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1.
Gynecol Endocrinol ; 39(1): 2181652, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36824010

RESUMO

AIM: Among the natural polyphenolic compounds, resveratrol (RES) is known for reducing the effects of declining reproductive power through resisting senility, anti-oxidant and anti-inflammatory, while the molecular mechanism of RES in human ovaries is unclear. We aimed to evaluate the most likely mechanisms of RES against apoptosis induced by H2O2 in human ovary granulosa cells. METHODS: Ovarian granulosa cells from infertile women (≤35 years old) were collected. Those patients defined as polycystic ovary syndrome (PCOS), poor ovarian responder (POR) and Endometriosis were excluded. Then they were randomly divided into control group, model group and the treatment group. Cellular apoptosis was analyzed by flow cytometer method. The related protein and mRNA expressions were detected by western blot and RT-PCR. RESULTS: Apoptosis rates of the treatment group containing RES with concentrations of 1 µM and 10 µM were significantly decreased (p < 0.001). Western blot results demonstrated that the proteins levels of transforming growth factor-ß (TGF-ß), Bax and Caspase 9 were decreased, and Bcl-2 was increased under RES treatment, while the protein levels of Caspase 8, Caspase 3, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) expressed no significant difference. The results by RT-PCR of follicle and ovarian development related mRNA factors were consistent with that of western blot assay. CONCLUSION: In conclusion, the present study provides the evidence that RES may affects apoptotic factors to protect human ovarian state.


Assuntos
Infertilidade Feminina , Síndrome do Ovário Policístico , Feminino , Humanos , Adulto , Ovário/metabolismo , Resveratrol/farmacologia , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Células da Granulosa/metabolismo , Síndrome do Ovário Policístico/metabolismo , Apoptose , RNA Mensageiro/metabolismo
2.
BMC Pregnancy Childbirth ; 21(1): 275, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794797

RESUMO

BACKGROUND: Adding clomiphene citrate (CC) and/or letrozole (LE) to in vitro fertilization (IVF) cycles for mild ovarian stimulation is a general approach. Although lots of researches have demonstrated partial benefits of the strategy, all-around effects of oral medications remained deficient. This paper aims to assess whether an addition of oral medication will result in considerable outcomes on T-Gn (total dose of gonadotropin), Gn days, total retrieved ova, high quality embryos, blastocyst number, ovarian hyperstimulation syndrome (OHSS) rate, clinical pregnancy rate and cumulative pregnancy rate, even if it was not conventional mild/minimal stimulations. RESULTS: Participants were categorized to three diverse populations as high responders, normal responders and poor responders according to basal antral follicle count. T-Gn in patients treated with CC/LE distinctly decreased from 2496.96 IU/d to 1827.68 IU/d, from 2860.28 IU/d to 2119.99 IU/d, and from 3182.15 IU/d to 1802.84 IU/d, respectively. For high ovary responders and normal responders, the OHSS incidence rate also declined from 29.2 to 4.3% (P < 0.001) and from 1.1 to 0.0% (P = 0.090). Other, there was no statistical difference with respect to the T-retrieved ova (total retrieved ova), high quality embryos, cultured blastocyst and blastocyst number in high responders. For normal responders and poor ovary responders, T-Gn, Gn days, T-retrieved ova, high quality embryos, cultured blastocyst and blastocysts number in oral medications group all apparently decreased. Clinical pregnancy rate per fresh cycle of poor responders with prior oral medications was significantly decreased (25.7% vs. 50.8%, P = 0.005), and no significant differences in high responders and normal responders were expressed (52.5% vs. 44.2%, P = 0.310; 51.9% vs. 42.4%, P = 0.163) between two groups of participants. The numbers of cumulative pregnancy rates were lower in the conventional group compared to the add group for high (75.90% versus 81.03%, P = 0.279), normal (62.69% versus 71.36%, P = 0.016) and poor (39.74% versus 68.21%, P < 0.001) responders. CONCLUSIONS: The addition of CC/LE to the ovulation induction during IVF has certain efficacy in terms of low cost, low OHSS incidence. CC/LE deserves more recommendations as a responsible strategy in high responders due to advantageous pregnancy outcomes. For normal responders, the strategy needs to be considered with more comprehensive factors.


