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Добірка наукової літератури з теми "8-iso-PGF2α"

Автор: Grafiati

Опубліковано: 11 березня 2023

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Статті в журналах з теми "8-iso-PGF2α"

Lahaie, Isabelle, Pierre Hardy, Xin Hou, Haroutioun Hasséssian, Pierre Asselin, Pierre Lachapelle, Guillermina Almazan та ін. "A novel mechanism for vasoconstrictor action of 8-isoprostaglandin F2α on retinal vessels". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, № 5 (1 травня 1998): R1406—R1416. http://dx.doi.org/10.1152/ajpregu.1998.274.5.r1406.

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Using a video-imaging technique, we characterized the effects of 8-isoprostaglandin F2α(8-iso-PGF2α) on retinal vasculature from piglets. 8-Iso-PGF2α potently contracted (EC50 = 5.9 ± 0.5 nM) retinal vessels. These effects were completely antagonized by the cyclooxygenase inhibitor indomethacin, the thromboxane synthase blocker CGS-12970, the thromboxane receptor antagonist L-670596, and the putative inhibitor of the non-voltage-dependent receptor-operated Ca2+ pathway SKF-96365; constrictor effects of 8-iso-PGF2α were also partly attenuated by the ETA-receptor blocker BQ-123 and an inhibitor of endothelin-converting enzyme, phosphoramidon, but was negligibly affected by the L-type voltage-gated Ca2+ channel blocker nifedipine. Correspondingly, 8-iso-PGF2αelicited endothelin release from retinal preparations, which was markedly reduced by SKF-96365. 8-Iso-PGF2α also increased thromboxane production in the retina and cultured endothelial cells, but not on retinovascular smooth muscle cells; these effects of 8-iso-PGF2α were blocked by indomethacin, CGS-12970, SKF-96365, and EGTA, but not by nifedipine. 8-Iso-PGF2α also increased Ca2+ transients in retinal endothelial cells, which were inhibited by SKF-96365 and EGTA, but not by nifedipine, whereas in smooth muscle cells U-46619, but not 8-iso-PGF2α, stimulated a rise in Ca2+ transients. Finally, H2O2+ FeCl2 (in vitro) and anoxia followed by reoxygenation (in vivo) stimulated formation of 8-iso-PGF2α in the retina. In conclusion, 8-iso-PGF2α-induced retinal vasoconstriction is mediated by cyclooxygenase-generated formation of thromboxane and, to a lesser extent, by endothelin after Ca2+ entry into cells, possibly through receptor-operated channels. Retinal vasoconstriction to 8-isoprostanes might play a role in the genesis of ischemic retinopathies.

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Belik, J., R. P. Jankov, J. Pan, M. Yi, C. R. Pace-Asciak та A. K. Tanswell. "Effect of 8-isoprostaglandin F2α on the newborn rat pulmonary arterial muscle and endothelium". Journal of Applied Physiology 95, № 5 (листопад 2003): 1979–85. http://dx.doi.org/10.1152/japplphysiol.00420.2003.

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8-Isoprostaglandin F2α (8-iso-PGF2α) is a bioactive lipid peroxidation product that is a vasoconstrictor at high concentrations. Paradoxically, at lower, and possibly physiological, concentrations, it is a pulmonary vascular muscle's relaxant. Its effects on newborn pulmonary vasculature are unknown. We hypothesized that the pulmonary arterial 8-iso-PGF2α responses may be developmentally regulated. Therefore, the purpose of this study was to evaluate and compare 8-iso-PGF2α effects between 1- and 2-wk-old newborn and adult rat isolated intrapulmonary arteries (100 μm) mounted on a myograph. Force after 8-iso-PGF2α stimulation was greatest in the adult ( P < 0.01). In newborns, force was significantly increased by the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) ( P < 0.01) and was suppressed by blockade of the thromboxane (Tx) A2 receptor. Whereas 8-iso-PGF2α induced a significant dose-dependent relaxation of adult precontracted vessels in the presence of a TxA2 mimetic (U-46619; 1 μM), contraction was observed in the 1-wk-old rat. This 8-iso-PGF2α-induced contraction was abolished by endothelium removal and l-NAME and was attenuated by the cyclooxygenase inhibitor ibuprofen. In the presence of a TxA2/prostaglandin H2 receptor blocker, 8-iso-PGF2α induced NO-mediated relaxation, the magnitude of which was greater in the newborn, compared with the adult ( P < 0.01). When exposed to 8-iso-PGF2α in vitro, only the newborn lung secreted TxB2. We conclude that, in contrast to its relaxant effect in the adult, 8-iso-PGF2α induces contraction of the pulmonary arteries in the early postnatal period, which is likely to be mediated by endothelium-derived TxA2. This phenomenon may contribute to the maintenance of a higher pulmonary vascular resistance in the early postnatal period.

