157 results found
Williams EA, Quinlan GJ, Anning PB, et al., 1999, Lung injury following pulmonary resection in the isolated, blood-perfused rat lung, EUROPEAN RESPIRATORY JOURNAL, Vol: 14, Pages: 745-750, ISSN: 0903-1936
Lamb NJ, Quinlan GJ, Westerman ST, et al., 1999, Nitration of proteins in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome receiving inhaled nitric oxide, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 160, Pages: 1031-1034, ISSN: 1073-449X
Lamb NJ, Gutteridge JMC, Baker C, et al., 1999, Oxidative damage to proteins of bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome: Evidence for neutrophil-mediated hydroxylation, nitration, and chlorination, CRITICAL CARE MEDICINE, Vol: 27, Pages: 1738-1744, ISSN: 0090-3493
Anning PB, Chen Y, Lamb NJ, et al., 1999, Iron overload upregulates haem oxygenase 1 in the lung more rapidly than in other tissues, FEBS LETTERS, Vol: 447, Pages: 111-114, ISSN: 0014-5793
Lamb NJ, Quinlan GJ, Westerman ST, et al., 1999, Increased tyrosine nitration in broncho-alveolar lavage fluid from patients with ARDS receiving inhaled nitric oxide., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A377-A377, ISSN: 1073-449X
Chen Y, Quinlan GJ, Evans TW, et al., 1999, Expression of transferrin receptor and ferritin mRNA in LPS treated rats: Comparisons between heart and lung, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A245-A245, ISSN: 1073-449X
Anning PB, Quinlan GJ, Williams EA, et al., 1999, Lung injury following pulmonary resection in the isolated blood-perfused rat lung., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A606-A606, ISSN: 1073-449X
Anning PB, Chen Y, Lamb NJ, et al., 1999, Iron overloaded rats display a tissue specific, time dependent upregulation of haem oxygenase 1 (HO-1)., AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A890-A890, ISSN: 1073-449X
Lamb NJ, Quinlan GJ, Evans TW, et al., 1999, Evidence for a pro-oxidant activity of heme oxygenase, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A889-A889, ISSN: 1073-449X
Chen Y, Quinlan GJ, Nicholson A, et al., 1999, Upregulation of inducible heme oxygenase in patients with ARDS: Possible implication for outcome, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 159, Pages: A377-A377, ISSN: 1073-449X
Quinlan GJ, Westerman ST, Mumby S, et al., 1999, Plasma hypoxanthine levels during crystalloid and blood cardioplegias: Warm blood cardioplegia increases hypoxanthine levels with a greater risk of oxidative stress, JOURNAL OF CARDIOVASCULAR SURGERY, Vol: 40, Pages: 65-69, ISSN: 0021-9509
Lamb NJ, Quinlan GJ, Westerman ST, et al., 1998, Increased tyrosine nitration in bronchoalveolar lavage fluid from patients with ARDS receiving inhaled nitric oxide, Thorax, Vol: 53, ISSN: 0040-6376
Inhaled nitric oxide (NO) improves oxygenation and reduces pulmonary vascular resistance in a proportion of patients with acute respiratory distress syndrome (ARDS). However, NO is also a free radical that reacts with superoxide to form the highly toxic peroxynitrite (ONOO-) anion. ONOO-, or its decomposition products, can nitrate tyrosine to form 3-nitrotyrosine (3NT), which can be used as a marker of peroxynitrite formation. In this study we measured 3-nitrotyrosine in bronchoalveloar lavage (BAL) samples from 10 patients with ARDS receiving NO, and ten patients with comparable lung injury who were not. BAL samples were collected and spun to remove debris. Following hydrolysis, amino acids were purified by ion-exchange and analysed by high performance liquid chromatography (HPLC). Peaks were identified and quantitated by comparison with known standards. Patients receiving inhaled NO showed significantly increased levels of 3NT in their BAL fluid compared to controls (6.76 ± 2.79 vs 0.4 ± 0.15 nmol/mg of protein, p=0.005). No significant correlation was found between levels of inhaled NO and levels of 3NT measured (r = 0.4), suggesting that levels of NO are not the only factor involved in determining the amount of protein nitration. We have demonstrated an association between the use of inhaled NO in patients with ARDS and increased levels of 3-nitrotyrosine. The significance of the protein nitration observed in these patients remains to be evaluated.