Assuntos
Clomifeno/administração & dosagem , Gonadotropinas/administração & dosagem , Letrozol/administração & dosagem , Síndrome de Hiperestimulação Ovariana/epidemiologia , Indução da Ovulação/métodos , Administração Oral , Adulto , Clomifeno/efeitos adversos , Relação Dose-Resposta a Droga , Transferência Embrionária , Estudos de Viabilidade , Feminino , Gonadotropinas/efeitos adversos , Humanos , Incidência , Infertilidade/terapia , Injeções Intramusculares , Letrozol/efeitos adversos , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Resultado do Tratamento , Adulto Jovem
3.
Neurochem Res ; 43(9): 1779-1790, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29995175

RESUMO

Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH + sham group, ischemia group and IH + ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (PB = 404 mmHg, PO2 = 84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition, L-NAME + ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration of L-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia.


Assuntos
Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/metabolismo , Hipóxia/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico/metabolismo , Animais , Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Hipóxia/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
4.
Neurochem Res ; 43(10): 2016, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30171421

RESUMO

The order of corresponding author was inadvertently published. Hence, the first and the second corresponding authors should be Min Zhang (hebmuzhangmin@163.com) and Jing-Ge Zhang (zhangjg001@163.com).

5.
Stem Cells ; 34(5): 1273-83, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26850336

RESUMO

Human mesenchymal stem cells (hMSCs) possess the potential to differentiate into endothelial cells (EC). DNA methylation plays an important role in cell differentiation during development. However, the role of the DNA methyltransferases Dnmt1 and Dnmt3a in specific arterial differentiation of hMSCs is not clear. Here, we show that the CpG islands in the promoter regions of the EC specification and arterial marker genes were highly methylated in hMSCs based on bisulfite genomic sequencing. Treatment with the DNMT inhibitor 5-aza-dc induced the reactivation of EC specification and arterial marker genes by promoting demethylation of these genes as well as stimulating tube-like structure formation. The hMSCs with stable knockdown of Dnmt1/Dnmt3a were highly angiogenic and expressed several arterial specific transcription factors and marker genes. A Matrigel plug assay confirmed that Dnmt1/Dnmt3a stable knockdown hMSCs enhanced blood vessel formation compared with WT MSCs. We also identified that the transcription factor E2F1 could upregulate the transcription of arterial marker genes by binding to the promoters of arterial genes, suggesting its critical role for arterial specification. Moreover, miRNA gain/loss-of-function analyses revealed that miR152 and miR30a were involved in endothelial differentiation of hMSCs by targeting Dnmt1 and Dnmt3a, respectively. Taken together, these data suggest that Dnmt1 and Dnmt3a are critical regulators for epigenetic silencing of EC marker genes and that E2F1 plays an important role in promoting arterial cell determination. Stem Cells 2016;34:1273-1283.


Assuntos
Artérias/citologia , Diferenciação Celular , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , Técnicas de Silenciamento de Genes , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/genética , Especificidade de Órgãos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , DNA Metiltransferase 3A , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Inibidores Enzimáticos/farmacologia , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética
6.
BMC Neurosci ; 13: 10, 2012 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-22257758

RESUMO

BACKGROUND: The aim of this study was to investigate whether serotonin (5-hydroxytryptamine, 5-HT) can modulate Na+/K+ pump in rat hippocampal CA1 pyramidal neurons. RESULTS: 5-HT (0.1, 1 mM) showed Na+/K+ pump current (Ip) densities of 0.40 ± 0.04, 0.34 ± 0.03 pA/pF contrast to 0.63 ± 0.04 pA/pF of the control of 0.5 mM strophanthidin (Str), demonstrating 5-HT-induced inhibition of Ip in a dose-dependent manner in hippocampal CA1 pyramidal neurons. The effect was partly attenuated by ondasetron, a 5-HT3 receptor (5-HT3R) antagonist, not by WAY100635, a 5-HT1AR antagonist, while 1-(3-Chlorophenyl) biguanide hydrochloride (m-CPBG), a 5-HT3R specific agonist, mimicked the effect of 5-HT on Ip. CONCLUSION: 5-HT inhibits neuronal Na+/K+ pump activity via 5-HT3R in rat hippocampal CA1 pyramidal neurons. This discloses novel mechanisms for the function of 5-HT in learning and memory, which may be a useful target to benefit these patients with cognitive disorder.