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Sun, Ying, Yan Yan та Xuejun Kang. "Packed-Fiber Solid Phase-Extraction Coupled with HPLC-MS/MS for Rapid Determination of Lipid Oxidative Damage Biomarker 8-Iso-Prostaglandin F2α in Urine". Molecules 27, № 14 (10 липня 2022): 4417. http://dx.doi.org/10.3390/molecules27144417.

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The 8-iso-prostaglandin F2α (8-iso-PGF2α) biomarker is used as the gold standard for tracing lipid oxidative stress in vivo. The analysis of urinary 8-iso-PGF2α is challenging when dealing with trace amounts of 8-iso-PGF2α and the complexity of urine matrixes. A packed-fiber solid-phase extraction (PFSPE)–coupled with HPLC-MS/MS–method, based on polystyrene (PS)-electrospun nanofibers, was developed for the specific determination of 8-iso-PGF2α in urine and compared with other newly developed LC-MS/MS methods. The method, which simultaneously processed 12 samples within 5 min on a self-made semi-automatic array solid-phase extraction processor, was the first to introduce PS-electrospun nanofibers as an adsorbent for the extraction of 8-iso-PGF2α and was successfully applied to real urine samples. After optimizing the PFSPE conditions, good linearity in the range of 0.05–5 ng/mL with R2 > 0.9996 and a satisfactory limit of detection of 0.015 ng/mL were obtained, with good intraday and interday precision (RSD < 10%) and recoveries of 95.3–103.8%. This feasible method is expected to be used for the batch quantitative analysis of urinary 8-iso-PGF2α.

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Cabral, Pablo D., Guillermo B. Silva, Sandra T. Baigorria, Luis A. Juncos, Luis I. Juncos та Néstor H. García. "8-iso-prostaglandin-F2α stimulates chloride transport in thick ascending limbs: role of cAMP and protein kinase A". American Journal of Physiology-Renal Physiology 299, № 6 (грудень 2010): F1396—F1400. http://dx.doi.org/10.1152/ajprenal.00225.2010.

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Salt reabsorption by the loop of Henle controls NaCl handling and blood pressure regulation. Increased oxidative stress stimulates NaCl transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2α (8-iso-PGF2α) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2α regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCl transport in several nephron segments, we hypothesized that 8-iso-PGF2α increases NaCl transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2α on NaCl transport by measuring chloride absorption ( JCl) in isolated microperfused cTALs. Adding 8-iso-PGF2α to the lumen increased JCl by 54% (from 288.7 ± 30.6 to 446.5 ± 44.3 pmol·min−1·mm−1; P < 0.01), while adding it to the bath enhanced JCl by 35% (from 236.3 ± 35.3 to 319.2 ± 39.8 pmol·min−1·mm−1; P < 0.05). This stimulation was blocked by Na-K-2Cl cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 ± 1.6 fmol·min−1·mm−1, and 8-iso-PGF2α raised it to 35.1 ± 1.4 fmol·min−1·mm−1, an increase of 94% ( P < 0.01). Because cAMP stimulates PKA, we measured JCl using the PKA-selective inhibitor H89. In the presence of H89 (10 μM), 8-iso-PGF2α failed to increase transport regardless of whether it was added to the lumen (216.1 ± 16.7 vs. 209.7 ± 23.8 pmol·min−1·mm−1; NS) or the bath (150.4 ± 32.9 vs. 127.1 ± 28.6 pmol·min−1·mm−1; NS). We concluded that 8-iso-PGF2α stimulates cAMP and increases Cl transport in cTALs via a PKA-dependent mechanism.

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Carnevale, Roberto, Alessio Farcomeni, Roberto Cangemi, Cristina Nocella, Simona Bartimoccia, Tommasa Vicario, Mirella Saliola, et al. "Serum NOX2 and urinary isoprostanes predict vascular events in patients with atrial fibrillation." Thrombosis and Haemostasis 113, no. 03 (May 2015): 617–24. http://dx.doi.org/10.1160/th14-07-0571.

