Endometrial pathology in abnormal uterine bleeding

Background: Abnormal uterine bleeding (AUB) is a common presenting symptom in gynecological outpatient department. Endometrial sampling could be used as the first diagnostic step in AUB. Aim of our study was to evaluate the endometrial causes of AUB and to observe the incidence of various pathology in different age groups.Methods: A study was conducted on 167 patients who presented with AUB, during the period from July 2015- January 2017.All endometrial curettage and hysterectomy specimens received in the Department of Pathology, Kannur Medical College during  this  period  were included.Results: Maximum numbers of patients were in the perimenopausal age group and normal cycling endometrium was the commonest pattern observed (41.3%).Abnormal patterns noted were hyperplasia without atypia (20.9%), disordered proliferative pattern (16.1%) and endometrial carcinoma (1.7%).Conclusion: Histopathological examination of endometrium showed wide spectrum of lesions from normal endometrium to malignancy. Accurate analysis of endometrial sampling is important in the management of AUB

Nudix hydrolases with Coenzyme A (CoA) and acyl-CoA pyrophosphatase activities confer growth advantage to Mycobacterium smegmatis

Nudix hydrolase family proteins hydrolyse toxic by-products of cellular metabolism such as mutagenic nucleoside triphosphates, sugar nucleotides and signalling molecules. We studied the substrate specificities of Nudix hydrolases encoded by rv3672c and rv3040c from Mycobacterium tuberculosis and their respective homologues, msmeg_6185 and msmeg_2327 from M. smegmatis. The rv3672c- and msmeg_6185-encoded proteins (Rv3672 and MSMEG_6185, respectively) showed CoA pyrophosphatase (CoAse) activity that converted acyl-CoA to adenosine-3',5'-diphosphate (3', 5'-ADP) and 4-acyl phosphopantetheine. The efficiencies of Rv3672 and MSMEG_6185 in hydrolysing CoA derivatives were found to be higher than those of the Rv3040 and MSMEG_2327 (encoded by rv3040c and msmeg_2327, respectively). Further, amongst the substrates tested, Rv3672 and MSMEG_6185 used CoA and oxidized CoA as the most preferred substrates. Use of the M. smegmatis model showed that the expression of msmeg_6185 occurs in the log and stationary phases but declines during the late stationary phase and becomes undetectable during hypoxia. The co-culture competition experiments performed between the wild-type and Delta msmeg_6185 strains of M. smegmatis in different carbon sources revealed that the presence of msmeg_6185 provided growth fitness advantage to M. smegmatis, irrespective of the carbon source, implicating its function in regulation for the optimal physiological levels of acyl-CoAs in the cell

Novel Inhibitors of Nicotinamide-<i>N</i>-Methyltransferase for the Treatment of Metabolic Disorders

Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). It is expressed in many tissues including the liver, adipose tissue, and skeletal muscle. Its expression in several cancer cell lines has been widely discussed in the literature, and recent work established a link between NNMT expression and metabolic diseases. Here we describe our approach to identify potent small molecule inhibitors of NNMT featuring different binding modes as elucidated by X-ray crystallographic studies