Assuntos
Região CA1 Hipocampal/citologia , Células Piramidais/efeitos dos fármacos , Serotonina/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Animais Recém-Nascidos , Biguanidas/farmacologia , Biofísica , Relação Dose-Resposta a Droga , Estimulação Elétrica , Técnicas In Vitro , Inibição Neural/efeitos dos fármacos , Técnicas de Patch-Clamp , Piperazinas/farmacologia , Células Piramidais/fisiologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Bloqueadores dos Canais de Sódio/farmacologia , Estrofantidina/farmacologia , Tetrodotoxina/farmacologia
7.
Toxicol Appl Pharmacol ; 262(1): 32-42, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22546087

RESUMO

The composition of different isoforms of Na+-K+-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H1-H2 domain of α1 and α2 isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α1 or α2 isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca²âº](i)), attenuated mitochondrial Ca²âº overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 µM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca²âº](i) and the contractility induced by 1 µM but not that induced by 1 mM OUA. These results indicate that the H1-H2 domain of the NKA α1 isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease.


Assuntos
Glicosídeos Cardíacos/toxicidade , Ventrículos do Coração/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Ouabaína/toxicidade , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Animais , Anticorpos/imunologia , Especificidade de Anticorpos , Sítios de Ligação , Western Blotting , Cálcio/metabolismo , Glicosídeos Cardíacos/administração & dosagem , Cardiotônicos/administração & dosagem , Cardiotônicos/toxicidade , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Ventrículos do Coração/citologia , Ventrículos do Coração/patologia , Isoenzimas , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/patologia , Ouabaína/administração & dosagem , Ratos , Ratos Sprague-Dawley , ATPase Trocadora de Sódio-Potássio/metabolismo
8.
J Clin Anesth ; 79: 110788, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35429906

RESUMO

STUDY OBJECTIVE: Emergence delirium is a common complication in preschool children after general anesthesia and may result in undesirable complications. This study aimed to determine whether breathing training after watching an informative video during the pre-operative visit could reduce the incidence of emergence delirium in preschool children after otorhinolaryngologic surgery under general anesthesia. DESIGN: A single-center, double-blinded, randomized controlled trial. SETTING: Perioperative care. PATIENTS: A total of 170 children undergoing otorhinolaryngologic surgery, aged 3-7 years, ASA physical status I or II were involved. INTERVENTIONS: Patients were randomized to receive breathing training during the pre-operative visit (Training group) or to receive pre-operative visit only (Control group) the day before surgery. MEASUREMENTS: Emergence delirium was measured by the Pediatric Anesthesia Emergence Delirium score during the anesthesia recovery time. Data regarding extubation time and post-anesthesia care unit stay time were collected. MAIN RESULTS: Children who received breathing training during the pre-operative visit had a significantly lower incidence of emergence delirium than those who only underwent the pre-operative visit (10.4% vs. 35.1%, P < 0.001). The awakening time score and the maximum score in the post-anesthesia care unit were significantly lower in the training group compared with the control group [4.4 ± 3.4 vs. 6.9 ± 4.2, P < 0.001 and 5.0 (5.0) vs 7.0 (7.0), P = 0.001, respectively]. We found no differences in the extubation time and post-anesthesia care unit stay time between groups. CONCLUSIONS: We concluded that breathing training based on video learning during the pre-operative visit in preschool children undergoing otorhinolaryngologic surgery could significantly decrease the incidence of emergence delirium. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Reference number: ChiCTR1900026162); registered on September 24, 2019.


Assuntos
Delírio do Despertar , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Criança , Pré-Escolar , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Delírio do Despertar/prevenção & controle , Humanos , Incidência , Estudos Prospectivos
9.
Parkinsons Dis ; 2022: 6915627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36483978

