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Effet protecteur du préconditionnement hypoxique sur les effets délétères de l'ischémie-reperfusion
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Year: 2010 Publisher: Bruxelles: UCL. Faculté de pharmacie et des sciences biomédicales,

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Ischemic preconditioning allows protecting the endothelium against the irreversible injuries like endothelial dysfunctions caused by ischemial/reperfusion episodes. The aim of this study was to develop an in vitro model of hypoxic preconditioning on Human Umbilical Vein Endothelial Cells (HUVEC) to understand the mechanisms of this protection and to investigate the role of some proteins in the protective effects of hypoxia preconditioning. Leucocytes Jurkats adhesion to the endothelial cells was chosen as read-out. Western blot have been realized to analyze the changes in expression of potential interesting proteins.Our results confirm the fundamental role of HSP90 in protecting HIF-1, ERKl/2 and Akt from proteosomal degradation. It also shows that the endothelial dysfunction caused by hypoxia is a consequence of an alteration in eNOS activation by phosphorylation. Finally, this study allows validating the hypothesis of the ER1l/2 participation in HIF-1 activation which expression seems to be reduced by hypoxic preconditioning. However, the preconditioning model used didn’t show a protective effect of preconditioning. Le préconditionnement ischémique permet de protéger l'endothélium contre les effets délétères de l'ischémie/reperfusion et notamment en prévenant les dysfonctions endothéliales.Le but de cette étude était de développer un modèle in vitro de préconditionnement hypoxique sur des cultures de cellules endothéliales issues de cordons ombilicaux humains (HUVEC) afin de comprendre les mécanismes de cette protection et d'investiguer Je rôle de certaines protéines dans la protection offerte par le préconditionnem ent. Le read-out choisi pour la mise au point de ce modèle était l'adhésion de cellules leucocytaires Jurkats sur les HUVECs. Des analyses expressionnelles des protéines d'intérêt ont été réalisées par Western Blot.Nos résultats confirment le rôle fondamental de la protéine HSP90 dans la protection contre la dégradation de HIF-1, ERKl/2 et d'Akt. Ils démontrent également que la dysfonction endothéliale consécutive à l'hypoxie passe par l'altération de l'activation de eNOS via l'inhibition de sa phosphorylation par Akt. Enfin, cette étude permet de valider l'hypothèse de la participation de ERKl/2 dans l'activation de HIF-l a dont l'expression semble diminuée suite au préconditionnement.Le modèle de préconditionnement hypoxique utilisé ne permet cependant pas d'observer un effet protecteur du préconditionnement.


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Cyanide concentrations in nitrile intoxications and smoke inhalations - levels and therapeutical consequences

