneity using the admixture test (odds ratio, 15, 135:1). The estimated proportion of linked families within the 53 families examined varied between 0.40 and 0.65, depending on the genetic model assumed and APOE status. The precise location of the AD gene could not be determined, but includes the entire region suggested previously. Nonparametric linkage analysis confirmed linkage to chromosome 12 with the strongest evidence at D12S96 (P<.001). Conclusions.— Our data provide independent confirmation of the existence of an AD susceptibility locus on chromosome 12 and suggest the existence of AD susceptibility genes on other chromosomes. Screening a larger set of families with additional chromosome markers will be necessary for identifying the chromosome 12 AD gene.