Sepsis, the body's response to infection, is associated with extremely high mortality rates. Why a protective mechanism turns into a deadly clinical picture is a matter of debate, and goes largely unexplained. In previous work we demonstrated that platelet-derived microparticles (MP) can induce endothelial and vascular smooth muscle cell apoptosis in septic patients through NADPH oxidasedependent superoxide release [1]. In this work we sought to create a model for ex vivo generation of septic-like MP and to identify the pathways responsible for MP free radical release and effects. Septic shock is a condition related to the generation of high amounts of thrombin, TNFα and nitrogen reactive species. Human platelets exposed to the NO donors diethylamine-NONOate (0.5 mM) and nitroprusside (2 mM) for 20 minutes generated MP similar to those found in the blood of septic shock patients. Flow cytometry and western blot analysis of those MP, like their septic counterparts, revealed exposure of the tetraspanin markers CD9, CD63, and CD81, but little phosphatidylserine. Such a membrane exposure, associated with their size, characterizes them as exosomes. Furthermore, we identified the Nox2 and p22phox NADPH oxidase subunits and the inducible isoform of NO synthase (NOS), but not the NOS I and III isoforms. On the other hand, platelets exposed to thrombin or TNFα released particles with clearly distinct characteristics, such as high phosphatidylserine and low tetraspanin. Like the septic MP, the MP obtained by NO exposure generated the superoxide radical and NO, as disclosed by lucigenin (5 µM) and coelenterazine (5 µM) chemiluminescence and by 4,5-diaminofluorescein (10 mM) and 2′,7′-dichlorofluorescein (10 mM) fluorescence. As expected, NOS inhibitors or NADPH oxidase inhibitors significantly reduced signals. In addition, endothelial cells exposed to this type of MP underwent apoptotic death, while control MP had negligible effects. NADPH oxidase as well as NOS inhibition significantly reduced apoptosis rates. Concomitant generation of NO and superoxide suggests biological effects of the highly reactive radical peroxynitrite. In fact, the peroxynitrite scavenger urate (1 mM) showed an additive effect on fluorescent signal inhibition, as well as on endothelial apoptosis rate reduction. We thus propose that platelet-derived exosomes may be another class of actors in the complex play known as 'vascular redox signaling'. In this sense, an exosome-based approach can provide novel tools for further understanding and even treating vascular dysfunction related to sepsis. Introduction The intestinal hypothesis of sepsis has been attributed to bacterial translocation (BT), and the aggravation of sepsis is related to the increased vascular permeability state that potentates the BT index. In this study we examined the BT index during sepsis with or without mesenteric lymph exclusion. Materials and methods Wistar rats (±200 g) were submitted to the BT process (E. coli R6 10 ml of 10 10 CFU/ml) and nonlethal sepsis (E. cloacae 89 2 ml ...

Introduction Many authors have written about the need to treat patients closer to their beds, in order to observe them more as distinct people. The FAST HUG mnemonic, which consists of a checklist, was suggested as an idea to be employed everyday, by professionals dealing with patients who are critically ill. Minding these questions and motivated by an idea of follow patients' treatment closer, we have put into practice the instrument developed by Jean-Louis Vincent, evaluating the seven most important procedures in critically ill patients, and performed the FAST HUG. This checklist consists of seven items to be evaluated: Feeding, Analgesia, Sedation, Thromboembolic prophylaxis, Head-of-bed elevation, stress Ulcer prevention, and Glucose control. Knowing that the pressure ulcer is one of the challenges faced by ICU nurses, related to patients' need to stay at rest, to be under rigorous control or more complex therapy, it was decided to create the eighth item on the checklist: S, for skin. It stands for skin treatment, with the techniques used in the unit (Braden Scale), monitoring and evaluating closer skin integrity, and allowing nurses to calculate the scoring average of the Braden Scale, and greater incidence of ulcer in interned patients. Objective To expose the shortcomings found during the FAST HUG application, and to show results obtained with the eighth item of the FAST HUG mnemonic: S-Skin. Methods A descriptive study, based on institutional data, was carried out in the adult ICU of a private hospital. It was performed from 2 to 27 June 2008, except on weekends. Three hundred and twenty-three patients were involved. The checklist was carried out during the afternoons by the head nurse, or the assistant nurse of the unit. In order to do this job, a spreadsheet was elaborated to control data, updated every week. This spreadsheet provided graphics for a more objective control of the results obtained. The idea was exposed to the team, during a training program, and so we started the activities. Results and discussion For 20 days of the checklist, 323 patients were evaluated for the eight items. The real shortcomings most frequently found were related to thromboembolic prophylaxis (85%) and glucose control (90%). These shortcomings were immediately evaluated and, depending on this analysis, this item would go on or not, according to the patient's clinical situation. The shortcomings found were tracked just as they were detected, and their cause would be discussed in a multidisciplinary group, and a solution was found. If the item was not observed, it would be 1. Vincent JL: Give your patient a fast hug (at least) once a day.

No abstract