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1.
Crit Care ; 24(1): 219, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410714

RESUMO

BACKGROUND: A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. METHODS: A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. RESULTS: A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57-70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5-17) days, and the duration from onset of symptoms to the study date was 31 (24-36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2-8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. CONCLUSIONS: Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Surtos de Doenças , Unidades de Terapia Intensiva , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Resultado do Tratamento
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(3): 336-340, 2020 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-32385999

RESUMO

OBJECTIVE: To compare the severity of brain injury between asphyxia and electrical stimulation induced cardiac arrest in rats. METHODS: Forty-two healthy male Sprague-Dawley (SD) rats were randomized into sham group (n = 6), asphyxia group (n = 18) and electrical stimulation group (n = 18). Rats in each group were given invasive mechanical ventilation and femoral blood vessels catheterization for monitoring blood pressure and fluid infusion. In the asphyxia group, the tracheal tube was clamped to induce cardiac arrest, and in the electrical stimulation group, the esophageal electrical stimulation was used to induce cardiac arrest, and cardiopulmonary resuscitation (CPR) was performed 4 minutes after cardiac arrest. In the sham group, only tracheal intubation and femoral artery intubation were performed after anesthesia, but cardiac arrest was not induced. Animals were allowed to survive until 72 hours after resuscitation, and survival analysis was performed using Kaplan-Meier curves. At 24 hours and 72 hours after resuscitation, the neurological deficit score (NDS) was measured. The vena cava blood was collected, and the brain injury associated serum biomarkers, neuron-specific enolase (NSE) and S100B, were detected by enzyme-linked immunosorbent assay (ELISA). The brain tissues were then harvested to perform hematoxylin-eosin (HE) staining for observing pathological changes in the hippocampal CA1 area with light microscopy. RESULTS: Cardiac arrest was successfully induced in both the asphyxia group and the electrical stimulation group, 94.4% (17/18) and 88.9% (16/18) animals were resuscitated successfully in the two groups respectively. Kaplan-Meier curves analysis showed that 72-hour cumulative survival rate was similar in the asphyxia group and the electrical stimulation group (Log-Rank test: χ2 = 0.040, P = 0.841). Both asphyxia group and electrical stimulation group had higher NDS score than sham group at 24 hours after resuscitation (37.50±4.26, 32.17±4.02 vs. 8.33±2.33, both P < 0.01). NDS score showed a downwards trend at 72 hours after resuscitation in both model groups, and the decline was more significant in the electrical stimulation group, which was significantly different as compared with asphyxia group (14.00±2.89 vs. 26.33±4.84, P < 0.05). ELISA results showed that the levels of serum NSE at 24 hours after resuscitation in the asphyxia and electrical stimulation groups were significantly higher than those in the sham group (µg/L: 1.02±0.07, 1.02±0.02 vs. 0.87±0.02, both P < 0.05). NSE kept increasing at 72 hours after resuscitation in the asphyxia group, which showed significant difference as compared with sham group (µg/L: 1.03±0.05 vs. 0.87±0.02, P < 0.01). But it had almost recovered to the normal level in the electrical stimulation group without significant difference as compared with sham group (µg/L: 0.96±0.04 vs. 0.87±0.02, P > 0.05). There was no significant difference in S100B level at different time points after resuscitation among three groups. It was displayed under light microscope that there was no significant neuronal damage in the hippocampal CA1 area in the two model groups at 24 hours after resuscitation as compared with the sham group. At 72 hours, there were certain damages in the hippocampal CA1 area in both model groups, which were more obvious in the asphyxia group. CONCLUSIONS: Both cardiac arrest models induced by asphyxia and electrical stimulation show a certain degree of brain injuries after resuscitation. Brain injuries are more severe in asphyxia-induced cardiac arrest compared with trans-esophageal electrical stimulation method.

