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Organic-inorganic hybrid thermoelectric (TE) materials have attracted tremendous interest for harvesting waste heat energy. Due to their mechanical flexibility, inorganic-organic hybrid TE materials are considered to be promising candidates for flexible energy harvesting devices. In this work, enhanced TE properties of Tellurium (Te) nanowires (NWs)- poly (3-hexylthiophene-2, 5-diyl) (P3HT) hybrid materials are reported by improving the charge transport at interfacial layer mediated via controlled oxidation. A power factor of ≈9.8 µW (mK2)-1 is obtained at room temperature for oxidized P3HT-TeNWs hybrid materials, which increases to ≈64.8 µW (mK2)-1 upon control of TeNWs oxidation. This value is sevenfold higher compared to P3HT-TeNWs-based hybrid materials reported in the literature. MD simulation reveals that oxidation-free TeNWs demonstrate better templating for P3HT polymer compared to oxidized TeNWs. The Kang-Snyder model is used to study the charge transport in these hybrid materials. A large σE0 value is obtained which is related to better templating of P3HT on oxygen-free TeNWs. This work provides evidence that oxidation control of TeNWs is critical for better interface-driven charge transport, which enhances the thermoelectric properties of TeNWs-P3HT hybrid materials. This work provides a new avenue to improve the thermoelectric properties of a new class of hybrid thermoelectric materials.
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OBJECTIVE: To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. METHODS: Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 ß protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. RESULTS: Compared with the Sham group, the serum levels of NSE and S100ß after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 ß starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (µg/L): 24.1±2.4 vs. 28.2±2.1, S100 ß (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (µmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. CONCLUSIONS: Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
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Lesões Encefálicas , Reanimação Cardiopulmonar , Ferroptose , Masculino , Animais , Suínos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Glutationa , Ligases , FerroRESUMO
Development of nanoscale multicomponent solid inorganic materials is often hindered by slow solid diffusion kinetics and poor precursor mixing in conventional solid-state synthesis. These shortcomings can be alleviated by combining nanosized precursor mixtures and low temperature reaction, which could reduce crystal growth and accelerate the solid diffusion at the same time. However, high throughput production of nanoparticle mixtures with tunable composition via conventional synthesis is very challenging. In this work, we demonstrate that â¼10 nm homogeneous mixing of sub-10 nm nanoparticles can be achieved via spark nanomixing at room temperature and pressure. Kinetically driven Spark Plasma Discharge nanoparticle generation and ambient processing conditions limit particle coarsening and agglomeration, resulting in sub-10 nm primary particles of as-deposited films. The intimate mixing of these nanosized precursor particles enables intraparticle diffusion and formation of Cu/Ni nanoalloy during subsequent low temperature annealing at 100 °C. We also discovered that cross-particle diffusion is promoted during the low-temperature sulfurization of Cu/Ag which tends to phase-segregate, eventually leading to the growth of sulfide nanocrystals and improved homogeneity. High elemental homogeneity, small diffusion path lengths, and high diffusibility synergically contribute to faster diffusion kinetics of sub-10 nm nanoparticle mixtures. The combination of â¼10 nm homogeneous precursors via spark nanomixing, low-temperature annealing, and a wide range of potentially compatible materials makes our approach a good candidate as a general platform toward accelerated solid state synthesis of nanomaterials.
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Introduction: Short video communities have proliferated recently, opening up a new channel for the promotion of online businesses. The main challenge in marketing with short videos is how to inspire consumers. Methods: This study employs viewer social identification and self-expansion as its entrance point to to explain how uploader-viewer similarity affects viewers' short video inspiration. We use empirical investigation method based on the data of 310 short video viewers to test our conceptual model. Results: We found that there is a double-edged relationship between uploader-viewer similarity and short video inspiration. Particularly, uploader-viewer similarity enhances perceived social identification while reducing perceived self-expansion. The association between Uploader-viewer similarity and short video inspiration is moderated by viewers' cognitive demands. Discussion: These results provide a new perspective for enterprises to manage the relationship between viewers and media.
