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1.
Ann Oncol ; 29(9): 1911-1917, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30060061

RESUMO

Background: Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. γ-Secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patients with advanced or metastatic cancer. Methods: This phase I, open-label, multicenter, nonrandomized, and dose-escalation phase study determined and confirmed the recommended phase II dose of LY3039478 (oral dose: 2.5-100 mg, thrice weekly (TIW) on a 28-day cycle). The primary objectives are to determine (part A) and confirm (part B) a recommended phase II dose that may be safely administered to patients with advanced or metastatic cancer, and secondary objectives include evaluation of safety, tolerability, PK parameters, and preliminary antitumor activity of LY3039478. Results: A total of 110 patients were treated with LY3039478 monotherapy between 31 October 2012 and 15 July 2016. Dose-limiting toxicities were thrombocytopenia, colitis, and nausea. Most adverse events were gastrointestinal. The recommended phase II dose was 50 mg TIW, because of its better tolerability compared with 75 mg. The PKs of LY3039478 appeared dose proportional. Pharmacodynamic data indicate an ∼80% inhibition of plasma Aß, and >50% inhibition of Notch-regulated genes hairy and enhancer of split-1, cyclin D1, and Notch-regulated ankyrin repeat at 45-100-mg dose. Clinical activity (tumor necrosis, metabolic response, or tumor shrinkage) was observed in patients with breast cancer, leiomyosarcoma, and adenoid cystic carcinoma. Conclusion: Potent inhibition of Notch signaling by LY3039478 was well tolerated at doses associated with target engagement, and demonstrated evidence of clinical activity in heavily pretreated patients. Further investigation with LY3039478 as monotherapy and in combination with targeted agent or chemotherapy is ongoing. Clinicaltrials.gov ID: NCT01695005.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Antineoplásicos/administração & dosagem , Benzazepinas/administração & dosagem , Neoplasias/tratamento farmacológico , Receptores Notch/antagonistas & inibidores , Administração Oral , Adolescente , Adulto , Idoso , Secretases da Proteína Precursora do Amiloide/sangue , Antineoplásicos/efeitos adversos , Benzazepinas/efeitos adversos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/genética , Receptores Notch/genética , Receptores Notch/metabolismo , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto Jovem
2.
Data Brief ; 19: 82-85, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29892620

RESUMO

In recent past, the respiratory infection has emerged as a great challenge to the poultry farmers. Various pathogens including Avian pneumovirus (APV), Avian influenza virus (AIV), Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), Avibacterium paragallinarum, Ornithobacterium rhinotracheale (ORT), Mycoplasma synoviae (MS), Mycoplasma gallisepticum (MG) and Avian pathogenic Escherichia coli (APEC) are involved in the respiratory disease complex in birds [1], [2] (Bradbury, 1984; Roussan et al., 2008). Hence, respiratory disease complex is the most serious disease affecting to poultry and causes heavy economic losses in the poultry industry worldwide [3] (Murthy et al., 2008). In recent years, metagenomics is powerful analyzing tool for detection of pathogens directly from clinical samples without any prior knowledge of the organism in a given sample [4], [5] (Schuster, 2008; Pereira et al., 2010). High throughput Next-Generation-Sequencing technology was used for sequencing the isolated genomic DNA. These data provides an insight about taxonomic and functional status of microorganisms responsible for causing respiratory infection in broiler. The data of these metagenome are available in the BioSample Submission Portal as Bioproject PRJNA339659 and SRA accession number SRR5997823, SRR5992854, SRR6037376, SRR6024702, SRR6012248 and SRR6008913.