RESUMO

Introduction: Postoperative delirium can increase cognitive impairment and mortality in patients with Parkinson's disease. The purpose of this study was to develop and internally validate a clinical prediction model of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. Methods: We conducted a retrospective observational cohort study on the data of 240 patients with Parkinson's disease who underwent deep brain stimulation of the subthalamic nucleus under general anesthesia. Demographic characteristics, clinical evaluation, imaging data, laboratory data, and surgical anesthesia information were collected. Multivariate logistic regression was used to develop the prediction model for postoperative delirium. Results: A total of 159 patients were included in the cohort, of which 38 (23.90%) had postoperative delirium. Smoking (OR 4.51, 95% CI 1.56-13.02, p < 0.01) was the most important risk factor; other independent predictors were orthostatic hypotension (OR 3.42, 95% CI 0.90-13.06, p=0.07), inhibitors of type-B monoamine oxidase (OR 3.07, 95% CI 1.17-8.04, p=0.02), preoperative MRI with silent brain ischemia or infarction (OR 2.36, 95% CI 0.90-6.14, p=0.08), Hamilton anxiety scale score (OR 2.12, 95% CI 1.28-3.50, p < 0.01), and apolipoprotein E level in plasma (OR 1.48, 95% CI 0.95-2.29, p=0.08). The area under the receiver operating characteristic curve (AUC) was 0.76 (95% CI 0.66-0.86). A nomogram was established and showed good calibration and clinical predictive capacity. After bootstrap for internal verification, the AUC was 0.74 (95% CI 0.66-0.83). Conclusion: This study provides evidence for the independent inducing factors of delirium after deep brain stimulation of the subthalamic nucleus in Parkinson's disease under general anesthesia. By predicting the development of delirium, our model may identify high-risk groups that can benefit from early or preventive intervention.

10.
Am J Physiol Heart Circ Physiol ; 300(6): H2280-7, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21441313

RESUMO

Chronic intermittent hypobaric hypoxia (CIHH) has been shown to attenuate intracellular Na(+) accumulation and Ca(2+) overload during ischemia and reperfusion (I/R), both of which are closely related to the outcome of myocardial damage. Na/K pump plays an essential role in maintaining the equilibrium of intracellular Na(+) and Ca(2+) during I/R. It has been shown that enhancement of Na/K pump activity by ischemic preconditioning may be involved in the cardiac protection. Therefore, we tested whether Na/K pump was involved in the cardioprotection by CIHH. We found that Na/K pump current in cardiac myocytes of guinea pigs exposed to CIHH increased 1.45-fold. The K(1) and f(1), which reflect the portion of α(1)-isoform of Na/K pump, dramatically decreased or increased, respectively, in CIHH myocytes. Western blot analysis revealed that CIHH increased the protein expression of the α(1)-isoform by 76%, whereas the protein expression of the α(2)-isoform was not changed significantly. Na/K pump current was significantly suppressed in simulated I/R, and CIHH preserved the Na/K pump current. CIHH significantly improved the recovery of cell length and contraction during reperfusion. Furthermore, inhibition of Na/K pump by ouabain attenuated the protective effect afforded by CIHH. Collectively, these data suggest that the increase of Na/K pump activity following CIHH is due to the upregulating α(1)-isoform of Na/K pump, which may be one of the mechanisms of CIHH against I/R-induced injury.


Assuntos
Hipóxia/fisiopatologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/fisiopatologia , ATPase Trocadora de Sódio-Potássio/fisiologia , Animais , Cobaias , Masculino , Modelos Animais , Contração Miocárdica/fisiologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Ouabaína/farmacologia , Técnicas de Patch-Clamp , Isoformas de Proteínas/fisiologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , Resultado do Tratamento
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1845-1850, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34893121

