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Phase 2, Randomized, Dose-Ranging Study Evaluating the Safety and Efficacy of Anidulafungin in Invasive Candidiasis and Candidemia. David S. Krause, 2004.This study evaluated the safety and efficacy of anidulafungin, a novel echinocandin, in patients with invasive candidiasis, including candidemia . A total of 123 eligible patients were randomized to one of three intravenous regimens, 50, 75, or 100 mg once daily . Treatment continued for 2 weeks beyond resolution or improvement of signs and symptoms . The primary efficacy criterion was a successful global response rate (i.e., clinical and microbiological success) in the evaluable population at the follow-up (FU) visit, 2 weeks after end of therapy (EOT) . One hundred twenty (120) patients received at least one dose of anidulafungin; 68 were evaluable . Review of adverse events and laboratory data indicated no dose response for safety parameters . Non-albicans Candida species accounted for approximately one-half of all isolates . Success rates at EOT were 84, 90, and 89% in the 50-, 75-, and 100-mg groups, respectively . At FU, the success rates were 72, 85, and 83% . Phase 3 studies of anidulafungin for the treatment of invasive candidiasis and candidemia are warranted . Evaluation of a Clostridium perfringens Predictive Model, Developed under Isothermal Conditions in Broth, To Predict Growth in Ground Beef during Cooling. Sarah Smith, 2004.Proper temperature control is essential in minimizing Clostridium perfringens germination, growth, and toxin production . The U.S . Department of Agriculture (USDA) Food Safety and Inspection Service (FSIS) offers two options for the cooling of meat products: follow a standard time-temperature schedule or validate that alternative cooling regimens result in no more than a 1-log10 CFU/g increase of C . perfringens and no growth of Clostridium botulinum . A mathematical model developed by Juneja et al . (Food Microbiol . 16:335-349, 1999) may be helpful in determining if the C . perfringens performance standard has been achieved, but this model has not been extensively validated . The objective of this study was to validate the Juneja 1999 model in ground beef under a variety of changing temperature and temperature abuse situations . The Juneja 1999 model consistently underpredicted growth of C . perfringens during exponential cooling of ground beef . The model also underpredicted growth of C . perfringens in ground beef cooled at two different rates . The results presented here show generally good agreement with published data on the growth of C . perfringens in similar products . The model error may be due to faster-than-expected exponential growth rates in ground beef during cooling or an error in the mathematical formulation of the model . Design of Antisense RNA Constructs for Downregulation of the Acetone Formation Pathway of Clostridium acetobutylicum. Seshu B. Tummala, 2003.We investigated the effect of antisense RNA (asRNA) structural properties on the downregulation efficacy of enzymes in the acetone-formation pathway (acetoacetate decarboxylase [AADC] and coenzyme A-transferase [CoAT]) of Clostridium acetobutylicum strain ATCC 824 . First, we generated three strains, C . acetobutylicum ATCC 824 (pADC38AS), 824(pADC68AS), and 824(pADC100AS), which contain plasmids that produce asRNAs of various lengths against the AADC (adc) transcript . Western analysis showed that all three strains exhibit low levels of AADC compared to the plasmid control [ATCC 824(pSOS95del)] . By using computational algorithms, the three different asRNAs directed toward AADC, along with previously reported clostridial asRNAs, were examined for structural features (free nucleotides and components) . When the normalized metrics of these structural features were plotted against percent downregulation, only the component/nucleotide ratio correlated well with in vivo asRNA effectiveness . Despite the significant downregulation of AADC in these strains, there were no concomitant effects on acetone formation . These findings suggest that AADC does not limit acetone formation and, thus, we targeted next the CoAT . Using the component/nucleotide ratio as a selection parameter, we developed three strains [ATCC 824 (pCTFA2AS), 824(pCTFB1AS), and 824(pCOAT11AS)] which express asRNAs to downregulate either or both of the CoAT subunits . Compared to the plasmid control strain, these strains produced substantially low levels of acetone and butanol and Western blot analyses showed significantly low levels of both CoAT subunits . These results show that CoAT is the rate-limiting enzyme in acetone formation and strengthen the hypothesis that the component/nucleotide ratio is a predictive indicator of asRNA effectiveness . Use of a Packed-Column Bioreactor for Isolation of Diverse Protease-Producing Bacteria from Antarctic Soil. Nathalie Wery, 2003.Seventy-five aerobic heterotrophs have been isolated from a packed-column bioreactor inoculated with soil from Antarctica . The column was maintained at 10°C and continuously fed with a casein-containing medium to enrich protease producers . Twenty-eight isolates were selected for further characterization on the basis of morphology and production of clearing zones on skim milk plates . Phenotypic tests indicated that the strains were mainly psychrotrophs and presented a high morphological and metabolical diversity . The extracellular protease activities tested were optimal at neutral pH and between 30 and 45°C . 16S ribosomal DNA sequence analyses showed that the bioreactor was colonized by a wide variety of taxons, belonging to various bacterial divisions:  -, ß-, and
 -Proteobacteria; the Flexibacter-Cytophaga-Bacteroides group; and high G+C gram-positive bacteria and low G+C gram-positive bacteria . Some strains represent candidates for new species of the genera Chryseobacterium and Massilia . This diversity demonstrates that the bioreactor is an efficient enrichment tool compared to traditional isolation strategies .
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