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[18F]Ciprofloxacin, a New Positron Emission Tomography Tracer for Noninvasive Assessment of the Tissue Distribution and Pharmacokinetics of Ciprofloxacin in Humans. Martin Brunner, 2004.The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [18F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET) . Special attention was paid to characterizing the distribution of [18F]ciprofloxacin to select target tissues . Healthy volunteers (n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin . On day 6, subjects received a tracer dose (mean injected amount, 700 ± 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [18F]ciprofloxacin as an intravenous bolus . Thereafter, PET imaging and venous blood sampling were initiated . Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration . The first application of [18F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution . Two different tissue compartments of radiotracer distribution could be identified . The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [t1/2s], 68, 57, and 106 min, respectively) . The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention (t1/2, >130 min) . The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 ± 1.0 and 9.9 ± 4.4, respectively) . The brain radioactivity concentrations were very low (<1 kBq · g–1) and could therefore not be quantified . Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens . In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated . New Real-Time Quantitative PCR Procedure for Quantification of Bifidobacteria in Human Fecal Samples. Miguel Gueimonde, 2004.The application of a real-time quantitative PCR method (5' nuclease assay), based on the use of a probe labeled at its 5' end with a stable, fluorescent lanthanide chelate, for the quantification of human fecal bifidobacteria was evaluated . The specificities of the primers and the primer-probe combination were evaluated by conventional PCR and real-time PCR, respectively . The results obtained by real-time PCR were compared with those obtained by fluorescent in situ hybridization, the current gold standard for intestinal microbiota quantification . In general, a good correlation between the two methods was observed . In order to determine the detection limit and the accuracy of the real-time PCR procedure, germfree rat feces were spiked with known amounts of bifidobacteria and analyzed by both methods . The detection limit of the method used in this study was found to be about 5 x 104 cells per g of feces . Both methods, real-time PCR and fluorescent in situ hybridization, led to an accurate quantification of the spiked samples with high levels of bifidobacteria, but real-time PCR was more accurate for samples with low levels . We conclude that the real-time PCR procedure described here is a specific, accurate, rapid, and easy method for the quantification of bifidobacteria in feces . Identification and Characterization of Genes Required for Biosynthesis and Transport of the Siderophore Vibrioferrin in Vibrio parahaemolyticus. Tomotaka Tanabe, 2003.In response to low iron availability, Vibrio parahaemolyticus synthesizes and secretes a polyhydroxycarboxylate-type siderophore vibrioferrin which is composed of 1 mol each of 2-ketoglutaric acid, L-alanine, ethanolamine, and citric acid . We have previously reported the cloning and characterization of the pvuA gene, which encodes the 78-kDa outer membrane receptor protein for ferric vibrioferrin . In this study, nine genes involved in the biosynthesis and transport of vibrioferrin have been identified in the genomic regions surrounding the pvuA gene . The genes were sequenced, and gene disruptants were constructed by insertion mutation for phenotype analysis . Five of the genes, named pvsABCDE, constitute an operon that is expressed under iron-limiting conditions . Homology searches of their predicted protein products suggested that the four genes pvsABDE are implicated in the biosynthesis of the siderophore . Another gene in the same operon, pvsC, encodes a putative exporter that is homologous to members of the major facilitator superfamily of multidrug efflux pumps . The remaining four genes, named pvuBCDE, encode proteins strongly homologous to Escherichia coli FecBCDE, respectively, which are components of the ATP-binding cassette transporter system for ferric dicitrate . Reverse transcriptase PCR analysis revealed that these transport genes are transcribed as a single mRNA with the upstream genes, psuA and pvuA . Phenotypic comparison between the wild-type strain and its targeted gene disruptants supported the biological functions for the respective operons that were expected on the basis of the homology search .
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