Sanjay Gandhi Postgraduate Institute of Medical Sciences is a medical Institute under State Legislature Act, located in Lucknow, Uttar Pradesh 14 km (8.7 mi) south of Hazratganj on Raebareli road. It was established in 1983 and is named after Sanjay Gandhi.The institute is on a 550 acres (2.2 km2) residential campus at Raebareli Road. The institute offers degrees which are recognised by the Medical Council of India. It also has tertiary medical care, super-specialty teaching, training and research. Degrees are provided at the DM, MCh, MD, and Ph.D. levels, and also include postdoctoral fellowships, postdoctoral certificate courses, and senior residency. It also has degree courses in nursing and paramedical.D.
Pancreas is embryologically an unique organ with foregut and midgut origins. Functionally endocrine and exocrine roles contribute to this uniqueness. Clinically it is considered a meeting place of both surgeons and physicians alike. Pancreas has perplexed mankind for centuries and this chapter summarizes the embryology, gross anatomy and common congenital malformations of human pancreas with clinical perspective.
The small GTPase RAS is a signalling hub activating multiple pathways, which may respond differently to a constitutively active RAS mutation. We explored this issue in fission yeast, where RAS-mediated pheromone signalling (PS) activates two downstream pathways: the MAPKSpk1 and Cdc42 pathways. We observed that the yeast RAS mutation ras1.G17V, an equivalent of the mammalian ras.G12V oncogenic mutation, causes prolonged Cdc42 activation, whereas MAPKSpk1 activation was transient and attenuated. To explain this observation, we generated a PS framework by conducting genetic epistasis analysis of PS mutants and biochemical analysis of two Ras1 effectors, Cdc42-GEFScd1 and MAPKKKByr2, each of which triggers activation of the Cdc42 and MAPKSpk1 pathways, respectively. Cdc42-GEFScd1 and MAPKKKByr2 directly interacted with Ras1 in vitro in a competitive manner, and overexpression of the Ras binding domain of either Cdc42-GEFScd1 or MAPKKKByr2 in cells inhibited both downstream pathways, confirming that Ras1 signalling branches into the MAPKSpk1 and Cdc42 pathways. In conjunction with the genetic epistasis analysis, we developed the PS framework-based mathematical model to test which network structures can explain the transient MAPKSpk1 activation profile. Incorporating a negative-feedback circuit acting on pheromone production or sensing enabled the model to quantitatively reproduce MAPKSpk1 dynamics in the wild type and 20 additional PS mutants. The predicted PS negative-feedback was experimentally confirmed by deleting Sxa2, the carboxypeptidase that degrades one of the mating pheromones, which led to hyperactivation of both MAPKSpk1 and Cdc42. Our study provides a holistic understanding of the fission yeast pheromone signalling network, explaining how RAS signalling propagates differently through two downstream pathways. Our PS mathematical model may serve as a valuable reference framework for analysing other RAS signalling systems.
Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of mortality worldwide. Several inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), the key hepatic cholesterogenic enzyme, are prescribed to treat hypercholesterolemia and ASCVD. Statins, the established HMG-R inhibitors, exhibit promising cholesterol-lowering effects; however, their long-term use has prompted significant concerns, necessitating the search for additional therapeutic candidates with strong HMG-R inhibitory activity. Therefore, this study aims to find potential HMG-R inhibitor/s that may help reduce excess cholesterol levels via targeting HMG-R activity. In this study, 1285 FDA-approved small molecules were assessed for their HMG-R inhibitory potential using high-throughput virtual screening (HTVS) and molecular docking simulations (MDS). Based on lowest binding energies and favourable docking interactions, seven compounds were selected for further studies. These compounds satisfied the Lipinski’s rules, ADME, and toxicity evaluations. Computational molecular informatics analysis revealed that all screened compounds efficiently occupied the catalytic domain of HMG-R, with binding energy (∆G) ranging from − 5.82 to -7.73 kcal/mol. In contrast, amongst other compounds, glipizide showed the lowest ∆G (-7.73 kcal/mol), surpassing the ∆G of the substrate HMG-CoA and standard drug atorvastatin (-3.99 and − 4.22 kcal/mol, respectively). A 100 ns MDS demonstrated that glipizide exhibited better stability compared with atorvastatin. Molecular mechanical-generalized Born surface area (MM-GBSA) analysis further showed that free ∆G of glipizide (-21.59 kcal/mol) was better than that of atorvastatin (-18.05 kcal/mol). In conclusion, as an FDA-approved antidiabetic drug, glipizide may be used for managing patients with both diabetes and hyperlipidaemia by additionally targeting human HMG-R.
Background Hepatitis virus-associated glomerulonephritis (HVGN) is a recognized extrahepatic manifestation of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection. We report the prevalence and histological spectrum of HVGN in a tertiary care center in North India. Materials and Methods The study was done on renal biopsies of patients showing serological evidence of HBV and/or HCV infection (2014-2022). Clinical data and viral serological markers were recorded. Renal biopsies were evaluated by light microscopy, immunofluorescence, and electron microscopy. Surface antigens in HBV-positive patients were detected using immunohistochemistry (IHC). Results A total of 5179 native kidney biopsies were collected, of which 49 and 10 tested positive for HBV and HCV infection, respectively. IgA nephropathy (IgAN) (26.5%), followed by membranous nephropathy (16.3%), were the most common histological patterns in HBV-associated renal disease. The most common histologies were membranoproliferative glomerulonephritis (MPGN) pattern of injury (20%) and IgAN (20%). At the time of renal biopsy, liver function tests were deranged in 37% (n=18) and 40% of (n=4) HBV and HCV patients, respectively. IHC of no renal biopsies of patients with HBV infection were positive for HbsAg. Conclusion IgAN is the most common glomerulonephritis (GN) associated with HBV infection and MPGN and IgAN were most commonly HCV-related GN.
Tympanic paragangliomas (glomus tympanicum tumors) are rare benign vascular neoplasms of middle ear paraganglionic tissue. This ambispective single-institutional study evaluates the strategic approaches adopted in the management of tympanic paragangliomas, analyzing the effectiveness of a newly implemented treatment algorithm with respect to surgical outcomes and recurrence rates. This study analyzed 28 patients with tympanic paragangliomas managed by a proposed algorithm between 2020 and 2024. Surgical approaches varied by tumor stage, from transcanal and endaural to mastoidectomy and infratemporal techniques. Key outcomes assessed included hearing preservation, recurrence, intraoperative complications, and long-term functional results. Of the 28 patients, 57.1
