Drugs online research references
Biotechnol Appl Biochem. 2000 Dec;32 ( Pt 3):173-7.
Optimization of 6-aminopenicillanic acid (6-APA) production by using a new immobilized penicillin acylase.
Torres-Bacete J, Arroyo M, Torres-Guzman R, de La Mata I, Castillon MP, Acebal C.
Departamento de Bioquimica y Biologia Molecular, Facultad de Ciencias Biologicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
A new immobilized penicillin acylase (ECPVA) was obtained by covalent binding of penicillin acylase from Streptomyces lavendulae on Eupergit C. Enzymic hydrolysis of penicillin V catalysed by ECPVA was optimized using a 2(3) factorial design of experiments, and the selected parameters for this study were pH, temperature and substrate concentration. The immobilized enzyme showed an optimal pH value of 9.5-10.5, and an optimal temperature of 60 degrees C, whereas its soluble counterpart showed the same optimal pH value and a lower optimal temperature of 50 degrees C.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11115389&dopt=Abstract
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The benefits of oral prophylaxis for neutropenia have remained controversial up to now. We evaluated retrospectively the effect of antibiotic prophylaxis with ciprofloxacin and penicillin on the prevention of bacterial infections in 112 cases of prolonged neutropenia in adult patients treated for haematological malignancies. 41 patients received prophylaxis between December 1993 and November 1994 while 71 patients did not receive prophylaxis between December 1994 and November 1995. There were no significant differences between groups in age, sex, type or stage of haemopathy, type of chemotherapy and duration of neutropenia. The antibiotic prophylaxis reduced the number of overall infections (p = 0.05) and the number of gram-negative bacteraemias (p = 0.02). The median time to the onset of fever, the duration of fever, the duration of antibiotic treatment, the duration of hospitalization or admission to the intensive care unit, the number of serious complications or death were not influenced by antibiotic prophylaxis. The prophylaxis did not reduce the overall incidence of bacteraemia, of clinically documented infections or of fever of unknown origin. This retrospective study confirms that oral prophylaxis with ciprofloxacin and penicillin decreases the incidence of infections and, in particular, of gram-negative bacteraemia, but does not modify the overall morbidity and mortality in our patients. In view of the risk of emergence of bacterial resistance, these data do not support the routine use of oral antibiotic prophylaxis in neutropenic patients with haematological malignancies.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11132527&dopt=Abstract
Biotechnol Bioeng. 2001 Feb 20;72(4):379-88.
Quantitative analysis of Penicillium chrysogenum Wis54-1255 transformants overexpressing the penicillin biosynthetic genes.
Theilgaard H, van Den Berg M, Mulder C, Bovenberg R, Nielsen J.
Center for Process Biotechnology, Department of Biotechnology, Building 223, Technical University of Denmark, DK-2800 Lyngby, Denmark.
The low penicillin-producing, single gene copy strain Wis54-1255 was used to study the effect of overexpressing the penicillin biosynthetic genes in Penicillium chrysogenum. Transformants of Wis54-1255 were obtained with the amdS expression-cassette using the four combinations: pcbAB, pcbC, pcbC-penDE, and pcbAB-pcbC-penDE of the three penicillin biosynthetic genes. Transformants showing an increased penicillin production were investigated during steady-state continuous cultivations with glucose as the growth-limiting substrate. The transformants were characterized with respect to specific penicillin productivity, the activity of the two pathway enzymes delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS) and isopenicillin N synthetase (IPNS) and the intracellular concentration of the metabolites: delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), bis-delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (bisACV), isopenicillin N (IPN), glutathione (GSH), and glutathione disulphide (GSSG). Transformants with the whole gene cluster amplified showed the largest increase in specific penicillin productivity (r(p))-124% and 176%, respectively, whereas transformation with the pcbC-penDE gene fragment resulted in a decrease in r(p) of 9% relative to Wis54-1255. A marked increase in r(p) is clearly correlated with a balanced amplification of both the ACVS and IPNS activity or a large amplification of either enzyme activity. The increased capacity of a single enzyme occurs surprisingly only in the transformants where all the three biosynthetic genes are overexpressed but is not found within the group of pcbAB or pcbC transformants. The indication of the pcbAB and pcbC genes being closely regulated in fungi might explain why high-yielding strains of P. chrysogenum have been found to contain amplifications of a large region including the whole penicillin gene cluster and not single gene amplifications. Measurements of the total ACV concentration showed a large span of variability, which reflected the individual status of enzyme overexpression and activity found in each strain. The ratio ACV:bisACV remained constant, also at high ACV concentrations, indicating no limitation in the capacity of the thioredoxin-thioredoxin reductase (TR) system, which is assumed to keep the pathway intermediate LLD-ACV in its reduced state. The total GSH pool was at a constant level of approx. 5.7 mM in all cultivations. Copyright 2001 John Wiley & Sons, Inc.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11180058&dopt=Abstract
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