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B K Patel

Publications and source records attributed to B K Patel.

At least 19 recordsLinked to original sources

Disposition of flurbiprofen in man: influence of stereochemistry and age.

1. The stereoselective metabolism and pharmacokinetics of the enantiomers of flurbiprofen were investigated following the oral administration of the racemic drug (100 mg) to four young and four elderly healthy volunteers (two males and two females per group). 2. The stereochemical composition of the drug and the 4'-hydroxy- metabolite in serum and the drug, 4'-hydroxy- and 3'-hydroxy-4'-methoxy- metabolites, both free and conjugated, in urine were determined by a direct chromatographic method of enantiomeric analysis. 3. Modest enantioselectivity in clearance (CL S/R: young, 0.86; elderly, 0.88) was largely responsible for the apparent elimination half-life of (S)-flurbiprofen being significantly greater (p<0.01) than that of the R-enantiomer in both age groups (young, S: 5.2 +/- 0.7 versus R: 4.5 +/- 0.6 h; elderly, S: 9.6 +/- 1.2 versus R: 7.1 +/- 1.0 h). The serum concentrations of 4'-hydroxyflurbiprofen were five- to 20-fold lower than those of the corresponding drug enantiomers, stereoselective disposition being evident in the significantly greater (p<0.05) apparent half-lives of the S- compared with the R-enantiomer in both groups (young, S: 10.6 +/- 2.4 versus R: 6.7 +/- 1.1 h; elderly, S: 13.7 +/- 1.7 versus R: 10.2 +/- 1.2 h). 4. Some 60 and 72% of the dose was excreted in 24-h urine in elderly and young volunteers, respectively, a significantly greater (p<0.05) proportion of which was of the R-configuration in both age groups (S/R: young, 0.87; elderly, 0.81). The major urinary excretion products were flurbiprofen and 4'-hydroxyflurbiprofen, and their acyl-conjugates in both groups. 5. Age-associated differences in the pharmacokinetics of flurbiprofen occurred in a non-stereoselective manner and were primarily as a consequence of a significant approximately 40% decrease (p<0.01) in clearance of both enantiomers in the elderly due to reduced metabolic activity. Consequently, the elderly had greater exposure to both enantiomers, as reflected by the AUCs(0-inf) being significantly higher (p<0.05), by 60%, in this age group compared with the young. 6. The findings suggest that age-related alterations in the disposition of flurbiprofen could have significant implications for the use of the drug in the elderly.

Administration, Oral↗

Stereoselectivity of ibuprofen metabolism and pharmacokinetics following the administration of the racemate to healthy volunteers.

1. The stereoselective metabolism and pharmacokinetics of the enantiomers of ibuprofen have been investigated following the oral administration of the racemic drug (400 mg) to 12 healthy volunteers.2. The stereochemical composition of the drug in serum, both total and unbound, and drug and metabolites, both free and conjugated, in urine were determined by a combination of the direct and indirect chromatographic procedures to enantiomeric analysis. 3. The oral clearance of (S)-ibuprofen was significantly greater than that of the R-enantiomer (74.5 +/- 18.1 versus 57.1 +/- 11.7 ml min(-1); p < 0.05) and the clearance of (R)-ibuprofen via inversion was ca two fold that via alternative pathways. 4. Some 74.0 +/- 9.6% of the dose was recovered in urine over 24 h as ibuprofen, 2-hydroxyibuprofen and carboxyibuprofen, both free and conjugated with glucuronic acid. Analysis of the stereochemical composition of the urinary excretion products indicated that 68% of the dose of (R)-ibuprofen had undergone chiral inversion. 5. Metabolism via glucuronidation and both routes of oxidation, showed enantio-selectivity for (S)-ibuprofen, the enantiomeric ratios (S/R) in partial metabolic clearance being 7.1, 4.8 and 3.4 for formation of ibuprofen glucuronide, 2-hydroxyibuprofen and carboxyibuprofen respectively.6. Modest stereoselectivity was observed in the formation of (2'R, 2R)- and (2'S, 2S)-carboxyibuprofen in comparison to the alternative diastereoisomers, the ratios in formation clearance being 1.6 and 1.2 respectively.

Adult↗

Random sequence analysis of genomic DNA of an anaerobic, thermophilic, halophilic bacterium, Halothermothrix orenii.