Salmon M, Koto H, Lynch OT, et al., 1998, Proliferation of airway epithelium after ozone exposure: Effect of apocynin and dexamethasone, American Journal of Respiratory and Critical Care Medicine, Vol: 157, Pages: 970-977, ISSN: 1073-449X
Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 ± 1.3% (percent of nuclear cells expressing PCNA) to 4.4 ± 1.3% (mean ± SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 ± 2.3% to 10.9 ± 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone-induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 ± 0.7% versus 6.0 ± 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably in-volving neutrophils.
Lamb NJ, Quinlan GJ, Evans TW, et al., 1998, Evidence for a pro-oxidant activity of heme oxygenase, Thorax, Vol: 53, ISSN: 0040-6376
The acute respiratory distress syndrome (ARDS) is known to be associated with increased oxidative stress. Heme oxygenase (HO) catalyses the intracellular breakdown of heme proteins to biliverdin and bilirubin, with the release of carbon monoxide and free iron. HO-1, a heat shock protein (hsp32), is widely induced under conditions of oxidative stress. Much interest has focused on the antioxidant properties of bilirubin. We investigated the fate of the released free iron in a microsomal system, and demonstrate a pro-oxidant capacity of heme oxygenase. Rat liver microsomes were incubated with liposomes, hemoglobin (Hb, substrate), and NADPH. Microsomes and liposomes alone served as a control. We used the TBA test, to measure μM MDA formed as an index of lipid peroxidation (LPO). Various iron chelators, and an antibody to HO-1 were also added as appropriate controls. On addition of substrate there was an increase in lipid peroxidation (see figure). Figure shows HO-mediated peroxidation of liposomes, (where baseline is microsomes (HO) and liposomes, and the reaction is microsomes, liposomes, Hb, and NADPH. Ab; HO-1 polyclonal antibody). LPO was inhibited to baseline levels by SnPP (tin protoporphyrin, a selective inhibitor of HO). The antibody decreased LPO by 36%. BHT and Vit E, both chain-breaking lipid phase antioxidants, inhibited LPO to baseline levels. The iron chelators desferrioxamine (Df) and EDTA also significantly decreased LPO. We have demonstrated that, in a microsomal-lipid system, HO can exert pro-oxidant activity, which is mediated by free iron. The importance of this reaction is under investigation, and may have wider implications in conditions such as ARDS. (Graph Presented).
Quinlan GJ, Margarson MP, Mumby S, et al., 1998, Administration of albumin to patients with sepsis syndrome: a possible beneficial role in plasma thiol repletion, CLINICAL SCIENCE, Vol: 95, Pages: 459-465, ISSN: 0143-5221
Williams EA, Quinlan GJ, Goldstraw P, et al., 1998, Postoperative lung injury and oxidative damage in patients undergoing pulmonary resection, EUROPEAN RESPIRATORY JOURNAL, Vol: 11, Pages: 1028-1034, ISSN: 0903-1936
Salmon M, Koto H, Lynch OT, et al., 1998, Proliferation of airway epithelium after ozone exposure - Effect of apocynin and dexamethasone, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 157, Pages: 970-977, ISSN: 1073-449X
Niebauer J, Webb-Peploe KM, Jourdan K, et al., 1998, Chronic exercise training modulates oxidative stress in patients with chronic heart failure, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, Vol: 31, Pages: 509A-509A, ISSN: 0735-1097
Brett SJ, Quinlan GJ, Mitchell J, et al., 1998, Production of nitric oxide during surgery involving cardiopulmonary bypass, CRITICAL CARE MEDICINE, Vol: 26, Pages: 272-278, ISSN: 0090-3493
Gutteridge JMC, Quinlan GJ, Yamamoto Y, 1998, Hypothesis - Are fatty acid patterns characteristic of essential fatty acid deficiency indicative of oxidative stress?, FREE RADICAL RESEARCH, Vol: 28, Pages: 109-114, ISSN: 1071-5762
Quinlan GJ, Lamb NJ, Evans TW, et al., 1998, Increased levels of markers of protein oxidation in bronchoalveolar lavage fluid from patients with ARDS, NATO Advanced Study Institute on Acute Respiratory Distress Syndrome - Cellular and Molecular Mechanisms and Clinical Management, Publisher: PLENUM PRESS DIV PLENUM PUBLISHING CORP, Pages: 263-264, ISSN: 0258-1213
