Alterações nos compartimentos hídricos e energéticos do organismo durante a greve de fome

Prolonged total food deprivation in non-obese adults is rare, and few studies have documented body composition changes in this setting. In a group of eight hunger strikers who refused alimentation for 43 days, water and energy compartments were estimated, aiming to assess the impact of progressive starvation. Measurements included body mass index (BMI), triceps skinfold (TSF), arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water, fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also performed in one occasion. The age of the group was 43.3±6.2 years (seven males, one female). Only water, intermittent vitamins and electrolytes were ingested, and average weight loss reached 17.9%. On the last two days of the fast (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment were provided before proceeding with realimentation. Body fat decreased approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was estimated by BIA as 52.2±5.4% of body weight, and even on the 43rd day it was still measured as 19.7±3.8% of weight. TSF findings were much lower and commensurate with other anthropometric results. Water was comparatively low with high total resistance, and these findings rapidly reversed upon the intravenous rapid hydration. At the end of the starvation period, BMI (21.5±2.6 kg/m²) and most anthropometric determinations were still acceptable, suggesting efficient energy and muscle conservation. Conclusions: 1) All compartments diminished during fasting, but body fat was by far the most affected; 2) Total water was low and total body resistance comparatively elevated, but these findings rapidly reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests and simultaneous increase in lean body mass estimates suggested that this method was inappropriate for assessing energy compartments in the studied population; 4) Patients were not morphologically malnourished after 43 days of fasting; however, the prognostic impact of other impairments was not considered in this analysis.A privação total e prolongada de alimentos em adultos não-obesos é raramente vista, e poucos estudos documentaram as modificações da composição corpórea neste contexto.Num grupo de oito casos de greve de fome durante 43 dias, procedeu-se à estimativa dos compartimentos hídricos e energéticos, visando averiguar a influência sobre os mesmos da desnutrição progressiva.Os métodos incluiram índice de massa corporal (IMC), prega cutânea do tríceps (PCT), circunferência muscular do braço, e determinação através da bioimpedância (BIA) da água, massa gorda, massa magra e resistência corpórea total..A calorimetria indireta foi realizada em uma ocasião apenas.A idade do grupo era de 43,3± 6,2 anos (sete homens, uma mulher), somente água e ocasionais eletrólitos e vitaminas foram ingeridos no jejum, e a perda de peso média foi de 17,9%. Por volta do 43º dia da greve iniciou-se a reposição venosa rápida de fluidos, vitaminas e eletrólitos,antes de se prosseguir com a realimentação.A gordura corporal diminuiu em aproximadamente 60% (BIA e PCT), ao passo que o IMC caiu apenas 18%.A estimativa da gordura total inicial por BIA foi de 52,2± 5,4% do peso corporal, e mesmo no 43º dia do evento o valor calculado era de 19,7± 3,8% do peso.Os valores correspondentes deduzidos da PCT mostraram-se substancialmente inferiores, e mais compatíveis com os demais índices antropométricos. A água corporal revelou-se inicialmente contraída, com resistência elevada,sendo que estes achados se reverteram rapidamente por ocasião da hidratação venosa rápida.Quando do término da greve de fome o IMC (21,5± 2,6 kg/m²) e outras variáveis antropométricas revelavam-se numericamente aceitáveis, sugerindo eficiente conservação de musculatura e energia na fase de dieta zero.Conclui-se que: 1) Todos os compartimentos orgânicos se contrairam na greve de fome, porém o tecido adiposo foi de longe o mais afetado; 2) A água corporal mostrou-se reduzida com elevada resistência total, mas estes achados inverteram-se prontamente mediante hidratação parenteral; 3) O encontro de gordura total excessiva e de aumento da massa magra com o avançar do jejum sugerem que as leituras de BIA são inapropriadas para esta população e fornecem resultados incoerentes; 4) Com base nos parâmetros expostos os doentes não estavam morfologicamente desnutridos ao cabo de 43 dias, todavia não foram aqui avaliados outros transtornos de considerável importância prognóstica

Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction

Abstract\ud \ud \ud \ud Introduction\ud \ud Several studies link hematological dysfunction to severity of sepsis. Previously we showed that platelet-derived microparticles from septic patients induce vascular cell apoptosis through the NADPH oxidase-dependent release of superoxide. We sought to further characterize the microparticle-dependent vascular injury pathway.\ud \ud \ud \ud Methods\ud \ud During septic shock there is increased generation of thrombin, TNF-α and nitric oxide (NO). Human platelets were exposed for 1 hour to the NO donor diethylamine-NONOate (0.5 μM), lipopolysaccharide (LPS; 100 ng/ml), TNF-α (40 ng/ml), or thrombin (5 IU/ml). Microparticles were recovered through filtration and ultracentrifugation and analyzed by electron microscopy, flow cytometry or Western blotting for protein identification. Redox activity was characterized by lucigenin (5 μM) or coelenterazine (5 μM) luminescence and by 4,5-diaminofluorescein (10 mM) and 2',7'-dichlorofluorescein (10 mM) fluorescence. Endothelial cell apoptosis was detected by phosphatidylserine exposure and by measurement of caspase-3 activity with an enzyme-linked immunoassay.\ud \ud \ud \ud Results\ud \ud Size, morphology, high exposure of the tetraspanins CD9, CD63, and CD81, together with low phosphatidylserine, showed that platelets exposed to NONOate and LPS, but not to TNF-α or thrombin, generate microparticles similar to those recovered from septic patients, and characterize them as exosomes. Luminescence and fluorescence studies, and the use of specific inhibitors, revealed concomitant superoxide and NO generation. Western blots showed the presence of NO synthase II (but not isoforms I or III) and of the NADPH oxidase subunits p22phox, protein disulfide isomerase and Nox. Endothelial cells exposed to the exosomes underwent apoptosis and caspase-3 activation, which were inhibited by NO synthase inhibitors or by a superoxide dismutase mimetic and totally blocked by urate (1 mM), suggesting a role for the peroxynitrite radical. None of these redox properties and proapoptotic effects was evident in microparticles recovered from platelets exposed to thrombin or TNF-α.\ud \ud \ud \ud Conclusion\ud \ud We showed that, in sepsis, NO and bacterial elements are responsible for type-specific platelet-derived exosome generation. Those exosomes have an active role in vascular signaling as redox-active particles that can induce endothelial cell caspase-3 activation and apoptosis by generating superoxide, NO and peroxynitrite. Thus, exosomes must be considered for further developments in understanding and treating vascular dysfunction in sepsis.LRL and MJ have research grants from Fundação de Amparo a Pesquisa do Estado de São Paulo – FAPESP. MJ received a research grant from Sociedade Beneficente Israelita-Brasileira Hospital Albert Einstein.LRL and MJ have research grants from Fundação de Amparo a Pesquisa do Estado de São Paulo – FAPESP. MJ received a research grant from Sociedade Beneficente IsraelitaBrasileira Hospital Albert Einstein

