共查询到20条相似文献,搜索用时 15 毫秒
1.
Gerald B. Lee Eric B. Brandt Chang Xiao Aaron M. Gibson Timothy D. Le Cras Lou Ann S. Brown Anne M. Fitzpatrick Gurjit K. Khurana Hershey 《PloS one》2013,8(3)
Background
Diesel exhaust particle (DEP) exposure enhances allergic inflammation and has been linked to the incidence of asthma. Oxidative stress on the thiol molecules cysteine (Cys) and glutathione (GSH) can promote inflammatory host responses. The effect of DEP on the thiol oxidation/reduction (redox) state in the asthmatic lung is unknown.Objective
To determine if DEP exposure alters the Cys or GSH redox state in the asthmatic airway.Methods
Bronchoalveolar lavage fluid was obtained from a house dust mite (HDM) induced murine asthma model exposed to DEP. GSH, glutathione disulfide (GSSG), Cys, cystine (CySS), and s-glutathionylated cysteine (CySSG) were determined by high pressure liquid chromatography.Results
DEP co-administered with HDM, but not DEP or HDM alone, decreased total Cys, increased CySS, and increased CySSG without significantly altering GSH or GSSG.Conclusions
DEP exposure promotes oxidation and S-glutathionylation of cysteine amino acids in the asthmatic airway, suggesting a novel mechanism by which DEP may enhance allergic inflammatory responses. 相似文献2.
Jean Louis Corhay Catherine Moermans Monique Henket Delphine Nguyen Dang Bernard Duysinx Renaud Louis 《Respiratory research》2014,15(1)
Background
Neutrophils have been involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Underlying mechanisms of neutrophil accumulation in the airways of stable and exacerbated COPD patients are poorly understood. The aim of this study was to assess exhaled breath condensate (EBC) neutrophil chemotactic activity, the level of two chemoattractants for neutrophils (GRO-α and LTB4) during the course of an acute exacerbation of COPD (AECOPD).Methods
50 ex smoking COPD patients (33 with acute exacerbation and 17 in stable disease) and 20 matched ex smoking healthy controls were compared. EBC was collected by using a commercially available condenser (EcoScreen®). EBC neutrophil chemotactic activity (NCA) was assessed by using Boyden microchambers. Chemotactic index (CI) was used to evaluate cell migration. LTB4 and GROα levels were measured by a specific enzyme immunoassay in EBC.Results
Stable COPD and outpatients with AECOPD, but not hospitalized with AECOPD, had raised EBC NCA compared to healthy subjects (p < 0.05 and p < 0.01 respectively). In outpatients with AECOPD EBC NCA significantly decreased 6 weeks after the exacerbation. Overall EBC NCA was weakly correlated with sputum neutrophil counts (r = 0.26, p < 0.05).EBC LTB4 levels were increased in all groups of COPD compared to healthy subjects while GRO-α was only raised in patients with AECOPD. Furthermore, EBC LTB4 and GRO-α significantly decreased after recovery of the acute exacerbation. Increasing concentrations (0.1 to 10 μg/mL) of anti- human GRO-α monoclonal antibody had no effect on EBC neutrophil chemotactic activity of 10 exacerbated COPD patients.Conclusions
EBC NCA rose during acute exacerbation of COPD in ambulatory patients and decreased at recovery. While LTB4 seems to play a role both in stable and in exacerbated phase of the disease, the role of GRO-α as a chemotactic factor during AECOPD is not clearly established and needs further investigation. 相似文献3.
Jun Kojima Jun Araya Hiromichi Hara Saburo Ito Naoki Takasaka Kenji Kobayashi Satoko Fujii Chikako Tsurushige Takanori Numata Takeo Ishikawa Kenichiro Shimizu Makoto Kawaishi Keisuke Saito Noriki Kamiya Jun Hirano Makoto Odaka Toshiaki Morikawa Hiroshi Hano Satoko Arai Toru Miyazaki Yumi Kaneko Katsutoshi Nakayama Kazuyoshi Kuwano 《Respiratory research》2013,14(1):30
Background
Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure.Methods
Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM.Results
The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure.Conclusions
These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD. 相似文献4.