A pBluescriptSK+ vector library consisting of 3.360 clones with an average insert size of 3.5 kb was constructed from the genome of Halothermothrix orenii, a halophilic and thermoanaerobic member of the family Haloanaerobiaceae. From both ends, 77 clones were sequenced using T3 and T7 vector primers generating 154 sequence tags, representing approximately 85 kb of the genome. Comparison of sequence tags against the Gen-Bank database using BLASTX identified 66 known proteins and 15 conserved hypothetical proteins. The putative proteins included a V-ATPase, hydrogenases, and enzymes with potential for industrial applications. The overall G + C% of the codons used was 42.9% with a third-position G + C content of 38.6%. High levels of excess acidic amino acids were not detected in the putative proteins of H. orenii as compared to the mesophilic haloanaerobes. This lack may be the result of reduced activity of acidic, halophilic enzymes at high temperatures and intermediate salt concentrations.

Amino Acid Sequence↗

Transfer of thermobacteroides leptospartum and Clostridium thermolacticum as Clostridium stercorarium subsp. leptospartum subsp. thermolacticum subsp. nov., comb. nov. and C. stercorarium subsp. thermolacticum subsp. nov., comb. nov.

16S rRNA sequencing and sequence analysis of the sole member of the genus Thermobacteroides, Thermobacteroides leptospartum, revealed that it was related to members of cluster III (according to the scheme of Collins et al. 1994) represented exclusively by cellulolytic Clostridium species. Phenotypic studies indicated that Thermobacteroides leptospartum was also able to grow on cellulose, providing further evidence of its affiliation to members of cluster III. Its closest phylogenetic relatives, Clostridium thermolacticum and Clostridium stercorarium, were almost equidistantly placed with a similarity value of 99%. DNA hybridization studies also indicated that Thermobacteroides leptospartum, C. thermolacticum and C. stercorarium were closely related to each other (values of over 95% homology). Similarities based on the comparison of the 16S rRNA gene sequences and DNA homology are sufficiently high to regard all three strains as subspecies of a single species. It is therefore proposed that Thermobacteroides leptospartum and C. thermolacticum be transferred to cluster III as C. stercorarium subsp. leptospartum subsp. nov., comb. nov. and C. stercorarium subsp. thermolacticum subsp. nov., comb. nov., respectively, thus automatically creating C. stercorarium subsp. stercorarium subsp. nov., comb. nov. The transfer of the sole member of Thermobacteroides invalidates the taxonomic status of the genus.

Clostridium↗

Propionibacterium microaerophilum sp. nov., a microaerophilic bacterium isolated from olive mill wastewater.

A new gram-positive, facultative anaerobic, microaerophilic bacterium, designated strain M5T, was isolated from a decantation reservoir of olive mill wastewater. The cells were rod-shaped, non-motile, non-spore-forming and catalase-negative. Growth occurred at pH ranging from 4.5 to 9.5, with optimum growth at 7.0. The optimum temperature for growth was around 30 degrees C. Although growth occurred under anaerobic and aerobic conditions, the optimum O2 concentration for growth was determined as 5% in the gas phase of the culture. During anaerobic growth, glucose or lactate were mainly fermented to propionate, acetate and CO2. In the presence of O2 (more than 2%), glucose was oxidized completely to CO2. The G+C content of the DNA was 67.7+/-0.6 mol% and 16S rRNA gene analysis revealed that the new isolate belonged to the cluster of 'dairy' propionibacteria, Propionibacterium acidipropionici being its closest phylogenic relative (97.5% similarity). However, the level of DNA relatedness between strain M5T and P. acidipropionici was 56.2%. Consequently, both the phenotypic (range of substrates used) and genotypic characteristics of strain M5T allow it to be assigned as a new species of the genus Propionibacterium, Propionibacterium microaerophilum sp. nov. The type strain is strain M5T (= CNCM I-2360T = DSM 13435T).

Aerobiosis↗

Desulforegula conservatrix gen. nov., sp. nov., a long-chain fatty acid-oxidizing, sulfate-reducing bacterium isolated from sediments of a freshwater lake.