3.
Can J Microbiol ; 63(7): 644-647, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28460189

RESUMO

Neisseria meningitidis serogroups B and C have been responsible for the majority of invasive meningococcal disease in Australia, with serogroup B strains causing an increasing proportion of cases in recent years. Serogroup Y has typically caused sporadic disease in Australia. In 2002, a cluster of 4 cases was reported from a rural region in Queensland. Three of these cases were serogroup C, with 1 case diagnosed by molecular detection only, and the fourth case was identified as a serogroup Y infection. Genomic analysis, including antigen finetyping, multilocus sequence typing (MLST), and core genome MLST, demonstrated that the serogroup Y case, though spatially and temporally linked to a serogroup C disease cluster, was not the product of a capsule switch and that one of the serogroup C isolates had a deletion of the entire porA sequence.


Assuntos
Surtos de Doenças , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/genética , Porinas/genética , Análise por Conglomerados , Humanos , Infecções Meningocócicas/epidemiologia , Tipagem de Sequências Multilocus , Neisseria meningitidis/imunologia , Neisseria meningitidis/isolamento & purificação , Queensland , Análise de Sequência de DNA , Sorogrupo
4.
Vet World ; 8(11): 1370-4, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27047045

RESUMO

AIM: Tropical theileriosis is fatal hemoprotozoal disease of dairy animals caused by Theileria annulata. The aim of the present study was to detect the T. annulata and comparison of results of molecular and microscopic techniques. MATERIALS AND METHODS: A total of 52 blood samples were collected from the cattle suspected for theileriosis across the Banaskantha district. All the samples were screened for theileriosis using Giemsa's staining technique and polymerase chain reaction (PCR). RESULTS: Total of 17 (32.69%) and 24 (46.15%) samples were found positive for theileriosis by microscopic examination and PCR test, respectively. It revealed that the study area is endemic for theileriosis, and the microscopic technique has 70.83% sensitivity and 100% specificity with respect to PCR technique. CONCLUSION: It may be concluded from the present study that the PCR is comparatively sensitive technique than microscopic examination and may be recommended to use in the field for screening of theileriosis in the study area, where a high prevalence of diseases have been reported due to intensive dairy farming.

5.
Braz. j. microbiol ; 41(3): 707-717, Oct. 2010. ilus, tab
Artigo em Inglês | LILACS | ID: lil-549412

RESUMO

We studied the peptide-degrading anaerobic communities of methanogenic reactors from two mesophilic full-scale modified upflow anaerobic sludge blanket (UASB) reactors treating brewery wastewater in Colombia. Most probable number (MPN) counts varied between 7.1 x 10(8) and 6.6 x 10(9) bacteria/g volatile suspended solids VSS (Methanogenic Reactor 1) and 7.2 x 10(6) and 6.4 x 10(7) bacteria/g (VSS) (Methanogenic Reactor 2). Metabolites detected in the highest positive MPN dilutions in both reactors were mostly acetate, propionate, isovalerate and, in some cases, negligible concentrations of butyrate. Using the highest positive dilutions of MPN counts, 50 dominant strains were isolated from both reactors, and 12 strains were selected for sequencing their 16S rRNA gene based on their phenotypic characteristics. The small-subunit rRNA gene sequences indicated that these strains were affiliated to the families Propionibacteriaceae, Clostridiaceae and Syntrophomonadaceae in the low G + C gram-positive group and Desulfovibrio spp. in the class d-Proteobacteria. The main metabolites detected in the highest positive dilutions of MPN and the presence of Syntrophomonadaceae indicate the effect of the syntrophic associations on the bioconversion of these substrates in methanogenic reactors. Additionally, the potential utilization of external electron acceptors for the complete degradation of amino acids by Clostridium strains confirms the relevance of these acceptors in the transformation of peptides and amino acids in these systems.


