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Inflammatory Injury (inflammatory + injury)
Selected AbstractsEffect of intravenous lidocaine administration on laminar inflammation in the black walnut extract model of laminitisEQUINE VETERINARY JOURNAL, Issue 3 2010J. M. WILLIAMS Summary Reasons for performing study: Laminitis is a serious complication of horses suffering from sepsis/endotoxaemia-related events. Laminitis in horses and organ injury in human sepsis are both reported to involve inflammatory injury to the laminae/organs including early activation of endothelium and leucocytes leading to emigration of neutrophils into the tissue interstitium. In the black walnut extract (BWE) model, systemic inflammatory events coincide with marked increase in laminar mRNA concentrations of inflammatory genes including proinflammatory cytokines (i.e. IL-1,, IL-6), COX-2, chemokines (i.e. IL-8) and endothelial adhesion molecules (i.e. ICAM-1 and E-selectin). In models of human sepsis, i.v. lidocaine has been reported to decrease leucocyte and endothelial activation, and the expression of proinflammatory cytokines and chemokines. Objectives: To evaluate the effect of i.v. lidocaine therapy on the inflammatory processes documented to occur in the BWE model of laminitis. Methods: Twelve horses were administered BWE and treated immediately with either lidocaine (1.3 mg/kg bwt bolus, followed by 0.05 mg/kg bwt/min CRI, n = 6) or saline (n = 6) for 10 h. At 10 h post BWE administration, laminar samples were obtained under general anaesthesia for assessment of proinflammatory gene expression (using RT-qPCR) and leucocyte emigration (via CD13 immunohistochemistry). At 0, 3 and 10 h post BWE administration, skin samples were obtained for assessment of leucocyte emigration (via calprotectin immunohistochemistry). Results: No significant differences between groups were noted for inflammatory gene mRNA concentrations (IL-1,, IL-6, IL-8, COX-2) or for number of leucocytes present within the laminar interstitium or skin dermis. Increased (P<0.05) laminar E-selectin mRNA concentrations were present in the LD group (vs. SAL group). Conclusions: Continuous administration of i.v. lidocaine does not inhibit inflammatory events in either the laminae or skin in the horse administered black walnut extract. Potential relevance: This work questions the use of continuous i.v. administration of lidocaine as an effective anti-inflammatory therapy for systemic inflammation. [source] Decreased iNOS synthesis mediates dexamethasone-induced protection of neurons from inflammatory injury in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003Sabine Golde Abstract Brain inflammation is accompanied by transection of axons and death of neurons in the acute lesions of multiple sclerosis. We explored mechanisms of inflammatory damage to neurons in vitro using cocultures of rat embryonal cortical neurons with microglia activated by interferon-gamma (IFN,) and lipopolysaccharide (LPS). Previously, we have demonstrated that microglia are highly toxic to neurons and that nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) is necessary and sufficient to mediate this toxicity. Here, we show that addition of dexamethasone (1 µM) to activated cocultures provides effective neuroprotection. We demonstrate that dexamethasone down-regulates NO production of primary microglia by ,,50% and reduces steady-state iNOS protein and mRNA expression by ,,70%. These changes were reversed by the glucocorticoid receptor blocker RU-486. Furthermore, we analysed the stability of iNOS protein and show that whilst inhibitors of the proteasome blocked iNOS degradation they did not reverse the dexamethasone effect. Our results indicate that the main mechanism of corticosteroid activity on iNOS is reduction in protein synthesis, not destabilization as previously suggested. [source] Interleukin 15 expression in the CNS: Blockade of its activity prevents glial activation after an inflammatory injuryGLIA, Issue 5 2008Diego Gómez-Nicola Abstract Although reactive glia formation after neuronal degeneration or traumatic damage is one of the hallmarks of central nervous system (CNS) injury, we have little information on the signals that direct activation of resting glia. IL-15, a pro-inflammatory cytokine involved in regulating the response of T and B cells, may be also key for the regulation of early inflammatory events in the nervous system. IL-15 was expressed in the CNS, most abundantly in cerebellum and hippocampus, mainly in astrocytes and in some projection neurons. Using a rodent model of acute inflammatory injury [lipopolysaccharide (LPS) injection], we found enhanced expression of IL-15 in both reactive astroglia and microglia, soon after CNS injury. Blockade of IL-15 activity with an antibody to the cytokine, reversed activation of both glial types, suggesting that IL-15 has a major role in the generation of gliotic tissue and in the regulation of neuroimmune responses. Because IL-15 appears to modulate the inflammatory environment acutely generated after CNS injury, regulating IL-15 expression seems a clear antiinflammatory therapy to improve the outcome of neurodegenerative diseases and CNS trauma. © 2008 Wiley-Liss, Inc. [source] Systematic Organ Protection in Coronary Artery Surgery With or Without Cardiopulmonary BypassJOURNAL OF CARDIAC SURGERY, Issue 6 2002Ph.D., Song Wan M.D. Off-pump coronary surgery has been shown to attenuate the inflammatory injury compared to the conventional approach, thereby reducing the incidence of postoperative cardiopulmonary, renal, or neurological dysfunction. It is believed that off-pump experience may greatly impact on improving the outcome of coronary surgery in certain high-risk patients. Moreover, a better understanding of the underlying mechanism would also help to improve our current CPB management. Accumulating evidence to date indicates that a balance between pro- and antiinflammatory responses is crucial in limiting the extent of such systemic inflammatory injury following surgical myocardial revascularization. [source] Protective ventilation to reduce inflammatory injury from one lung ventilation in a piglet modelPEDIATRIC ANESTHESIA, Issue 4 2010MARY C. THEROUX MD Summary Objectives:, To test the hypothesis that protective ventilation strategy (PVS) as defined by the use of low stretch ventilation (tidal volume of 5 ml·kg,1 and employing 5 cm of positive end expiratory pressure (PEEP) during one lung ventilation (OLV) in piglets would result in reduced injury compared to a control group of piglets who received the conventional ventilation (tidal volume of 10 ml·kg,1 and no PEEP). Background:, PVS has been found to be beneficial in adults to minimize injury from OLV. We designed the current study to test the beneficial effects of PVS in a piglet model of OLV. Methods:, Ten piglets each were assigned to either ,Control' group (tidal volume of 10 ml·kg,1 and no PEEP) or ,PVS' group (tidal volume of 5 ml·kg,1 during the OLV phase and PEEP of 5 cm of H2O throughout the study). Experiment consisted of 30 min of baseline ventilation, 3 h of OLV, and again 30 min of bilateral ventilation. Respiratory parameters and proinflammatory markers were measured as outcome. Results:, There was no difference in PaO2 between groups. PaCO2 (P < 0.01) and ventilatory rate (P < 0.01) were higher at 1.5 h OLV and at the end point in the PVS group. Peak inflating pressure (PIP) and pulmonary resistance were higher (P < 0.05) in the control group at 1.5 h OLV. tumor necrosis factor-alpha (P < 0.04) and IL-8 were less (P < 0.001) in the plasma from the PVS group, while IL-6 and IL-8 were less (P < 0.04) in the lung tissue from ventilated lungs in the PVS group. Conclusions:, Based on this model, PVS decreases inflammatory injury both systemically and in the lung tissue with no adverse effect on oxygenation, ventilation, or lung function. [source] Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance, oxygen transport and tissue inflammationCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2010Dongmei Wu Summary 1. The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage,resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-, by 37% and myeloperoxidase activity by 38%. Nuclear factor-,B DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury. [source] | |||||||||||||