Hyperuricemia is associated with cardiovascular and renal diseases, as glomerulosclerosis. Noncrystalline uric acid induces deleterious effects on endothelial and vascular smooth muscle cells. In the present study, we analyzed the damage induced by UA on human mesangial cells (HMC), the potential mechanism involved in this injury, and its consequences during infection. HMC were exposed to noncrystalline UA (8 mg/dl) and/or lipopolysaccharide (LPS, 100 μg/ml) for 24 h. In the experiments of cellular viability, HMC were exposed to 8-50 mg/dl of UA. Necrosis was assessed by acridine orange and ethidium bromide. Reactive oxygen species (ROS) were analyzed by 2',7'-dichlorofluorescein. Prostaglandin E2 (PGE2) was evaluated by ELISA. Cyclooxygenase 2 (COX-2) expression was assessed by real-time PCR. UA induced necrosis only at supraphysiological concentrations. Nevertheless, it significantly increased ROS production at 8 mg/dl. LPS increased necrosis and ROS production. Interestingly, the association between UA and LPS decreased ROS and necrosis. UA associated or not with LPS induced COX-2 expression and PGE2 increases in HMC. Results suggest that UA has pro- and anti-oxidant effects in HMC. During infections, it acts like scavenger increasing cellular viability, but alone it can induce ROS production and cellular death in higher concentrations. Additionally, UA has direct pro-inflammatory effects inducing COX-2 expression and PGE2 synthesis. It is concluded that elevated concentrations of uric acid potentially contributes to glomerular damage.
P2Model-based neuro-fuzzy control of FiO 2 for intensive care mechanical ventilation HF Kwok, GH Mills, M Mahfouf, DA Linkens Introduction: In our experience, very often, even with a nonrebreathing mask (NRM), high oxygen delivery to patient with the existent materials is insufficient. However, many of these patients need high oxygen therapy for a limited period of time. In this study we report our experience with a new device that serves to increase the concentration of oxygen delivered by a classical nasal cannula or catheter. It is not an oxygen mask. Aim:To demonstrate how a simple adjunctive system to classical nasal cannula or catheter improves considerably the oxygenation of patients at constant O 2 flow rate.Design: Prospective, observational study. Method:The double trunk mask (DTM) is a modified tusk mask described by Hnatiuk. It is composed by a normal aerosol mask with 22 mm of diameter lateral holes, 38 cm of long flexible tubing are inserted to each side of the mask. The DTM is just applied to the face of the patients who already receive O 2 through a nasal cannula or catheter. Forty-five consecutive patients, admitted in the ER or ICU, and needing oxygen delivery, are included in our study. The data collected are: PaO 2 , PaCO 2 , breathing rate with a mean flow rate of 3.58 l/min, at t0, t30 min prior to DTM and then 30 min after DTM application. Results:Nasal The knowledge-based approach to fuzzy logic control of mechanical ventilation on the ICU can be prone to bias in the experts' knowledge and errors resulting from poor communication during rule-base derivation. Therefore, a different approach was explored in the development of a fuzzy controller to control the inspired oxygen fraction (FiO 2 ). The performance of such a controller was compared with the performance of the clinicians.Method: (1) The development of a neuro-fuzzy controller. This was developed by training a neural network to generate an optimal change in the FiO 2 in order to achieve a target arterial oxygen tension (PaO 2 ) on a mathematical model of the gas exchange system (SOPAVent). The neural network learnt the relationship between the blood gases, FiO 2 and PEEP and other ventilator settings. This was done by exposing the neural network to the blood gas results produced by applying a range of FiO 2 and PEEP values to the SOPAVent model. This first neural network was then combined with another neural network which represented a fuzzy logic rule-base. The fuzzy rule-base consists of a set of 'If …, Then …' statements based around combinations of FiO 2 , PEEP and PaO 2 . The fuzzy rule-base was then adjusted by changing the weights of the neuro-controller (which correspond to the 'Then …' part of the fuzzy rules) during neural network training. The neuro-controller output is equivalent to the output from a fuzzy inference system of three inputs (the difference between the actual PaO 2 and the target, the PEEP level and the FiO 2 ).(2) Comparing neuro-fuzzy and clinicians' control. The scenarios were based on the data from th...
Introduction Cardiac surgery with cardiopulmonary bypass (CPB) is a recognized trigger of systemic inflammatory response, usually related to postoperative acute lung injury (ALI). As an attempt to dampen inflammatory response, steroids have been perioperatively administered to patients. Macrophage migration inhibitory factor (MIF), a regulator of the endotoxin receptor, is implicated in the pathogenesis of ALI. We have previously detected peak circulating levels of MIF, 6 hours post CPB. Experimental data have shown that steroids may induce MIF secretion by mononuclear cells. This study aims to correlate levels of MIF assayed 6 hours post CPB to the intensity of postoperative pulmonary dysfunction, analysing the impact of perioperative steroid administration. MethodsWe included patients submitted to cardiac surgery with CPB, electively started in the morning, performed by the same team under a standard technique except for the addition of methylprednisolone (15 mg/kg) to the CPB priming solution for patients from group MP (n = 37), but not for the remaining patients -group NS (n = 37). MIF circulating levels were assayed at the anesthesia induction, 3, 6, and 24 hours after CPB. A standard weaning protocol with fast track strategy was adopted, and indicators of organ dysfunction and therapeutic intervention were registered during the first 72 hours postoperative.Results Levels of MIF assayed 6 hours post CPB correlated directly to the postoperative duration of mechanical ventilation (P = 0.014, rho = 0.282) and inversely to PaO 2 /FiO 2 ratio (P = 0.0021, rho = -0.265). No difference in MIF levels was noted between the groups. The duration of mechanical ventilation was higher (P = 0.005) in the group MP (7.92 ± 6.0 hours), compared with the group NS (4.92 ± 3.6 hours). ConclusionCirculating levels of MIF assayed 6 hours post CPB are correlated to postoperative pulmonary performance. Immunosuppressive doses of methylprednisolone did not affect circulating levels of MIF and may be related to prolonged mechanical ventilation. P2Immediate and short-term safety of catheter-based autologous bone marrow-derived mononuclear cell transplantation into myocardium of patients with severe ischemic heart failure Background Bone marrow-derived mononuclear cell (BM-MNC) transplantation into the myocardium has been proposed as a new therapy for ischemic heart failure (HF). Successful cellular therapy for HF using myoblast transplantation has been reported previously but malignant arrhythmias (MA) were an issue. We investigated the safety of BM-MNC transplantation into the myocardium for MA.Methods A prospective study to evaluate the safety of autologous BM-MNC transplantation in patients with severe ischemic HF not amenable to myocardial revascularization was conducted. Bone marrow was harvested from the iliac crest and BM-MNCs were selected by Ficoll gradient. Hibernating myocardium areas were targeted using electromechanical mapping in catheter-based subendocardial injections (MyoStar, Cordis, Miami Lakes, FL, USA). All patien...
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