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ABSTRACT: Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 10 6 /kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid-binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.
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Traumatismos Abdominais , Amina Oxidase (contendo Cobre) , Reanimação Cardiopulmonar , Parada Cardíaca , Células-Tronco Mesenquimais , Humanos , Masculino , Animais , Suínos , Reanimação Cardiopulmonar/métodos , Creatinina , Parada Cardíaca/tratamento farmacológico , Ureia/uso terapêutico , Modelos Animais de DoençasRESUMO
BACKGROUND: The purpose of this study was to investigate whether platelet count was associated with mortality in acute respiratory distress syndrome (ARDS) patients. METHODS: We analyzed patients with ARDS from Multi-parameter Intelligent Monitoring in Intensive Care Database III (MIMIC-III). Platelet count was measured at the time of intensive care unit (ICU) admission. The cox proportional hazard model and subgroup analysis were used to determine the relationship between the platelet count and mortality of ARDS, as well as the consistency of its association. The primary outcome of this study was 365-day mortality from the date of ICU admission. RESULT: This study enrolled a total of 395 critically ill patients with ARDS. After adjustment for age, gender and ethnicity, the multivariate cox regression model showed that the hazard ratios (HRs) (95% confidence intervals [CIs]) of platelet count <192 × 109 /L and >296 × 109 /L were 2.08 (1.43, 3.04) and 1.35 (0.91, 2.01), respectively, compared with the reference (192-296 ×109 /L). After adjusting for confounding factors, lower platelet count (<192 × 109 /L) was associated with increased mortality (adjusted HR, 1.71; 95% CI 1.06-2.76, p = 0.0284). However, there was no similar trend in the 30-day (adjusted HR,1.02; 95% CI 0.54-1.94) or 90-day (adjusted HR, 1.65; 95% CI 0.94-2.89) mortality. In the subgroup analysis, lower platelet count showed significant interactions with specific populations (p interaction = 0.0413), especially in patients with atrial fibrillation. CONCLUSION: Taken together, our analysis showed that platelet count is an independent predictor of mortality in critically ill patients with ARDS.
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Estado Terminal , Síndrome do Desconforto Respiratório , Estudos de Coortes , Humanos , Unidades de Terapia Intensiva , Contagem de Plaquetas , Fatores de RiscoRESUMO
Reduced molybdenum oxide, generally MoO3- x, becomes increasingly metallic as the oxygen level decreases during the reduction of MoO3 to MoO2. Its interesting properties have recently intrigued research on MoO3- x in electrical and electrochemical areas. Lacking effective tools to control the oxygen level is one of the research difficulties for MoO3- x. Herein, we report facile temperature-controlled synthesis of triangular MoO2 and square Mo4O11. The triangular and square flakes showed metallic behavior with conductivity as high as â¼940 and â¼28 S/cm in DC measurement, respectively. The decrease in oxygen level from Mo4O11 to MoO2 affected the density of states mapped in Mo 4d orbitals, leading to higher conductivity for triangular MoO2. Further Mott-Schottky analysis on MoO3- x regrown on carbon fiber paper (CFP) revealed hole mobility of 105-108 cm2 V-1 s-1. The hole carriers at high frequencies are attributed to potential oxygen acceptors, and molybdenum vacancies resulted from limited reduction power of hydrogen.
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BACKGROUND: Acute lung injury (ALI) is an inflammatory disorder. Semen Cassiae has potent anti-inflammatory activities. The aim of our study was to investigate whether Semen Cassiae plays a protective effect on lipopolysaccharide (LPS)-induced ALI and, if so, to elucidate its potential mechanism. METHODS: Male Sprague-Dawley rat lungs were injured by intratracheal instillation of LPS. Rats were treated with Semen Cassiae or vehicle 3 h after LPS challenge. Samples were harvested 24 h post-LPS administration. We also investigated the effects of Semen Cassiae on LPS stimulation in RAW 264.7 cells. RESULTS: LPS administration markedly induced pulmonary edema and polymorphonuclear neutrophil influxes. These changes were significantly attenuated in Semen Cassiae treated group. Moreover, Semen Cassiae markedly reduced pulmonary interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. The pulmonary soluble epoxide hydrolase (sEH) activity and the DNA binding activity of Nuclear factor (NF)-κB were significantly inhibited in Semen Cassiae treated group. Furthermore, Semen Cassiae treatment significantly increased epoxyeicosatrienoic acids (EETs), and heme oxygenase-1 (HO-1) activity. Our in vitro study demonstrates that Semen Cassiae treatment may inhibit LPS induced IκBα phosphorylation and NF-κB p65 nucleus translocation. CONCLUSION: Semen Cassiae protects LPS-induced ALI in rats. Semen Cassiae can be developed as a novel treatment for ALI.