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SummaryThere are limited prospective data evaluating the role of urinary F2-IsoP and NOX2 as predictive markers in atrial fibrillation (AF). The aim of this study was to analyse the role of urinary prostaglandin PGF2alpha (8-iso-PGF2α) and NOX2, markers of systemic oxidative stress, in predicting cardiovascular (CV) events and mortality in anticoagulated non-valvular AF patients. This was a prospective study including 1,002 anticoagulated AF patients, followed for a median time of 25.7 months (interquartile range: 14.8–50.9). All major CV events, CV deaths and all-cause deaths were considered as primary outcomes of the study. CV events included fatal/nonfatal ischaemic stroke, fatal/ nonfatal myocardial infarction (MI), cardiac revascularisation and transient ischaemic attack (TIA). Oxidative stress biomarkers, such as urinary 8-iso-PGF2α and serum sNOX2-dp, a marker of NOX2 activation, were measured. A CV event occurred in 125 patients (12.5 %); 78 CV deaths and 31 non-CV deaths were registered. 8-iso-PGF2α and sNOX2-dp were correlated (Rs=0.765 p> 0.001). A significant increased cumulative incidence of CV events and CV deaths was observed across tertiles for 8-iso-PGF2α and sNOX2-dp. An increased rate of all-cause death was observed across tertiles of urinary 8-iso-PGF2α.In Cox or Fine and Gray models, 8-iso-PGF2α predicted CV events and CV and non-CV deaths. The addition of tertiles of 8-iso-PGF2α to CHA2DS2-VASc score improved ROC curves for each outcome and NRI for CV events (0.24 [0.06–0.53] p=0.0067). The study shows that in AF patients 8-iso-PGF2α and NOX2 levels are predictive of CV events and total mortality. F2-IsoP may complement conventional risk factors in prediction of CV events.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief. Clinical Trial Registration: ClinicalTrials.gov NCT01882114.

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Crawford, Brittany, Dale Sandler, Hazel Nichols, Ginger Milne, Susan Steck, and Yong-Moon Park. "Association Between Healthy Dietary Patterns and Markers of Oxidative Stress." Current Developments in Nutrition 6, Supplement_1 (June 2022): 355. http://dx.doi.org/10.1093/cdn/nzac054.010.

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Abstract Objectives Oxidative stress is involved in chronic disease etiology and the aging process and is related to antioxidant intake. However, less is known about the relationship between dietary patterns and markers of oxidative stress. We assessed cross-sectionally the association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary F2-isoprostanes (8-iso-PGF2α and 8-iso-PGF2α-M), which are established biomarkers of oxidative stress. Methods Data were obtained from 844 premenopausal and 454 postmenopausal women participating in the Sister Study who had urinary samples analyzed for F2-isoprostanes. Responses from a 110-item validated food frequency questionnaire (FFQ) at baseline were used to calculate dietary pattern scores. Concentrations of 8-iso-PGF2α and its metabolite (8-iso-PGF2α-M) were measured by GC/MS for samples from premenopausal women and LC/MS for samples from postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes among pre-menopausal and post-menopausal women separately. Results Among premenopausal women, we observed significant inverse associations between the four dietary indices and mean 8-iso-PGF2α (aMED βQ4vsQ1: −0.15, 95% CI: −0.25, −0.05; DASH βQ4vsQ1: −0.15, 95% CI: −0.25, −0.25; aHEI βQ4vsQ1: −0.15, 95% CI: −0.25, −0.05; HEI-2015 βQ4vsQ1: −0.17, 95% CI: −0.27, −0.07). These associations were modified by age, education, income, and BMI, though there was no evidence of statistical interaction. In a sensitivity analysis, estimates did not substantially differ by the presence or absence of chronic disease. Among postmenopausal women, aHEI was associated with mean 8-iso-PGF2α and 8-iso-PGF2α-M (β8-iso-PGF2α: −0.003, 95% CI: −0.01, −0.005, β8-iso-PGF2α-M: −0.003, 95% CI: −0.01, −0.005). No other significant findings were observed among postmenopausal women. Conclusions Healthy dietary patterns may be associated with reduced oxidative stress, particularly among premenopausal women. Funding Sources National Institute of Environmental Health Sciences, NIH Office of Dietary Supplements, Avon Foundation, T32 from NIH-NIGMS.

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Tsikas, Dimitrios. "The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F2α and prostaglandin F2α". Journal of Controversies in Biomedical Research 3, № 1 (28 червня 2017): 11–15. http://dx.doi.org/10.15586/jcbmr.2017.20.