RESUMO

OBJECTIVE: To investigate the efficacy of high-risk myelodysplastic syndrome (MDS) patients treated by different doses of decitabine (DAC) and its safety. METHODS: Thirty patients with high-risk MDS were all treated by demethylation drug DAC. According to the doses of DAC, 30 patients were divided into 10-day regimen [6 mg/(m2·d)×10 d, 15 patients] group and 5-day regimen [15 mg/(m2·d)×5 d, 15 patients] group. The efficacy and adverse events of the patients in the two groups were observed. RESULTS: The patients were followed up to May 2020, in the 10-day regimen group, 10 cases achieved complete remission (CR), 3 cases achieved partial remission (PR), and 2 cases were progressive disease (PD). Four cases died, including 1 case for heart failure, 2 cases for respiratory failure and 1 case for serious infection. In the 5-day regimen group, 11 cases achieved CR, 1 case achieved PR, 3 cases were PD. Five cases died, including 2 cases for heart failure and 3 for serious infection. The CR rate and ORR of the patients in the two groups were 66.67% vs 73.33%, 86.67% vs 80.00%, respectively, which showed no significant differences, and the efficacy also showed no significant difference. After treatment, the levels of WBC, NE, Hb and PLT of the patients in 10-day regimen group were higher than those in 5-day regimen. In the 10-day regimen group, there were 11 cases of pneumonia, 2 cases of bacteremia, 1 case of skin infection and 1 case of urinary tract infection. While in the 5-day regimen group, 13 cases of pneumonia, 5 cases bacteremia, 1 case of skin infection and 3 cases of urinary tract infection. There were 2 cases with mild gastrointestinal response in the 10-day regimen group, and 7 cases with obvious nausea and anorexia in the 5-day regimen group. The symptoms were relieved after the treatment of acid suppression, stomach protection and antiemetic. The liver, kidney and heart function were monitored. One case liver function damage and 2 cases cardiac insufficiency were observed in the 10-day regimen group. Seven cases regimen cardiac insufficiency and 4 cases regimen liver function damage were observed in the 5-day regimen group. CONCLUSION: 10-day regimen and 5-day regimen are equally effective, but 10-day regimen is less myelosuppressive and more safer, which can be applied in clinical.


Assuntos
Azacitidina , Síndromes Mielodisplásicas , Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/uso terapêutico , Citarabina/uso terapêutico , Decitabina/uso terapêutico , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Resultado do Tratamento
12.
Neurol Ther ; 10(2): 785-802, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34095990

RESUMO

INTRODUCTION: Propofol is a general anesthetic option for deep brain stimulation (DBS) of the subthalamic nucleus (STN) of patients with Parkinson's disease (PD). However, its effects on STN activity and neuropsychological outcomes are controversial. The optimal propofol anesthesia for asleep DBS is unknown. This study investigated the safety and effectiveness of an optimized propofol anesthesia regimen in asleep DBS. METHODS: This retrospective study enrolled 68 PD patients undergoing bilateral STN-DBS surgery. All patients received local scalp anesthesia, with (asleep group, n = 35) or without (awake group, n = 33) propofol-remifentanil general anesthesia by target-controlled infusion under electroencephalogram monitoring. The primary outcome was subthalamic neuronal spiking characterization during microelectrode recording. The secondary outcomes were clinical outcomes including motor, cognition, mind, sleep, and quality of life at 6 months. RESULTS: Significantly increased delta and theta power were obtained under propofol anesthesia (awake vs. asleep group, mean ± standard deviation; delta: 31.97 ± 9.87 vs. 39.77 ± 10.56, p < 0.01; theta: 21.09 ± 5.55 vs. 24.82 ± 6.63, p = 0.01). After excluding the influence of confounding factors of age and preoperative motor scores, there was a statistically significant influence on the delta, theta, and alpha power of STN neuronal activity under different anesthesia regimens (delta: ß = 2.64, p < 0.01; theta: ß = 2.11, p < 0.01; alpha: ß = 1.42, p = 0.01). There were no differences in modified burst index, firing rate, tract numbers of microelectrode recording, and other clinical outcomes between the two groups. CONCLUSION: Optimized propofol anesthesia enhanced the delta, theta, and alpha power in STN compared with the awake technique and likely contributed to target recognition under propofol anesthesia. These results demonstrate that propofol is suitable, but needs to be optimized, for asleep STN-DBS. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identification number: ChiCTR2100045942. Registered 29 April 2021-Retrospectively registered.

