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2.
Biol Pharm Bull ; 42(9): 1491-1499, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31204351

RESUMO

Endothelial cell injury and apoptosis induced by oxidative stress serve important roles in many vascular diseases. The repair of endothelial cell vascular injury relies on the function of local endothelial progenitor cells (EPCs). Our previous study indicated that epimedin C, a major flavonoid derived from Herba epimedii (yin yang huo), could promote vascularization by inducing endothelial-like differentiation of mesenchymal stem cells C3H/10T1/2 both in vivo and in vitro. In view of the significant cardiovascular protective effects of Herba epimedii, we detected a protective effect of epimedin C on hydrogen peroxide (H2O2)-induced peroxidation injury in human umbilical vein endothelial cells (HUVECs) and the role of EPC in this process. The results show that epimedin C increased the expression of the stem cell marker, CD34 and PROM1, and subsequently enhanced the expression and function of vascular endothelial growth factor and matrix metalloproteinase (MMP)-2 in local vascular endothelial cells. In conclusion, epimedin C protects H2O2-induced peroxidation injury by enhancing the function of endothelial progenitor HUVEC populations.


Assuntos
Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
Neuroreport ; 29(1): 59-64, 2018 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-29112675

RESUMO

Cytosolic phospholipase A2α (cPLA2α) is implicated in the progression of excitotoxic neuronal injury and cerebral ischemia. Previous work suggests that cPLA2α increases aberrant electrophysiologic events through attenuating K channel functions. Nevertheless, which K channels are affected by cPLA2α needs to be determined. Here we examined K channels-mediated electrophysiologic responses in hippocampal CA1 pyramidal neurons from wild-type and cPLA2α mice using simultaneous patch-clamp recording and confocal Ca imaging. After the exposure to the blockers of Ca-sensitive and A-type K channels, all CA1 neurons developed spike broadening and increased dendritic Ca transients. These effects were occluded in CA1 neurons from cPLA2α mice. Therefore, cPLA2α modulates the functions of Ca-sensitive and A-type K channels in neurotoxicity.


Assuntos
Albuminas 2S de Plantas/metabolismo , Hipocampo/citologia , Canais de Potássio/metabolismo , Células Piramidais/metabolismo , Albuminas 2S de Plantas/genética , 4-Aminopiridina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Animais , Apamina/farmacologia , Cálcio/metabolismo , Estimulação Elétrica , Fenômenos Eletrofisiológicos , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , Técnicas de Patch-Clamp , Paxilina/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Células Piramidais/efeitos dos fármacos
4.
Chin Med J (Engl) ; 129(14): 1643-51, 2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27411450

RESUMO

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.


Assuntos
Lesões Encefálicas/terapia , Respiração Artificial , Adulto , Idoso , Lesões Encefálicas Traumáticas/terapia , China , Estudos Transversais , Feminino , Humanos , Hipóxia-Isquemia Encefálica/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/terapia , Inquéritos e Questionários
5.
J Investig Med ; 64(3): 752-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26912007

RESUMO

The aim of this study was to assess the effect of continuous propofol sedation plus prolonged mechanical ventilation on adrenal insufficiency (AI) in patients with traumatic brain injury (TBI). Eighty-five adult patients diagnosed with moderate TBI (Glasgow Coma Scale (GCS) score 9-13) from October 2011 to October 2012 were included in this prospective study. The patients comprised three groups: no mechanical ventilation and sedation (n=27), mechanical ventilation alone (n=24) and mechanical ventilation plus sedation (n=34). The low-dose short Synacthen test was performed at 8:00 on the first, third, and fifth days after TBI. Logistic regression analysis was performed to identify factors affecting the use of mechanical ventilation and sedation, and the incidence of AI. On the fifth day after injury, the mean baseline cortisol and simulated cortisol levels were significantly lower in the mechanical ventilation plus sedation group compared with the other two groups. Multivariate regression analysis showed that the Acute Physiology and Chronic Health Evaluation (APACHE) score was independently associated with treatment with mechanical ventilation and sedation compared to mechanical ventilation alone. Furthermore, hypoxemia on admission and shock were associated with the development of AI. The findings showed that sedation is associated with an increased incidence of AI. Patients with TBI who are treated with continuous sedation should be monitored for AI carefully.


Assuntos
Insuficiência Adrenal/complicações , Lesões Encefálicas Traumáticas/complicações , Sedação Profunda , Respiração Artificial , Insuficiência Adrenal/sangue , Insuficiência Adrenal/epidemiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Lesões Encefálicas Traumáticas/sangue , Feminino , Humanos , Hidrocortisona/sangue , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
6.
Cerebellum ; 14(1): 12-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25471260

RESUMO

Mutations in leucine-rich glioma inactivated 1 (LGI1) are linked to human autosomal dominant lateral temporal lobe epilepsy. It has been shown that LGI1 prevents the inactivation of voltage-gated potassium channels, mediates postnatal maturation of glutamatergic synapses, and regulates excitatory neurotransmission. However, other functions of LGI1 in the central nervous system have not been elucidated. We found that LGI1 is involved in the development of the cerebellum and cortex. The thickness of external granule layer was reduced, and foliation was affected in the cerebellum of LGI1 knockout mice. Double staining with Pax6 and BrdU showed a significant inhibition of proliferation of granule cell precursors of knockout embryos. The differentiation of radial glia cells was also suppressed in knockout mice, as shown by increased radial glial cells and decreased Bergmann glias in the areas of the cerebellum and cortex. Thus, our data demonstrate that LGI1 may be an essential player in the development of the brain.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologia , Proteínas/metabolismo , Animais , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Neurogênese/fisiologia , Neuroglia/fisiologia , Neurônios/fisiologia
7.
J Thorac Dis ; 6(12): 1765-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25589971

RESUMO

BACKGROUND: Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous ß-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients' outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease. METHODS: All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients' outcomes were evaluated with logistics regression. RESULTS: A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil (median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine (with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123). CONCLUSIONS: Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.