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The toxicity of cyanide or hydrocyanic acid is well know since decades. Typically such intoxications will have an apoplectic course, sometimes reported as “all or nothing” – immediate death or survival [e.g.163], while other publications challenge this [198].
A variety of antidotes has been introduced for the treatment of such poisonings, starting with methylene blue, to nitrites and 4-dimethylaminophenol as methemoglobin forming agents, to cobalt-containing drugs like Co-EDTA or hydroxocobalamin. A consistently recommended antidote still is sodium thiosulfate.
It is less know that cyanide poisoning can occur as sequelae to intoxications with cyanogenic agents like organic nitriles, aliphatic as well as olefinic ones. In the emergency room of the occupational medical department of a large chemical plant we have been surprised in the last years by several very severe poisonings with cyanide levels in the potentially dangerous range. Such a degree of cyanide formation so far had not been seen. Thus it is important to report our observations.
Whereas nitriles mainly are handled in chemicals plants by chemical workers, they may – rarely- also play a role in acute exposures of the general public, as shown by a railroad accident with liberation of acrylonitrile in Germany in February 2002 (unpublisheb), and in reports on oral ingestions of nail-removers containing acetonitrile. In the industry acetonitrile is a very common, propionitrile a rare solvent, whereas acrylonitile is used in latices production and especially in the productions of ABS (acrylonitrile-butadiene-styrene)-plastics. Nevertheless, reports in literature on such poisoning are scarce, and they do not deal primarily with aspects of metabolism, cyanide levels, and treatment options. Clearly there is a lack of data and guidelines concerning such poisonings, even in occupational medicine, but also in clinical toxicology.
In contrast, another indirect source of cyanide exposures is discussed widely in the last years, mainly because of possible exposures of the general public, but also of firefighters and rescue personnel. This source is smoke inhalation. Many substances from natural ones like wool to plastics like ABS-plastics and polyurethanes can yield a substantial amount of HCN gas when burning or smouldering. Together with the enormous amount of other toxins released in fires, from chlorine, phosgene, hydrochloric acid gases, nitrous oxides, carbon monoxide and dioxide, to organics like acrolein and benzene, HCN may well play an important part in the toxicity of smoke. However, there is an intense discussion in literature about the importance of cyanide in smoke inhalations, of its occurrence, its amount, its sequelae, but also about practical measures to be taken in the treatment of smoke inhalation patients that is the necessity and choice of cyanide antidotes.
The aims of the study are first to report on poisonings with different nitriles seen in the last decade in a large chemical plant, including biomonitoring data. From these casuistics the clinical symptoms of such poisonings, an eventual influence of different routes of exposure, results of repeated biomonitoring, and especially the treatment options will be shown.
In addition, a study has been performed in smoke inhalation victims from residential fires. The concentrations of carbon monoxide and cyanide were measured, and eventual correlations between these parameters and clinical data reported in the literature were examined. The choice of antidotes in smoke inhalations in hampered by the fact, that the patients may present with a CO-hemoglobinemia, which means the part of the hemoglobin is unable to bind and transport oxygen. Thus the choice of cyanide antidotes, if required, would be problematic, as some will induce a further hypoxemia. So it is of interest to assess, what role cyanides really do play in smoke inhalations, whether and what antidotes are needed, and what room is left for which antidotes.
The existing literature has to be discussed under different aspects. First the reports and recommendations for nitrile poisonings and smoke inhalations have to be assessed, but in addition questions like evidence for occurrence of HCN in smoke, lethal cyanide levels in blood, and their possible correlations to COHb and clinical signs must be addressed.
From the data of the nitrile casuistics and the smoke inhalation study and from the literature discussion treatment recommendations for both situations can be derived.


Book
Morality and ethics at war : bridging the gaps between the soldier and the state
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ISBN: 9781350104549 135010454X Year: 2020 Publisher: London: Bloomsbury academic,

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In Morality and Ethics of War, which includes a foreword by Major General Susan Coyle, ethicist Deane-Peter Baker goes beyond existing treatments of military ethics to address a fundamental problem: the yawning gap that exists between the diverse moral frameworks defining personal identity in a multicultural society on the one hand, and the professional military ethic on the other. Baker argues that overcoming this chasm is essential to minimising the ethical risks that can lead to operational and strategic failure for military forces engaged in today's complex conflict environment. He contends that spanning the gap is vital in preventing moral injury from befalling the nation's uniformed servants. Drawing on a revised account of what he calls 'the Just War Continuum', Baker develops a bridging framework that combines conceptual clarity and rigour with insights from cutting edge psychological research and creates a practical means for military leaders to negotiate the moral chasm in military affairs.


