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1.
ACS Omega ; 9(29): 31533-31545, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39072111

RESUMO

In order to study the effects of temperature, wind speed, and leakage volume on the diffusion of heavy gas leakage, this paper establishes a scaling model for the experimental study of gas leakage and diffusion by using the similarity theory with a certain factory as the target. And carbon dioxide gas is selected to replace the toxic and harmful heavy gas to carry out experiments under different temperatures (0-40 °C), wind speeds (0-2 m/s), and leakage velocities (2.5-12.5 L/min), respectively. The results showed that the diffusion rate of heavy gas expanded with increasing temperature under the conditions of wind speed of 0.25 m/s and leakage velocity of 1.5 L/min. When the temperature was increased from 0 to 40 °C, the concentration increase at each location was 125-290% at 600 s. Under the condition of temperature of 20 °C and leakage velocity of 5 L/min, the concentration at each location increased linearly with diffusion time when there was wind, while the linear relationship was not obvious when there was no wind. The effect on the concentration was larger when the wind speed was less than 1 m/s and smaller when the wind speed was greater than 1 m/s. At 20 °C and a wind speed of 0.5 m/s, the concentration of carbon dioxide at each location was increasing as the leakage increased. As the leakage velocity increases from 2.5 to 12.5 L/min, the carbon dioxide concentration at 600 s spreads 2-14 times. The research in this paper provides some decision support for the rescue work, which is important for improving the emergency rescue capability of the leakage accident.

2.
Aging (Albany NY) ; 13(8): 11738-11751, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33878030

RESUMO

Mounting evidence suggests that mitochondrial dysfunction and impaired mitophagy lead to Parkinson's disease (PD). Quercetin, one of the most abundant polyphenolic flavonoids, displays many health-promoting biological effects in many diseases. We explored the neuroprotective effect of quercetin in vivo in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD and in vitro in 6-OHDA-treated PC12 cells. In vitro, we found that quercetin (20 µM) treatment improved mitochondrial quality control, reduced oxidative stress, increased the levels of the mitophagy markers PINK1 and Parkin and decreased α-synuclein protein expression in 6-OHDA-treated PC12 cells. Moreover, our in vivo findings demonstrated that administration of quercetin also relieved 6-OHDA-induced progressive PD-like motor behaviors, mitigated neuronal death and reduced mitochondrial damage and α-synuclein accumulation in PD rats. Furthermore, the neuroprotective effect of quercetin was suppressed by knockdown of either Pink1 or Parkin.


Assuntos
Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson Secundária/tratamento farmacológico , Quercetina/administração & dosagem , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Oxidopamina/administração & dosagem , Oxidopamina/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/patologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ratos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , alfa-Sinucleína/metabolismo
3.
Front Pharmacol ; 10: 660, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275144

RESUMO

Prolonged pulsatile administration of Levodopa (L-dopa) can generate L-dopa-induced dyskinesia (LID). Numerous research has reported that continuous dopamine delivery (CDD) was useful in reducing the severity of LID. 6-OHDA lesioned rats were divided into two groups to receive intermittent L-dopa stimulation (L-dopa/benserazide) or Levodopa/benserazide PLGA microsphere (LBPM) for 3 weeks. rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablation of ß-arrestin2. We found that LBPM developed less AIM severity compared with standard L-dopa administration, whereas selective deletion of ß-arrestin2 in striatum neurons dramatically enhanced the severity of dyskinesia by LBPM. On the contrary, the effects of LBPM in terms of ALO AIM were further relieved by ß-arrestin2 overexpression. Furthermore, no significant change in motor behavior was seen either in inhibition or overexpression of ß-arrestin2. In short, our experiments provided evidence that LBPM's prevention of LID behavior was likely due to ß-arrestin2, suggesting that a therapy modulating ß-arrestin2 may offer a more efficient anti-dyskinetic method with a low risk of untoward effects.

