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Introduction: Laparoscopic cholecystectomy is now preferred over the open procedure due to advantages such as reduced blood loss and shorter hospital stays. However, concerns have been raised regarding the potential for increased Intra-abdominal Pressure (IAP) during laparoscopic procedures, which may impact haemodynamic stability and respiratory parameters. However, there is a lack of comprehensive analysis directly comparing both surgical approaches from both haemodynamic and capnographic perspectives. Aim: To compare the haemodynamic and capnographic changes between laparoscopic and open cholecystectomy. Materials and Methods: This randomised clinical study was conducted at Department of Anaesthesiology, Assam Medical College and Hospital, Dibrugarh, Assam, India from May 2021 to June 2022. The study included 300 patients scheduled for cholecystectomy, divided into two groups: Laparoscopic Cholecystectomy (LC) Group I (n=150) and Open Cholecystectomy (OC) Group II (n=150). Haemodynamic parameters, including Pulse Rate (PR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Pressure (MAP), and Oxygen Saturation (SpO2), were recorded. Capnographic parameters, such as End-Tidal Carbon Dioxide (EtCO2) levels, were also measured at regular intervals. Data analysis was performed using the student's t-test and Chi-square test with Statistical Package for Social Sciences (SPSS) version 21.0 software and Microsoft excel. Results: There were no significant differences in age, body weight, and sex distribution between Group I and Group II. However, significant differences were observed in PR and SBP at 15 minutes (PR: 101.46 and 95.86; SBP: 148.57 and 140.97), 30 minutes (PR: 104.52 and 99.82; SBP: 141.28 and 136.07), and 45 minutes (PR: 102.52 and 97.70; SBP: 140.59 and 133.95) (p-value <0.01). Highly significant differences were observed in MAP and EtCO2 postinsufflation at 15 minutes (MAP: 118.38 and 108.61; EtCO2: 36.48 and 33.89), 30 minutes (MAP: 111.11 and 106.01; EtCO2: 41.02 and 36.15), 45 minutes (MAP: 110.73 and 103.48; EtCO2: 42.65 and 38.36), and 60 minutes (MAP: 106.08 and 101.45; EtCO2: 41.10 and 38.21) (p-value <0.01). DBP showed high significance at 15 minutes (103.21 and 93.23), 30 minutes (96.74 and 92.57), and 60 minutes (93.14 and 86.92) (p-value <0.01), and significant (p-value=0.01) at 45 minutes (95.53 and 87.59). Oxygen saturation showed significance (p-value <0.05) at 15 minutes (99.93 and 100). Conclusion: The present study demonstrated a significant increase in both haemodynamic and capnographic parameters, even in American Society of Anaesthesiologists (ASA) Grade-I and Grade-II patients undergoing laparoscopic cholecystectomy compared to the open surgical technique. These findings emphasise the need for careful monitoring during laparoscopic procedures. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis(Mtu), a successful pathogen, has developed resistance against the existing anti-tubercular drugs necessitating discovery of drugs with novel action. Enzymes involved in peptidoglycan biosynthesis are attractive targets for antibacterial drug discovery. The bifunctional enzyme mycobacterial GlmU (Glucosamine 1-phosphate N-acetyltransferase/ N- acetylglucosamine-1-phosphate uridyltransferase) has been a target enzyme for drug discovery. Its C- and N- terminal domains catalyze acetyltransferase (rxn- 1) and uridyltransferase (rxn-2) activities respectively and the final product is involved in peptidoglycan synthesis. However, the bifunctional nature of GlmU poses difficulty in deciding which function to be intervened for therapeutic advantage. Genetic analysis showed this as an essential gene but it is still unclear whether any one or both of the activities are critical for cell survival. Often enzymatic activity with suitable high-throughput assay is chosen for random screening, which may not be the appropriate biological function inhibited for maximal effect. Prediction of rate-limiting function by dynamic network analysis of reactions could be an option to identify the appropriate function. With a view to provide insights into biochemical assays with appropriate activity for inhibitor screening, kinetic modelling studies on GlmU were undertaken. Kinetic model of Mtu GlmU-catalyzed reactions was built based on the available kinetic data on Mtu and deduction from Escherichia coli data. Several model variants were constructed including coupled/ decoupled, varying metabolite concentrations and presence/absence of product inhibitions. This study demonstrates that in coupled model at low metabolite concentrations, inhibition of either of the GlmU reactions cause significant decrement in the overall GlmU rate. However at higher metabolite concentrations, rxn-2 showed higher decrement. Moreover, with available intracellular concentration of the metabolites and in vivo variant of model, uncompetitive inhibition of rxn-2 caused highest decrement. Thus, at physiologically relevant metabolite concentrations, targeting uridyltranferase activity of Mtu GlmU would be a better choice for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The M ycobacterium tuberculosis murG gene, Rv2153, was expressed in E scherichia coli murG( Ts) strain OV58 on a plasmid under the control of the arabinose-inducible araBAD promoter. M ycobacterium tuberculosis murG rescued the growth of E . coli murG( Ts) at the nonpermissive temperature: transformants were only obtained in the presence of 0.2% arabinose at 42 ° C, and their growth rate was dependent on arabinose concentrations. However, no MurG activity was detected in membranes from the transformant grown in arabinose at 42 °C, while MraY activity was normal. This observation led to the development of a membrane-based scintillation proximity assay for exogenous sources of MurG. Addition of purified E . coli MurG resulted in the reconstitution of MurG and peptidoglycan synthesis in these membranes. MurG is an attractive target for drug discovery, but assays to measure the activity of purified MurG are challenging. This presents an easy method to measure the activity of exogenous sources of MurG for structure-activity studies of mutant MurG proteins. It can also be used to compare the activity of, or effect of inhibitors on, MurG from other bacterial species. [ABSTRACT FROM AUTHOR]

Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)