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1.
BMJ Open ; 11(2): e040718, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608398

RESUMO

INTRODUCTION: Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU). METHODS AND ANALYSIS: This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum. ETHICS AND DISSEMINATION: The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations. TRIAL REGISTRATION: NCT03175328.

2.
Infect Drug Resist ; 13: 2053-2061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636658

RESUMO

Purpose: Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Patients and Methods: A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome. Results: Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes. Conclusion: The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

3.
Appl Opt ; 58(4): 1158-1163, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874167

RESUMO

We report on a non-contact method for external right-angle measurement using two autocollimators. A precise mathematical model is deduced to evaluate and deduct the measuring error. The values measured with our method are very coincident compared with the results measured by a ZYGO interferometer. The measuring accuracy is superior to 0.1 arcsec for the right-angle errors within 3.0 arcsec and becomes 0.4 arcsec for the extended right-angle errors within 8.0 arcsec. This method can be widely used in situations for external right-angle measurement, such as angle measurement for the body of torsion balance and test mass in spaceborne laser interferometry.

4.
J Neurosci Res ; 95(10): 2059-2070, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28186348

RESUMO

Cardiac arrest-induced global cerebral ischemia is a main cause of neurological dysfunction in emergency medicine. Transplantation with bone marrow mesenchymal stem cells (MSCs) has been used in stroke models to repair the ischemic brain injury, but it is little studied in models with global cerebral ischemia. In the present study, a hypoxia precondition was used to improve the efficacy of MSC transplantation, given the low survival and migration rates and limited differentiation capacities of MSCs. We found that hypoxia can increase the expansion and migration of MSCs by activating the PI3K/AKT and hypoxia-inducible factor-1α/CXC chemokine receptor-4 pathways. By using a cardiac arrest-induced global cerebral ischemic model in rats, we found that transplantation of hypoxia-preconditioned MSCs promoted the migration and integration of MSCs and decreased neuronal death and inflammation in the ischemic cortex. © 2017 Wiley Periodicals, Inc.


Assuntos
Lesões Encefálicas/patologia , Isquemia Encefálica/patologia , Parada Cardíaca/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Lesões Encefálicas/etiologia , Isquemia Encefálica/etiologia , Hipóxia , Precondicionamento Isquêmico/métodos , Masculino , Ratos , Ratos Sprague-Dawley
5.
J Surg Res ; 193(1): 344-54, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25091341

RESUMO

BACKGROUND: Recent findings showed advantages of a novel pyruvate-enriched oral rehydration solution (Pyr-ORS) in resuscitation of burns. This study focused on effects of Pyr-ORS on the visceral blood perfusion (VBP), gastrointestinal function, and survival rate, compared with the bicarbonate-based World Health Organization-guided oral rehydration solution (WHO-ORS), during intragastric rehydration of lethal hemorrhagic shock in rats. METHODS: Sixty adult rats were subjected to 45% total blood volume loss and were randomly allocated to the following three groups (n = 20): group NR (no fluid resuscitation), group PORS (oral Pyr-ORS rehydration), and group BORS (oral WHO-ORS rehydration), respectively. Other 10 rats were served as group NH (the sham group). Enteral rehydration lasted for 4 h after hemorrhage. The mean arterial pressure (MAP), VBP, and plasma enzymes activities of heart, liver, and kidney, and intestinal fatty acid binding protein were measured. Liver, kidney, and ileum were harvested for the evaluation of activities of oxidative enzymes and intestinal barrier protein (ZO-1). Other 84 rats with identical procedures without sampling were observed for their 24-h survival rates. RESULTS: Pyr-ORS was more effective in enhancing the MAP and VBP, inhibiting tissue oxidative damage, and improving organ function, compared with WHO-ORS. Hypoxic lactic acidosis was fully corrected in group PORS in 4 h, whereas it worsened in group BORS, and the 24-h survival rate was twice higher in group PORS than in group BORS (45.8 versus 20.8%, P < 0.05). CONCLUSIONS: A small amount of pyruvate in Pyr-ORS was more therapeutically beneficial than equivalent bicarbonate in WHO-ORS and greatly raised survival in enteral rehydration of lethal hemorrhagic shock. The Pyr-ORS may be an ideal oral fluid in resuscitation of hypovolemic shock, especially in prehospital and resource-poor settings.


