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Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults. Robert DiCenzo, 2004.Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment . The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir . HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days . VPA blood samples drawn before (C0) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy . Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences . The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC0-24s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17) . The GMR (90% CI) of the AUC0-8s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94) . The differences (90% CI) in mean C0 and 8-h VPA concentrations versus the control (n = 11) were –1.0 (–9.4, 7.4) µg/ml and –2.1 (–11.1, 6.9) µg/ml for EFV (n = 10) and –5.0 (–13.2, 3.3) µg/ml and –6.7 (–17.6, 4.2) µg/ml for LPV/r (n = 11), respectively . EFV administration alone is bioequivalent to EFV and VPA coadministration . LPV concentrations tended to be higher when the drug was combined with VPA . Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA . Molecular and Functional Analysis of the lepB Gene, Encoding a Type I Signal Peptidase from Rickettsia rickettsii and Rickettsia typhi. M. Sayeedur Rahman, 2003.The type I signal peptidase lepB genes from Rickettsia rickettsii and Rickettsia typhi, the etiologic agents of Rocky Mountain spotted fever and murine typhus, respectively, were cloned and characterized . Sequence analysis of the cloned lepB genes from R . rickettsii and R . typhi shows open reading frames of 801 and 795 nucleotides, respectively . Alignment analysis of the deduced amino acid sequences reveals the presence of highly conserved motifs that are important for the catalytic activity of bacterial type I signal peptidase . Reverse transcription-PCR and Northern blot analysis demonstrated that the lepB gene of R . rickettsii is cotranscribed in a polycistronic message with the putative nuoF (encoding NADH dehydrogenase I chain F), secF (encoding protein export membrane protein), and rnc (encoding RNase III) genes in a secF-nuoF-lepB-rnc cluster . The cloned lepB genes from R . rickettsii and R . typhi have been demonstrated to possess signal peptidase I activity in Escherichia coli preprotein processing in vivo by complementation assay . Bacterial Colonization of Particles: Growth and Interactions. Hans-Peter Grossart, 2003.Marine particles in the ocean are exposed to diverse bacterial communities, and colonization and growth of attached bacteria are important processes in the degradation and transformation of the particles . In an earlier study, we showed that the initial colonization of model particles by individual bacterial strains isolated from marine aggregates was a function of attachment and detachment . In the present study, we have investigated how this colonization process was further affected by growth and interspecific interactions among the bacteria . Long-term incubation experiments showed that growth dominated over attachment and detachment after a few hours in controlling the bacterial population density on agar particles . In the absence of grazing mortality, this growth led to an equilibrium population density consistent with the theoretical limit due to oxygen diffusion . Interspecific interaction experiments showed that the presence of some bacterial strains ("residents") on the agar particles either increased or decreased the colonization rate of other strains ("newcomers") . Comparison between an antibiotic-producing strain and its antibiotic-free mutant showed no inhibitory effect on the newcomers due to antibiotic production . On the contrary, hydrolytic activity of the antibiotic-producing strain appeared to benefit the newcomers and enhance their colonization rate . These results show that growth- and species-specific interactions have to be taken into account to adequately describe bacterial colonization of marine particles . Changes in colonization pattern due to such small-scale processes may have profound effects on the transformation and fluxes of particulate matter in the ocean .
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