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Alex Dmitrienko - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of ly315920na s 5920 a selective inhibitor of 14 kda group iia Secretory Phospholipase A2 in patients with suspected sepsis and organ failure
Critical Care Medicine, 2003Co-Authors: Edward Abraham, Chris Naum, Venkata Bandi, Daniel Gervich, Stephen F Lowry, Richard Wunderink, Roland M H Schein, William L Macias, Simona Skerjanec, Alex DmitrienkoAbstract:ObjectiveConcentrations of group IIA Secretory Phospholipase A2, an inflammatory response mediator, are increased in the plasma of patients with sepsis and septic shock, and the extent of elevation is correlated with mortality. LY315920Na/S-5920 is a selective inhibitor of group IIA Secretory phosph
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Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA Secretory Phospholipase A2, in patients with suspected sepsis and organ failure
Critical care medicine, 2003Co-Authors: Edward Abraham, Chris Naum, Venkata Bandi, Daniel Gervich, Stephen F Lowry, Richard Wunderink, Roland M H Schein, William L Macias, Simona Skerjanec, Alex DmitrienkoAbstract:ObjectiveConcentrations of group IIA Secretory Phospholipase A2, an inflammatory response mediator, are increased in the plasma of patients with sepsis and septic shock, and the extent of elevation is correlated with mortality. LY315920Na/S-5920 is a selective inhibitor of group IIA Secretory phosph
Daniele De Luca - One of the best experts on this subject based on the ideXlab platform.
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Effect of Cooling on Lung Secretory Phospholipase A2 Activity in Vitro, Ex Vivo, and in Vivo
American journal of physiology. Lung cellular and molecular physiology, 2019Co-Authors: Chiara Autilio, Angelo Minucci, Shivani Shankar-aguilera, Lhoussaine Touqui, Daniele De LucaAbstract:Hypothermia can modify surfactant composition and function. Secretory Phospholipase A2 (sPLA2) hydrolyses surfactant phospholipids and is important in the pathobiology of several critical respirato...
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Clinical and biological role of Secretory Phospholipase A2 in acute respiratory distress syndrome infants.
Critical care (London England), 2013Co-Authors: Daniele De Luca, Angelo Minucci, Giorgio Conti, Marco Piastra, Elena Lopez-rodriguez, Francesca Vendittelli, Leonarda Gentile, Eleonora Stival, Massimo Antonelli, Mercedes EchaideAbstract:Introduction: Secretory Phospholipase A2 is supposed to play a role in acute lung injury but no data are available for pediatric acute respiratory distress syndrome (ARDS). It is not clear which enzyme subtypes are secreted and what the relationships are between enzyme activity, biophysical and biochemical parameters, and clinical outcomes. We aimed to measure the enzyme and identify its subtypes and to study its biochemical and biophysical effect. The secondary aim was to correlate enzyme activity with clinical outcome. Methods: Bronchoalveolar lavage was performed in 24 infants with ARDS and 14 controls with no lung disease. Samples were assayed for Secretory Phospholipase A2 and molecules related to its activity and expression. Western blotting and captive bubble surfactometry were also performed. Clinical data were real time downloaded. Results: Tumor necrosis factor-a (814 (506-2,499) vs. 287 (111-1,315) pg/mL; P = 0.04), enzyme activity (430 (253600) vs. 149 (61-387) IU/mL; P = 0.01), free fatty acids (4.3 (2.8-8.6) vs. 2 (0.8-4.6) mM; P = 0.026), and minimum surface tension (25.6 ± 6.1 vs. 18 ± 1.8 mN/m; P = 0.006) were higher in ARDS than in controls. Phospholipids are lower in ARDS than in controls (76.5 (54-100) vs. 1,094 (536-2,907) μg/mL; P = 0.0001). Three enzyme subtypes were identified (-IIA, -V, -X), although in lower quantities in controls; another subtype (-IB) was mainly detected in ARDS. Significant correlations exist between enzyme activity, free fatty acids (r = 0.823; P < 0.001), and surface tension (r = 0.55; P < 0.028). Correlations also exist with intensive care stay (r = 0.54; P = 0.001), PRISM-III24 (r = 0.79; P< 0.001), duration of ventilation (r = 0.53; P = 0.002), and oxygen therapy (r = 0.54; P = 0.001). Conclusions: Secretory Phospholipase A2 activity is raised in pediatric ARDS and constituted of four subtypes. Enzyme correlates with some inflammatory mediators, surface tension, and major clinical outcomes. Secretory Phospholipase A2 may be a clinically relevant target in pediatric ARDS.
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Ex Vivo Effect of Varespladib on Secretory Phospholipase A2 Alveolar Activity in Infants with ARDS
PloS one, 2012Co-Authors: Daniele De Luca, Angelo Minucci, Paola Cogo, Giorgio Conti, Marco Piastra, Francesca Vendittelli, Leonarda Gentile, Laura Marzano, Bruno Giardina, Ettore CapoluongoAbstract:Background Secretory Phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available.