Assuntos
Águas Residuárias , Sequência de Bases , Bactérias Anaeróbias Gram-Negativas/genética , Bactérias Anaeróbias Gram-Negativas/isolamento & purificação , Peptídeos/análise , Peptídeos/genética , Estabilidade de RNA , RNA Bacteriano , Reatores Biológicos Sequenciais , Metabolismo , Métodos , Métodos , Virulência
6.
Int J Syst Evol Microbiol ; 60(Pt 4): 850-853, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19661517

RESUMO

A mesophilic, strictly anaerobic, slightly halophilic bacterium, designated strain USBA 82(T), was isolated from a terrestrial saline spring in the Colombian Andes. The non-spore-forming curved rods (5-7 x 1.3 microm) with pointed or rounded ends, stained Gram-negative and were motile by means of laterally inserted flagella. The strain grew optimally at 30 degrees C (growth range 20-40 degrees C), pH 7.3 (growth range pH 5.5-8.5) and 2 % (w/v) NaCl (growth range 0.1-7 % NaCl). The strain fermented peptides, amino acids and a few organic acids, but growth was not observed on carbohydrates, alcohols or fatty acids. The strain reduced thiosulfate and sulfur to sulfide. Sulfate, sulfite, nitrate and nitrite were not used as electron acceptors. On peptone alone, acetate, succinate, propionate and traces of ethanol were formed, but in the presence of thiosulfate, acetate and succinate were formed. The G+C content of the chromosomal DNA was 52 mol% (T(m)). 16S rRNA gene sequence analysis indicated that strain USBA 82(T) was affiliated to Dethiosulfovibrio peptidovorans within the phylum Synergistetes with a similarity value of approximately 93 %. Based on the differences between the new strain and the type species of the genus Dethiosulfovibrio, we suggest that strain USBA 82(T) represents a novel species of the genus for which the name Dethiosulfovibrio salsuginis sp. nov. is proposed. The type strain is USBA 82(T) (=DSM 21565(T)=KCTC 5659(T)).


Assuntos
Bactérias Anaeróbias/classificação , Bactérias Anaeróbias/isolamento & purificação , Água Doce/microbiologia , Cloreto de Sódio , Bactérias Anaeróbias/genética , Bactérias Anaeróbias/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Colômbia , DNA Ribossômico/análise , DNA Ribossômico/genética , Genes de RNAr , Genótipo , Dados de Sequência Molecular , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da Espécie
7.
Int J Syst Evol Microbiol ; 60(Pt 6): 1437-1443, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19671725

RESUMO

A Gram-negative, aerobic, mesophilic, non-spore-forming, chemotrophic, chlorophyll-lacking, nitrogen-fixing bacterium, designated strain USBA 355(T), was isolated from the saline spring 'Salado de Consotá' situated in the Colombian Andes. The non-flagellated cells of strain USBA 355(T) were straight to slightly curved rods (0.6-0.7 x 3.0-3.5 microm). Growth occurred optimally at 30 degrees C (growth temperature range between 20 and 40 degrees C), at pH 6.5-6.7 (pH growth range between 5.0 and 8.0) and at 0.5 % NaCl (w/v) (range between 0 and 4 %). The major quinone present was Q-10 and the predominant fatty acids identified were C(19 : 0) cyclo omega8c, C(18 : 1)omega7c and C(18 : 0). The G+C content of the chromosomal DNA was 71+/-1 mol%. 16S rRNA gene sequence analysis indicated that strain USBA 355(T) formed a distant phylogenetic line of descent with members of the genus Thalassobaculum, family Rhodospirillaceae, class Alphaproteobacteria (90 % gene sequence similarity). Comparison of the phylogenetic, chemotaxonomic and physiological features of strain USBA 355(T) with all other members of the family Rhodospirillaceae suggested that it represents a novel genus and species for which the name Tistlia consotensis gen. nov., sp. nov. is proposed. The type strain of the type species is USBA 355(T) (=JCM 15529(T)=KCTC 22406(T)).


