An efficient, short synthesis and potent anti-hepatitis B viral activity of a novel ring-expanded purine nucleoside analogue containing a 5:7-fused, planar, aromatic, imidazo[4,5-e][1,3]diazepine ring system.

An efficient, short synthesis of a ring-expanded nucleoside analogue containing a novel 5:7-fused, planar, and potentially aromatic imidazo[4,5-e][1,3]diazepine heterocyclic ring system is reported. The target compound, 6-amino-8-hydroxy-4H-1-beta-D- ribofuranosylimidazo[4,5-e][1,3]diazepin-4-one (2) was synthesized in a single step in > or = 90% yield by condensation of guanidine with either methyl 1-beta-D-ribofuranosylimidazole-4,5- dicarboxylate(1a) or its 2',3',5'-tri-O-benzoyl derivative (1b). Compound 2 showed potent anti-hepatitis B virus (anti-HBV) activity with an EC50 value of 0.17 microM in the transfected hepatoma cell line 2.2.15, and a low cellular toxicity with a CC50 value of 2.4 mM (TI > 14,000).     

Histoenzymological compartmentation of butyryl cholinesterase in the Glossimetra orientalis Mehra 1937

Butyryl cholinesterase activity in Glossimetra orientalis was studied histochemically with Gomori's method using butyrylthiocholine as substrate. Eserine sulphate (10(-5) M) was used as inhibitor for AChE. The study reveals that the enzyme is present mainly in the musculature of the reproductive system, excretory canal, nerve cells and fibers, tegument and subtegumentary cells and suckers. The testes, ovary and parenchyma are completely negative. The functional significance of the enzyme in the various locations have been discussed.     

Dose and duration related methylmercury deposition, glycosidases inhibition, myelin degeneration and chelation therapy

Methylmercury accumulation in different parts of the CNS (olfactory bulbs, cerebral hemispheres, cerebellum, medulla oblongata and spinal cord) in relation to the cytoarchitectural changes in myelin sheath as well as in glycosidases levels have been reported. Male albino rats were treated with low and high doses of methylmercury chloride (1 mg/kg and 10 mg/kg) N-acetyl-DL-homocysteine thiolactone (40 mg/kg and 80 mg/kg) and glutathione (100 mg/kg and 150 mg/kg) for varied time periods. The study shows a dose and duration dependent accumulation of mercury in all the CNS areas coinciding with a progressive myelin degeneration and inhibition of the glycosidases. A casual relationship between the amount of mercury accumulation and the extent of enzymes inhibition, in any particular area of CNS, could not be established. Similarly none of the antagonists is (though has been successful in recovering the enzymes and lessening the mercury burden in a few isolated cases) able to bring an absolute control value in any group.     

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.