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221.
222.
Krishna Rao Seth T. Walk Dejan Micic Elizabeth Chenoweth Lili Deng Andrzej T. Galecki Ruchika Jain Itishree Trivedi Marie Yu Kavitha Santhosh Cathrin Ring Vincent B. Young Gary B. Huffnagle David M. Aronoff 《PloS one》2013,8(3)
Objective
Clostridium difficile infection (CDI) is a major cause of morbidity and biomarkers that predict severity of illness are needed. Procalcitonin (PCT), a serum biomarker with specificity for bacterial infections, has been little studied in CDI. We hypothesized that PCT associated with CDI severity.Design
Serum PCT levels were measured for 69 cases of CDI. Chart review was performed to evaluate the presence of severity markers and concurrent acute bacterial infection (CABI). We defined the binary variables clinical score as having fever (T >38°C), acute organ dysfunction (AOD), and/or WBC >15,000 cells/mm3 and expanded score, which included the clinical score plus the following: ICU admission, no response to therapy, colectomy, and/or death.Results
In univariate analysis log10 PCT associated with clinical score (OR 3.13, 95% CI 1.69–5.81, P<.001) and expanded score (OR 3.33, 95% CI 1.77–6.23, P<.001). In a multivariable model including the covariates log10 PCT, enzyme immunoassay for toxin A/B, ribotype 027, age, weighted Charlson-Deyo comorbidity index, CABI, and extended care facility residence, log10 PCT associated with clinical score (OR 3.09, 95% CI 1.5–6.35, P = .002) and expanded score (OR 3.06, 95% CI 1.49–6.26, P = .002). PCT >0.2 ng/mL was 81% sensitive/73% specific for a positive clinical score and had a negative predictive value of 90%.Conclusion
An elevated PCT level associated with the presence of CDI severity markers and CDI was unlikely to be severe with a serum PCT level below 0.2 ng/mL. The extent to which PCT changes during CDI therapy or predicts recurrent CDI remains to be quantified. 相似文献223.
Pseudomonas sp. strains C4, C5 and C6 degrade carbaryl (1-naphthyl N-methylcarbamate) via 1-naphthol, 1,2-dihydroxynaphthalene, salicylate and gentisate. Carbon source-dependent metabolic studies suggest that enzymes responsible for carbaryl degradation are probably organized into ‘upper’ (carbaryl to salicylate), ‘middle’ (salicylate to gentisate) and ‘lower’ (gentisate to TCA cycle) pathway. Carbaryl and 1-naphthol were found to induce all carbaryl pathway enzymes, while salicylate and gentisate induce middle and lower pathway enzymes. The strains were found to harbor plasmid(s), and carbaryl degradation property was found to be stable. Genes encoding enzymes of the degradative pathway such as 1-naphthol 2-hydroxylase, salicylaldehyde dehydrogenase, salicylate 5-hydroxylase and gentisate 1,2-dioxygenase were amplified from chromosomal DNA of these strains. The gene-specific PCR products were sequenced from strain C6, and phylogenetic tree was constructed. Southern hybridization and PCR analysis using gel eluted DNA as template supported the presence of pathway genes onto the chromosome and not on the plasmid(s). 相似文献
224.
Prasant Kumar Jena Disha Trivedi Kirati Thakore Harshita Chaudhary Sib Sankar Giri Sriram Seshadri 《Microbiology and immunology》2013,57(6):407-416
The objective of the present study was to characterize lactobacilli isolates from the feces of male Wistar rats. Various physiological features of the candidate probiotic isolates were preliminarily investigated, including tolerance to simulated gastric juice and bile salts, antimicrobial activity, antibiotic susceptibility and in vitro aggregation. Based on their morphological and biochemical characteristics, four potential probiotic isolates (CS2, CS3, CS4, and CS7) were screened. The isolates showed good tolerance to stimulated gastric juice and bile salts. CS4 and CS7 exhibited strong antibacterial activities against the pathogens tested as assessed in neutral pH culture supernatants. All lactobacilli isolates were susceptible to all the tested antibiotics, except vancomycin. Moreover, the isolate CS4 and CS7 were found to possess stronger cell surface traits such as hydrophobicity, auto‐aggregation and co‐aggregation capacity. In addition, CS4 and CS7 had greater β‐galactosidase activities than the others. Biochemical tests and 16S rRNA gene sequencing confirmed that CS2, CS3, CS4 and CS7 are Lactobacillus intestinalis PJ2, L. sakei PJ3, L. helveticus PJ4, and L. plantarum PJ7, respectively. Based on the obtained results, L. helveticus PJ4 and L. plantarum PJ7 are ideal in vitro probiotic candidates and require further in vivo evaluation. 相似文献
225.
