|
|
|
|
|
|
Novel Pharmacokinetic-Pharmacodynamic Model for Prediction of Outcomes with an Extended-Release Formulation of Ciprofloxacin. Alison K. Meagher, 2004.The pharmacokinetics of an extended-release (XR) formulation of ciprofloxacin has been compared to that of the immediate-release (IR) product in healthy volunteers . The only significant difference in pharmacokinetic parameters between the two formulations was seen in the rate constant of absorption, which was approximately 50% greater with the IR formulation . The geometric mean plasma ciprofloxacin concentrations were applied to an in vitro pharmacokinetic-pharmacodynamic model exposing three different clinical strains of Escherichia coli (MICs, 0.03, 0.5, and 2.0 mg/liter) to 24 h of simulated concentrations in plasma . A novel mathematical model was derived to describe the time course of bacterial CFU, including capacity-limited replication and first-order rate of bacterial clearance, and to model the effects of ciprofloxacin concentrations on these processes . A "mixture model" was employed which allowed as many as three bacterial subpopulations to describe the total bacterial load at any moment . Comparing the two formulations at equivalent daily doses, the rates and extents of bacterial killing were similar with the IR and XR formulations at MICs of 0.03 and 2.0 mg/liter . At an MIC of 0.5 mg/liter, however, the 1,000-mg/day XR formulation showed a moderate advantage in antibacterial effect: the area under the CFU-time curve was 45% higher for the IR regimen; the nadir log CFU and 24-h log CFU values for the IR regimen were 3.75 and 2.49, respectively; and those for XR were 4.54 and 3.13, respectively . The mathematical model explained the differences in bacterial killing rate for two regimens with identical AUC/MIC ratios . RecA Protein from the Extremely Radioresistant Bacterium Deinococcus radiodurans: Expression, Purification, and Characterization. Jong-Il Kim, 2002.The RecA protein of Deinococcus radiodurans (RecADr) is essential for the extreme radiation resistance of this organism . The RecADr protein has been cloned and expressed in Escherichia coli and purified from this host . In some respects, the RecADr protein and the E . coli RecA (RecAEc) proteins are close functional homologues . RecADr forms filaments on single-stranded DNA (ssDNA) that are similar to those formed by the RecAEc . The RecADr protein hydrolyzes ATP and dATP and promotes DNA strand exchange reactions . DNA strand exchange is greatly facilitated by the E . coli SSB protein . As is the case with the E . coli RecA protein, the use of dATP as a cofactor permits more facile displacement of bound SSB protein from ssDNA . However, there are important differences as well . The RecADr protein promotes ATP- and dATP-dependent reactions with distinctly different pH profiles . Although dATP is hydrolyzed at approximately the same rate at pHs 7.5 and 8.1, dATP supports an efficient DNA strand exchange only at pH 8.1 . At both pHs, ATP supports efficient DNA strand exchange through heterologous insertions but dATP does not . Thus, dATP enhances the binding of RecADr protein to ssDNA and the displacement of ssDNA binding protein, but the hydrolysis of dATP is poorly coupled to DNA strand exchange . The RecADr protein thus may offer new insights into the role of ATP hydrolysis in the DNA strand exchange reactions promoted by the bacterial RecA proteins . In addition, the RecADr protein binds much better to duplex DNA than the RecAEc protein, binding preferentially to double-stranded DNA (dsDNA) even when ssDNA is present in the solutions . This may be of significance in the pathways for dsDNA break repair in Deinococcus . Identification of Catabolite Repression as a Physiological Regulator of Biofilm Formation by Bacillus subtilis by Use of DNA Microarrays. Nicola R. Stanley, 2003.Biofilms are structured communities of cells that are encased in a self-produced polymeric matrix and are adherent to a surface . Many biofilms have a significant impact in medical and industrial settings . The model gram-positive bacterium Bacillus subtilis has recently been shown to form biofilms . To gain insight into the genes involved in biofilm formation by this bacterium, we used DNA microarrays representing >99% of the annotated B . subtilis open reading frames to follow the temporal changes in gene expression that occurred as cells transitioned from a planktonic to a biofilm state . We identified 519 genes that were differentially expressed at one or more time points as cells transitioned to a biofilm . Approximately 6% of the genes of B . subtilis were differentially expressed at a time when 98% of the cells in the population were in a biofilm . These genes were involved in motility, phage-related functions, and metabolism . By comparing the genes differentially expressed during biofilm formation with those identified in other genomewide transcriptional-profiling studies, we were able to identify several transcription factors whose activities appeared to be altered during the transition from a planktonic state to a biofilm . Two of these transcription factors were Spo0A and sigma-H, which had previously been shown to affect biofilm formation by B . subtilis . A third signal that appeared to be affecting gene expression during biofilm formation was glucose depletion . Through quantitative biofilm assays and confocal scanning laser microscopy, we observed that glucose inhibited biofilm formation through the catabolite control protein CcpA . Inactivation of Vegetative Cells, but Not Spores, of Bacillus anthracis, B . cereus, and B . subtilis on Stainless Steel Surfaces Coated with an Antimicrobial Silver- and Zinc-Containing Zeolite Formulation. Belinda Galeano, 2003.Stainless steel surfaces coated with paints containing a silver- and zinc-containing zeolite (AgION antimicrobial) were assayed in comparison to uncoated stainless steel for antimicrobial activity against vegetative cells and spores of three Bacillus species, namely, B . anthracis Sterne, B . cereus T, and B . subtilis 168 . Under the test conditions (25°C and 80% relative humidity), the zeolite coating produced approximately 3 log10 inactivation of vegetative cells within a 5- to 24-h period, but viability of spores of the three species was not significantly affected .
|
© 2005
Transgalactic Ltd (manufacturer of Bioscreen C software) |
Privacy Statement | P.O. Box
1393, 00101 Helsinki, Finland,
Last modified: May 25, 2005
| ||||||