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Secretory Phospholipase A2 pathway during pediatric acute respiratory distress syndrome: A preliminary study
Pediatric Critical Care Medicine, 2011Co-Authors: Daniele De Luca, Angelo Minucci, Paola Cogo, Ettore Capoluongo, Giorgio Conti, Domenico Pietrini, Virgilio P. Carnielli, Marco PiastraAbstract:Objective:To verify if Secretory Phospholipase A2 (sPLA2) is increased in pediatric acute respiratory distress syndrome (ARDS) triggered or not by respiratory syncytial virus infection and to clarify how the enzyme may influence the disease severity and the degree of ventilatory support.Design:Prosp
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Pulmonary Secretory Phospholipase A2 is Produced Along with Clara Protein in Human Neonates with Meconium Aspiration and Correlates with Oxygenation Impairment and Epithelial Damage
Pediatric Research, 2011Co-Authors: Daniele De Luca, Angelo Minucci, Ettore Capoluongo, Domenico Pietrini, Virgilio P. Carnielli, Marco Piastra, Domenico Tripodi, Giorgio ContiAbstract:Pulmonary Secretory Phospholipase A2 is Produced Along with Clara Protein in Human Neonates with Meconium Aspiration and Correlates with Oxygenation Impairment and Epithelial Damage
Ziad Mallat - One of the best experts on this subject based on the ideXlab platform.
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Reply: limits of Mendelian randomization analyses in selection of Secretory Phospholipase A2-IIA as a valid therapeutic target for prevention of cardiovascular disease.
Journal of the American College of Cardiology, 2013Co-Authors: Michael V Holmes, Ziad Mallat, Marc S. Sabatine, Holly J Exeter, Tabassome Simon, Aroon D. Hingorani, Juan P. Casas, Philippa J. TalmudAbstract:We appreciate the remarks of Drs. Rosenson and Hurt-Camejo regarding our work [(1)][1]. We agree that the association of levels of Secretory Phospholipase A2-IIA (sPLA2-IIA) mass and sPLA2 enzyme activity may differ in subjects with and without coronary heart disease (CHD). For this reason, all
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metabolic syndrome and carotid intima media thickness in young adults roles of apolipoprotein b apolipoprotein a i c reactive protein and Secretory Phospholipase A2 the cardiovascular risk in young finns study
Arteriosclerosis Thrombosis and Vascular Biology, 2010Co-Authors: Noora Mattsson, Ziad Mallat, Joelle Benessiano, Costan G Magnussen, Tapani Ronnemaa, Antti Jula, Leena Taittonen, Mika Kahonen, Markus Juonala, Jorma ViikariAbstract:Objective— Aberrations in apolipoprotein (apo) metabolism and increased systemic inflammation associate with the metabolic syndrome (MetS) and may contribute to its atherogenicity. We examined whether the association between carotid atherosclerosis and MetS in a population of young adults is mediated by apoB and apoA-I and/or by inflammatory markers C-reactive protein and type II Secretory Phospholipase A2. Methods and Results— We used cross-sectional and 6-year prospective data from the cardiovascular risk in young Finns study. In young adults (aged 24 to 39 years), apoB, C-reactive protein, and type II Secretory Phospholipase A2 enzyme activity were significantly higher and apoA-I lower in subjects with MetS (N=325) than in subjects without MetS (N=1858). In prospective analysis (N=1587), both MetS and high apoB predicted ( P 90th percentile and/or plaque. The association between MetS and incident high carotid intima-media thickness was attenuated by ≈40% after adjustment with apoB. Adjustments with apoA-I, C-reactive protein, or type II Secretory Phospholipase A2 did not diminish the association. Conclusion— High levels of apoB, C-reactive protein, and type II Secretory Phospholipase A2 and low levels of apoA-I associate with MetS in young adults. The atherogenicity of MetS in this population assessed by incident high carotid intima-media thickness appears to be substantially mediated by elevated apoB but not inflammatory markers.
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Abstract 1131: The Prognostic Utility of Secretory Phospholipase A2 in Patients With Stable Coronary Artery Disease
Circulation, 2009Co-Authors: Michelle L. O’donoghue, Ziad Mallat, David A. Morrow, Joelle Benessiano, Sarah Sloan, Alain Tedgui, Marc S. SabatineAbstract:Background: Secretory Phospholipase A2 (sPLA2) is believed to be involved in atherogenesis. To date, few prospective studies have examined the utility of sPLA2 for risk stratification. We examined ...
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Abstract 5459: Unexpected Acceleration of Atherosclerosis in Ldlr-null Mice Reconstituted With Group X Secretory Phospholipase A2-Deficient Bone Marrow
Circulation, 2009Co-Authors: Hafid Ait-oufella, Christelle Coatrieux, Bhama Ramkhelawon, Olivier Blanc-brude, Jérôme Sirvent, Ludivine Laurans, Gérard Lambeau, Ziad MallatAbstract:Group X (GX) Secretory Phospholipase A2 (sPLA2) has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid among several types of sPLA2. GX...