4.
Lancet Respir Med ; 8(5): 475-481, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32105632

RESUMO

BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Síndrome do Desconforto Respiratório do Adulto/terapia , Síndrome do Desconforto Respiratório do Adulto/virologia , Estudos Retrospectivos , Resultado do Tratamento
5.
J Cell Physiol ; 234(10): 18906-18916, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30953350

RESUMO

Bone marrow mesenchymal stem cells (BMSC) can ameliorate ischemic injury of various tissues. However, the molecular mechanisms involved remain to be clarified. In this study, we intend to investigate the effects of BMSC-derived conditioned medium (BMSC-CM) on hypoxia/reoxygenation (H/R)-induced injury of H9c2 myocardial cells, and the potential mechanisms. Cell injury was determined through level of cell viability, lactate dehydrogenase (LDH) release, total intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), and cell apoptosis. Autophagic activity of cells was detected through levels of the autophagy-associated proteins and autophagic flux. Results showed that BMSC-CM alleviated H/R-induced injury in H9c2 cells, as demonstrated by increased cell viability and Δψm, decreased ROS production, LDH release, and cell apoptosis. Furthermore, the H/R treatment induced a decrease in autophagic activity and an increase in Notch2 signaling activation in H9c2 cells. In the presence of BMSC-CM, the autophagic activity impaired by the H/R treatment was upregulated with decreased phosphorylation of mTOR, and the activation of Notch2 signaling was downregulated. These effects of BMSC-CM could be replicated by Notch signaling inhibitor. In contrast, inhibitors of cell autophagy including chloroquine (CQ) and 3-methyladenine, diminished the protective effects of BMSC-CM. Taken together results, our study showed that BMSC-CM could protect H9c2 cells from H/R-induced injury potentially through regulating Notch2/mTOR/autophagy signaling. These findings may provide a novel insight into the mechanisms of BMSC-CM in therapy of myocardial ischemia/reperfusion injury as well as other ischemic diseases.

6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(3): 371-374, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30914104

RESUMO

OBJECTIVE: With the popularization of cardiopulmonary resuscitation (CPR) technology, the success rate of restoration of spontaneous circulation (ROSC) is gradually improved, and the survival rate and neurological outcome of patients with cardiac arrest are improved. Currently, therapeutic methods for cerebral resuscitation after cardiac arrest are limited. In addition to mild hypothermia for clinical application, the majority of drugs remain in the animal experimental stage. Finding effective brain protection drugs has become a hot spot in the field of brain resuscitation research. This article will review the pharmaceutical progress of research for cerebral resuscitation after cardiac arrest, so that we can study the brain protection mechanism of these drugs better and more targeted.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Parada Cardíaca/tratamento farmacológico , Pesquisa Farmacêutica/tendências , Ressuscitação/métodos , Humanos
7.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(1): 50-54, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30707869

RESUMO

OBJECTIVE: To compare the differences in cardiac functions and myocardial injury between asphyxia and trans-oesophageal pacing induced rat cardiac arrest models. METHODS: Healthy adult male Sprague-Dawley (SD) rats were randomly divided into sham group, asphyxia group and electrical stimulation group by random number table. The rats in the latter two groups were randomly divided into two subgroups (24 hours and 72 hours) according to the sampling time after successful resuscitation, with 6 rats in each group. All rats were mechanically ventilated for 20 minutes, in electrical stimulation group, cardiac arrest was induced by trans-oesophageal cardiac pacing for about 3 minutes (intensity 30 V, frequency 50 Hz, pulse duration 2 ms), and in asphyxia group, cardiac arrest was induced by clipping trachea for about 3 minutes. Cardiopulmonary resuscitation (CPR) was initiated 4 minutes after cardiac arrest. Echocardiographic examination was performed at 2 hours after return of spontaneous circulation (ROSC) with cardiac color ultrasound apparatus. Cardiac tissues were harvested at 24 hours and 72 hours after ROSC, hematoxylin-eosin (HE) staining was performed, and myocardial damage was observed under light microscope. The levels of cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) in serum were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference in ROSC rate between the asphyxia group and electrical stimulation group [94.4% (17/18) vs. 88.9% (16/18), P > 0.05]. The heart rate (HR), mean arterial pressure (MAP), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) at 2 hours after ROSC in asphyxia group and electrical stimulation group were significantly lower than those in sham group [HR (bpm): 401.50±19.76, 370.67±18.63 vs. 430.17±18.38, MAP (mmHg, 1 mmHg = 0.133 kPa): 107.17±12.92, 92.50±9.35 vs. 125.67±5.72, LVEF: 0.60±0.02, 0.54±0.03 vs. 0.63±0.01, LVFS: (48.40±2.52)%, (40.33±3.32)% vs. (55.47±2.38)%, all P < 0.05], and the decrease in electrical stimulation group was more significant (all P < 0.05). Compared with sham group, the levels of cTnI and BNP in serum of electrical stimulation group were significantly increased at 24 hours after ROSC [cTnI (ng/L): 51.57±13.04 vs. 38.23±5.57, BNP (ng/L): 1 919.61±823.22 vs. 977.47±445.18, both P < 0.05], but there was no significant difference in cTnI or BNP of serum between asphyxia group and sham group [cTnI (ng/L): 46.84±11.04 vs. 38.23±5.57, BNP (ng/L): 1 144.13±390.05 vs. 977.47±445.18, both P > 0.05]. There was no significant difference in cTnI or BNP of serum at 72 hours after ROSC among all the groups. The results of HE stain showed that the pathological injury of myocardium in electrical stimulation group was more serious than that in asphyxia group, characterized by more severe myocardial edema and partial myocardial cell lysis. CONCLUSIONS: The cardiac function after cardiac arrest-CPR was decreased in both asphyxia group and electrical stimulation group, but electrical stimulation had a heavier cardiac function injury than asphyxia.