A novel sulfate-reducing bacterium, strain Mb1PaT, was isolated from the sediments of a freshwater floodplain lake. Cells of strain Mb1PaT were rod-shaped, 1-1.3 microm wide and 2.6-3 microm long, motile and Gram-negative. The bacterium grew on straight-chain carboxylic acids with 4-17 carbon atoms. Electron donors with an even number of carbon atoms were oxidized to acetate and electron donors with an odd number of carbon atoms were oxidized to acetate and propionate. No other compounds were found to be used as electron donors. No growth occurred in the absence of sulfate. The optimum temperature for growth was between 25 and 30 degrees C and the maximum temperature for growth was 32 degrees C. Strain Mb1PaT grew very slowly in medium with 5 g NaCl l(-1) with optimum growth occurring with up to 1.0 g NaCl l(-1). Analysis of the 16S rRNA gene showed that strain Mb1PaT belonged to the delta-subclass of the Proteobacteria, was a member of the family Desulfobacteraceae, but lacked similarity with any currently described representatives. The combined phylogenetic analysis and physiological data indicate that strain Mb1PaT represents a new genus and the name Desulforegula conservatrix is proposed. The type strain is Mb1PaT (= DSM 13527T = ATCC BAA-134T).

DNA, Ribosomal↗

Isolation of a cinnamic acid-metabolizing Clostridium glycolicum strain from oil mill wastewaters and emendation of the species description.

A strictly anaerobic, gram-positive, motile, sporulated bacterium, designated strain CIN5, was isolated from olive mill wastewaters after enrichment on cinnamic acid. The rod-shaped cells were slightly curved (0.4-1.1 x 2.0-15 microm) and occurred singly or in pairs. Strain CIN5 utilized a limited number of carbohydrates (glucose, fructose, maltose, sorbitol), grew optimally at 37 degrees C and at pH 7.3-7.5 and had a DNA G+C content of 29.1+/-0.3 mol%. Strain CIN5 was very closely related to Clostridium glycolicum DSM 1288T. Both strain CIN5 and the type strain of C. glycolicum transformed cinnamic acid to hydrocinnamic acid and a wide range of other cinnamic acid derivatives, including o-, m- and p-coumaric, o-, m- and p-methoxycinnamic, p-methylcinnamic, caffeic, ferulic and isoferulic acids, to their corresponding 3-phenylpropionic acids by reducing the double bond of the side chain. Glucose supplementation increased the rate of conversion markedly. The emendation of the description of C. glycolicum is proposed to include these new characteristics.

Biodegradation, Environmental↗

Multiple growth factor induction of a murine early response gene that complements a lethal defect in yeast ribosome biogenesis.

Identification of the transcriptionally activated targets of receptor tyrosine kinases is critical to understanding biologic programs directing both normal and neoplastic growth. To elucidate these molecular processes, we identified genes induced by a potent mesenchymal mitogen, platelet-derived growth factor (PDGF). Using differential display reverse transcription-polymerase chain reaction technology, we isolated a novel growth factor-induced cDNA, San5. San5 transcript induction occurred within 60 min in NIH 3T3 fibroblasts and proceeded in the presence of cycloheximide. Maximal induction of the San5 transcript occurred between 8 and 16 h, concurrent with passage of fibroblasts through G(1). San5 message was potently induced by PDGF AA and BB and acidic and basic fibroblast growth factors, all strong activators of fibroblast proliferation, but not by epidermal growth factor and interleukin-4. In a murine hematopoietic progenitor cell line, San5 transcript induction strictly correlated with [(3)H]thymidine uptake. Isolation and sequencing of the murine San5 cDNA revealed amino acid sequence homology to yeast Nop5p, a nucleolar protein required for pre-rRNA processing and ribosome assembly. Strikingly, SAN5 was able to rescue a nop5 null mutant, implicating SAN5 in the process of ribosome biogenesis. Consistent with this result, SAN5 was localized to the nucleolus in both yeast and mouse. Thus, San5 may provide a link between growth factor receptor activation and the cellular translational machinery.

3T3 Cells↗

Microbiology of petroleum reservoirs.

Although the importance of bacterial activities in oil reservoirs was recognized a long time ago, our knowledge of the nature and diversity of bacteria growing in these ecosystems is still poor, and their metabolic activities in situ largely ignored. This paper reviews our current knowledge about these bacteria and emphasises the importance of the petrochemical and geochemical characteristics in understanding their presence in such environments.

Animals↗

A fluorescently-labelled r-RNA targeted oligonucleotide probe for the in situ detection of G-bacteria of the genus Amaricoccus in activated sludge.

