Since its initial description in 1964,research hastransformed spontaneous bacterial peritonitis (SBP)from a feared disease (with reported mortality of 90%)to a treatable complication of decompensated cirrhosis,albeit ...Since its initial description in 1964,research hastransformed spontaneous bacterial peritonitis (SBP)from a feared disease (with reported mortality of 90%)to a treatable complication of decompensated cirrhosis,albeit with steady prevalence and a high recurrencerate. Bacterial translocation,the key mechanism in thepathogenesis of SBP,is only possible because of theconcurrent failure of defensive mechanisms in cirrhosis.Variants of SBP should be treated. Leucocyte esterasereagent strips have managed to shorten the 'tap-to-shot' time,while future studies should look into theircombined use with ascitic fluid pH. Third generationcephalosporins are the antibiotic of choice becausethey have a number of advantages. Renal dysfunctionhas been shown to be an independent predictor ofmortality in patients with SBP. Albumin is felt to reducethe risk of renal impairment by improving effectiveintravascular volume,and by helping to bind pro-inflammatory molecules. Following a single episodeof SBP,patients should have long-term antibioticprophylaxis and be considered for liver transplantation.展开更多
An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of n...An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.展开更多
文摘Since its initial description in 1964,research hastransformed spontaneous bacterial peritonitis (SBP)from a feared disease (with reported mortality of 90%)to a treatable complication of decompensated cirrhosis,albeit with steady prevalence and a high recurrencerate. Bacterial translocation,the key mechanism in thepathogenesis of SBP,is only possible because of theconcurrent failure of defensive mechanisms in cirrhosis.Variants of SBP should be treated. Leucocyte esterasereagent strips have managed to shorten the 'tap-to-shot' time,while future studies should look into theircombined use with ascitic fluid pH. Third generationcephalosporins are the antibiotic of choice becausethey have a number of advantages. Renal dysfunctionhas been shown to be an independent predictor ofmortality in patients with SBP. Albumin is felt to reducethe risk of renal impairment by improving effectiveintravascular volume,and by helping to bind pro-inflammatory molecules. Following a single episodeof SBP,patients should have long-term antibioticprophylaxis and be considered for liver transplantation.
文摘An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.