Assuntos
Modelos Animais de Doenças , Parada Cardíaca/fisiopatologia , Animais , Asfixia , Reanimação Cardiopulmonar , Estimulação Elétrica , Parada Cardíaca/terapia , Masculino , Miocárdio , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
8.
Aging Dis ; 9(1): 31-39, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29392079

RESUMO

Experimental cardiac arrest (CA) in aging research is infrequently studied in part due to the limitation of animal models. We aimed to develop an easily performed mouse CA model to meet this need. A standard mouse KCl-induced CA model using chest compressions and intravenous epinephrine for resuscitation was modified by blood withdrawal prior to CA onset, so as to decrease the requisite KCl dose to induce CA by decreasing the circulating blood volume. The modification was then compared to the standard model in young adult mice subjected to 8 min CA. 22-month old mice were then subjected to 8 min CA, resuscitated, and compared to young adult mice. Post-CA functional recovery was evaluated by measuring spontaneous locomotor activity pre-injury, and on post-CA days 1, 2, and 3. Neurological score and brain histology were examined on day 3. Brain elF2α phosphorylation levels were measured at 1 h to verify tissue stress. Compared to the standard model, the modification decreased cardiopulmonary resuscitation duration and increased 3-day survival in young mice. For aged mice, survival was 100 % at 24 h and 54% at 72 h. Neurological deficit was present 3 days post-CA, although more severe versus young mice. Mild neuronal necrosis was present in the cortex and hippocampus. The modified model markedly induced elF2α phosphorylation in both age groups. This modified procedure makes the CA model feasible in aged mice and provides a practical platform for understanding injury mechanisms and developing therapeutics for elderly patients.

9.
Stroke ; 48(6): 1646-1654, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28487326

RESUMO

BACKGROUND AND PURPOSE: Impaired protein homeostasis induced by endoplasmic reticulum dysfunction is a key feature of a variety of age-related brain diseases including stroke. To restore endoplasmic reticulum function impaired by stress, the unfolded protein response is activated. A key unfolded protein response prosurvival pathway is controlled by the endoplasmic reticulum stress sensor (inositol-requiring enzyme-1), XBP1 (downstream X-box-binding protein-1), and O-GlcNAc (O-linked ß-N-acetylglucosamine) modification of proteins (O-GlcNAcylation). Stroke impairs endoplasmic reticulum function, which activates unfolded protein response. The rationale of this study was to explore the potentials of the IRE1/XBP1/O-GlcNAc axis as a target for neuroprotection in ischemic stroke. METHODS: Mice with Xbp1 loss and gain of function in neurons were generated. Stroke was induced by transient or permanent occlusion of the middle cerebral artery in young and aged mice. Thiamet-G was used to increase O-GlcNAcylation. RESULTS: Deletion of Xbp1 worsened outcome after transient and permanent middle cerebral artery occlusion. After stroke, O-GlcNAcylation was activated in neurons of the stroke penumbra in young mice, which was largely Xbp1 dependent. This activation of O-GlcNAcylation was impaired in aged mice. Pharmacological increase of O-GlcNAcylation before or after stroke improved outcome in both young and aged mice. CONCLUSIONS: Our study indicates a critical role for the IRE1/XBP1 unfolded protein response branch in stroke outcome. O-GlcNAcylation is a prosurvival pathway that is activated in the stroke penumbra in young mice but impaired in aged mice. Boosting prosurvival pathways to counterbalance the age-related decline in the brain's self-healing capacity could be a promising strategy to improve ischemic stroke outcome in aged brains.