13.
Fundam Clin Pharmacol ; 35(5): 870-881, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33481320

RESUMO

Glutamate excitotoxicity in cerebral ischemia/reperfusion is an important cause of neurological damage. The aim of this study was to investigate the mechanism of Na+, K+-ATPase (NKA) involved in l ow concentration of ouabain (Oua, activating NKA)-induced protection of rat cerebral ischemia-reperfusion injury. The 2,3,5-triphenyltetrazolium chloride (TTC) staining and neurological deficit scores (NDS) were performed to evaluate rat cerebral injury degree respectively at 2 h, 6 h, 1 d and 3 d after reperfusion of middle cerebral artery occlusion (MCAO) 2 h in rats. NKA α1/α2 subunits and glutamate transporter-1 (GLT-1) protein expression were investigated by Western blotting. The cerebral infarct volume ratio were evidently decreased in Oua group vs MCAO/R group at 1 d and 3 d after reperfusion of 2 h MCAO in rats (*p < 0.05 ). Moreover, NDS were not significantly different (p > 0.05 ). NKA α1 was decreased at 6 h and 1 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. However, NKA α1 and α2 were increased at 3 d after reperfusion of 2 h MCAO in rats, and was decreased in Oua group. GLT-1 was decreased at 6 h, 1 d and 3 d after reperfusion of 2 h MCAO in rats, and was improved in Oua group. These data indicated that l ow concentration of Oua could improve MCAO/R injury through probably changing NKA α1/α2 and GLT-1 protein expression, then increasing GLT-1 function and promoting Glu transport and absorption, which could be useful to determine potential therapeutic strategies for patients with stroke. Low concentration of Oua improved rat MCAO/R injury via NKA α1/α2 and GLT-1.


Assuntos
Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média , Traumatismo por Reperfusão/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Isquemia Encefálica/induzido quimicamente , Modelos Animais de Doenças , Masculino , Ouabaína , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/induzido quimicamente , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo
14.
Acta Pharmacol Sin ; 30(4): 404-12, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19305421

RESUMO

AIM: The present study investigated the effect of adenosine on Na(+)-K(+) pumps in acutely isolated guinea pig (Cavia sp.) ventricular myocytes. METHODS: The whole-cell, patch-clamp technique was used to record the Na(+)-K(+) pump current (I(p)) in acutely isolated guinea pig ventricular myocytes. RESULTS: Adenosine inhibited the high DHO-affinity pump current (I(h)) in a concentration-dependent manner, which was blocked by the selective adenosine A(1) receptor antagonist DPCPX and the general protein kinase C (PKC) antagonists staurosporine, GF 109203X or the specific delta isoform antagonist rottlerin. In addition, the inhibitory action of adenosine was mimicked by a selective A(1) receptor agonist CCPA and a specific activator peptide of PKC-delta, PP114. In contrast, the selective A(2A) receptor agonist CGS21680 and A(3) receptor agonist Cl-IB-MECA did not affect I(h). Application of the selective A(2A) receptor antagonist SCH58261 and A(3) receptor antagonist MRS1191 also failed to block the effect of adenosine. Furthermore, H89, a selective protein kinase A (PKA) antagonist, did not exert any effect on adenosine-induced I(h) inhibition. CONCLUSION: The present study provides the electrophysiological evidence that adenosine can induce significant inhibition of I(h) via adenosine A(1) receptors and the PKC-delta isoform.


Assuntos
Adenosina/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Animais , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Cobaias , Ventrículos do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Isoformas de Proteínas/fisiologia , Proteína Quinase C-delta/fisiologia , Receptor A1 de Adenosina/fisiologia , Receptor A2A de Adenosina/fisiologia , Receptor A3 de Adenosina/fisiologia
15.
Acta Pharmacol Sin ; 30(7): 947-55, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19543301

RESUMO

AIM: To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts. METHODS: Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(O2)=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence. RESULTS: After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)) were attenuated by CIHH and CAT. CONCLUSIONS: These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009.


Assuntos
Antioxidantes/metabolismo , Hipóxia , Miocárdio/enzimologia , Miocárdio/patologia , Traumatismo por Reperfusão/prevenção & controle , Amitrol (Herbicida)/metabolismo , Animais , Peso Corporal , Catalase/metabolismo , Inibidores Enzimáticos/metabolismo , Cobaias , Peróxido de Hidrogênio/metabolismo , Masculino , Malondialdeído/metabolismo , Miocárdio/citologia , Tamanho do Órgão , Oxidantes/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Superóxido Dismutase/metabolismo
18.
Mol Med Rep ; 19(3): 1521-1528, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30592287