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In general, the term “oxidative stress” describes an imbalance between oxidants and antioxidants in favor of the oxidants. While antioxidant defense is widely accepted to involve both enzymatic and non-enzymatic reactions, oxidants are generally assumed to be produced by non-enzymatic processes involving chemically produced free radicals. However, many oxidants are also formed by numerous enzymes and proteins. The F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α) and malondialdehyde (MDA) are widely used as biomarkers of oxidative stress, although there is evidence that both 8-iso-PGF2α and MDA are also produced enzymatically from arachidonic acid by the action of cyclooxygenase (COX). On the contrary, there is also evidence that PGF2α is produced from arachidonic acid both by the action of COX and non-enzymatically. The duality of oxidative stress, personified by 8-iso-PGF2α and PGF2α, is a serious dilemma and demands new definitions and strategies from the scientists.

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Miyazaki, Yusuke, Tatsuro Nakamura, Shinya Takenouchi, Akane Hayashi, Keisuke Omori та Takahisa Murata. "Urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of colitis-associated colorectal cancer in mice". PLOS ONE 16, № 1 (27 січня 2021): e0245292. http://dx.doi.org/10.1371/journal.pone.0245292.

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Early diagnosis of colorectal cancer is needed to reduce the mortal consequence by cancer. Lipid mediators play critical role in progression of colitis and colitis-associated colon cancer (CAC) and some of their metabolites are excreted in urine. Here, we attempted to find novel biomarkers in urinary lipid metabolite of a murine model of CAC. Mice were received single administration of azoxymethane (AOM) and repeated administration of dextran sulfate sodium (DSS). Lipid metabolites in their urine was measured by liquid chromatography mass spectrometry and their colon was collected to perform morphological study. AOM and DSS caused inflammation and tumor formation in mouse colon. Liquid chromatography mass spectrometry-based comprehensive analysis of lipid metabolites showed that cyclooxygenase-mediated arachidonic acid (AA) metabolites, prostaglandins, and reactive oxygen species (ROS)-mediated AA metabolites, isoprostanes, were predominantly increased in the urine of tumor-bearing mice. Among that, urinary prostaglandin (PG)E2 metabolite tetranor-PGEM and PGD2 metabolite tetranor-PGDM were significantly increased in both of urine collected at the acute phase of colitis and the carcinogenesis phase. On the other hand, two F2 isoprostanes (F2-IsoPs), 8-iso PGF2α and 2,3-dinor-8-iso PGF2α, were significantly increased only in the carcinogenesis phase. Morphological study showed that infiltrated monocytes into tumor mass strongly expressed ROS generator NADPH (p22phox). These observations suggest that urinary 8-iso PGF2α and 2,3-dinor-8-iso PGF2α can be indexes of CAC.

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Cañizo Vázquez, Débora, Stephanie M. Hadley, Marta Pérez Ordóñez, Miriam Lopez-Abad, Anna Valls, Marta López Viñals, Bosco A. Moscoso, Sergio Benito Fernandez, Marta Camprubí-Camprubí, and Joan Sanchez-de-Toledo. "Oxidative Stress and Indicators of Brain Damage Following Pediatric Heart Surgery." Antioxidants 11, no. 3 (February 28, 2022): 489. http://dx.doi.org/10.3390/antiox11030489.

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Pediatric cardiac surgery induces an increased oxidative stress (OS) response. Increased OS is associated with poor neurologic outcomes in neonatal populations with similar patterns of brain injury. We investigated OS and brain injury in infants undergoing heart surgery. Patients 6 months or younger, undergoing cardiac surgery with or without cardiopulmonary bypass (CPB), were included in this prospective, observational study. Patients were divided into infant (30 days–6 months) and neonatal (<30 days) groups for analysis. Urine OS biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) was quantified pre-surgery and at 0 and 24 h post-surgery. A serum brain damage biomarker S100B protein was also measured pre-surgery and at 0 and 72 h post-surgery. Amplitude-integrated electroencephalography during surgery was analyzed. Neuropsychological evaluation using the Bayley III or Vineland test was performed in all patients at 24 months of age. Sixty-two patients were included, 44 of whom underwent follow-up neurologic evaluation. 8-iso-PGF2α and S100B levels were increased after surgery. Postoperative levels of S100B were positively correlated with 8-iso-PGF2α levels 24 h after surgery (rho = 0.5224; p = 0.0261). There was also a correlation between immediate post-surgery levels of 8-iso-PGF2α and intra-surgery seizure burden (rho = 0.4285, p = 0.0205). Patients with an abnormal neurological evaluation had increased levels of S100B 72 h after surgery (p = 0.048). 8-iso-PGF2α levels 24 h after surgery were also related to abnormal neurologic outcomes. Levels of 8-iso-PGF2α following pediatric cardiac surgery are associated with several indicators of brain injury including brain damage biomarkers, intra-operative seizures, and abnormal neurological evaluation at follow-up, suggesting the importance of oxidative stress response in the origin of brain damage in this population.