Assuntos
Acetilglucosamina/metabolismo , Isquemia Encefálica/metabolismo , Proteínas de Membrana/metabolismo , Neuroproteção/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Piranos/farmacologia , Acidente Vascular Cerebral/metabolismo , Tiazóis/farmacologia , Resposta a Proteínas não Dobradas/fisiologia , Proteína 1 de Ligação a X-Box/metabolismo , Fatores Etários , Animais , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dobramento de Proteína
10.
Biomed Mater Eng ; 28(s1): S129-S138, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28372288

RESUMO

BACKGROUND: Mesenchymal stem cells (MSC) have been shown to have potent immunoregulatory effects. They are able to mitigate inflammation in many contexts of immune disorders, including autoimmune diseases and graft-versus-host disease (GVHD). Endotoxemia can induce systematic inflammation in the body. In this study, we try to investigate whether MSC can attenuate inflammation in models of LPS-induced endotoxemia. METHODS: Bone marrow MSC (BMSC) were isolated and expanded from rats of 4~6-week age. Adult mice were divided randomly into Control group, Model group and BMSC group. LPS were injected peritoneally into mice of Model group and BMSC group to induce endotoxemia. For BMSC group mice, 1×106 BMSC were injected through tail vein 1 hour after LPS application. Animals were sacrificed after 24 hours. Inflammatory damage in lungs and livers were detected through histochemistry. Wet/dry ratio of lung tissues was calculated, levels of inflammatory factors as IL-1ß and TNF-α in lung tissues were measured through ELISA. RESULTS: Inflammatory pathological changes in lung and liver in BMSC group were comparable to those in Model group. Moreover, in some animals, the injuries were exacerbated after BMSC treatment. Accordingly, wet/dry ratio of lung in BMSC group mice was higher than that in Model group mice. IL-1ß level in BMSC-treated group mice was significantly augmented, however, no significant changes were detected between these two groups for level of TNF-α. CONCLUSION: Our results showed that application of BMSC in LPS-induced endotoxemia models couldn't attenuate the inflammatory injuries in tissues. Although BMSC have been shown to be able to induce immune inhibition, however, in some instances, their immuno-inhibitory function might be regulated by the local environment.


Assuntos
Endotoxemia/terapia , Inflamação/terapia , Transplante de Células-Tronco Mesenquimais , Animais , Células Cultivadas , Modelos Animais de Doenças , Endotoxemia/complicações , Endotoxemia/imunologia , Endotoxemia/patologia , Inflamação/complicações , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/análise , Interleucina-1beta/imunologia , Lipopolissacarídeos/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Camundongos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia
11.
Biomed Mater Eng ; 28(s1): S237-S241, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28372300

RESUMO

Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called "low triiodothyronine (T3)" syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of thyroid hormone disorder in the development and prognosis of sepsis.


