Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa member of the Ig superfamily that is expressed on platelets and leukocytes and is highly enriched at endothelial cell-cell junctions. Previous studies showed that this vascular cell adhesion and signaling receptor functions to regulate platelet activation and thrombosis, to suppress apoptotic cell death, to mediate transendothelial migration of leukocytes, and to maintain the integrity of the vasculature. Because systemic exposure to the bacterial endotoxin LPS triggers an acute inflammatory response that involves many of these same processes, we compared the pathophysiological responses of wild-type versus PECAM-1-deficient mice to LPS challenge. We found that PECAM-1-deficient mice were significantly more sensitive to systemic LPS administration than their wild-type counterparts and that the lack of PECAM-1 expression at endothelial cell-cell junctions could account for the majority of the increased LPS-induced mortality observed. The diverse functional roles played by PECAM-1 in thrombosis, inflammation, apoptosis, and the immune response may make this molecule an attractive target for the development of novel therapeutics to manage and treat endotoxic shock.
The aim of this study was to find the fastest, easiest and safest method of achieving orotracheal intubation for general anaesthesia in laboratory pigs. Twenty-one Yorkshire  Landrace crossbreed male castrated pigs (32.9 + 4.8 kg) were investigated. Dorsal and ventral recumbency are the alternatives most frequently described for animal positioning during intubation procedures. Based on standardized induction of general anaesthesia using pentobarbital and remifentanil, the dorsoventral and ventrodorsal positions were compared with regard to the time needed, changes in oxygenation and circulatory response. Positioning was found to be crucial for fast orotracheal intubation. The time required for safe intubation is significantly shorter with the ventrodorsal position (17.3 s) in comparison with the dorsoventral position (58.4 s; P , 0.001). Hypoxia did not occur in either group. A significant drop in systolic blood pressure was observed in both groups. Diastolic and mean arterial pressures were not influenced by intubation. A significant increase in heart rate was observed in pigs intubated in ventral recumbency, but not after intubation in the dorsal position. Preoxygenation before intubation is vitally important for preventing hypoxia. With regard to clinical practice, the haemodynamic changes observed in this investigation do not appear to be relevant, as the mean arterial pressure was not altered and heart rates only increased moderately. It may be concluded that the ventrodorsal position can be recommended for orotracheal intubation in pigs as the first choice for providing a smooth and fast airway.
OBJECTIVEAwake craniotomies have become a feasible tool over time to treat brain tumors located in eloquent regions. Different techniques have been applied in neurooncology centers. Both “asleep-awake-asleep” (asleep) and “conscious sedation” were used subsequently at the authors’ neurosurgical department. Since 2013, the authors have only performed conscious sedation surgeries, predominantly using the α2-receptor agonist dexmedetomidine as the anesthetic drug. The aim of this study was to compare both mentioned techniques and evaluate the clinical use of dexmedetomidine in the setting of awake craniotomies for glioma surgery.METHODSThe authors retrospectively analyzed patients who underwent operations either under the asleep condition using propofol-remifentanil or under conscious sedation conditions using dexmedetomidine infusions. In the asleep group patients were intubated with a laryngeal mask and extubated for the assessment period. Adverse events, as well as applied drugs with doses and frequency of usage, were recorded.RESULTSFrom 224 awake surgeries between 2009 and 2015, 180 were performed for the resection of gliomas and included in the study. In the conscious sedation group (n = 75) significantly fewer opiates (p < 0.001) and vasoactive (p < 0.001) and antihypertensive (p < 0.001) drugs were used in comparison with the asleep group (n = 105). Furthermore, the postoperative length of stay (p < 0.001) and the surgical duration (p < 0.001) were significantly lower in the conscious sedation group.CONCLUSIONSUse of dexmedetomidine creates excellent conditions for awake surgeries. It sedates moderately and acts as an anxiolytic. Thus, after ceasing infusion it enables quick and reliable clinical neurological assessment of patients. This might lead to reducing the amount of administered antihypertensive and vasoactive drugs as well as the length of hospitalization, while likely ensuring more rapid surgery.
Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) functions to control the activation and survival of the cells on which it is expressed. Many of the regulatory functions of PECAM-1 are dependent on its tyrosine phosphorylation and subsequent recruitment of the Src homology (SH2) domain containing protein tyrosine phosphatase SHP-2. The recent demonstration that PECAM-1 tyrosine phosphorylation occurs in cells exposed to the reactive oxygen species hydrogen peroxide (H2O2) suggested that this form of oxidative stress may also support PECAM-1/SHP-2 complex formation. In the present study, we show that PECAM-1 tyrosine phosphorylation in response to exposure of cells to H2O2 is reversible, involves a shift in the balance between kinase and phosphatase activities, and supports binding of SHP-2 and recruitment of this phosphatase to cell-cell borders. We speculate, however, that the unique ability of H2O2 to reversibly oxidize the reactive site cysteine residues of protein tyrosine phosphatases may result in transient inactivation of the SHP-2 that is bound to PECAM-1 under these conditions. Finally, we provide evidence that PECAM-1 tyrosine phosphorylation and SHP-2 binding in endothelial cells requires exposure to an "oxidative burst" of H2O2, but that exposure of these cells to sufficiently high concentrations of H2O2 for a sufficiently long period of time abrogates binding of SHP-2 to tyrosine-phosphorylated PECAM-1. These findings support a role for PECAM-1 as a sensor of oxidative stress, perhaps most importantly during the process of inflammation.
Massive bleeding with coagulopathy and hemorrhagic shock poses a potential threat to life in numerous clinical settings. Optimal treatment including the prevention of exsanguination necessitates a standardized and interdisciplinary approach. Several studies have shown the importance of massive transfusion protocols and standardized coagulation algorithms to improve survival of severely bleeding patients and to avoid secondary complications. Thus, the Helsinki declaration for patient safety in anesthesiology demands the implementation of clinical practice guidelines for the treatment of patients requiring massive transfusion. This paper introduces a standardized algorithm for the treatment of patients with massive bleeding which was developed in consensus with the German Society of Anaesthesiology and Intensive Care Medicine (DGAI).
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