8.
Cerebellum ; 12(3): 297-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23307660

RESUMO

Cytosolic phospholipase A2 alpha (cPLA2α) responds to micromolar intracellular Ca(2+) and produces arachidonic acid, which regulates cellular homeostasis, neurotoxicity, and inflammation. Endocannabinoids are the derivates of arachidonic acid and widely distributed in the cerebellum. However, the role of cPLA2α/arachidonic acid pathway in cerebellar synaptic transmission and plasticity is unknown. We utilized cPLA2α knockout mice and slice whole-cell patch clamp to study the action of cPLA2α/arachidonic acid signaling on the depolarization-induced suppression of excitation (DSE) and long-term potentiation at parallel fiber-Purkinje cell synapses. Our data showed that DSE was significantly inhibited but rescued by arachidonic acid in cPLA2α knockout mice. The degradation enzyme of 2-arachidonoylglycerol (2-AG), monoacylglycerol lipase, blocked DSE, while another catabolism enzyme for N-arachidonoylethanolamine, fatty acid amide hydrolase, did not, suggesting that 2-AG is responsible for DSE in Purkinje cells. Co-application of paxilline reversed the blockade of DSE by internal K(+), indicating that large-conductance Ca(2+)-activated potassium channel is sufficient to inhibit cPLA2α/arachidonic acid-mediated DSE. On the other hand, we found that 1 Hz parallel fiber stimuli-triggered long-term potentiation (LTP) was deficient in cPLA2α knockout mice. LTP was also inhibited when AACOCF3, an inhibitor of cPLA2α, was given. Arachidonic acid was necessary for the LTP induction. Therefore, these data showed that cPLA2α/arachidonic acid/2-AG signaling pathway mediates DSE and LTP at parallel fiber-Purkinje cell synapse.


Assuntos
Ácido Araquidônico/metabolismo , Ácidos Araquidônicos/metabolismo , Cerebelo/fisiologia , Endocanabinoides/metabolismo , Glicerídeos/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Potenciação de Longa Duração/fisiologia , Transdução de Sinais/fisiologia , Animais , Ácidos Araquidônicos/farmacologia , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Fosfolipases A2 do Grupo IV/deficiência , Técnicas In Vitro , Indóis/farmacologia , Potenciação de Longa Duração/genética , Camundongos , Camundongos Knockout , Fibras Nervosas/fisiologia , Técnicas de Patch-Clamp , Bloqueadores dos Canais de Potássio/farmacologia , Transdução de Sinais/genética
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 35(2): 215-8, 2006 03.
Artigo em Chinês | MEDLINE | ID: mdl-16610092

RESUMO

OBJECTIVE: To investigate the relationship between cerebral vasospasm and occurrence of delayed ischemic neurological deficit (DIND). METHODS: The clinical records and radiographic images of 118 patients with subarachnoid hemorrhage admitted during last 5 years were reviewed. The incidence,degree and localization of cerebral vasospasm were evaluated, and morbidity of related DIND was analyzed. Patients with cerebral vasospasm were divided into three groups: Group MCA (middle cerebral artery), Group ACA (anterior cerebral artery) and Group ICA (intracranial carotid artery) according to the location of cerebral vasospasm. The consistency of DIND and image of cerebral infarction were examined. RESULT: There was a weak correlation between cerebral vasospasm and incidence of DIND (r=0.22; P=0.016). The incidence of DIND was increased with severity of cerebral vasospasm (U=2.589, P<0.05). The group MCA had a significantly higher incidence of DIND than that of ACA and ICA groups (68.0% compared with 36.7% and 25.0%, respectively, chi(2)=8.195, P=0.004), the difference between later two groups was not statistically significant (chi(2)=0.646, P=0.421). CONCLUSION: Cerebral vasospasm may be an important factor leading to DIND occurrence; the severity and location of cerebral vasospasm is related to the incidence of DIND.


Assuntos
Aneurisma Roto/complicações , Artéria Carótida Interna , Ataque Isquêmico Transitório/etiologia , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia , Adulto , Idoso , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea , Fatores de Tempo
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 32(5): 415-7, 426, 2003 10.
Artigo em Chinês | MEDLINE | ID: mdl-14610742

RESUMO

OBJECTIVE: To investigate the distribution of G894T mutation of the endothelial nitric oxide synthase (eNOS) gene in Chinese Han nationality. METHODS: G894T mutation of the eNOS gene of 108 unrelated healthy individuals was studied by means of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. RESULT: All subjects were genotyped for eNOS gene; the frequencies of the GG, GT and TT genotypes were 0.9095, 0.0883 and 0.0021, respectively. In the Han nationality, the frequency of the GT, TT genotypes was lower than that in Japanese and Caucasian of UK (P< 0.05). CONCLUSION: These results suggest that there are significant differences in G894T mutation of eNOS gene between the Chinese Han nationality and other ethnic populations.


Assuntos
Povo Asiático/genética , Mutação , Óxido Nítrico Sintase/genética , China/etnologia , Genótipo , Humanos , Óxido Nítrico Sintase Tipo III , Reação em Cadeia da Polimerase
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