Gutteridge JMC, Quinlan GJ, Kovacic P, 1998, Phagomimetic action of antimicrobial agents, FREE RADICAL RESEARCH, Vol: 28, Pages: 1-14, ISSN: 1071-5762
Lamb NJ, Hamilton L, Quinlan GJ, et al., 1997, Is heme oxygenase present in plasma and BALF from patients with ARDS?, Thorax, Vol: 52, ISSN: 0040-6376
Heme oxygenase is the microsomal-bound enzyme responsible for cleavage of heme to biliverdin, with the concomitant release of free iron and carbon monoxide. Two isoforms have been identified and cloned: HO-1 (inducible) and HO-2 (constitutive). HO-1 (heat shock protein 32) is induced by various forms of oxidative stress, where it is thought to have a "protective" effect through the production of bilirubin and induction of ferritin. Patients with ARDS are known to be under severe oxidative stress and the expression of heat shock proteins in these patients has been well established. Here, we analysed plasma and bronchoalveolar lavage fluid (BALF) samples from patients with ARDS to see if HO-1 was released into extracellular fluids. BALF samples from 7 patients with ARDS and 3 intensive care controls were routinely collected, spun to remove cellular debris and mucus, and stored at -80°C until use. Blood samples from 6 patients with ARDS and 4 healthy controls were collected, the plasma obtained by centrifugation, and stored at -80°C. The presence of heme oxygenase was determined using standard immunoblotting (Western) techniques and levels indexed to a 2ng sample of the recombinant enzyme. Using this technique, we found no evidence for the presence of HO-1 in plasma or BALF in either patients with ARDS or control groups. If heme oxygenase is present in extracellular fluids then it is below 2ng, or rapidly degraded by proteolytic enzymes to impair immunoreactivity. These possibilities are currently under investigation.
Jourdan KB, Evans TW, Quinlan G, et al., 1997, Oxidant stress induces the release of both PGE<inf>2</inf> and 8-iso PGF<inf>2α</inf> by a COX-2 dependent pathway, Thorax, Vol: 52, ISSN: 0040-6376
Introduction 8-iso prostaglandin (PG) F2α is one of a series of prostaglandin-like compounds the isoprostanes. 8-iso PGF2α has been shown to have potent vasoactive properties on both rat and human pulmonary artery (PA). Their synthesis was initially described as independent of the enzyme cyclooxygenase and through free radical action on arachidonic acid, although recent evidence suggests the involvement of cyclooxygenase. We have compared the release of PGE2 (a typical COX metabolite) and 8-iso PGF2α from human PA smooth muscles cells subjected to oxidant stress by a combination of xanthine oxidase (XO) and its substrate hypoxanthine (HX). Methods Human PA smooth muscle cells were cultured by explant from human PA denuded of endothelium in culture medium containing 20% foetal calf serum. PGE2 was measured by radioimmumoassay and 8-iso PGF2α by enzyme immunoassay. Cell respiration was measured by the conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide to a blue formazan product. Results 8-iso PGF2α was increased approximately two-fold after incubation with XO and it's substrate HX compared to XO alone. This ratio of increase was the same for PGE2 (fig. A). Oxidant stress was confirmed by a reduction of cellular respiration in the presence of XO and HX (fig. B). The release of both the prostanoids was inhibited more than 80% by the COX-2 specific inhibitor L-745,337. Similar observations were made when prostanoid release was stimulated by cytokines. (Graph Presented) Conclusion Oxidant stress stimulates the release of the isoporstane, 8-iso PGF2α and the typical COX metabolite, PGE2. Moreover, COX-2 appears to be important in the release of both prostanoids. These observations may help to explain why prostaglandin and isoprostane release is increased in conditions of oxidant stress.