Assuntos
Sepse/diagnóstico , Sepse/imunologia , Hormônios Tireóideos/imunologia , Animais , Coagulação Sanguínea , Coração/fisiopatologia , Humanos , Pulmão/imunologia , Pulmão/fisiopatologia , Miocárdio/imunologia , Prognóstico , Sepse/sangue , Sepse/fisiopatologia , Hormônios Tireóideos/análise , Hormônios Tireóideos/sangue , Tri-Iodotironina/análise , Tri-Iodotironina/sangue , Tri-Iodotironina/imunologia
12.
J Cereb Blood Flow Metab ; 37(3): 1069-1079, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27217380

RESUMO

Impaired function of the endoplasmic reticulum (ER stress) is a hallmark of many human diseases including stroke. To restore ER function in stressed cells, the unfolded protein response (UPR) is induced, which activates 3 ER stress sensor proteins including activating transcription factor 6 (ATF6). ATF6 is then cleaved by proteases to form the short-form ATF6 (sATF6), a transcription factor. To determine the extent to which activation of the ATF6 UPR branch defines the fate and function of neurons after stroke, we generated a conditional and tamoxifen-inducible sATF6 knock-in mouse. To express sATF6 in forebrain neurons, we crossed our sATF6 knock-in mouse line with Emx1-Cre mice to generate ATF6-KI mice. After the ATF6 branch was activated in ATF6-KI mice with tamoxifen, mice were subjected to transient middle cerebral artery occlusion. Forced activation of the ATF6 UPR branch reduced infarct volume and improved functional outcome at 24 h after stroke. Increased autophagic activity at early reperfusion time after stroke may contribute to the ATF6-mediated neuroprotection. We concluded that the ATF6 UPR branch is crucial to ischemic stroke outcome. Therefore, boosting UPR pro-survival pathways may be a promising therapeutic strategy for stroke.


Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Resposta a Proteínas não Dobradas , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/farmacologia , Animais , Autofagia , Infarto Encefálico , Técnicas de Introdução de Genes , Infarto da Artéria Cerebral Média , Camundongos , Recuperação de Função Fisiológica
13.
J Cereb Blood Flow Metab ; 36(2): 393-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26661187

RESUMO

To evaluate the effect of age on the response of brains to an ischemic challenge, we subjected young and aged mice to transient forebrain ischemia, and analyzed the heat shock response and unfolded protein response, ubiquitin conjugation and SUMO conjugation, and O-linked ß-N-acetylglucosamine modification of proteins (O-GlcNAcylation). The most prominent age-related difference was an inability of aged mice to activate O-GlcNAcylation. Considering many reports on the protective role of O-GlcNAcylation in various stress conditions including myocardial ischemia, this pathway could be a promising target for therapeutic intervention to improve functional recovery of aged patients following brain ischemia.


Assuntos
Acetilglucosamina/metabolismo , Envelhecimento/patologia , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicologia , Encéfalo/patologia , Processamento de Proteína Pós-Traducional/genética , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/psicologia , Animais , Isquemia Encefálica/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/genética , Isquemia Miocárdica/fisiopatologia , Desempenho Psicomotor , Recuperação de Função Fisiológica , Proteína SUMO-1/metabolismo , Estresse Fisiológico/genética , Ubiquitinação , Resposta a Proteínas não Dobradas/genética
14.
Biomed Mater Eng ; 22(1-3): 49-55, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22766702

RESUMO

OBJECTIVES: To investigate the effects of thyroid hormone on L-type calcium channel mRNA and L-type calcium current of atrium and ventricle. METHODS: Sixteen New Zealand white rabbits were randomized into Thyroxine group (n=8) and Control group (n=8). In Throxine group, rabbits were injected intraperitoneally with L-thyroxine solution for 2 weeks (1 mg/kg·d(-1)) to induce hyperthyroidism. In Control group, rabbits were injected with the same volume of saline as for Thyroxine group. On day 15, 4 rabbits in each group were killed randomly to exam the L-type calcium current of atrium and ventricle using whole cell patch clamp; the other 4 rabbits were killed to detect the expression of L-type calcium channel mRNA using RT-PCR. RESULTS: The mean peak of L-type calcium current densities (pA/pF) at -10 mV was higher in Thyroxine group than in Control group (-8.59±0.68 vs. -6.54±0.49 in atrium, n=8, p<0.001; -9.24±0.67 vs. -7.06±0.21 in ventricle, n=8, p<0.001). L-calcium channel mRNA expression of both atrial myocytes and ventricular cells in Thyroxine group was significantly higher than those in Control group (p<0.05). CONCLUSIONS: Extrinsic thyroid hormone increased expression of L-type calcium channel mRNA and ICa,L current densities in both atrium and ventricle. These changes infer that supplement of thyroid hormone may ameliorate myocardial contraction in some special conditions such as sepsis.


