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Interactions between Atazanavir-Ritonavir and Tenofovir in Heavily Pretreated Human Immunodeficiency Virus-Infected Patients. Anne-Marie Taburet, 2004.The aim of the present study was to assess the pharmacokinetic behavior of atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate (DF) in human immunodeficiency virus (HIV)-infected patients . Eleven patients enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS Research, Paris, France) trial 107 were included in this pharmacokinetic study . They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from day 1 to the end of study . For the first 2 weeks, their nucleoside analog reverse transcriptase inhibitor (NRTI) treatments remained unchanged . Tenofovir DF was administered QD from day 15 to the end of the study . Ongoing NRTIs were selected according to the reverse transcriptase genotype of the HIV isolates from each patient . The values of the pharmacokinetic parameters for atazanavir and ritonavir were measured before (day 14 [week 2]) and after (day 42 [week 6]) initiation of tenofovir DF and are reported for the 10 patients who completed the study . There was a significant decrease in the area under the concentration-time curve from 0 to 24 h (AUC0-24) for atazanavir with the addition of tenofovir DF (AUC0-24 ratio, 0.75; 90% confidence interval, 0.58 to 0.97; P = 0.05) . There was a trend for a decrease in the minimum concentrations of atazanavir and ritonavir in plasma when they were combined with tenofovir, but none of the differences reached statistical significance . The median decreases in the HIV RNA loads at week 2 and week 6 were 0.1 and 0.2 log copies/ml, respectively . In summary, our data are consistent with the existence of a significant interaction between atazanavir and tenofovir DF . Two Different Lantibiotic-Like Peptides Originate from the Ericin Gene Cluster of Bacillus subtilis A1/3. Torsten Stein, 2002.A lantibiotic gene cluster was identified in Bacillus subtilis A1/3 showing a high degree of homology to the subtilin gene cluster and occupying the same genetic locus as the spa genes in B . subtilis ATCC 6633 . The gene cluster exhibits diversity with respect to duplication of two subtilin-like genes which are separated by a sequence similar to a portion of a lanC gene . Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analyses of B . subtilis A1/3 culture extracts confirmed the presence of two lantibiotic-like peptides, ericin S (3,442 Da) and ericin A (2,986 Da) . Disruption of the lanB-homologous gene eriB resulted in loss of production of both peptides, demonstrating that they are processed in an eriB-dependent manner . Although precursors of ericins S and A show only 75% of identity, the matured lantibiotic-like peptides reveal highly similar physical properties; separation was only achieved after multistep, reversed-phase high-performance liquid chromatography . Based on Edman and peptidase degradation in combination with MALDI-TOF MS, for ericin S a subtilin-like, lanthionine-bridging pattern is supposed . For ericin A two C-terminal rings are different from the lanthionine pattern of subtilin . Due to only four amino acid exchanges, ericin S and subtilin revealed similar antibiotic activities as well as similar properties in response to heat and protease treatment . For ericin A only minor antibiotic activity was found . Sequence of the 165-Kilobase Catabolic Plasmid pAO1 from Arthrobacter nicotinovorans and Identification of a pAO1-Dependent Nicotine Uptake System. Gabor L. Igloi, 2003.The 165-kb catabolic plasmid pAO1 enables the gram-positive soil bacterium Arthrobacter nicotinovorans to grow on the tobacco alkaloid L-nicotine . The 165,137-nucleotide sequence, with an overall G+C content of 59.7%, revealed, besides genes and open reading frames (ORFs) for nicotine degradation, a complete set of ORFs for enzymes essential for the biosynthesis of the molybdenum dinucleotide cofactor, as well as ORFs related to uptake and utilization of carbohydrates, sarcosine, and amino acids . Of the 165 ORFs, approximately 50% were related to metabolic functions . pAO1 conferred to A . nicotinovorans the ability to take up L-[14C]nicotine from the medium, with an Km of 5.6 ± 2.2 µM . ORFs of putative nicotine transporters formed a cluster with the gene of the D-nicotine-specific 6-hydroxy-D-nicotine oxidase . ORFs related to replication, chromosome partitioning, and natural transformation functions (dprA) were identified on pAO1 . Few ORFs showed similarity to known conjugation-promoting proteins, but pAO1 could be transferred by conjugation to a pAO1-negative strain at a rate of 10-2 to 10-3 per donor . ORFs with no known function represented approximately 35% of the pAO1 sequence . The positions of insertion sequence elements and composite transposons, corroborated by the G+C content of the pAO1 sequence, suggest a modular composition of the plasmid . Bioaugmentation as a Tool To Protect the Structure and Function of an Activated-Sludge Microbial Community against a 3-Chloroaniline Shock Load. Nico Boon, 2003.Bioaugmentation of bioreactors focuses on the removal of xenobiotics, with little attention typically paid to the recovery of disrupted reactor functions such as ammonium-nitrogen removal . Chloroanilines are widely used in industry as a precursor to a variety of products and are occasionally released into wastewater streams . This work evaluated the effects on activated-sludge reactor functions of a 3-chloroaniline (3-CA) pulse and bioaugmentation by inoculation with the 3-CA-degrading strain Comamonas testosteroni I2 gfp. Changes in functions such as nitrification, carbon removal, and sludge compaction were studied in relation to the sludge community structure, in particular the nitrifying populations . Denaturing gradient gel electrophoresis (DGGE), real-time PCR, and fluorescent in situ hybridization (FISH) were used to characterize and enumerate the ammonia-oxidizing microbial community immediately after a 3-CA shock load . Two days after the 3-CA shock, ammonium accumulated, and the nitrification activity did not recover over a 12-day period in the nonbioaugmented reactors . In contrast, nitrification in the bioaugmented reactor started to recover on day 4 . The DGGE patterns and the FISH and real-time PCR data showed that the ammonia-oxidizing microbial community of the bioaugmented reactor recovered in structure, activity, and abundance, while the number of ribosomes of the ammonia oxidizers in the nonbioaugmented reactor decreased drastically and the community composition changed and did not recover . The settleability of the activated sludge was negatively influenced by the 3-CA addition, with the sludge volume index increasing by a factor of 2.3 . Two days after the 3-CA shock in the nonbioaugmented reactor, chemical oxygen demand (COD) removal efficiency decreased by 36% but recovered fully by day 4 . In contrast, in the bioaugmented reactor, no decrease of the COD removal efficiency was observed . This study demonstrates that bioaugmentation of wastewater reactors to accelerate the degradation of toxic chlorinated organics such as 3-CA protected the nitrifying bacterial community, thereby allowing faster recovery from toxic shocks .
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