Rodrigo L Castillo Andrea B Zepeda Stefania E Short Elías Figueroa Eduardo Bustos-Obregon Jorge G Farías 《Journal of biomedical science》2015,22(1)
Background
Intermittent hypobaric hypoxia (IHH) induces changes in the redox status and structure in rat testis. These effects may be present in people at high altitudes, such as athletes and miners. Polyunsaturated fatty acids (PUFA) can be effective in counteracting these oxidative modifications due to their antioxidants properties. The aim of the work was to test whether PUFA supplementation attenuates oxidative damage in testis by reinforcing the antioxidant defense system. The animals were divided into four groups (7 rats per group): normobaric normoxia (~750 tor; pO2 156 mmHg; Nx); Nx + PUFA, supplemented with PUFA (DHA: EPA = 3:1; 0.3 g kg−1 of body weight per day); hypoxic hypoxia (~428 tor; pO2 90 mmHg; Hx) and, Hx + PUFA. The hypoxic groups were exposed in 4 cycles to 96 h of HH followed by 96 h of normobaric normoxia for 32 days. Total antioxidant capacity (FRAP) and lipid peroxidation (malondialdehyde, MDA) in plasma and reduced (GSH)/oxidized glutathione (GSSG) ratio, tissue lipid peroxidation (TBARS) and antioxidant enzymes activity were assessed at the end of the study in testis. Also, SIRTUIN 1 and HIF-1 protein expression in testis were determined.Results
IHH increased lipid peroxidation in plasma and HIF-1 protein levels in testis. In addition, IHH reduced FRAP levels in plasma, antioxidant enzymes activities and SIRTUIN 1 protein levels in testis. PUFA supplementation attenuated these effects, inducing the increases in FRAP, in the antioxidant enzymes activity and HIF-1 levels.Conclusions
These results suggest that the IHH model induces a prooxidant status in plasma and testis. The molecular protective effect of PUFA may involve the induction of an antioxidant mechanism. 相似文献5.
Zhike Liang Qingling Zhang Catherine MR Thomas Kirandeep K Chana David Gibeon Peter J Barnes Kian Fan Chung Pankaj K Bhavsar Louise E Donnelly 《Respiratory research》2014,15(1):72
Background
Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.Methods
Phagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.Results
There were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.Conclusions
Persistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation. 相似文献6.
Küster A Tea I Ferchaud-Roucher V Le Borgne S Plouzennec C Winer N Rozé JC Robins RJ Darmaun D 《PloS one》2011,6(11):e27626
Background
Depletion of blood glutathione (GSH), a key antioxidant, is known to occur in preterm infants.Objective
Our aim was to determine: 1) whether GSH depletion is present at the time of birth; and 2) whether it is associated with insufficient availability of cysteine (cys), the limiting GSH precursor, or a decreased capacity to synthesize GSH.Methodology
Sixteen mothers delivering very low birth weight infants (VLBW), and 16 mothers delivering healthy, full term neonates were enrolled. Immediately after birth, erythrocytes from umbilical vein, umbilical artery, and maternal blood were obtained to assess GSH [GSH] and cysteine [cys] concentrations, and the GSH synthesis rate was determined from the incorporation of labeled cysteine into GSH in isolated erythrocytes ex vivo, measured using gas chromatography mass spectrometry.Principal Findings
Compared with mothers delivering at full term, mothers delivering prematurely had markedly lower erythrocyte [GSH] and [cys] and these were significantly depressed in VLBW infants, compared with term neonates. A strong correlation was found between maternal and fetal GSH and cysteine levels. The capacity to synthesize GSH was as high in VLBW as in term infants.Conclusion
The current data demonstrate that: 1) GSH depletion is present at the time of birth in VLBW infants; 2) As VLBW neonates possess a fully active capacity to synthesize glutathione, the depletion may arise from inadequate cysteine availability, potentially due to maternal depletion. Further studies would be needed to determine whether maternal-fetal cysteine transfer is decreased in preterm infants, and, if so, whether cysteine supplementation of mothers at risk of delivering prematurely would strengthen antioxidant defense in preterm neonates. 相似文献7.
8.
Toby K McGovern William S Powell Brian J Day Carl W White Karuthapillai Govindaraju Harry Karmouty-Quintana Normand Lavoie Ju Jing Tan James G Martin 《Respiratory research》2010,11(1):138
Background
Exposure to chlorine (Cl2) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl2-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.Methods
Balb/C mice were exposed to Cl2 gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl2, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl2 exposure.Results
Mice exposed to Cl2 had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl2 exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl2-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl2 prevented lipid peroxidation in the lung. Following Cl2 exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl2 exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.Conclusion
Our data show that the anti-oxidant DMTU is effective in attenuating Cl2 induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress. 相似文献9.
