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Novel Concentration-Killing Curve Method for Estimation of Bactericidal Potency of Antibiotics in an In Vitro Dynamic Model. Y. Q. Liu, 2004.The bactericidal pharmacodynamics of antibiotics against Escherichia coli were analyzed by a concentration-killing curve (CKC) approach, and the novel parameters median bactericidal concentration (BC50) and bactericidal intensity (r) for bactericidal potency were proposed . By using the agar plate method, about 500 E . coli cells were inoculated onto Luria-Bertani plates containing a series of antibiotic concentrations, and after 24 h of incubation at 37°C, all the viable colonies were enumerated . This resulted in a sigmoidal CKC that could be perfectly fitted (R2 > 0.9) with the function N = N0/[1 + er(x – BC50)], where N is number of colonies surviving on each plate with an x series of concentrations of an antibiotic, and N0 represents the meaningful inoculum size . Construction of the CKC method was based on the bactericidal effect of each antibiotic against the bacterial strain versus the concentration in two dimensions and may be a more valid, accurate, and reproducible method for estimating the bactericidal effect than the endpoint minimum bactericidal concentration (MBC) method . Mathematically, the CKC approach was point symmetrical toward its inflexion (BC50, N0/2); thus, 2BC50 could replace MBC . The parameter BC1 can be defined as BC50 + [ln(N0 – 1)/r], which is the drug concentration at which only one colony survived and which is the least critical value of MBC in the CKC . The variate r, which determined the tangent slope on inflexion when N0 was limited, could estimate the bactericidal intensity of an antibiotic . This verified that the CKC approach may be useful in studies with other classes of antibiotics and has considerable value as a tool for the accurate and proper administration of antibiotics . The Melaminophenyl Arsenicals Melarsoprol and Melarsen Oxide Interfere with Thiamine Metabolism in the Fission Yeast Schizosaccharomyces pombe. M. Ernst Schweingruber, 2004.The melaminophenyl arsenical melarsoprol is the main drug used against late-stage sleeping sickness caused by Trypanosoma brucei subspecies . Its active metabolite in the human body is melarsen oxide . Here, it is shown that this metabolite inhibits growth of the fission yeast Schizosaccharomyces pombe and that its toxicity can be abolished efficiently by thiamine (vitamin B1), thiamine analogues, and the pyrimidine moiety of the thiamine molecule . Uptake of melarsen oxide is mediated by a membrane protein (car1p), which is involved in the uptake of thiamine and its pyrimidine moiety . Melarsoprol is taken up by cells in a thiamine- and car1p-dependent manner but is not toxic to cells . Pretty Good Guessing: Protein Structure Prediction at CASP5. Rosemarie Swanson, 2003. Crystal Structure of Bacillus subtilis  -Amylase in Complex with Acarbose.Masayuki Kagawa, 2003.The crystal structure of Bacillus subtilis -amylase, in complex with the pseudotetrasaccharide inhibitor acarbose, revealed an hexasaccharide in the active site as a result of transglycosylation . After comparison with the known structure of the catalytic-site mutant complexed with the native substrate maltopentaose, it is suggested that the present structure represents a mimic intermediate in the initial stage of the catalytic process .
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