6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects.

Current common analgesics are mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. However, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that many of these compounds have dual agonism on kappa and mu opioid receptors. In vivo studies on the lead dual kappa and mu opioid receptor agonist demonstrated supraspinal thermal analgesic activity while avoiding anxiogenic effects in male mice, thus providing further strong evidence in support of the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.

Development and validation of a photographic food atlas for portion size assessment in the southern plains of Nepal.

OBJECTIVE: To develop and validate a photographic food atlas of common foods for dietary assessment in southern Nepal. DESIGN: We created a life-sized photographic atlas of forty locally prepared foods. Between March and June 2014, data collectors weighed portion sizes that respondents consumed during one mealtime and then a different data collector revisited the household the next day to record respondents' estimations of their previous day's intakes using the atlas. Validity was assessed by percentage error, Cohen's weighted kappa (κ w) and Bland-Altman limits of agreement. SETTING: Dhanusha and Mahottari districts in southern Nepal. SUBJECTS: A random sample of ninety-five adults in forty-eight rural households with a pregnant woman. RESULTS: Overall, respondents underestimated their intakes (mean error =-4·5 %). Rice and dal (spiced lentil soup) intakes were underestimated (-14·1 % and -34·5 %, respectively), but vegetable curry intake was overestimated (+20·8 %). Rice and vegetable curry portion size images were significantly reliably selected (Cohen's κ w (se): rice=0·391 (0·105); vegetable curry=0·430 (0·139)), whereas dal images were not. Energy intake over one mealtime was under-reported by an average of 569 kJ (136 kcal; 4·5 % error) using recall compared with the weighing method. CONCLUSIONS: The photographic atlas is a useful tool for field estimation of dietary intake. Average errors were low, and there was 'modest' agreement between weighed and recalled portion size image selection of rice and vegetable curry food items. Error in energy estimation was low but with wide limits of agreement, suggesting that there is scope for future work to reduce error further.

An efficient and novel approach for the synthesis of substituted N-aryl lactams.

A quick, efficient, one-pot method for the synthesis of substituted N-aryl lactams through the reaction of various kinds of corresponding substituted arenes with a variety of ω-azido alkanoic acid chlorides using a Lewis acid (i.e. EtAlCl(2)) at room temperature, through the in situ involvement of a Friedel-Crafts reaction followed by intramolecular Schimdt rearrangement was developed, and afforded good to excellent yields.

Sensitive and rapid polymerase chain reaction based diagnosis of mycotic keratitis through single stranded conformation polymorphism.

PURPOSE: To report a method for early and correct diagnosis of mycotic keratitis. DESIGN: Clinical laboratory diagnostic study. METHODS: Corneal scraping of all the four patients were processed for DNA extraction which were amplified by fungal specific primers of internal transcribed spacer region I (ITS1). These products were sequenced and analyzed by single stranded conformation polymorphism (SSCP) for species identification. RESULTS: The DNA samples from corneal scrapings of all the four patients were successfully amplified by the primer pair ITS1 and ITS2 and similarity/dissimilarity were established by Jaccard's coefficient. Patient isolate 1 was identified as Nectria hematococca, isolate 2 as Candida albicans, and isolates 3 and 4 were identified as Bipolaris papendorfii. This led to prompt initiation of antifungal therapy in all the four cases where useful vision could be restored. CONCLUSIONS: Early and correct diagnosis of mycotic keratitis by polymerase chain reaction could be obtained in all the four cases compared with conventional methods, which helped in the prompt initiation of antifungal therapy in patients.