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Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Cassia , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Heme Oxigenase-1/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Neutrófilos/metabolismo , Extratos Vegetais/farmacologia , Edema Pulmonar/prevenção & controle , Células RAW 264.7 , Ratos Sprague-Dawley , SementesRESUMO
Arterial stiffness contributes to heart failure and is decreased by angiotensin receptor blockers (ARBs). This cross-sectional study aimed to assess associations of lung function and ARB with arterial stiffness in patients with chronic heart failure. 354 outpatients (168 males; 186 females; 68.2 ± 7.2 years old) with chronic heart failure were evaluated. Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1 to FVC ratio (FEV1/FVC), were assessed. The cardio-ankle vascular index (CAVI) was used to estimate arterial stiffness. Unadjusted correlation analyses revealed a positive association of CAVI with ARB but not ACEI, and a negative correlation with FEV1 (r = -0.2987, p < 0.0001). Multiple stepwise regression analyses showed that ARB and FEV1 (p < 0.0001) were independent predicting factors for CAVI. These findings suggest that reduced pulmonary function is associated with increased CAVI. Pulmonary function protection could be used to improve the prognosis in heart failure, but additional studies are necessary.
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Antagonistas de Receptores de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Idoso , Doença Crônica/tratamento farmacológico , Ecocardiografia , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Capacidade Vital/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the role of ß 3 -integrin in lipopolysaccharide (LPS)-induced autophagy in cardiomyocytes and its underlying mechanism. METHODS: ß 3 -Integrin expression in cardiomyocytes was up- or downregulated by adenovirus transfection or cyclic arginine-glycine-aspartic acid (cRGD) peptide treatment before LPS stimulation. The expression of autophagy-associated proteins (LC3-II, Beclin-1 and Bcl-2) and the activation of Akt were determined using Western blotting. Autophagosomes and autophagic vacuoles were observed using monodansylcadaverine (MDC) dye and transmission electron microscopy, respectively. RESULTS: Downregulation of ß 3 -integrin with cRGD peptide resulted in enhanced LC3-II and Beclin-1 and decreased Bcl-2 expression. Low Beclin-1 levels were detected after LPS stimulation in adenovirus ß 3 -integrin-transfected cardiomyocytes. There was no significant difference in LC3-II levels between control and adenovirus ß 3 -integrin-transfected cardiomyocytes. Enhanced accumulation of MDC dye and autophagosomes, which were inhibited by ß 3 -integrin overexpression, were detected after LPS treatment. The increased phosphorylation of Akt after LPS stimulation was inhibited by cRGD and enhanced by ß 3 -integrin overexpression. Furthermore, the Akt inhibitor triciribine inhibited the negative effect of ß 3 - integrin on autophagy, as shown by LC3-II and Beclin-1 upregulation. CONCLUSIONS: ß 3 -Integrin inhibits LPS-induced autophagy in cardiomyocytes. The inhibition of Akt signaling might be an important mechanism in this process.
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Autofagia , Integrina beta3/genética , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Humanos , Lipopolissacarídeos/efeitos adversos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microscopia Eletrônica , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Miócitos Cardíacos/ultraestrutura , Peptídeos Cíclicos/uso terapêutico , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , TransfecçãoRESUMO
BACKGROUND: Severe sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock. METHODS: A total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit. RESULTS: PARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%. CONCLUSION: PARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.