RESUMO

Glutamate excitotoxicity is responsible for neuronal death in acute neurological disorders, including stroke, trauma and neurodegenerative diseases. Astrocytes are the main cells for the removal of glutamate in the synaptic cleft and may affect the tolerance of neurons to the glutamate excitotoxicity. Therefore, the present study aimed to investigate the tolerance of rat cortical neurons to glutamate excitotoxicity in the presence and absence of astrocytes. Rat cortical neurons in the presence or absence of astrocytes were exposed to different concentrations of glutamate (10­2,000 µM) and 10 µM glycine for different incubation periods. After 24 h, the Cell Counting kit­8 (CCK­8) assay was used to measure the cytotoxicity to neurons in the presence or absence of astrocytes. According to the results, in the absence of astrocytes, glutamate induced a concentration­dependent decrease of neuronal survival rate compared with the control rat cortical neurons, and the neurotoxic half­maximal inhibitory concentration (IC50) at 15, 30 and 60 min was 364.5, 258.5 and 138.3 µM, respectively. Furthermore, in the presence of astrocytes, glutamate induced a concentration­dependent decrease of neuronal survival rate compared with the control rat cortical neurons, and the neurotoxic IC50 at 15, 30 and 60 min was 1,935, 932.8 and 789.3 µM, respectively. However, astrocytic toxicity was not observed when the rat cortical astrocytes alone were exposed to different concentrations of glutamate (500, 1,000 and 2,000 µM) for 6, 12 and 24 h. In conclusion, the glutamate­induced neurotoxic IC50 values at 15, 30 and 60 min were respectively higher in the presence of astrocytes as compared with those in the absence of astrocytes, suggesting that astrocytes can protect against rat cortical neuronal acute damage induced by glutamate.


Assuntos
Astrócitos/metabolismo , Córtex Cerebral/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Neurônios/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Tolerância a Medicamentos/genética , Ácido Glutâmico/toxicidade , Glicina/administração & dosagem , Glicina/efeitos adversos , Neurônios/patologia , Ratos
19.
J Mol Med (Berl) ; 97(3): 281-289, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30675649

RESUMO

The accumulation of glutamate (Glu) in the synaptic cleft during cerebral ischemia triggers the death of neurons, causing mental or physical handicap. However, the mechanisms of the alteration in Glu homeostasis and the imbalance between the release and clearance of Glu in ischemia are not yet completely understood. Additionally, the role of Glu transporters in regulating Glu concentration in the synaptic cleft is controversial. This review aims to provide readers with an in-depth understanding of Glu transporters in the early or later stages of ischemic events, or in mild or severe cerebral ischemia via alteration of Glu transporter expression, reversal of Glu transporters function, and trafficking between membrane and cytoplasm, to further clarify whether the Glu transporters are neuroprotective or neurodegenerative during cerebral ischemia. We provide the insights for deeper understanding of the mechanism of Glu transporters regulation after different periods and severities of cerebral ischemia.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Isquemia Encefálica/metabolismo , Animais , Humanos , Neuroproteção , Transporte Proteico
20.
Life Sci ; 193: 124-131, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29158051

RESUMO

Cell proliferation, apoptosis, autophagy, oxidative stress and metabolic dysregulation are the basis of many diseases. Forkhead box transcription factor O1 (FOXO1) changes in response to cellular stimulation and maintains tissue homeostasis during the above-mentioned physiological and pathological processes. Substantial evidences indicate that FOXO1's function depends on the modulation of downstream targets such as apoptosis- and autophagy-associated genes, anti-oxidative stress enzymes, cell cycle arrest genes, and metabolic and immune regulators. In addition, oxidative stress, high glucose and other stimulations induce the regulation of FOXO1 activity via PI3k-Akt, JNK, CBP, Sirtuins, ubiquitin E3 ligases, etc., which mediate multiple signalling pathways. Subsequent post-transcriptional modifications, including phosphorylation, ubiquitination, acetylation, deacetylation, arginine methylation and O-GlcNAcylation, activate or inhibit FOXO1. The regulation of FOXO1 and its role might provide a significant avenue for the prevention and treatment of diseases. However, the subtle mechanisms of the post-transcriptional modifications and the effect of FOXO1 remain elusive and even conflicting in the development of many diseases. The determination of these questions potentially has implications for further research regarding FOXO1 signalling and the identification of targeted drugs.


Assuntos
Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Acetilação , Apoptose/genética , Autofagia/genética , Proliferação de Células/genética , Progressão da Doença , Fatores de Transcrição Forkhead/metabolismo , Humanos , Estresse Oxidativo/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ubiquitinação
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