Platelet-derived exosomes from septic shock patients induce myocardial dysfunction

Abstract\ud \ud \ud \ud Introduction\ud \ud Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway. We hypothesized that circulating platelet-derived exosomes could contribute to inotropic dysfunction of sepsis.\ud \ud \ud \ud Methods\ud \ud We collected blood samples from 55 patients with septic shock and 12 healthy volunteers for exosome separation. Exosomes from septic patients and healthy individuals were investigated concerning their myocardial depressant effect in isolated heart and papillary muscle preparations.\ud \ud \ud \ud Results\ud \ud Exosomes from the plasma of septic patients significantly decreased positive and negative derivatives of left ventricular pressure in isolated rabbit hearts or developed tension and its first positive derivative in papillary muscles. Exosomes from healthy individuals decreased these variables non-significantly. In hearts from rabbits previously exposed to endotoxin, septic exosomes decreased positive and negative derivatives of ventricular pressure. This negative inotropic effect was fully reversible upon withdrawal of exosomes. Nitric oxide (NO) production from exosomes derived from septic shock patients was demonstrated by fluorescence. Also, there was an increase in myocardial nitrate content after exposure to septic exosomes.\ud \ud \ud \ud Conclusion\ud \ud Circulating platelet-derived exosomes from septic patients induced myocardial dysfunction in isolated heart and papillary muscle preparations, a phenomenon enhanced by previous in vivo exposure to lipopolysaccharide. The generation of NO by septic exosomes and the increased myocardial nitrate content after incubation with exosomes from septic patients suggest an NO-dependent mechanism that may contribute to myocardial dysfunction of sepsis.This work received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).This work received financial support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Brazilian Sepsis Epidemiological Study (BASES study)

INTRODUCTION: Consistent data about the incidence and outcome of sepsis in Latin American intensive care units (ICUs), including Brazil, are lacking. This study was designed to verify the actual incidence density and outcome of sepsis in Brazilian ICUs. We also assessed the association between the Consensus Conference criteria and outcome METHODS: This is a multicenter observational cohort study performed in five private and public, mixed ICUs from two different regions of Brazil. We prospectively followed 1383 adult patients consecutively admitted to those ICUs from May 2001 to January 2002, until their discharge, 28th day of stay, or death. For all patients we collected the following data at ICU admission: age, gender, hospital and ICU admission diagnosis, APACHE II score, and associated underlying diseases. During the following days, we looked for systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock criteria, as well as recording the sequential organ failure assessment score. Infection was diagnosed according to CDC criteria for nosocomial infection, and for community-acquired infection, clinical, radiological and microbiological parameters were used. RESULTS: For the whole cohort, median age was 65.2 years (49–76), median length of stay was 2 days (1–6), and the overall 28-day mortality rate was 21.8%. Considering 1383 patients, the incidence density rates for sepsis, severe sepsis and septic shock were 61.4, 35.6 and 30.0 per 1000 patient-days, respectively. The mortality rate of patients with SIRS, sepsis, severe sepsis and septic shock increased progressively from 24.3% to 34.7%, 47.3% and 52.2%, respectively. For patients with SIRS without infection the mortality rate was 11.3%. The main source of infection was lung/respiratory tract. CONCLUSION: Our preliminary data suggest that sepsis is a major public health problem in Brazilian ICUs, with an incidence density about 57 per 1000 patient-days. Moreover, there was a close association between ACCP/SCCM categories and mortality rate

Holographic Lessons for Quark Dynamics

We give a brief overview of recent results obtained through the gauge/gravity correspondence, concerning the propagation of a heavy quark in strongly-coupled conformal field theories (such as N=4 super-Yang-Mills), both at zero and finite temperature. In the vacuum, we discuss energy loss, radiation damping, signal propagation and radiation-induced fluctuations. In the presence of a thermal plasma, our emphasis is on early-time energy loss, screening and quark-antiquark evolution after pair creation. Throughout, quark dynamics is seen to be efficiently encapsulated in the usual string worldsheet dynamics.Comment: Invited review for a Journal of Physics G topical volume on gauge/gravity duality applications to QCD matter and ultrarelativistic heavy-ion collisions. v2: Reference adde