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Leucócitos Mononucleares/enzimologia , Poli(ADP-Ribose) Polimerases/metabolismo , Choque Séptico/enzimologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pregnancy-associated plasma protein A (PAPPA) is an emerging biomarker used in various medical fields but has yet to be evaluated in critical care medicine. This study evaluates the value of PAPPA as a biomarker in predicting myocardial dysfunction and 28-day mortality in patients with severe sepsis. METHODS: Serum concentrations of PAPPA and traditional cardiac biomarkers including cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) were measured on admission in 118 severely septic patients. The value of PAPPA for the diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was subsequently evaluated using statistical methods. RESULTS: PAPPA was elevated (≥4.5 ng/mL) in 76 (64.4%) patients; patients with elevated PAPPA were more likely to have SRMD (76.3% vs. 38.1%, P < 0.001). By comparison of the area under the curve (AUC) in receiver operating characteristics analysis, PAPPA had comparable value (AUC 0.661, P = 0.003) to conventional biomarkers (BNP: AUC 0.699, P < 0.001; cTnI: AUC 0.647, P = 0.007) in the diagnosis of SRMD and offered superior value (AUC 0.771, P < 0.001) over them (all AUC<0.7, P > 0.05) in the prediction of 28-day death. Increased PAPPA (≥5.4 ng/mL) was associated with lower 28-day survival (χ(2) = 19.78, P < 0.001) and independently predicted 28-day mortality in septic patients. CONCLUSIONS: Serum PAPPA concentration frequently increases in patients with severe sepsis and appears to be associated with SRMD. PAPPA can be used as a novel biomarker for the diagnosis of SRMD and the prediction of outcomes in critically ill patients.
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Biomarcadores/sangue , Cardiomiopatias/sangue , Proteína Plasmática A Associada à Gravidez/metabolismo , Sepse/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Cardiomiopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Prognóstico , Sepse/complicações , Sepse/mortalidade , Sepse/patologiaRESUMO
BACKGROUND: The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis, but there is controversial in choosing a parenteral nutrition formulation. This study was designed to compare the therapeutic effects of structured lipid emulsion, physically mixed medium, and long-chain fat emulsion in the treatment of severe sepsis in elderly patients. METHODS: A total number of 64 elder patients with severe sepsis were enrolled in the study. After a week of enteral nutritional support, the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation). The alterations of plasma albumin, lipid metabolism, and blood glucose level were recorded after parenteral alimentation and were compared between the two groups. RESULTS: The plasma levels of albumin, prealbumin, cholesterol, and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t = 7.78, P = 0.000; t = 10.21, P = 0.000; t = 7.99, P = 0.000; and t = 10.99, P = 0.000). Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t = 3.316, P = 0.002; t = 3.200, P = 0.002), whilst had no effects on the blood glucose and triglyceride level (t = 7.78, P = 0.000; t = 4.228, P = 0.000). In addition, the two groups had a significantly different Apache II score, ventilator time, and hospital stay time (t = -2.213, P = 0.031; t = 2.317, P = 0.024; t = 2.514, P = 0.015). CONCLUSIONS: The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis. It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.
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Emulsões Gordurosas Intravenosas/uso terapêutico , Nutrição Parenteral/métodos , Sepse/tratamento farmacológico , Idoso , Emulsões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/sangue , Albumina Sérica/análise , Triglicerídeos/sangueRESUMO
BACKGROUND: Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression. However, the underlying mechanism remains unknown. This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats. METHODS: Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection. Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy. In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis. Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage. Oxidative stress was assessed by mitochondrial lipid and protein oxidation, and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity. RESULTS: Sepsis-induced inflammatory cell infiltration, myocardium degeneration and dropsy were time-dependent. Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge. Compared with sham-treated rats, the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours, 12 hours and 24 hours post-injection (P < 0.05). The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis, indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B. Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner. Both superoxide dismutase and glutathione peroxidase activities decreased, while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge. CONCLUSIONS: Septic challenge induced myocardial apoptosis and mitochondrial damage. Furthermore, mitochondrial damage via alteration of defenses against reactive oxygen species might play an important role in myocardial apoptosis during sepsis.