Assuntos
Alphaproteobacteria/genética , Alphaproteobacteria/metabolismo , Alphaproteobacteria/isolamento & purificação , Alphaproteobacteria/ultraestrutura , Colômbia , DNA Bacteriano/genética , Amplificação de Genes , Genes Bacterianos , Fontes Termais/microbiologia , Microscopia Eletrônica , Dados de Sequência Molecular , Fixação de Nitrogênio , Reação em Cadeia da Polimerase
8.
Braz J Microbiol ; 41(3): 707-17, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24031547

RESUMO

We studied the peptide-degrading anaerobic communities of methanogenic reactors from two mesophilic full-scale modified upflow anaerobic sludge blanket (UASB) reactors treating brewery wastewater in Colombia. Most probable number (MPN) counts varied between 7.1 x 10(8) and 6.6 × 10(9) bacteria/g volatile suspended solids VSS (Methanogenic Reactor 1) and 7.2 × 10(6) and 6.4 × 10(7) bacteria/g (VSS) (Methanogenic Reactor 2). Metabolites detected in the highest positive MPN dilutions in both reactors were mostly acetate, propionate, isovalerate and, in some cases, negligible concentrations of butyrate. Using the highest positive dilutions of MPN counts, 50 dominant strains were isolated from both reactors, and 12 strains were selected for sequencing their 16S rRNA gene based on their phenotypic characteristics. The small-subunit rRNA gene sequences indicated that these strains were affiliated to the families Propionibacteriaceae, Clostridiaceae and Syntrophomonadaceae in the low G + C gram-positive group and Desulfovibrio spp. in the class δ-Proteobacteria. The main metabolites detected in the highest positive dilutions of MPN and the presence of Syntrophomonadaceae indicate the effect of the syntrophic associations on the bioconversion of these substrates in methanogenic reactors. Additionally, the potential utilization of external electron acceptors for the complete degradation of amino acids by Clostridium strains confirms the relevance of these acceptors in the transformation of peptides and amino acids in these systems.

9.
Indian J Pharm Sci ; 71(1): 1-7, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20177448

RESUMO

Pregnancy is a special physiological condition where drug treatment presents a special concern because the physiology of pregnancy affects the pharmacokinetics of medications used and certain medications can reach the fetus and cause harm. Total avoidance of pharmacological treatment in pregnancy is not possible and may be dangerous because some women enter pregnancy with medical conditions that require ongoing and episodic treatment (e.g. asthma, epilepsy, hypertension). Also during pregnancy new medical problems can develop and old ones can be exacerbated (e.g. migraine, headache) requiring pharmacological therapy. The fact that certain drugs given during pregnancy may prove harmful to the unborn child is one of the classical problems in medical treatment. In 1960's pregnant ladies who ingested thalidomide gave birth to children with phocomalia. Various other examples of teratogenic effects of drugs are known. It has been documented that congenital abnormalities caused by human teratogenic drugs account for less than 1% of total congenital abnormalities. Hence in 1979, Food and Drug Administration developed a system that determines the teratogenic risk of drugs by considering the quality of data from animal and human studies. FDA classifies various drugs used in pregnancy into five categories, categories A, B, C, D and X. Category A is considered the safest category and category X is absolutely contraindicated in pregnancy. This provides therapeutic guidance for the clinician. This article focuses on various aspects relating to drug use during pregnancy.

10.
Int J Syst Evol Microbiol ; 57(Pt 8): 1914-1918, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17684281

RESUMO

Strain ILE-2(T) was isolated from an upflow anaerobic sludge bed reactor treating brewery wastewater. The motile, non-sporulating, slightly curved cells (2-4 x 0.1 microm) stained Gram-negative and grew optimally at 42 degrees C and pH 7.1 with 0.5 % NaCl. The strain required yeast extract for growth and fermented Casamino acids, peptone, isoleucine, arginine, lysine, alanine, valine, glutamate, histidine, glutamine, methionine, malate, fumarate, glycerol and pyruvate to acetate, propionate and minor amounts of branched-chain fatty acids. Carbohydrates, formate, acetate, propionate, butyrate, isovalerate, methanol, ethanol, 1-propanol, butanol, lactate, succinate, starch, casein, gelatin, xylan and a number of other amino acids were not utilized. The DNA G+C content of strain ILE-2(T) was 52.7 mol%. 16S rRNA gene sequence analysis revealed that ILE-2(T) was distantly related to members of the genera Aminobacterium (83 % similarity) and Aminomonas (85 % similarity) in the family Syntrophomonadaceae, order Clostridiales, phylum Firmicutes. On the basis of the results of our polyphasic analysis, strain ILE-2(T) represents a novel species and genus within the family Syntrophomonadaceae, for which the name Aminiphilus circumscriptus gen. nov., sp. nov. is proposed. The type strain of Aminiphilus circumscriptus is ILE-2(T) (=DSM 16581(T) =JCM 14039(T)).