4.
Aging (Albany NY) ; 11(24): 12315-12327, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31891566

RESUMO

The cause of the L-dopa-induced dyskinesia (LID) has been ascribed to G-protein coupled receptor (GPCR) supersensitivity and uncontrolled downstream signaling. It is now supposed that ß-arrestin2 affects GPCR signaling through its ability to scaffold various intracellular molecules. We used the rAAV (recombinant adeno-associated virus) vectors to overexpress and ablation of ß-arrestin2. L-dopa-induced changes in expression of signaling molecules and other proteins in the striatum were examined by western blot and immunohistochemically. Our data demonstrated that via AAV-mediated overexpression of ß-arrestin2 attenuated LID performance in 6-OHDA-lesioned rodent models. ß-arrestin2 suppressed LID behavior without compromising the antiparkinsonian effects of L-dopa. Moreover, we also found that the anti-dyskinetic effect of ß-arrestin2 was reversed by SKF38393, a D1R agonist. On the contrary, the rat knockdown study demonstrated that reduced availability of ß-arrestin2 deteriorated LID performance, which was counteracted by SCH23390, a D1R antagonist. These data not only demonstrate a central role for ß-arrestin2/GPCR signaling in LID, but also show the D1R signal pathway changes occurring in response to dopaminergic denervation and pulsatile administration of L-dopa.


Assuntos
Levodopa/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Receptores de Dopamina D1/metabolismo , beta-Arrestina 2/metabolismo , Adenoviridae , Animais , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Masculino , Ratos , beta-Arrestina 2/genética
5.
Biomed Res Int ; 2018: 5818937, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29998135

RESUMO

OBJECTIVE: To compare the current treatment approach in elderly patients with poor-grade aneurysmal subarachnoid hemorrhage (SAH) and identify the independent predictors of the outcome after aggressive surgical treatment. METHOD: This prospective, multicenter cohort study included 104 poor-grade aneurysmal SAH elderly patients, 60 years or older, treated in our institution from October 2010 to March 2013. Patients were grouped according to three treatment arms. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at baseline and at a 12-month follow-up. Univariate and multivariate analysis were performed using the following factors: sex, age, smoking history, breathing ability, alcohol consumption, cerebral hernia, aneurysm location, aneurysm diameter, WFNS grade, CT Fisher grade, treatment approach, and the timing of the aneurysm surgery. RESULTS: At the 12-month follow-up, patients in the coiling group and clipping group had better prognosis than patients in the palliative treatment group. Univariate analysis confirmed that the treatment approach, WFNS grade, CT Fisher grade, and age are critical factors for neurological outcomes in poor-grade SAH. Multivariate analysis indicated that WFNS grade V, CT Fisher grades 3-5, and palliative treatment were independent predictors of poor prognoses. CONCLUSION: Aggressive surgical treatment improves the prognoses in poor-grade aneurysm elderly patients with SAH. Elderly Patients of WFNS grade IV and CT Fisher grades 1-2 are more likely to have a better outcome.


Assuntos
Aneurisma Roto/cirurgia , Aneurisma Intracraniano/cirurgia , Hemorragia Subaracnóidea/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
6.
J Stroke Cerebrovasc Dis ; 26(10): 2087-2092, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28623118

RESUMO

BACKGROUND: Isolated distal deep venous thrombosis (IDDVT) is a common complication after ischemic stroke. However, there is a paucity of evidence regarding the clinical features and risk factors of IDDVT in patients with acute ischemic stroke. This study aimed to establish and validate a clinical prediction scale of IDDVT at an early stage of ischemic stroke development. METHODS: We retrospectively studied consecutive patients with stroke admitted to our neurology department between January and December 2016. Selected clinical variables were assessed by multivariable logistic regression to determine the independent risk factors for IDDVT. A prediction scale was developed and verified by the receiver operating characteristic curve. RESULTS: A total of 671 patients with ischemic stroke were included in the study, with 450 patients allocated into the derivation group and 221 patients into the validation group. A substantial proportion (22.1%) of patients developed IDDVT. A 16-point prediction scale (female gender = 2, older age [≥60 years] = 3, atrial fibrillation = 2, acute infection = 2, active cancer = 5, and higher [≥2.6 mmol/L] level of low-density lipoprotein = 2) derived from a multivariable logistic regression model was highly predictive of 10-day risk of IDDVT in both the validation group (c statistic = .70, 95% confidence interval [CI], .63-0.78, P < .0001) and the derivation group (c statistic = .68, 95% CI, .63-0.74, P < .0001). CONCLUSIONS: This prediction scale may help to identify patients with ischemic stroke who are at a higher risk of developing IDDVT.


Assuntos
Isquemia Encefálica/complicações , Técnicas de Apoio para a Decisão , Acidente Vascular Cerebral/complicações , Trombose Venosa/etiologia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Isquemia Encefálica/diagnóstico , Distribuição de Qui-Quadrado , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Ultrassonografia Doppler em Cores , Trombose Venosa/diagnóstico por imagem
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