A fluorescently-labelled r-RNAtargeted oligonucleotide probe specific for members of the genus Amaricoccus, which includes one group of the Gram-negative G-Bacteria seen in activated sludge systems, is described. These organisms, previously 'identified' on their distinctive morphology of cocci in tetrads, have been associated with poor performance of biological nutrient removal (EBNR) plants, by out-competing the polyphosphate accumulating bacteria. Methods of sample preparation for probing activated sludge are detailed, and preliminary surveys of 46 plants, using this probe, show that G-Bacteria belonging to the genus Amaricoccus are seen not only in large numbers in EBNR systems but also in conventional plants. The presence of single cells of this organism was common, emphasizing the dangers of relying on morphology and cell arrangement to identify these bacteria.

Australia↗

Microbiology of the 'G-bacteria' in activated sludge.

This review discusses a group of bacteria, the 'G-bacteria', which have a distinctive morphology of cocci in tetrads, sheets or clusters, that are seen in large numbers in many activated sludge biomass samples. Isolates of 'G-bacteria' that have been grown axenically are phylogenetically diverse. The Gram-negative members include several alpha- and beta-proteobacteria, among which is the genus Amaricoccus, while the Gram-positive 'G-bacteria' contain several members of the actinobacteria. It is probable that other, as yet uncharacterized, 'G-bacteria' exist in activated sludge. The hypothesis that these 'G-bacteria' are detrimental to the process of enhanced biological phosphate removal by competing for substrates anaerobically with the phosphate-accumulating bacteria in such systems, based as it is largely on mixed-culture studies, receives little support from studies using those available in pure culture. The evidence on which these conclusions are founded is discussed, as are the arguments used to explain why these 'G-bacteria' all appear to thrive under conditions found in certain activated sludge systems.

Actinobacteria↗

Aminobacterium mobile sp. nov., a new anaerobic amino-acid-degrading bacterium.

A novel, curved (0.3 x 4.0-5.0 microm), Gram-negative, non-sporulating, mesophilic bacterium, designated strain ILE-3T (T = type strain), was isolated from an anaerobic lagoon in a dairy wastewater treatment plant. Optimal growth occurred at 37 degrees C and pH 7.4 on a medium containing serine as an energy source and yeast extract. The strain was motile by means of one or two lateral flagella. It required yeast extract for growth on serine, glycine, threonine and pyruvate. Poor growth was obtained on cysteine, Casamino acids, biotrypcase, peptone and 2-oxoglutarate. In the presence of Methanobacterium formicicum, strain ILE-3T oxidized alanine, glutamate, leucine, isoleucine, valine and aspartate to a minor extent. The G+C content of the DNA was 44 mol%. Phylogenetic analysis of the 16S rRNA gene of strain ILE-3T indicated that it was related to Aminobacterium colombiense (95% similarity value). On the basis of the phenotypic and phylogenetic characteristics, strain ILE-3T is designated as a new species of the genus Aminobacterium, namely Aminobacterium mobile sp. nov. (= DSM 12262T).

Amino Acids↗

Saccharococcus caldoxylosilyticus sp. nov., an obligately thermophilic, xylose-utilizing, endospore-forming bacterium.

Several closely related, xylanolytic, thermophilic bacilli were isolated from local soils on xylose-containing minimal medium. On the basis of morphology and biochemical characteristics, one of the isolates, designated strain S1812T (T = type strain), was studied further. Strain S1812T was a xylanolytic, sporulating, Gram-positive, rod-shaped bacterium. Its Gram-positive nature was confirmed by electron microscopic examination of thin sections of the cells. The isolate was a thermophilic (optimum temperature for growth, 65 degrees C), facultative anaerobe that grew on a wide range of carbon sources including glucose, lactose, starch and xylose. It expressed high levels of both xylose isomerase and xylulokinase on xylose and also on glucose. The DNA G + C content was 44 mol%. rRNA gene sequence analysis placed strain S1812T in Bacillus cluster 5; it was more closely related to Saccharococcus thermophilus than to thermophilic Bacillus species. DNA-DNA hybridization also indicated its close relationship to S. thermophilus. Based on the evidence presented, it is proposed that strain S1812T be designated Saccharococcus caldoxylosilyticus sp. nov. Strain S1812T is the type strain (= ATCC 700356T = DSM 97-987T).

Base Composition↗

Methanobacterium oryzae sp. nov., a novel methanogenic rod isolated from a Philippines ricefield.