Chen Y, Quinlan GJ, Evans TW, et al., 1997, Tissue distribution of constitutive and inducible haem oxygenase mRNA in normal and lipopolysaccharide (LPS) treated rats, Thorax, Vol: 52, ISSN: 0040-6376
Haem oxygenase catalyses the conversion of haem to biliverdin, free iron, and CO. It exists in two isoforms, one is constitutively expressed (HO-2), the other (HO-1) is induced by a variety of stresses including haem, endotoxin and hyperthermia. HO-1 is a heat shock protein (HSP) and is known as HSP 32. Evidence, suggests that haem oxygenase, has antioxidant properties and that its induction protects against oxidative damage. Production of bilirubin, a known antioxidant, from biliverdin may partly be responsible for these effects. Sepsis is often a complication of ARDS, and induction of heat shock proteins may help protect against tissue damage associated with the onset of ARDS. We have used a rat model of endotoxemia to establish the distribution of HO-1 and HO-2 mRNA expression in different tissues and compared these to normal healthy rats. (See table). *P<0.05. n=4. Units are HO mRNA / β-actin mRNA. Kidney Diaphrame Liver Spleen Lung HO-1 Normal 0,180 ± 0,072* 2,198 ± 0,844 3,145 ± 0,903 1,640 ± 0,216 0,395 ± 0,124* HO-1 LPS 2,615 ± 0,746* 5,300 ± 1,493 4,057 ± 0,921 1,803 ± 0,956 1,410 ± 0,135* HO-2 Normal 2,970 ± 0,952 8,812 ± 1,994 4,460 ± 1,063 1,047 ± 0,232 0,978 ± 0,418 HO-2 LPS 2,488 ± 0,432 6,928 ± 2,035 2,430 ± 0,920 0,802 ± 0,311 0,855 ± 0,385 In normal healthy rats HO-2 mRNA predominates in all tissues except the spleen. However, after 4 hours treatment with endotoxin significant upregulation of HO-1 is seen in most tissues. In particular, the lung and trachea show pronounced HO-1 mRNA upregulation, which in the case of the trachea is a novel finding. Induction of this protein may represent one of the first lines of defence against lung associated oxidative stress and have implications for ARDS and sepsis in patients.
Mumby S, Margarson M, Quinlan GJ, et al., 1997, Is bleomycin-detectable iron present in the plasma of patients with septic shock?, INTENSIVE CARE MEDICINE, Vol: 23, Pages: 635-639, ISSN: 0342-4642
Chabot F, Mitchell JA, Quinlan GJ, et al., 1997, Characterization of the vasodilator properties of peroxynitrite on rat pulmonary artery: Role of poly(adenosine 5'-diphosphoribose) synthase, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 121, Pages: 485-490, ISSN: 0007-1188
Messent M, Sinclair DG, Quinlan GJ, et al., 1997, Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress, CRITICAL CARE MEDICINE, Vol: 25, Pages: 425-429, ISSN: 0090-3493
Quinlan GJ, Lamb NJ, Tilley R, et al., 1997, Plasma hypoxanthine levels in ARDS: Implications for oxidative stress, morbidity, and mortality, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 155, Pages: 479-484, ISSN: 1073-449X
Chabot F, Mitchell JA, Quinlan G, et al., 1996, Role of poly-ADP ribosyltransferase in the vasodilator actions of peroxynitrite, Thorax, Vol: 51, ISSN: 0040-6376
The pulmonary vasculature is constantly exposed to oxygen species such as nitric oxide (NO) and superoxide anions which are usually metabolised by anti-oxidant enzymes. However, during inflammatory conditions, oxidants may be formed in excess leading to cellular damage or dysfunction. NO reacts rapidly with superoxide anions to form the putative toxic oxidant, peroxynitrite ONOO-. ONOO- has been shown to activate poly-ADP ribosyltransferase (PARS) leading to a depletion NAD+ and ATP, an event that is likely to greatly compromise energetic processes such as the maintenance of vascular tone. We have shown that ONOO- is a vasodilator of rat pulmonary arteries. Thus, we have investigated the possible contribution of PARS activation in the vasodilator properties of ONOO-. Pulmonary arteries were cut into rings and mounted in 2 ml organ baths containing warmed (37°C) and gassed (95%O2:5%CO2) Krebs' buffer. Tone (0.5 g) was induced by the addition of U46619 (1×10-6M). Under these conditions ONOO- (1×10-6-1×10-4M), acetylcholine (1×10-8-1×10-6M), and sodium nitroprusside (1×10-8-1×10-6M) caused concentration-dependent relaxation of pulmonary arteries. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (1×10-4M), inhibited the effects of acetylcholine but not ONOO- or sodium nitroprusside. Superoxide dismutase had no effect on any of the vasodilator agents. The PARS inhibitor 3-aminobenzamide (1×10-2M) significantly inhibited the relaxation caused by ONOO- but did not effect that caused by acetylcholine or sodium nitroprusside. Thus, ONOO- relaxes rat pulmonary artery directly, without causing the release of NO or superoxide. Moreover, ONOO-, unlike endogenously released NO (by acetylcholine) or nitrovasodilators appears to cause relaxation by activation of PARS. We propose that ONOO- activates PARS resulting in the depletion of cellular ATP reducing active processes of vascular smooth muscle including vaso-c
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