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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.

Reperfusion Injury --- Hypoxia, Brain

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Acute Kidney Injury --- Shock

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Acute kidney injury --- Mortality

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Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. The definition of TBI has not been consistent and tends to vary according to specialties and circumstances. The term brain injury is often used synonymously with head injury, which may not be associated with neurological deficits. The definition has also been problematic due to variations in inclusion criteria. Both American and Brazilian data indicate that more than 700,000 people suffer TBI annually, with 20% afflicted with moderate or severe TBI. According to this data, 80% of people who suffered mild TBI can return to work, whist only 20% of moderate, and 10% of victims of severe TBI can return to their daily routine. Cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions, altered as a result of cerebral injury, is extremely important for these individuals. The aim of a cognitive and motor rehabilitation program is to recover an individual's ability to process, interpret and respond appropriately to environmental inputs, as well as to create strategies and procedures to compensate for lost functions that are necessary in familial, social, educational and occupational relationships. In general, the cognitive rehabilitation programs tend to focus on specific cognitive domains, such as memory, motor, language and executive functions. By contrast, the focus of compensatory training procedures is generally on making environmental adaptations and changes to provide grater autonomy for patients. Successful cognitive rehabilitation programs are those whose aim is both recovery and compensation based on an integrated and interdisciplinary approach. The purpose of this Research Topic is to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in mild, moderate and severe TBI survivors, and the most cognitive and motor impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. Within this context, the importance of an interdisciplinary rehabilitation for TBI is underlined.

Traumatic Brain Injury --- Diffuse Axonal Injury --- concussion --- cognitive impairment

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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.

Poisoning --- Smoke Inhalation Injury --- Cyanides