A rod (0.3-0.4 micron x 3-10 microns) to filamentous (up to 40 microns) non-motile methanogenic bacterium, designated strain FPiT (T = type strain), was isolated from ricefield soil in the Philippines. The strain uses H2 + CO2 or formate for growth and produces CH4. Optimum growth temperature is 40 degrees C; no growth is observed at 15 degrees C or 45 degrees C. Optimum pH for growth is 7; no growth is observed at pH 5.5 or 9.0. Strain FPiT is halotolerant and grows at NaCl concentrations of 0-25 g l-1. The G + C content of its DNA is 31 mol%. Based on 16S rRNA gene sequence analysis, the isolate was identified as a new species of the genus Methanobacterium: Methanobacterium oryzae sp. nov. The type strain is FPiT (= DSM 11106T).

Agriculture↗

Thermohalobacter berrensis gen. nov., sp. nov., a thermophilic, strictly halophilic bacterium from a solar saltern.

A new thermophilic, strictly halophilic, anaerobic, non-sporulating rod-shaped bacterium, measuring 0.5 x 3.0-8.0 microns and designated strain CTT3T, was isolated from a solar saltern. Strain CTT3T stained Gram-negative, was motile by means of laterally inserted flagella, had a genome G + C content of 33 mol% and grew optimally at 65 degrees C and pH 7.0 with 5% NaCl. The strain also grew readily at 70 degrees C in the presence of 15% NaCl. Strain CTT3T fermented cellobiose, fructose, glucose, maltose, mannitol, mannose, sucrose, glycerol, N-acetylglucosamine, starch, pyruvate and bio-Trypticase. It produced acetate, ethanol, H2 and presumably CO2 from glucose. 16S rRNA gene sequence analysis indicated that it is a member of cluster XII of the Clostridiales and related genera of the subphylum of the Gram-positive bacteria containing genomes of low G + C content. Its phenotypic and phylogenetic characteristics clearly differentiated it from all other members of this cluster. Based on the findings it is proposed that strain CTT3T be designated as a new species of a new genus, Thermohalobacter berrensis gen. nov., sp. nov. The type strain is CTT3T (= CNCM 105955T).

Base Composition↗

Three isolates of novel polyphosphate-accumulating gram-positive cocci, obtained from activated sludge, belong to a new genus, Tetrasphaera gen. nov., and description of two new species, Tetrasphaera japonica sp. nov. and Tetrasphaera australiensis sp. nov.

Two isolates of Gram-positive cocci (Ben 109T and Ben 110) which could accumulate polyphosphate and were microscopically similar in appearance to so-called 'G-bacteria', appearing as tetrads, were isolated from samples of activated sludge biomass by micromanipulation and grown in axenic culture. On the basis of their phenotypic and chemotaxonomic characters and 16S rDNA sequences, these isolates, together with strain T1-X7T isolated and described previously in Japan, belong to a new genus. These isolates are phylogenetically different from Tessaracoccus bendigoensis, Friedmanniella spumicola and Friedmanniella capsulata, Gram-positive cocci isolated previously in this laboratory. They are characterized by type A1 gamma peptidoglycan, with meso-diaminopimelic acid as the diagnostic diamino acid. The main cellular fatty acid of Ben 109T, Ben 110 and T1-X7T is 14-methylpentadecanoic acid (i-C16:0). The major menaquinones of Ben 109T are MK-8(H4), with MK-8(H2) and MK-8 in trace amounts. In Ben 110 MK-8(H4) and MK-6(H4) are the major menaquinones, while T1-X7T has MK-8(H4), MK-7(H4) and MK-6(H4) as its menaquinones. All three contain phosphatidylinositol, phosphatidylglycerol and diphosphatidylglycerol as their polar lipids. These properties, together with 16S rDNA sequence data, suggest that they all belong to a single new genus for which the name Tetrasphaera gen. nov. is proposed. However, the lipid, cellular fatty acid profiles and DNA-DNA similarity data suggest that Ben 109T and Ben 110 are sufficiently different from T1-X7T to represent a different species of the genus Tetrasphaera. Strain T1-X7T represents the type species Tetrasphaera japonica sp. nov. of this new genus, and strains Ben 109T and Ben 110 belong to the other species, Tetrasphaera australiensis sp. nov.

Actinomycetales↗