Richa Singh Alexander J Mackay Anant RC Patel Davinder S Garcha Beverly S Kowlessar Simon E Brill Louise E Donnelly Peter J Barnes Gavin C Donaldson Jadwiga A Wedzicha 《Respiratory research》2014,15(1)
Background
There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients. We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.Methods
We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012. Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.Results
Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively). Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05). Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads. Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs. No association was observed between inflammation and health status (p > 0.05).Conclusions
Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique. The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae. However, discordance between inflammation and health status was observed.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. 相似文献10.
Magdalena Wiecek Marcin Maciejczyk Jadwiga Szymura Zbigniew Szygula Malgorzata Kantorowicz 《PloS one》2015,10(11)
Purpose
The aim of this study was to compare changes in total oxidative status (TOS), total antioxidative capacity (TAC) and the concentration of VitA, VitE, VitC, uric acid (UA), reduced (GSH) and oxidized glutathione (GSSG) in blood within 24 hours following anaerobic exercise (AnEx) among men and women.Methods
10 women and 10 men performed a 20-second bicycle sprint (AnEx). Concentrations of oxidative stress indicators were measured before AnEx and 3, 15 and 30 minutes and 1 hour afterwards. UA, GSH and GSSH were also measured 24 hours after AnEx. Lactate and H+ concentrations were measured before and 3 minutes after AnEx.Results
The increase in lactate and H+ concentrations following AnEx was similar in both sexes. Changes in the concentrations of all oxidative stress indicators were significant and did not differ between men and women. In both sexes, TOS, TAC, TOS/TAC and VitA and VitE concentrations were the highest 3 minutes, VitC concentration was the highest 30 minutes, and UA concentration was the highest 1 hour after AnEx. GSH concentration was significantly lower than the initial concentration from 15 minutes to 24 hour after AnEx. GSSG concentration was significantly higher, while the GSH/GSSG ratio was significantly lower than the initial values 1 hour and 24 hour after AnEx.Conclusions
With similar changes in lactate and H+ concentrations, AnEx induces the same changes in TAC, TOS, TOS/TAC and non-enzymatic antioxidants of low molecular weight in men and women. Oxidative stress lasted at least 24 hours after AnEx. 相似文献11.
Craig M Patterson Richard L Morrison Alain D’Souza Xu S Teng Kyle I Happel 《Respiratory research》2012,13(1):40
Background
Recent trials demonstrate increased pneumonia risk in chronic obstructive pulmonary disease patients treated with the inhaled corticosteroid (ICS) fluticasone propionate (FP). There is limited work describing FP effects on host defenses against bacterial pneumonia.Methods
C57BL/6 mice received daily, nose-only exposure to nebulized FP or vehicle for 8 days, followed by pulmonary challenge with Klebsiella pneumoniae. Bacterial burden, phagocytosis, leukocyte recruitment, cytokine expression, nitric oxide release, and survival were measured.Results
Inhaled FP increased bacterial burden in lungs and blood 48 h after infection but affected neither in vivo phagocytosis of bacteria by alveolar macrophages (AM) nor alveolar neutrophil recruitment. AM from FP-treated mice showed impaired expression of infection induced TNF-alpha, IP-10 (CXCL-10), and interleukin 6 (IL-6), and AM also showed a trend towards impaired intracellular pathogen control following in vivo infection. In vitro FP treatment resulted in a dose-dependent impairment of cytokine expression by AM. Furthermore, infection-induced nitric oxide (but not hydrogen peroxide) production was impaired by FP in vivo and in vitro. FP decreased survival in this model.Conclusions
Exposure to inhaled FP impairs pulmonary clearance of K. pneumoniae in mice, an effect associated with greater systemic bacteremia and death. Decreased AM cytokine and nitric oxide expression parallel the failure to control infection. These results support the study of ICS effects on human pulmonary host defenses. 相似文献12.