226.
We used FRET to examine the kinetics and thermodynamics of structural changes associated with ADP release in myosin V, which is thought to be a strain-sensitive step in many muscle and non-muscle myosins. We also explored essential dynamics using FIRST/FRODA starting with three different myosin V X-ray crystal structures to examine intrinsic flexibility and correlated motions. Our steady-state and time-resolved FRET analysis demonstrates a temperature-dependent reversible conformational change in the nucleotide-binding pocket (NBP). Our kinetic results demonstrate that the NBP goes from a closed to an open conformation prior to the release of ADP, while the actin-binding cleft remains closed. Interestingly, we find that the temperature dependence of the maximum actin-activated myosin V ATPase rate is similar to the pocket opening step, demonstrating that this is the rate-limiting structural transition in the ATPase cycle. Thermodynamic analysis demonstrates that the transition from the open to closed NBP conformation is unfavorable because of a decrease in entropy. The intrinsic flexibility analysis is consistent with conformational entropy playing a role in this transition as the MV.ADP structure is highly flexible compared to the MV.APO structure. Our experimental and modeling studies support the conclusion of a novel post-power-stroke actomyosin.ADP state in which the NBP and actin-binding cleft are closed. The novel state may be important for strain sensitivity as the transition from the closed to open NBP conformation may be altered by lever arm position. 相似文献
227.
Makadia P Shah SR Pingali H Zaware P Patel D Pola S Thube B Priyadarshini P Suthar D Shah M Giri S Trivedi C Jain M Patel P Bahekar R 《Bioorganic & medicinal chemistry》2011,19(2):771-782
A novel series of thaizole and oxazole containing phenoxy acetic acid derivatives is reported as PPAR-pan agonists. Incorporation of structurally constrained oxime-ether based linker in the chemotype of a potent PPARδ selective agonist GW-501516 was adapted as designing strategy. In vitro, selected test compounds 12a, 12c, 17a and 18a showed PPAR-pan agonists activities and among these four compounds tested, 12a emerged as highly potent and efficacious compound, while 17a exhibited moderate and balanced PPAR-pan agonistic activity. In vivo, selected test compounds 12a and 17a exhibited significant anti-hyperglycemic and anti-hyperlipidemic activities in relevant animal models. These results support our hypothesis that the introduction of structurally constrained oxime-ether linker between lipophilic tail and acidic head plays an important role in modulating subtype selectivity and subsequently led to the discovery of potent PPAR-pan agonists. 相似文献
228.
Oxidative stress causing widespread endothelial dysfunction has been proposed as a key factor involved in the development of preeclampsia (PE). With this background our objective was to study oxidative stress biomarkers like nitric oxide and malondialdehyde (MDA) and to correlate these markers with endothelial nitric oxide synthase (eNOS) (Glu298Asp) gene polymorphism. This cross-sectional study included 300 pregnant women diagnosed with PE and 200 women with normal pregnancy. Plasma NO and MDA levels were analyzed using student's t test and eNOS gene polymorphism was studied by performing polymerase chain reaction amplification and restriction length polymorphism and frequencies were distributed by using χ(2) analysis. The mean plasma levels of NO were significantly lower in study group while MDA levels were significantly higher in study group (P < 0.001). Genotypic and allelic frequency of eNOS gene in both groups was found to be significant (P < 0.05). The intergenotypic variation of NO and MDA levels was found to be significant (P < 0.001). We concluded that the plasma levels of NO are decreased while MDA levels are increased in subjects with PE and that might contribute to the pathophysiology of PE. As observed in this study Glu298Asp eNOS gene polymorphism showed significant association with PE. 相似文献
229.
230.
C. Lunniss C. Eldred N. Aston A. Craven K. Gohil B. Judkins S. Keeling L. Ranshaw E. Robinson T. Shipley N. Trivedi 《Bioorganic & medicinal chemistry letters》2010,20(1):137-140
Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described. 相似文献