Synthesis and antitubercular activity of nucleoside analogs based on L-ascorbic acid and bases

5,6-O-isopropylidene-2,3-di-O-methyl ascorbic acid (2), obtained by reaction of acetone with ascorbic acid (1) followed by methylation with methyl iodide, on 1,8-Diazabicyclo[5.4.0]undec-7-ene-catalyzed elimination of acetone moiety led to the formation of respective 2,3-di-O-methyl didehydro-L-ascorbic acid (4) in good yield. The latter, on methanesulfonylation with methanesulfonyl chloride and subsequent reaction of the crude methanesulfonyloxy derivative with imidazole, benzimidazole, and adenine resulted in the corresponding tetronolactonyl nucleoside analogs 5, 6, and 7. Compound 5 on reaction with benzyl amine led to the N-benzylated teramyl nucleoside analog, while compounds 6 and 7 did not react under similar conditions. All the synthesized compounds were evaluated for their antitubercular activity against M. tuberculosis H₃₇R_a and H₃₇R_v, exhibiting a minimum inhibitory concentration (MIC) of more than12.5 μg/mL.     

The necessity of integrated medicine to treat SARS‐Cov‐2/COVID‐19 patient: A case report

Health policymakers and clinicians should also prioritize mental, emotional and social health while treating SARS‐CoV‐2/COVID‐19, and for this, different treatment varieties of eastern medicine would be a better option to integrate into western medicine so that we could have a better result in all dimensions of health.     

Gut Microbial Metabolite-Mediated Regulation of the Intestinal Barrier in the Pathogenesis of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disease. The disease has a multifactorial aetiology, involving genetic, microbial as well as environmental factors. The disease pathogenesis operates at the host–microbe interface in the gut. The intestinal epithelium plays a central role in IBD disease pathogenesis. Apart from being a physical barrier, the epithelium acts as a node that integrates environmental, dietary, and microbial cues to calibrate host immune response and maintain homeostasis in the gut. IBD patients display microbial dysbiosis in the gut, combined with an increased barrier permeability that contributes to disease pathogenesis. Metabolites produced by microbes in the gut are dynamic indicators of diet, host, and microbial interplay in the gut. Microbial metabolites are actively absorbed or diffused across the intestinal lining to affect the host response in the intestine as well as at systemic sites via the engagement of cognate receptors. In this review, we summarize insights from metabolomics studies, uncovering the dynamic changes in gut metabolite profiles in IBD and their importance as potential diagnostic and prognostic biomarkers of disease. We focus on gut microbial metabolites as key regulators of the intestinal barrier and their role in the pathogenesis of IBD.     

The All India Ophthalmological Society - Academic and Research Committee pan-India diabetic retinopathy project “Fixing the missing link”: Prevalence data from West Bengal

Purpose:The aim of this study was to determine the prevalence of diabetic retinopathy (DR) and its risk factors among diabetic patients in rural and urban West Bengal (WB).Methods:Patients were screened in the physician''s clinic by a team of ophthalmologist, optometrist and counsellor. Demographic details, diabetic control, compliance to eye checkup, awareness regarding diabetic blindness, and visual acuity were recorded using a questionnaire. DR was graded both by indirect ophthalmoscopy and fundus photo taken with a portable fundus camera.Results:A total of 1553 subjects were screened over 39 camps across 14 districts of WB over 17 months. The prevalence of DR was 21.51%, with a significant difference between rural (26.55%) and urban (13.89%) areas (P < 0.01). No significant difference with gender was seen (P = 0.99). Presence and grade of DR were related to age, loss of vision, diabetic age, diabetic control, awareness of diabetic blindness and last eye checkup.Conclusion:This study provides the first major prevalence data from WB, and gives valuable insight regarding modifiable risk factors for DR. It is also the first DR study in India to be conducted in the physician''s clinic. The study results emphasise the need to “fix the missing link” between ophthalmologists and treating physicians to win the battle against DR.     

All that a physician should know about gluten-free diet

Gluten-free diet (GFD) is the only definitive treatment for patients with celiac disease (CeD). Strict adherence to GFD improves the symptoms, nutritional deficiencies, and the overall well-being of the patients. The management of CeD is truly different and unique from the treatment of other medical or surgical diseases. While prescribing a GFD is easy, the key to the success lies in the dietary counseling by a nutrition specialist/physician and maintenance of adherence to the prescribed diet by the patient. When restricting gluten from all possible sources, it is pertinent to recommend a diet that is healthy and balanced for patients with celiac disease. Those following GFD must be counseled properly on the ways of balancing their diets and of avoiding cross contamination. They should be taught how to read food labels properly and given tips for dining out or during traveling. Regular follow up with patients is required for assessing the compliance and monitoring growth and the status of recovery. In this review article, we have compiled, for the physicians and gastroenterologists, the relevant information about GFD including counseling, adherence, nutritional adequacy, and many other related issues.     

The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat--a case study with KBR 3023 (a prospective insect repellent).

KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine, a prospective insect repellent being developed by the Bayer Corporation, was evaluated for reproductive toxicity in the Sprague-Dawley rat. As the intended human use of the test compound is topical, the test system was also exposed to the compound via the dermal route. Specifically, the adult rats (P generation) were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 100, or 200 mg KBR 3023/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Clinical signs and changes in body weight and food consumption were assessed throughout the study. All adults and neonates underwent a gross necropsy examination. Tissues retained for microscopic examination from all adult animals included the kidney, liver, pituitary, reproductive organs, and samples of skin from the shaved dose site. In addition to the parameters noted above, the animals were evaluated for the effect of the test compound on estrous cycling, mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. There were no test compound-related clinical signs or effects on body weight or food consumption observed in either the adults or the pups during any phase of the study. There were no compound-related effects on any reproductive or litter parameters. Dermal findings at the dose site (acanthosis and hyperkeratosis) were noted in both generations. Other than the dermal findings, no compound-related necropsy findings were seen in either the adults or the pups. No compound-related histopathologic findings were noted in the reproductive tissues of either the males or females. Based on these results, KBR 3023, administered as described in this study at dose levels as high as 200 mg/kg body weight (the physical limit of dermal application for this compound), did not demonstrate any reproductive toxicity.