Frederico Augusto Vieira Castro Diana Mariani Anita Dolly Panek Elis Cristina Araújo Eleutherio Marcos Dias Pereira 《PloS one》2008,3(12)
Background
Quinones are compounds extensively used in studies of oxidative stress due to their role in plants as chemicals for defense. These compounds are of great interest for pharmacologists and scientists, in general, because several cancer chemotherapeutic agents contain the quinone nucleus. However, due to differences in structures and diverse pharmacological effects, the exact toxicity mechanisms exerted by quinones are far from elucidatation.Methodology/Principal Findings
Using Saccharomyces cerevisiae, we evaluated the main mechanisms of toxicity of two naphthoquinones, menadione and plumbagin, by determining tolerance and oxidative stress biomarkers such as GSH and GSSG, lipid peroxidation levels, as well as aconitase activity. The importance of glutathione transferases (GST) in quinone detoxification was also addressed. The GSSG/GSH ratio showed that menadione seemed to exert its toxicity mainly through the generation of ROS while plumbagin acted as an electrophile reacting with GSH. However, the results showed that, even by different pathways, both drugs were capable of generating oxidative stress through their toxic effects. Our results showed that the control strain, BY4741, and the glutathione transferase deficient strains (gtt1Δ and gtt2Δ) were sensitive to both compounds. With respect to the role of GST isoforms in cellular protection against quinone toxicity, we observed that the Gtt2 deficient strain was unable to overcome lipid peroxidation, even after a plumbagin pre-treatment, indicating that this treatment did not improve tolerance when compared with the wild type strain. Cross-tolerance experiments confirmed distinct cytotoxicity mechanisms for these naphthoquinones since only a pre-treatment with menadione was able to induce acquisition of tolerance against stress with plumbagin.Conclusions/Significance
These results suggest different responses to menadione and plumbagin which could be due to the fact that these compounds use different mechanisms to exert their toxicity. In addition, the Gtt2 isoform seemed to act as a general protective factor involved in quinone detoxification. 相似文献13.
Rembert Koczulla Silvano Dragonieri Robert Schot Robert Bals Stefanie A Gauw Claus Vogelmeier Klaus F Rabe Peter J Sterk Pieter S Hiemstra 《Respiratory research》2009,10(1):78
Background
Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying the acidity (pH) of airway secretions in patients with inflammatory lung diseases.Aim
To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls.Methods
EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min.Results
In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05).Conclusion
We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold. 相似文献14.
15.
Jourd'heuil FL Lowery AM Melton EM Mnaimneh S Bryan NS Fernandez BO Park JH Ha CE Bhagavan NV Feelisch M Jourd'heuil D 《PloS one》2010,5(12):e14400
Background
S-nitrosation – the formation of S-nitrosothiols (RSNOs) at cysteine residues in proteins – is a posttranslational modification involved in signal transduction and nitric oxide (NO) transport. Recent studies would also suggest the formation of N-nitrosamines (RNNOs) in proteins in vivo, although their biological significance remains obscure. In this study, we characterized a redox-based mechanism by which N-nitroso-tryptophan residues in proteins may be denitrosated.Methodology/Principal Findings
The denitrosation of N-acetyl-nitroso Trp (NANT) by glutathione (GSH) required molecular oxygen and was inhibited by superoxide dismutase (SOD). Transnitrosation to form S-nitrosoglutathione (GSNO) was observed only in the absence of oxygen or presence of SOD. Protein denitrosation by GSH was studied using a set of mutant recombinant human serum albumin (HSA). Trp-214 and Cys-37 were the only two residues nitrosated by NO under aerobic conditions. Nitroso-Trp-214 in HSA was insensitive to denitrosation by GSH or ascorbate while denitrosation at Cys-37 was evident in the presence of GSH but not ascorbate. GSH-dependent denitrosation of Trp-214 was restored in a peptide fragment of helix II containing Trp-214. Finally, incubation of cell lysates with NANT revealed a pattern of protein nitrosation distinct from that observed with GSNO.Conclusions
We propose that the denitrosation of nitrosated Trp by GSH occurs through homolytic cleavage of nitroso Trp to NO and a Trp aminyl radical, driven by the formation of superoxide derived from the oxidation of GSH to GSSG. Overall, the accessibility of Trp residues to redox-active biomolecules determines the stability of protein-associated nitroso species such that in the case of HSA, N-nitroso-Trp-214 is insensitive to denitrosation by low-molecular-weight antioxidants. Moreover, RNNOs can generate free NO and transfer their NO moiety in an oxygen-dependent fashion, albeit site-specificities appear to differ markedly from that of RSNOs. 相似文献16.