Assuntos
Hidratação/métodos , Ácido Pirúvico/farmacologia , Ressuscitação/métodos , Choque Hemorrágico/tratamento farmacológico , Acidose Láctica/tratamento farmacológico , Acidose Láctica/metabolismo , Animais , Bicarbonatos/farmacologia , Modelos Animais de Doenças , Glucose/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Choque Hemorrágico/metabolismo , Cloreto de Sódio/farmacologia , Taxa de Sobrevida , Resultado do Tratamento , Vísceras/irrigação sanguínea
6.
Int J Clin Exp Pathol ; 8(11): 15106-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26823851

RESUMO

BACKGROUND: The available evidence suggests that simvastatin plays a beneficial role in lung injury. In addition, statins have been shown to inhibit the activity of inducible nitric oxide synthase (iNOS). The aim of the present study was to investigate the effects of simvastatin on iNOS expression based on a lipopolysaccharide (LPS)-induced septic rat model. METHODS: Thirty-six rats were randomly divided into 3 groups (control group, sepsis group and simvastatin group). A rat model of sepsis was established with LPS. The simvastatin group was pre-treated with simvastatin, whereas the control and sepsis groups were treated with saline before LPS treatment. LPS was injected into the rats in the simvastatin and sepsis groups, while as a negative control, the control group received saline alone. The oxygenation index, expression levels of iNOS and IL-6, and pathological integral of lung injury were analyzed to evaluate the effect of simvastatin on septic rats. RESULTS: Compared with the septic group, significant decreases in the oxygenation index and expression level of iNOS were observed in the simvastatin group. Furthermore, simvastatin treatment resulted in a significant decrease in iNOS levels and the pathological integral of lung injury score in septic rats. CONCLUSION: Simvastatin can relieve acute lung injury induced by sepsis in rats. Decreasing iNOS levels may contribute to the protective role of simvastatin in lung injury.


Assuntos
Lesão Pulmonar Aguda/patologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Óxido Nítrico Sintase Tipo II/biossíntese , Sinvastatina/farmacologia , Lesão Pulmonar Aguda/enzimologia , Lesão Pulmonar Aguda/etiologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Ratos , Ratos Sprague-Dawley , Sepse/complicações
7.
Int J Nanomedicine ; 6: 843-53, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21589652

RESUMO

BACKGROUND: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification. METHODS: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells. RESULTS: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100-150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%-21%, which was higher than for cationic liposomes. CONCLUSION: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells.


Assuntos
Técnicas de Transferência de Genes , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanopartículas/química , Plasmídeos/química , Polietilenoglicóis/química , Polietilenoimina/análogos & derivados , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Citometria de Fluxo , Microscopia de Força Atômica , Nanopartículas/administração & dosagem , Ressonância Magnética Nuclear Biomolecular , Plasmídeos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polietilenoimina/administração & dosagem , Polietilenoimina/química , Ratos , Ratos Sprague-Dawley
8.
Brain Res ; 1391: 24-35, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21420939

RESUMO

Cell tracking using iron oxide nanoparticles has been well established in MRI. However, in experimental rat models, the intrinsic iron signal derived from erythrocytes masks the labeled cells. The research evaluated a clinically applied Gd-DTPA for T1-weighted positive enhancement for cell tracking in spinal cord injury (SCI) rat models. MSCs were labeled with jetPEI/Gd-DTPA particles to evaluate the transfection efficiency by MRI in vitro. Differentiation assays were carried out to evaluate the differentiation ability of Gd-DTPA-labeled MSCs. The Gd-DTPA-labeled MSCs were transplanted to rat SCI model and monitored by MRI in vivo. Fluorescence images were taken to confirm the MRI results. Behavior test was assessed with Basso, Beattie, and Bresnahan (BBB) scoring in 6weeks after cell transplantation. The Gd-labeled MSCs showed a significant increase in signal intensity in T1-weighted images. After local transplantation, Gd-DTPA-labeled MSCs could be detected in SCI rat models by the persistent T1-weighted positive enhancement from 3 to 14days. Under electronic microscope, Gd-DTPA/jetPEI complexes were mostly observed in cytoplasm. Fluorescence microscopy examination showed that the Gd-labeled MSCs survived and distributed within the injured spinal cord until 2weeks. The Gd-labeled MSCs were identified and tracked with MRI by cross and sagittal sections. The BBB scores of the rats with labeled MSCs transplantation were significantly higher than those of control rats. Our results demonstrated that Gd-DTPA is appropriate for cell tracking in rat model of SCI, indicating that an efficient and nontoxic label method with Gd-DTPA could properly track MSCs in hemorrhage animal models.


