Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

Although the GABAA receptor(GABAAR)has been proposed as the main action site for sevoflurane,isoflurane,halothane,enflurane,propofol,and benzodiazepines(BZDs),binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses.Moreover,various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR.Methods:We performed in silico docking analysis to compare the binding modes of sevoflurane,isoflurane,halothane,enflurane,propofol,and BZDs to the GABAAR based on one of the most recently provided 3D structures.We performed the docking analysis and the affinity-based ranking of the binding sites.Results:Our docking studies revealed that isoflurane,halothane,and enflurane docked in an extracellular domain(ECD)on GABAARs,in contrast to sevoflurane.Conclusion:Our results supported a multi-site mechanism for the allosteric modulation of propofol.Propofol was bound to the pore or favored various subsites in the transmembrane domain(TMD).Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode,as previously suggested.

Early experience of the compression anastomosis ring (CAR^(TM) 27) in left-sided colon resection

AIM:To evaluate clinical validity of the compression anastomosis ring(CARTM27) anastomosis in left-sided colonic resection. METHODS:A non-randomized prospective data collection was performed for patients undergoing an elective left-sided colon resection,followed by an anastomosis using the CARTM27 between November 2009 and January 2011.Eligibility criteria of the use of the CARTM27 were anastomoses between the colon and at or above the intraperitoneal rectum.The primary short-term clinical endpoint,rate of anastomotic leakage,and other clinical outcomes,including intraand postoperative complications,length of operation time and hospital stay,and the ring elimination time were evaluated. RESULTS:A total of 79 patients(male,43;median age,64 years) underwent an elective left-sided colon resection,followed by an anastomosis using theCARTM27.Colectomy was performed laparoscopically in 70 patients,in whom two patients converted to open procedure(2.9%) .There was no surgical mortality.As an intraoperative complication,total disruption of the anastomosis occurred by premature enforced tension on the proximal segment of the anastomosis in one patient.The ring was removed and another new CARTM27 anastomosis was constructed.One patient with sigmoid colon cancer showed postoperative anastomotic leakage after 6 d postoperatively and temporary diverting ileostomy was performed.Exact date of expulsion of the ring could not be recorded because most patients were not aware that the ring had been expelled.No patients manifested clinical symptoms of anastomotic stricture. CONCLUSION:Short-term evaluation of the CARTM27 anastomosis in elective left colectomy suggested it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.