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151.
152.
Ahmet Yesildağ Ahmet Özden H. Ramazan Yılmaz Efkan Uz Yetkin Ağackıran Mihrican Yesildağ Nigar Yılmaz Rana Sırmalı Hüseyin Vural Mustafa Nazıroğlu 《Cell biochemistry and function》2009,27(3):142-147
It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)‐induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM‐induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH‐Px) values and histological evaluation. Twenty‐one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor‐driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH‐Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media‐induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
153.
154.
Rifampicin (Rif) is a first line drug used for tuberculosis treatment. However, the emergence of drug resistant strains has necessitated synthesis and testing of newer analogs of Rif. Mycobacterium smegmatis is often used as a surrogate for M. tuberculosis. However, the presence of an ADP ribosyltransferase (Arr) in M. smegmatis inactivates Rif, rendering it impractical for screening of Rif analogs or other compounds when used in conjunction with them (Rif/Rif analogs). Rifampicin is also used in studying the role of various DNA repair enzymes by analyzing mutations in RpoB (a subunit of RNA polymerase) causing Rif resistance. These analyses use high concentrations of Rif when M. smegmatis is used as model. Here, we have generated M. smegmatis strains by deleting arr (Δarr). The M. smegmatis Δarr strains show minimum inhibitory concentration (MIC) for Rif which is similar to that for M. tuberculosis. The MICs for isoniazid, pyrazinamide, ethambutol, ciprofloxacin and streptomycin were essentially unaltered for M. smegmatis Δarr. The growth profiles and mutation spectrum of Δarr and, Δarr combined with ΔudgB (udgB encodes a DNA repair enzyme that excises uracil) strains were similar to their counterparts wild-type for arr. However, the mutation spectrum of ΔfpgΔarr strain differed somewhat from that of the Δfpg strain (fpg encodes a DNA repair enzyme that excises 8-oxo-G). Our studies suggest M. smegmatis Δarr strain as an ideal model system in drug testing and mutation spectrum determination in DNA repair studies. 相似文献
155.
Paul E. Rolan Gilmore O’Neill Eve Versage Jitesh Rana Yongqiang Tang Gerald Galluppi Ernesto Aycardi 《PloS one》2015,10(5)
ObjectiveTo evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.MethodsThis was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier ; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28.ResultsBeyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase.ConclusionsThese data support the development of BG00010 for the treatment of neuropathic pain. NCT00961766
Trial Registration
ClinicalTrials.gov NCT00961766相似文献156.
Wei Luo Thin Nguyen Melanie Nichols Truyen Tran Santu Rana Sunil Gupta Dinh Phung Svetha Venkatesh Steve Allender 《PloS one》2015,10(5)
For years, we have relied on population surveys to keep track of regional public health statistics, including the prevalence of non-communicable diseases. Because of the cost and limitations of such surveys, we often do not have the up-to-date data on health outcomes of a region. In this paper, we examined the feasibility of inferring regional health outcomes from socio-demographic data that are widely available and timely updated through national censuses and community surveys. Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we constructed a machine-learning model to predict the prevalence of six non-communicable disease (NCD) outcomes (four NCDs and two major clinical risk factors), based on population socio-demographic characteristics from the American Community Survey. We found that regional prevalence estimates for non-communicable diseases can be reasonably predicted. The predictions were highly correlated with the observed data, in both the states included in the derivation model (median correlation 0.88) and those excluded from the development for use as a completely separated validation sample (median correlation 0.85), demonstrating that the model had sufficient external validity to make good predictions, based on demographics alone, for areas not included in the model development. This highlights both the utility of this sophisticated approach to model development, and the vital importance of simple socio-demographic characteristics as both indicators and determinants of chronic disease. 相似文献
157.
Saikat Boliar Supratik Das Manish Bansal Brihaspati N. Shukla Shilpa Patil Tripti Shrivastava Sweety Samal Sandeep Goswami C. Richter King Jayanta Bhattacharya Bimal K. Chakrabarti 《PloS one》2015,10(3)
An ideal HIV-1 Env immunogen is expected to mimic the native trimeric conformation for inducing broadly neutralizing antibody responses. The native conformation is dependent on efficient cleavage of HIV-1 Env. The clade B isolate, JRFL Env is efficiently cleaved when expressed on the cell surface. Here, for the first time, we report the identification of a native clade C Env, 4-2.J41 that is naturally and efficiently cleaved on the cell surface as confirmed by its biochemical and antigenic characteristics. In addition to binding to several conformation-dependent neutralizing antibodies, 4-2.J41 Env binds efficiently to the cleavage-dependent antibody PGT151; thus validating its native cleaved conformation. In contrast, 4-2.J41 Env occludes non-neutralizing epitopes. The cytoplasmic-tail of 4-2.J41 Env plays an important role in maintaining its conformation. Furthermore, codon optimization of 4-2.J41 Env sequence significantly increases its expression while retaining its native conformation. Since clade C of HIV-1 is the prevalent subtype, identification and characterization of this efficiently cleaved Env would provide a platform for rational immunogen design. 相似文献
158.
Nitrogen fertilizer and landscape position impacts on CO2 and CH4 fluxes from a landscape seeded to switchgrass
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Eric G. Mbonimpa Chang O. Hong Vance N. Owens R. Michael Lehman Shannon L. Osborne Thomas E. Schumacher David E. Clay Sandeep Kumar 《Global Change Biology Bioenergy》2015,7(4):836-849
This study was conducted to evaluate the impacts of N fertilizer and landscape position on carbon dioxide (CO2) and methane (CH4) fluxes from a US Northern Great Plains landscape seeded to switchgrass (Panicum virgatum L.). The experimental design included three N levels (low, 0 kg N ha−1; medium, 56 kg N ha−1; and high, 112 kg N ha−1) replicated four times. The experiment was repeated at shoulder and footslope positions. Soil CO2 and CH4 fluxes were monitored once every 2 weeks from May 2010 to October 2012. The CO2 fluxes were 40% higher at the footslope than the shoulder landscape position, and CH4 fluxes were similar in both landscape positions. Soil CO2 and CH4 fluxes averaged over the sampling dates were not impacted by N rates. Seasonal variations showed highest CO2 release and CH4 uptake in summer and fall, likely due to warmer and moist soil conditions. Higher CH4 release was observed in winter possibly due to increased anaerobic conditions. However, year to year (2010–2012) variations in soil CO2 and CH4 fluxes were more pronounced than the variations due to the impact of landscape positions and N rates. Drought conditions reported in 2012, with higher annual temperature and lower soil moisture than long-term average, resulted in higher summer and fall CO2 fluxes (between 1.3 and 3 times) than in 2011 and 2010. These conditions also promoted a net CH4 uptake in 2012 in comparison to 2010 when there was net CH4 release. Results from this study conclude that landscape positions, air temperature, and soil moisture content strongly influenced soil CO2 fluxes, whereas soil moisture impacted the direction of CH4 fluxes (uptake or release). However, a comprehensive life cycle analysis would be appropriate to evaluate environmental impacts associated with switchgrass production under local environmental conditions. 相似文献
159.
Excess body mass index‐ and waist circumference‐years and incident cardiovascular disease: The CARDIA study
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160.
Sanjay Basu Christopher Millett Sandeep Vijan Rodney A. Hayward Sanjay Kinra Rahoul Ahuja John S. Yudkin 《PLoS medicine》2015,12(5)