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Apoptose/fisiologia , Mitocôndrias Cardíacas/patologia , Miocárdio/patologia , Sepse/fisiopatologia , Animais , Masculino , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Sepse/metabolismoRESUMO
BACKGROUND: Recent studies demonstrated that the minute ventilation/carbon dioxide production (VE/VCO(2)) slope more powerfully predicted mortality, hospitalization, or both than peak oxygen consumption (VO(2)) in systolic heart failure. However, the prognostic values of these two parameters in diastolic heart failure remained unclear. METHODS: The patients with diastolic heart failure were recruited from April 2006 to May 2007, and underwent cardiopulmonary exercise testing. Plasma BNP concentration was measured using Triage BNP immunoassay method. RESULTS: Of the 224 patients enrolled, mean values for age and New York Heart Association (NYHA) class were 68.8 ± 9.0 years and 2.38 ± 0.53, respectively. During the mean follow-up of 30 months, 57 patients died (36 from cardiovascular death). Univariate Cox regression analysis showed that age, NYHA class, atrial fibrillation, diabetes mellitus, left ventricular diastolic dysfunction, peak VO(2), VE/VCO(2) slope, and plasma BNP were significantly associated with mortality. Multivariate analysis revealed that plasma BNP, VE/VCO(2) slope, and age remained independent predictors for cardiovascular and all-cause mortalities, with the strongest prognostic power of plasma BNP (χ(2) ≥ 31.4, P < 0.001). In addition to plasma BNP and clinical predictors, the VE/VCO(2) slope could provide independent and incremental prognostic value of cardiovascular (χ(2) = 60.6 vs 51.7; P = 0.009) and all-cause mortalities (χ(2) = 62.8 vs 54.2; P = 0.015) with increased χ(2) value of Cox regression model. CONCLUSION: In diastolic heart failure, plasma BNP is the strongest predictor of mortality, and VE/VCO(2) slope provides independent and additive prognostic information, which suggests that combination of plasma BNP and VE/VCO(2) slope can improve risk stratification.
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Dióxido de Carbono/sangue , Insuficiência Cardíaca Diastólica/sangue , Insuficiência Cardíaca Diastólica/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Ventilação Pulmonar/fisiologia , Idoso , Biomarcadores/sangue , Teste de Esforço/tendências , Feminino , Seguimentos , Insuficiência Cardíaca Diastólica/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco/tendênciasRESUMO
PURPOSE: The purpose of the study was to evaluate the value of heart-type fatty acid-binding protein (hFABP) as a novel clinical biomarker in patients with severe sepsis. METHODS: Serum concentrations of hFABP and traditional cardiac biomarkers including cardiac troponin I, creatine kinase-MB, and B-type natriuretic peptides levels were measured within 6 hours after admission in 93 severe septic patients. The value of hFABP for the diagnosis of sepsis-related myocardial dysfunction (SRMD) and for the prediction of 28-day mortality was evaluated by receiver operating characteristics curve analysis. The prognostic value of elevated hFABP was subsequently confirmed by multivariate Cox proportional hazards analysis and Kaplan-Meier survival analysis. RESULTS: Heart-type fatty acid-binding protein was elevated (≥ 4.5 ng/mL) in 58 (62.4%) patients; patients with elevated hFABP appeared more likely to have SRMD (84.5% vs 31.4%, P < .001) and have higher prevalence of 28-day death (37.9% vs 8.6%, P = .002). Heart-type fatty acid-binding protein offered superior value over conventional biomarkers in both diagnosis of SRMD (area under the curve, 0.767; P < .001) and prediction of 28-day death (area under the curve, 0.805; P < .001). CONCLUSIONS: Serum hFABP is frequently elevated among patients with severe sepsis and appears to be associated with SRMD. Elevated hFABP independently predicts 28-day mortality in severe sepsis.
