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Pharmacokinetics of Adjusted-Dose Lopinavir-Ritonavir Combined with Rifampin in Healthy Volunteers. C. J. L. la Porte, 2004.Coadministration of lopinavir-ritonavir, an antiretroviral protease inhibitor, at the standard dose (400/100 mg twice a day [BID]) with the antituberculous agent rifampin is contraindicated because of a significant pharmacokinetic interaction due to induction of cytochrome P450 3A by rifampin . In the present study, two adjusted-dose regimens of lopinavir-ritonavir were tested in combination with rifampin . Thirty-two healthy subjects participated in a randomized, two-arm, open-label, multiple-dose, within-subject controlled study . All subjects were treated with lopinavir-ritonavir at 400/100 mg BID from days 1 to 15 . From days 16 to 24, the subjects in arm 1 received lopinavir-ritonavir at 800/200 mg BID in a dose titration, and the subjects in arm 2 received lopinavir-ritonavir at 400/400 mg BID in a dose titration . Rifampin was given at 600 mg once daily to all subjects from days 11 to 24 . The multiple-dose pharmacokinetics of lopinavir, ritonavir, and rifampin were assessed . Twelve of 32 subjects withdrew from the study . For nine subjects lopinavir-ritonavir combined with rifampin resulted in liver enzyme level elevations . Pharmacokinetic data for 19 subjects were evaluable . Geometric mean ratios for the lopinavir minimum concentration in serum and the maximum concentration in serum (Cmax) on day 24 versus that on day 10 were 0.43 (90% confidence interval [CI], 0.19 to 0.96) and 1.02 (90% CI, 0.85 to 1.23), respectively, for arm 1 (n = 10) and 1.03 (90% CI, 0.68 to 1.56) and 0.93 (90% CI, 0.81 to 1.07), respectively, for arm 2 (n = 9) . Ritonavir exposure increased from days 10 to 24 in both arms . The geometric mean Cmax of rifampin was 13.5 mg/liter (day 24) and was similar between the two arms . Adjusted-dose regimens of lopinavir-ritonavir in combination with therapeutic drug monitoring and monitoring of liver function may allow concomitant use of rifampin . Calicivirus Inactivation by Nonionizing (253.7-Nanometer-Wavelength [UV]) and Ionizing (Gamma) Radiation. Ana Maria de Roda Husman, 2004.Noroviruses (previously Norwalk-like viruses) are the most common viral agents associated with food- and waterborne outbreaks of gastroenteritis . In the absence of culture methods for noroviruses, animal caliciviruses were used as model viruses to study inactivation by nonionizing (253.7-nm-wavelength [UV]) and ionizing (gamma) radiation . Here, we studied the respiratory feline calicivirus (FeCV) and the presumed enteric canine calicivirus (CaCV) and compared them with the well-studied bacteriophage MS2 . When UV irradiation was used, a 3-log10 reduction was observed at a fluence of 120 J/m2 in the FeCV suspension and at a fluence of 200 J/m2 for CaCV; for the more resistant phage MS2 there was a 3-log10 reduction at a fluence of 650 J/m2 . Few or no differences were observed between levels of UV inactivation in high- and low-protein-content virus stocks . In contrast, ionizing radiation could readily inactivate MS2 in water, and there was a 3-log10 reduction at a dose of 100 Gy, although this did not occur when the phage was diluted in high-protein-content stocks of CaCV or FeCV . The low-protein-content stocks showed 3-log10 reductions at a dose of 500 Gy for FeCV and at a dose of 300 for CaCV . The inactivation rates for both caliciviruses with ionizing and nonionizing radiation were comparable but different from the inactivation rates for MS2 . Although most FeCV and CaCV characteristics, such as overall particle and genome size and structure, are similar, the capsid sequences differ significantly, making it difficult to predict human norovirus inactivation . Adequate management of UV and gamma radiation processes for virus inactivation should limit public health risks . Identification of Long Intergenic Repeat Sequences Associated with DNA Methylation Sites in Caulobacter crescentus and Other  -Proteobacteria.Swaine L. Chen, 2003.A systematic search for motifs associated with CcrM DNA methylation sites revealed four long (>100-bp) motifs (CIR sequences) present in up to 21 copies in Caulobacter crescentus . The CIR1 and CIR2 motifs exhibit a conserved inverted repeat organization, with a CcrM site in the center of one of the repeats . Differences between Pseudomonas syringae pv . syringae B728a and Pantoea agglomerans BRT98 in Epiphytic and Endophytic Colonization of Leaves. Siva Sabaratnam, 2003.The leaf colonization strategies of two bacterial strains were investigated . The foliar pathogen Pseudomonas syringae pv . syringae strain B728a and the nonpathogen Pantoea agglomerans strain BRT98 were marked with a green fluorescent protein, and surface (epiphytic) and subsurface (endophytic) sites of bean and maize leaves in the laboratory and the field were monitored to see if populations of these strains developed . The populations were monitored using both fluorescence microscopy and counts of culturable cells recovered from nonsterilized and surface-sterilized leaves . The P . agglomerans strain exclusively colonized epiphytic sites on the two plant species . Under favorable conditions, the P . agglomerans strain formed aggregates that often extended over multiple epidermal cells . The P . syringae pv . syringae strain established epiphytic and endophytic populations on asymptomatic leaves of the two plant species in the field, with most of the P . syringae pv . syringae B728a cells remaining in epiphytic sites of the maize leaves and an increasing number occupying endophytic sites of the bean leaves in the 15-day monitoring period . The epiphytic P . syringae pv . syringae B728a populations appeared to originate primarily from multiplication in surface sites rather than from the movement of cells from subsurface to surface sites . The endophytic P . syringae pv . syringae B728a populations appeared to originate primarily from inward movement through the stomata, with higher levels of multiplication occurring in bean than in maize . A rainstorm involving a high raindrop momentum was associated with rapid growth of the P . agglomerans strain on both plant species and with rapid growth of both the epiphytic and endophytic populations of the P . syringae pv . syringae strain on bean but not with growth of the P . syringae pv . syringae strain on maize . These results demonstrate that the two bacterial strains employed distinct colonization strategies and that the epiphytic and endophytic population dynamics of the pathogenic P . syringae pv . syringae strain were dependent on the plant species, whereas those of the nonpathogenic P . agglomerans strain were not .
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