Assuntos
Clostridium/classificação , Clostridium/metabolismo , Esgotos/microbiologia , Aminoácidos/metabolismo , Anaerobiose , Reatores Biológicos , Clostridium/genética , Clostridium/isolamento & purificação , DNA Bacteriano , DNA Ribossômico/genética , Fermentação , Resíduos Industriais , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética
12.
Int J Syst Evol Microbiol ; 56(Pt 5): 1073-1077, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16627657

RESUMO

A strictly aerobic, rod-shaped bacterium (0.6-0.8 x2-3 microm), designated strain Kh10-101T, was isolated from a saltpan (22 degrees 15' N, 69 degrees 1' E) in the vicinity of Port Okha, India. The creamish pigmented colonies of strain Kh10-101T were round, flat and translucent with irregular margins and a smooth surface. The strain possessed up to three subpolar flagella, and was motile by a corkscrew motion. The strain grew optimally at 37 degrees C (temperature growth range 25-40 degrees C) in a complex glucose-containing medium with 5 % NaCl (NaCl growth range 0-10 %) at pH 9 (pH growth range pH 7-10), indicating that it was a mesophilic halotolerant alkaliphile. The strain was sensitive to lincomycin, meticillin, cefuroxime and cephalexin, but resistant to gentamicin, tetracycline and cotrimazine. Spores were not detected and cells were heat sensitive. The isolate metabolized a range of carbohydrates and hydrolysed casein, gelatin and starch. Growth was not observed on aromatic compounds, Tween 40 or Tween 80. Nitrate was not reduced and catalase was produced. Electron microscopic examination of thin sections revealed a single thick Gram-positive cell wall. The DNA G+C content was 41+/-1 mol%. Phylogenetic analyses of the 16S rRNA gene sequence revealed that strain Kh10-101T was a member of the sixth rRNA group of the genus Bacillus, which includes alkalitolerant, alkaliphilic and halotolerant species. The halotolerant obligate alkaliphile Bacillus krulwichiae is the closest relative of strain Kh10-101T (96 % similarity) but a number of phenotypic differences suggest that strain Kh10-101T (=JCM 13040T=ATCC BAA-1137T) should be designated the type strain of a new species, for which the name Bacillus okhensis sp. nov. is proposed.


Assuntos
Bacillus/classificação , Bacillus/isolamento & purificação , Aerobiose , Antibacterianos/farmacologia , Bacillus/citologia , Bacillus/fisiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Metabolismo dos Carboidratos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Farmacorresistência Bacteriana Múltipla , Flagelos/ultraestrutura , Genes de RNAr/genética , Inibidores do Crescimento/farmacologia , Concentração de Íons de Hidrogênio , Índia , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Movimento , Filogenia , Pigmentos Biológicos/biossíntese , Proteínas/metabolismo , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Cloreto de Sódio/farmacologia , Microbiologia do Solo , Temperatura
13.
Int J Syst Evol Microbiol ; 55(Pt 5): 2105-2111, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16166717