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Petersson, Helena, Ulf Risérus, Jolene McMonagle, Hanne L. Gulseth, Audrey C. Tierney, Sophie Morange, Olfa Helal, et al. "Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study." British Journal of Nutrition 104, no. 9 (June 23, 2010): 1357–62. http://dx.doi.org/10.1017/s000711451000228x.

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Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

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Більше джерел

Дисертації з теми "8-iso-PGF2α"

Moritz, Eileen [Verfasser], та Elke [Akademischer Betreuer] Oetjen. "Die Bedeutung der vasoaktiven Signallipide 8-iso-PGF2α und S1P für kardiovaskuläre Erkrankungen / Eileen Moritz ; Betreuer: Elke Oetjen". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1116604558/34.

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Moritz, Eileen Verfasser], та Elke [Akademischer Betreuer] [Oetjen. "Die Bedeutung der vasoaktiven Signallipide 8-iso-PGF2α und S1P für kardiovaskuläre Erkrankungen / Eileen Moritz ; Betreuer: Elke Oetjen". Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1116604558/34.

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SALVAGNO, GIAN LUCA. "Ruolo e significato dei metaboliti ossidati e della Fosfolipasi-A2 lipoproteica nei pazienti a rischio e con patologia aterosclerotica." Doctoral thesis, 2015. http://hdl.handle.net/11562/914384.

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All'inizio del 1990, diversi autori hanno scoperto la formazione di prostaglandine, composti F2-simili, F2-isoprostani (F2-IsoPs), mediante una reazione non-enzimatica di perossidazione dell’acido arachidonico che coinvolge i radicali(ROS). Gli IsoPs sono inizialmente formati come esterificati dei fosfolipidi e poi rilasciati in forma libera. L'evidenza suggerisce che i fattori di rischio comuni per aterosclerosi aumentano il rischio di produzione di ROS, non solo dalle cellule endoteliali, ma anche dalle cellule muscolari lisce e le cellule avventiziali. Si ipotozza che la produzione di radicali liberi ossidativi sia alla base del processo fisiopatologico della disfunzione endoteliale, una fase iniziale di aterogenesi. Lo stress ossidativo porta ad ossidazione delle LDL (ox-LDL), le quali sono inglobate da parte dei. Gli isoprostani sono prodotti di perossidazione lipidica stabili di acido arachidonico, la quantificazione dei quali fornisce un indice di stress ossidativo. Oggetto della presente Tesi è di descrivere un metodo per analizzare 8-iso-PGF2α nel plasma. Il metodo prevede l'estrazione in fase solida e valutazione con GC-MS.
At the beginning of the 1990,several authors discovered the formation of prostaglandin F2-like compounds, F2-isoprostanes (F2-IsoPs), in vivo by non-enzymatic free radical–induced peroxidation of arachidonic acid. IsoPs are initially formed esterified to phospholipids and then released in free form. Evidence suggests that common risk factors for atherosclerosis increase the risk of the production of free oxidative radicals (free ROS), not only from the endothelial cells, but also from the smooth muscle cells and the adventitial cells. The production of free oxidative radicals is believed to induce endothelial dysfunction, an initial step of atherogenesis. Oxidative stress leads to oxidation of LDL (ox-LDL), whose uptake by macrophages is easier compared to non-oxidized lipoproteins. F -Isoprostanes are stable lipid peroxidation products of arachidonic acid, the quantification of which provides an index of oxidative stress. We describe a method for analysing 8-iso-PGF2α) in plasma. The method involves solid-phase extraction and evaluation with GC-MS.

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Тези доповідей конференцій з теми "8-iso-PGF2α"

Marques, RH, CM Starling, FG Reis, R. Almeida-Reis, C. Cabido, RF Mizutani, E. Leick-Maldonado та ін. "Effects of iNOS Inhibition on Lung Tissue Mechanics and 8-Iso-PGF2α Expression Induced by Physical Stress in Animals with Chronic Pulmonary Inflammation." У American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a2842.

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