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Association between type II Secretory Phospholipase A2 plasma concentrations and activity and cardiovascular events in patients with coronary heart disease
European heart journal, 2009Co-Authors: Wolfgang Koenig, Ziad Mallat, Joelle Benessiano, C. Y. Vossen, Hermann Brenner, Dietrich RothenbacherAbstract:Aims Type II Secretory Phospholipase A2 (sPLA2-IIA) is widely expressed in various cell types and may trigger local inflammatory responses. We sought to evaluate whether systemic sPLA2 is associated with prognosis in patients with coronary heart disease (CHD). Methods and results Plasma concentrations of sPLA2 (ELISA) and sPLA2 activity (selective fluorometric assay) were measured at baseline in a cohort of 1024 patients aged 30–70 years with CHD. The Cox-proportional hazards model was used to determine the prognostic value of sPLA2 on a combined cardiovascular disease (CVD) endpoint after adjustment for covariates. During a mean follow-up of 4.1 years, 93 patients (9.1%) experienced a secondary CVD event. In a multivariable model, sPLA2 mass and activity were associated with hazard ratios of secondary CVD events of 2.07 (95% CI, 1.17–3.66) and 1.65 (95% CI 0.96–2.84) for mass and activity, respectively, when extreme tertiles were compared. Further adjustment for cystatin C, N-terminal-probrain natriuretic peptide, C-reactive protein, and lipoprotein-associated Phospholipase A2 attenuated the associations, still showing a positive trend for mass but a less clear pattern for activity. However, when sPLA2 mass and activity were analysed as continuous variables both still showed a statistically significant increase in risk in all models. Conclusion Secretory Phospholipase A2 mass and activity appear to be predictive of secondary CVD events in patients with CHD.
Eva Hurt-camejo - One of the best experts on this subject based on the ideXlab platform.
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Group IIA Secretory Phospholipase A2, Vascular Inflammation, and Incident Cardiovascular Disease.
Arteriosclerosis thrombosis and vascular biology, 2019Co-Authors: Akintunde O. Akinkuolie, Patrick R. Lawler, Audrey Y. Chu, Michael P. Caulfield, Bo Ding, Fredrik Nyberg, Robert J. Glynn, Paul M. Ridker, Eva Hurt-camejoAbstract:Objective— Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA2-IIA (group IIA Secretory Phospholipase A2) plays an integral role in regulating vascular inflammation. Althou...
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Limits of Mendelian randomization analyses in selection of Secretory Phospholipase A2-IIA as a valid therapeutic target for prevention of cardiovascular disease.
Journal of the American College of Cardiology, 2013Co-Authors: Robert S. Rosenson, Eva Hurt-camejoAbstract:Holmes et al. [(1)][1] investigated the association between Secretory Phospholipase A2-IIA (sPLA2-IIA) as a potential therapeutic target for prevention of cardiovascular disease, using observational studies between the PLA2G2A rs11573156 variant and cardiovascular events, and deductions from
Akbar Pirzadeh - One of the best experts on this subject based on the ideXlab platform.
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Tissue fatty acid composition and Secretory Phospholipase-A2 activity in oral squamous cell carcinoma
Clinical and Translational Oncology, 2015Co-Authors: M. Askari, M. Darabi, M. Oboodiat, Shabnam Fayezi, R. Zare Mahmudabadi, Z. Mostakhdemin Hosseini, Akbar PirzadehAbstract:Purpose Oral squamous cell carcinoma (OSCC) is a remarkable health problem worldwide, but its pathogenesis remains unknown. The aim of this study was to compare fat composition and Secretory Phospholipase-A2 (sPLA2) activity between the malignant and adjacent normal squamous tissues in patients with OSCC. Methods Paired samples of malignant squamous and adjacent normal-appearing tissues were collected from 27 patients with OSCC. The fatty acid composition in the obtained tissues was determined by gas liquid chromatography. Tissue enzyme activities of sPLA2 were measured using the standard assay with Diheptanoyl Thio-Phosphatidylcholine as substrate. Results In the OSCC tissue, the level of stearic acid (18:0) and activity of sPLA2 were higher ( P
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Tissue fatty acid composition and Secretory Phospholipase-A2 activity in oral squamous cell carcinoma
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexic, 2014Co-Authors: M. Askari, M. Darabi, R. Zare Mahmudabadi, M. Oboodiat, Shabnam Fayezi, Z. Mostakhdemin Hosseini, Akbar PirzadehAbstract:Purpose Oral squamous cell carcinoma (OSCC) is a remarkable health problem worldwide, but its pathogenesis remains unknown. The aim of this study was to compare fat composition and Secretory Phospholipase-A2 (sPLA2) activity between the malignant and adjacent normal squamous tissues in patients with OSCC.