Assuntos
Proteínas de Ligação a Ácido Graxo/biossíntese , Proteínas de Ligação a Ácido Graxo/sangue , Unidades de Terapia Intensiva/estatística & dados numéricos , Sepse/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatina Quinase Forma MB/biossíntese , Proteína 3 Ligante de Ácido Graxo , Feminino , Indicadores Básicos de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/biossíntese , Prognóstico , Modelos de Riscos Proporcionais , Sensibilidade e Especificidade , Sepse/diagnóstico , Sepse/mortalidade , Fatores Sexuais , Troponina I/biossínteseRESUMO
OBJECTIVE: To evaluate stroke volume variation (SVV) as a predictor of fluid responsiveness in mechanically ventilated (MV) elderly patients with severe sepsis. METHODS: A prospective observation of 31 fluid challenges during fluid resuscitation for treatment of hemodynamic instability in 17 elderly MV patients with severe sepsis was conducted. SVV was measured by pulse indicator continuous cardiac output (PiCCO) system. Fluid responsiveness was defined as the changes in cardiac index (CI) increase after fluid loading (DeltaCI) > or =10%. The changes in hemodynamic parameters and lung water index were observed at the onset of and after fluid therapy. The correlation between DeltaCI and SVV or central venous pressure (CVP) were analyzed. RESULTS: SVV was decreased significantly after fluid loading [(6.6+/-2.1)% vs.(12.1+/-3.7)%, P<0.01], whereas CVP increased significantly [(12.5+/-3.6) mm Hg vs. (8.9+/-4.1) mm Hg, 1 mm Hg=0.133 kPa, P<0.01]. DeltaCI in response to fluid loading were positively correlated to initial values of SVV (r=0.447, P=0.012), but there was no relationship between CVP and DeltaCI (r=-0.082, P=0.674). The areas under the receiver operating characteristic curve (ROC curve) for SVV was 0.672 [95% confidence interval (95%CI) 0.463-0.885] and CVP was 0.336 (95%CI 0.133-0.539), respectively. A SVV value of 11.5% had the sensitivity of 71% and specificity of 67% for prediction of fluid responsiveness. CONCLUSION: Functional hemodynamic parameter SVV can predict fluid responsiveness in elderly MV patients with severe sepsis during fluid resuscitation, it may serve as a useful index for guiding fluid therapy in elderly patients with severe sepsis.
Assuntos
Hidratação , Sepse/terapia , Volume Sistólico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Prospectivos , Respiração Artificial , Ressuscitação , Sepse/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the impacts of glutamine (Gln) and recombinant human growth hormone (rhGH) intensified nutrition support on critically ill elderly patients. METHODS: Ninety critically ill aged patients were included in a prospective, randomized and controlled clinical study, and randomly divided into three groups: group A (standard nutrition support), group B (standard nutrition support+10% Gln 100 ml/d), group C (standard nutrition support+ Gln 100 ml/d+rhGH 10 U/d). Before treatment and then 7 and 14 days after treatment, blood samples were collected for analysis of serum proteins including albumin (ALB), pre-albumin (PAB), C-reactive protein (CRP), immunoglobulin G (IgG). Meanwhile, the variables including T-cell subsets, CD14 human leukocyte antigen (locus) DR (CD14 HLA-DR), and total lymphocytes were measured. The changes in acute physiology and chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome (MODS) scores, the durations of intensive care unit (ICU) stay and mechanical ventilation, and 28-day survival rate were recorded. RESULTS: Comparing with group A and B, the levels of serum ALB, PAB and IgG were significantly elevated in group C. The T-cell subsets, CD14 HLA-DR and the number of total lymphocytes were markedly higher in group C (P<0.01), and the APACHE II and MODS scores were decreased significantly in group C (P<0.05 or P<0.01). The levels of serum CRP were lowered significantly in group C (P<0.01). There were no significant differences in the durations of ICU stay, mechanical ventilation and 28-day survival rate among three groups (all P>0.05). CONCLUSION: Gln and rhGH intensified nutrition support can improve nutritional condition and immune function, downregulate the inflammatory response in the critically ill elderly patients.