Assuntos
Canais de Cálcio Tipo L/genética , Cálcio/metabolismo , Miócitos Cardíacos/metabolismo , RNA Mensageiro/genética , Tiroxina/metabolismo , Animais , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Átrios do Coração/citologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Hipertireoidismo/genética , Hipertireoidismo/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Técnicas de Patch-Clamp , Coelhos , Sepse/tratamento farmacológico , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/farmacologia , Tiroxina/farmacologia
15.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 21(9): 529-31, 2009 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-19751560

RESUMO

OBJECTIVE: To observe the effect of low-dose hydrocortisone on the requirement of norepinephrine and lactate clearance in patients with refractory septic shock, and to investigate the effect of stress dose corticosteroids in reversing septic shock and improving tissue oxygen supply. METHODS: Seventy-seven septic shock patients with hypotension refractory to fluids and administration of norepinephrine were randomly divided into control and treatment groups. In treatment group intravenous injection of low-dose hydrocortisone was given on top of the treatment given in control group for 14 days. The mean arterial pressure (MAP), lactate clearance and the data of norepinephrine use were compared between two groups during the course of treatment. RESULTS: The number of patients requiring norepinephrine was significantly lower and the MAP was significantly higher in 24 hours, 7 days, 14 days than those at the beginning of treatment in both groups (all P<0.01). Compare to the control group, the course of using norepinephrine was shorter and the number of using norepinephrine was smaller in 7 days in treatment group (both P<0.05 ); the MAP and lactate clearance were higher in 24 hours and 7 days in treatment group (P<0.05 or P<0.01). But there were no differences in mortality and the length of stay in intensive care unit (ICU). CONCLUSION: For the patients with septic shock with refractory hypotension, low-dose hydrocortisone can decrease the time course and dosage of vasopressors, improve tissue oxygen supply, thus can reverse septic shock more rapidly.


Assuntos
Hidrocortisona/administração & dosagem , Norepinefrina/administração & dosagem , Choque Séptico/tratamento farmacológico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/uso terapêutico , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Choque Séptico/metabolismo , Vasoconstritores/administração & dosagem , Vasoconstritores/uso terapêutico , Adulto Jovem
16.
Clin Hemorheol Microcirc ; 41(2): 117-25, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19252234

RESUMO

Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Dexametasona/farmacologia , Óxido Nítrico Sintase Tipo II/biossíntese , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Lesão Pulmonar Aguda/enzimologia , Animais , Modelos Animais de Doenças , Lipopolissacarídeos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/biossíntese , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Oxigênio/sangue , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório do Adulto/enzimologia
17.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 22(5): 1020-3, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16294744

RESUMO

This article deals with the influence of shear stress on endothelial NO synthesis, and the role of caveolae in shear stress-induced eNOS activation. Human umbilical vascular endothelial cells (HUVEC) were cultured and exposed to different levels of laminal shear stress and Filipin, the perfused cultures were collected, and NO(2-)/NO(3-) was detected using nitrate reduction method. The structure of caveolae was observed through transmission electron microscopy (TEM). The level of NO(2-)-/NO(3-) was found to increase with the elevation of shear stress level (P < 0.01). It was the highest at 1.5 N/m2. After treatment with Filipin, the level of NO produced by HUVEC decreased significantly (P < 0.01), but after recovery and shear without Filipin, the level of NO synthesis bounded back (P < 0.01). It was then concluded that shear stress can induce endothelial NO synthesis and caveolae plays a key role in shear stress-induced eNOS activation.


Assuntos
Cavéolas/fisiologia , Endotélio Vascular/citologia , Óxido Nítrico Sintase Tipo III/metabolismo , Células Cultivadas , Filipina/farmacologia , Humanos , Resistência ao Cisalhamento , Veias Umbilicais/citologia
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