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Production de radicaux libres lors de la reperfusion d'organes ischémiés: étude à partir du rein de lapin
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Year: 1992 Publisher: Liège: Université de Liège. Faculté de médecine,

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Intérêt du dosage du NGAL dans l'insuffisance rénale aiguë d'origine toxique ou autre
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Year: 2011 Publisher: Bruxelles: UCL,

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Acute kidney injury (AKI) is a frequent and serious complication for hospitalized patients. In spite of considerable improvement in treatments, the morbidity and mortality associated with acute kidney injury remains relatively high. The major reason being that, at the moment, we don’t know of any sensitive and specific markers of the renal function which would allow for an early diagnosis of acute kidney injury. At present, traditional biomarkers of the renal function (creatinine and urea) do not detect kidney injury early enough. In renal transplantation, the identification of adequate biomarkers of the renal function are indispensable to evaluate the quality of the transplant before the transplantation but also to minimize the risk of acute rejection and acute tubular necrosis during the post-operative period. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an early biomarkers of acute kidney injury. This marker of tubular necrosis has been measured in the urine and in the blood of 54 patients before and at different time after a renal transplantation. Other biomarkers of the renal function (Cystatine C and β2-Microglobuline) have also been tested. The aim of the study is on the one hand to test the various biomarkers of “donor” patients according to their category (living or cadaveric donors’kidneys) and on the other hand to study these biomarkers for the “recipient” patients according to the events that occurred during the post-operative period. The preliminary results show that 13 patients developed an acute tubular necrosis (ATN) within the first 24 hours post-operation. The statistical tests show that the rates of urinary and blood NGAL were significantly higher for the patient’s who developed an ATN compared with those who didn’t. Furthermore, this difference between both groups is observed within 6 hours after the transplantation. L’atteinte rénale aiguë est une complication fréquente et sérieuse chez les patients hospitalisés. Malgré une amélioration considérable en matière de traitements, la morbidité et la mortalité associées à une atteinte rénale restent relativement élevées. La raison majeure vient du fait qu’on ne dispose pas, à l’heure actuelle, de marqueurs sensibles et spécifiques de la fonction rénale qui permettraient un diagnostic précoce de l’atteinte rénale aiguë. Actuellement les marqueurs principaux de la fonction rénale sont la créatinine et l’urée. Malheureusement ceux-ci ne détectent que tardivement des lésions rénales aiguës. Dans le domaine de la transplantation rénale, l’identification de biomarqueurs adéquats de la fonction rénale est devenue indispensable afin d’évaluer la qualité du greffon avant la transplantation mais également afin de minimiser le risque de rejet et de nécrose tubulaire aigu pendant la période postopératoire. La Neutrophil Gelatinase-Associated Lipocalin (NGAL) est un marqueur précoce d’atteinte rénale aiguè. Ce marqueur de nécrose tubulaire a été dosé dans l’urine et dans le sang de 54 patients avant et à différents temps après une transplantation rénale. D’autres marqueurs alternatifs de la fonction rénale ont également été testés comme la cystatine C et la f32 Microglobuline. L’objectif de l’étude est d’une part de tester les différents biomarqueurs chez les patients «donneurs» en fonction de leur catégorie (donneurs vivants ou donneurs cadavériques) et d’autre part d’étudier ces biomarqueurs chez les patients «receveurs» en fonction des événements survenus durant la période postopératoire. Les résultats préliminaires montrent que 13 patients ont développé une nécrose tubulaire aigu (ATN) endéans les 24H postopératoires. Les tests statistiques ont démontré que les taux de NGAL urinaire et sanguin étaient significativement plus élevés chez les patients ayant développé une ATN comparés aux patients qui n’ont pas fait d’ATN. De plus, cette différence entre les deux groupes s’observe endéans les 6H post-transplantation


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L'implémentation d'un early warning score aux urgences
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Year: 2015 Publisher: Bruxelles: UCL. Faculté de santé publique,

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Etude expérimentale de la toxicité respiratoire des nanotubes d'imogolites

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Plaintes des Membres Supérieurs chez des Travailleuses affectées à des Tâches Répétitives. Etude Médicale et Ergonomique
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Year: 1988 Publisher: Bruxelles: UCL. Faculté de médecine,

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Renover la réparation du dommage corporel traumatique et guide d'évaluation
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Year: 1978 Publisher: Bruxelles: Lielens,

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Insuffisance rénale aiguë en réanimation
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ISBN: 2842994469 9782842994464 Year: 2003 Publisher: Paris: Elsevier,

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