Background
The airway surface liquid (ASL) of Cystic Fibrosis (CF) patients contains a lower concentration of reduced glutathione (GSH) with respect to healthy people. It is not known whether this defect may favor lung colonization by opportunistic pathogens.Principal Findings
We have analyzed the effects of extracellular GSH on the ability of Burkholderia cenocepacia to penetrate and multiply in epithelial respiratory cells. Extracellular GSH proved to be able to drastically reduce the pathogen ability to adhere and invade airway epithelial cells. This effect is correlated to a GSH-dependent increase in the number of free thiols on the surface of epithelial cells, suggestive of a change in the oxidoreductive status of membrane proteins involved in B. cenocepacia recognition. Moreover, treatments with GSH led to a consistent reduction of the expression of IL-8, TNF-α and IL-1β in response to B. cenocepacia infection.Conclusions and Significance
Extracellular GSH modulates the interaction between B. cenocepacia and epithelial respiratory cells and inhibits the bacterial invasion into these cells. This suggests that therapies aimed at restoring normal levels of GSH in the ASL might be beneficial to control CF lung infections. 相似文献17.
Farida F Berkhof Nynke E Doornewaard-ten Hertog Steven M Uil Huib AM Kerstjens Jan WK van den Berg 《Respiratory research》2013,14(1):125
Background
Macrolides reduce exacerbations in patients with COPD. Their effects on health status has not been assessed as primary outcome and is less clear. This study assessed the effects of prophylactic azithromycin on cough-specific health status in COPD-patients with chronic productive cough.Methods
In this randomised controlled trial 84 patients met the eligibility criteria: age of ≥40 years, COPD GOLD stage ≥2 and chronic productive cough. The intervention-group (n = 42) received azithromycin 250 mg 3 times a week and the control-group (n = 42) received a placebo. Primary outcome was cough-specific health status at 12 weeks, measured with the Leicester Cough Questionnaire (LCQ). Secondary outcomes included generic and COPD-specific health status and exacerbations. Changes in adverse events and microbiology were monitored.Results
Mean age of participants was 68 ± 10 years and mean FEV1 was 1.36 ± 0.47 L. The improvement in LCQ total score at 12 weeks was significantly greater with azithromycin (difference 1.3 ± 0.5, 95% CI 0.3;2.3, p = 0.01) and met the minimal clinically important difference. Similar results were found for the domain scores, and COPD-specific and generic health status questionnaires. Other secondary endpoints were non-significant. No imbalances in adverse events were found.Conclusions
Prophylactic azithromycin improved cough-specific health status in COPD-patients with chronic productive cough to a clinically relevant degree.Trial registration
ClinicalTrials.gov NCT01071161相似文献18.
Background
Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. A vast body of literature exists on hyperglycemia namely in the field of diabetic retinopathy, but very little is known about the deleterious effect of hypoglycemia. Therefore, we decided to study the role of acute hypoglycemia in mouse retina.Methodology/Principal Findings
To test effects of hypoglycemia, we performed a 5-hour hyperinsulinemic/hypoglycemic clamp; to exclude an effect of insulin, we made a hyperinsulinemic/euglycemic clamp as control. We then isolated retinas from each group at different time-points after the clamp to analyze cells apoptosis and genes regulation. In parallel, we used 661W photoreceptor cells to confirm in vivo results. We showed herein that hypoglycemia induced retinal cell death in mouse via caspase 3 activation. We then tested the mRNA expression of glutathione transferase omega 1 (Gsto1) and glutathione peroxidase 3 (Gpx3), two genes involved in glutathione (GSH) homeostasis. The expression of both genes was up-regulated by low glucose, leading to a decrease of reduced glutathione (GSH). In vitro experiments confirmed the low-glucose induction of 661W cell death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. Moreover, decrease of GSH content by inhibition with buthionine sulphoximine (BSO) at high glucose induced apoptosis, while complementation with extracellular glutathione ethyl ester (GSHee) at low glucose restored GSH level and reduced apoptosis.Conclusions/Significance
We showed, for the first time, that acute insulin-induced hypoglycemia leads to caspase 3-dependant retinal cell death with a predominant role of GSH content. 相似文献19.
J. K. Mansoor Edward S. Schelegle Cristina E. Davis William F. Walby Weixiang Zhao Alexander A. Aksenov Alberto Pasamontes Jennifer Figueroa Roblee Allen 《PloS one》2014,9(4)
Background
An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH.Methodolgy and Findings
Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients.Conclusions
These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH. 相似文献20.
Kim Heang Ly Alexis Régent Elsa Molina Sofiane Saada Philippe Sindou Claire Le-Jeunne Antoine Brézin Véronique Witko-Sarsat Fran?ois Labrousse Pierre-Yves Robert Philippe Bertin Jean-Louis Bourges Anne-Laure Fauchais Elisabeth Vidal Luc Mouthon Marie-Odile Jauberteau 《Arthritis research & therapy》2014,16(6)