RESUMO

A novel Gram-negative coccus/coccobacillus, strain Ben 114(T), growing in tetrads, clusters or aggregates, was isolated from activated sludge by micromanipulation. 16S rRNA gene sequence analysis revealed that it belonged to the 'Alphaproteobacteria', with no close relatives among cultured bacterial isolates. On the basis of phylogenetic data, this organism is considered to belong to a new genus, Defluvicoccus, represented by the species Defluvicoccus vanus sp. nov., a name chosen because of the distinctive staining properties of this organism; only the cell wall stained strongly with a wide range of stains, giving the cell a hollow and empty appearance. No intracellular polyphosphate granules could be detected after staining, but poly-beta-hydroxyalkanoate inclusions were detected using Nile blue A staining. Because of its taxonomic distance from its closest relatives among the 'Alphaproteobacteria', namely members of the genera Azospirillum, Phaeospirillum, Rhodospirillum, Rhodocista, Magnetospirillum and Rhodospira, D. vanus is considered to represent a new phylogenetic lineage within subgroup 1 of the 'Alphaproteobacteria', the D. vanus subgroup. The type strain is Ben 114(T) (=NCIMB 13612(T)=CIP 107350(T)).


Assuntos
Rhodospirillaceae/classificação , Esgotos/microbiologia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/análise , DNA Ribossômico/análise , Genes de RNAr , Dados de Sequência Molecular , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Rhodospirillaceae/genética , Rhodospirillaceae/isolamento & purificação , Rhodospirillaceae/fisiologia , Análise de Sequência de DNA
14.
Xenobiotica ; 33(10): 1043-57, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14555340

RESUMO

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.


Assuntos
Envelhecimento , Anti-Inflamatórios não Esteroides/farmacocinética , Flurbiprofeno/farmacocinética , Administração Oral , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Modelos Químicos , Estereoisomerismo , Fatores de Tempo
15.
Xenobiotica ; 32(8): 683-97, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12296989

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Ibuprofeno/farmacocinética , Adulto , Cromatografia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Modelos Químicos , Oxigênio/metabolismo , Estereoisomerismo , Fatores de Tempo
16.
Int J Syst Evol Microbiol ; 52(Pt 2): 629-37, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11931177

RESUMO

Nine yellow-pigmented, spherical bacterial strains isolated from a medieval wall painting (strain D7), from indoor air (strains 3, 6, 7, 13C2, 38, 83 and 118) and from an activated-sludge plant (strain Ballarat) were classified by a polyphasic approach. Analyses of the 16S rRNA gene sequences of three representatives (strains D7, 118 and Ballarat) indicated that they all belong to the genus Micrococcus. The three isolates shared the highest sequence similarities with Micrococcus luteus DSM 20030T (97.9-98%), Micrococcus antarcticus AS 1.2372T (97.9-98.3%) and Micrococcus lylae DSM 20315T (97.5-97.9%). DNA-DNA reassociation studies clearly demonstrated that all nine isolates belong to the species M. luteus. However, neither their chemotaxonomic features nor their physiological and biochemical properties were consistent with those of M. luteus DSM 20030T. In contrast to M. luteus DSM 20030T, all isolates investigated possessed MK-8(H2) as the major respiratory quinone, and strain Ballarat had an A4alpha peptidoglycan type. On the basis of analyses of their Fourier transform-infrared spectroscopy spectra, isolates D7, 3, 6, 7, 13C2, 38, 83 and 118 could be grouped into a single cluster separate from M. luteus DSM 20030T, strain Ballarat and M. lylae DSM 20315T. In addition, all these isolates could be distinguished from M. luteus DSM 20030T by their ability to assimilate D-maltose, D-trehalose, DL-3-hydroxybutyrate, DL-lactate, pyruvate and L-histidine and to hydrolyse casein. Strains D7, 3, 6, 7, 13C2, 38, 83 and 118 differed from both M. luteus DSM 20030T and strain Ballarat by their ability to assimilate acetate, L-phenylalanine, L-serine and phenylacetate. Furthermore, REP-PCR fingerprinting yielded one common band for these strains, whereas this band was not observed for M. luteus DSM 20030T, strain Ballarat or M. lylae DSM 20315T. On the basis of these data, the species M. luteus can be divided into three biovars that are distinguished by several chemotaxonomic and biochemical traits: biovar I, represented by M. luteus DSM 20030T; biovar II, represented by strains D7 (= DSM 14234 = CCM 4959), 3, 6, 7, 13C2, 38, 83 and 118; and biovar III, represented by strain Ballarat (= DSM 14235 = CCM 4960). On the basis of the results generated in this study, emended descriptions of the genus Micrococcus and the species M. luteus and M. lylae are given.