Assuntos
Movimento Celular/fisiologia , Rastreamento de Células/métodos , Gadolínio DTPA , Hemorragia/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Traumatismos da Medula Espinal/patologia , Análise de Variância , Animais , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Proteínas de Fluorescência Verde/genética , Hemorragia/complicações , Imagem por Ressonância Magnética , Masculino , Microscopia Eletrônica de Transmissão , Polímeros/metabolismo , Ratos , Ratos Wistar , Espectrofotometria , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , Transfecção/métodos
9.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 21(6): 337-9, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19570337

RESUMO

OBJECTIVE: To explore the effect of inhibitor of matrix metalloproteinase-9 (MMP-9, SB-3CT) on blood brain barrier (BBB) after cardiopulmonary resuscitation (CPR) in rats. METHODS: Rats were randomly divided into three groups: the sham-operated group, the resuscitation control group, and the resuscitation treatment group. Cardiac arrest was produced by clamping the endotracheal intubation, and CPR was executed 1 minute later. In the resuscitation treatment group, SB-3CT (25 mg/kg) was injected intraperitoneally after the restoration of spontaneous circulation (ROSC). The rats were executed immediately, and 0, 3, 9, 24 and 48 hours after the treatment. BBB was examined, and the expression of MMP-9 protein and MMP-9 mRNA in brain tissue were detected, and the ultrastructure of brain tissue was studied with electron microscopy. RESULTS: In the sham-operated group, the water content, Evans blue content, MMP-9 protein, and MMP-9 mRNA did not change significantly, and there was no obvious change in microstructure of brain tissue. The expression of MMP-9 protein and MMP-9 mRNA in the resuscitation control group were obviously up-regulated at 3 hours after CPR, peaking at 24 hours. There was also significant change in BBB. The differences were significant statistically compared with sham-operated group. The changes in the resuscitation treatment group were similar to the resuscitation control group, but the levels were lower than those of the resuscitation control group (P<0.05 or P<0.01). CONCLUSION: The specific inhibitor of MMP-9 (SB-3CT) could decreased the expression of MMP-9, the injury of BBB, and cerebral edema in the cerebral ischemia model with CPR rats, and the protection of cerebral ischemia/reperfusion (I/R) injury after CPR is obvious.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Reanimação Cardiopulmonar , Compostos Heterocíclicos com 1 Anel/farmacologia , Inibidores de Metaloproteinases de Matriz , Sulfonas/farmacologia , Animais , Barreira Hematoencefálica/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Encéfalo/ultraestrutura , Modelos Animais de Doenças , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
10.
Chin Med J (Engl) ; 122(19): 2346-51, 2009 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-20079138

RESUMO

BACKGROUND: Neuroprotective strategies following cardiopulmonary resuscitation (CPR) are an important focus in emergency and critical care medicine. Matrix metalloproteinases (MMPs), especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemia-reperfusion injury after CPR. METHODS: One hundred and twenty rats were randomly assigned to sham-operated (n = 40), resuscitation treatment (n = 40), and resuscitation control (n = 40) groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation. In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation (ROSC), defined as restoration of supraventricular rhythm and mean arterial pressure (MAP) > or = 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours (n = 8). Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy. RESULTS: In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group (P < 0.05). Tissue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group (P < 0.05), they were lower than in the resuscitation control group (P < 0.05). CONCLUSIONS: Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Reanimação Cardiopulmonar , Compostos Heterocíclicos com 1 Anel/farmacologia , Inflamação/prevenção & controle , Inibidores de Metaloproteinases de Matriz , Fármacos Neuroprotetores/farmacologia , Sulfonas/farmacologia , Animais , Encéfalo/imunologia , Encéfalo/ultraestrutura , Citocinas/análise , Masculino , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 18(9): 542-5, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-16959152

RESUMO

OBJECTIVE: To investigate the effect of ulinastatin on apoptosis in ileal mucosa of rats with hemorrhagic shock. METHODS: A prospective, controlled animal study was performed. The rat model of hemorrhagic shock was replicated according to method described by Chaudry. After 60 minutes period of bleeding, rats were resuscitated by transfusion of shed blood and normal saline. A part of the animals were additionally treated with ulinastatin. The expression of tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA) content in serum, and expression of Bax, Bcl-2, caspase 3 protein in ileal mucosa were determined at different time points after reperfusion. RESULTS: Compared with the normal saline group, the expression levels of TNF-alpha, MDA content in serum, Bax and caspase 3 protein in ileal mucosa during hemorrhagic shock after resuscitation were significantly increased, while Bcl-2 protein was markedly decreased. After fluid resuscitation, obvious increase in MDA, Bcl-2 protein, significant decrease in the level of TNF-alpha, the expression of Bax and caspase 3 protein in ileal mucosa were observed in the ulinastatin group compared with normal saline group. CONCLUSION: Ulinastatin has protective effect on rats with hemorrhagic shock by suppressing the apoptosis in ileal mucosa.


Assuntos
Apoptose/efeitos dos fármacos , Glicoproteínas/farmacologia , Íleo/patologia , Choque Hemorrágico/tratamento farmacológico , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Feminino , Mucosa Intestinal/patologia , Masculino , Malondialdeído/sangue , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Choque Hemorrágico/metabolismo , Choque Hemorrágico/patologia , Fator de Necrose Tumoral alfa/metabolismo
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