Assuntos
Micrococcus/classificação , Microbiologia do Ar , Arte , Benzoquinonas/análise , Micrococcus/isolamento & purificação , Micrococcus/fisiologia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Paleontologia , Peptidoglicano/análise , RNA Bacteriano/química , RNA Ribossômico 16S/química , Homologia de Sequência do Ácido Nucleico , Esgotos/microbiologia , Especificidade da Espécie , Espectroscopia de Infravermelho com Transformada de Fourier
17.
Int J Syst Evol Microbiol ; 52(Pt 1): 223-228, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11858148

RESUMO

A gram-negative coccus, designated strain Ben 117T, was obtained in axenic culture by micromanipulation from an Australian activated sludge biomass sample, which had been subjected to chlorination in order to alleviate problems associated with foaming and bulking. This isolate was a strict aerobe and grew in axenic culture, also appearing in biomass samples as cocci or clusters of cocci in tetrads, thus resembling the morphotype 'G-bacteria' seen commonly in activated sludge samples. Strain Ben 117T was non-motile, aerobic, oxidase-negative and catalase-positive and grew between 15 and 30 degrees C, with an optimum of 25-30 degrees C. The pH range for growth was between 6.0 and 8.5, with an optimum of 7.5-8.5. The isolate stained positively for intracellular polyphosphate and poly-beta-hydroxybutyrate and its G+C content was 67 mol%. 16S rDNA sequence analysis suggests that strain Ben 117T is phylogenetically different from members of the genera Amaricoccus, gram-negative 'G-bacteria' isolated previously in this laboratory. Ben 117T is a member of the Rhodocyclus group in the beta-Proteobacteria and equidistantly placed (similarity value of 95%) between Ferribacterium limneticum and Dechloromonas agitata (mean similarity value of 92% with the genus Rhodocyclus). Based on phenotypic and phylogenetic evidence, it is proposed that strain Ben 117T be designated a novel species in a new genus, Quadricoccus australiensis gen. nov., sp. nov.; the type strain is Ben 117T (= NCIMB 13738T = CIP 107055T).


Assuntos
Betaproteobacteria/classificação , Biomassa , Esgotos/microbiologia , Betaproteobacteria/genética , Betaproteobacteria/crescimento & desenvolvimento , DNA Ribossômico/análise , Dados de Sequência Molecular , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
18.
Int J Syst Evol Microbiol ; 51(Pt 5): 1911-1916, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11594625

RESUMO

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).


Assuntos
Deltaproteobacteria/classificação , Ácidos Graxos/metabolismo , Água Doce/microbiologia , Sedimentos Geológicos/microbiologia , Sulfatos/metabolismo , DNA Ribossômico/análise , Deltaproteobacteria/genética , Deltaproteobacteria/isolamento & purificação , Deltaproteobacteria/fisiologia , Dados de Sequência Molecular , Oxirredução , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Int J Syst Evol Microbiol ; 51(Pt 4): 1373-1382, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11491335

RESUMO

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).


Assuntos
Propionibacterium/classificação , Propionibacterium/isolamento & purificação , Aerobiose , Anaerobiose , Composição de Bases , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/genética , Indústria Alimentícia , Glucose/metabolismo , Resíduos Industriais , Microscopia Eletrônica , Dados de Sequência Molecular , Azeite de Oliva , Filogenia , Óleos de Plantas , Propionibacterium/genética , Propionibacterium/metabolismo , Microbiologia da Água
20.
Int J Syst Evol Microbiol ; 51(Pt 3): 1127-1131, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11411681

RESUMO

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.


Assuntos
Clostridium/classificação , Filogenia , Clostridium/genética , Clostridium/fisiologia , DNA Bacteriano/genética , DNA Ribossômico/genética , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética
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