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1.
Eur J Intern Med ; 82: 105-111, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33067121

RESUMO

BACKGROUND: In the mobile Atrial Fibrillation App (mAFA)-II trial, the use of mobile health (mHealth) technology, incorporating AF screening and integrated management strategy, was associated with improved short-term clinical outcomes. The aim of this study was to report adherence/persistence and long term (≥1 year) clinical outcomes of the mAFA-II trial, with mHealth-supported optimised stroke prevention, symptom control and comorbidity management. METHODS: We studied an adult population screened for AF, where identified patients could enter a structured program of holistic and integrated care based on the ABC (Atrial fibrillation Better Care) pathway using mHealth with a mAFA intervention. In this cluster randomised trial, comparing mHeath intervention to usual care, the primary composite outcome was 'stroke/thromboembolism, all-cause death and rehospitalization'. RESULTS: The 1261 subjects (mean age 67.0 years, 38.0% female) who were followed up over one year (mean follow-up 687 (standard deviation, SD 191) days) in the intervention arm, had a lower risk of the composite outcome of 'ischaemic stroke/systemic thromboembolism, death, and rehospitalization' (hazard ratio, HR 0.18, 95% confidence interval, CI: 0.13-0.25, P < 0.001), compared to usual care (1212 subjects, mean age 70.1 years, 42.1% female). Of 842 patients using their smart devices for 'Better symptom management', 70.8% had good management adherence (monitoring time/follow-up since initial monitoring ≥ 70%), with the persistence of use of 91.7%. CONCLUSION: Amongst AF patients with long term use (≥1 year) of mHealth technology for optimising stroke prevention, symptom control and comorbidity management, adherence/persistence was good and associated with a reduction in adverse clinical outcomes.


Assuntos
Fibrilação Atrial , Isquemia Encefálica , Prestação Integrada de Cuidados de Saúde , Acidente Vascular Cerebral , Telemedicina , Adulto , Idoso , Anticoagulantes , Fibrilação Atrial/diagnóstico , Tecnologia Biomédica , Feminino , Humanos , Fatores de Transcrição Maf Maior , Masculino , Tecnologia
3.
High Alt Med Biol ; 21(3): 258-264, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32466660

RESUMO

Li, Zongbin, Jun Guo, Chunwei Liu, Yajun Shi, Yang Li, Jinli Wang, Dandan Li, Jing Wang, and Yundai Chen. Compound Danshen Dripping Pill promotes adaptation to acute high-altitude exposure. High Alt Med Biol. 21:258-264, 2020. Background: In this study, we aimed to investigate whether the traditional Chinese medicine, Compound Danshen Dripping Pill (CDDP), can prevent acute mountain sickness (AMS). We allocated CDDP and matching placebos to 160 volunteers before they ascended to a high altitude. Treadmill exercise tests, echocardiography, blood routine examinations, biochemical analysis, and blood gas analysis were performed upon arrival at high altitude. The primary outcome included incidence of AMS, exercise times, and metabolic equivalents (METs) of treadmill exercise tests. Second endpoints included the heart rates and rate-pressure product (RPP) before and after treadmill exercise tests. Results: After high-altitude exposure, the incidence of AMS in the CDDP group was lower than that in the placebo group (48.6% vs. 67.6%, p = 0.022). The exercise time of the treadmill exercise test was significantly longer (507 ± 77.9 seconds vs. 457 ± 90.8 seconds, p = 0.004), the heart rate was lower (pre-exercise: 91.8 ± 11.7 beats/min vs. 97.2 ± 12.7 beats/min, p = 0.016; postexercise: 114 ± 22.2 beats/min vs. 121 ± 22.6 beats/min, p = 0.019), the pre-exercise and postexercise RPP were lower (pre-exercise: 1.13 × 104 ± 1.68 × 103 mmHg·beats/min vs. 1.23 × 104 ± 1.84 × 103 mmHg·beats/min, p = 0.027; postexercise: 1.19 × 104 ± 1.75 × 103 mmHg·beats/min vs. 1.31 × 104 ± 2.00 × 103 mmHg·beats/min, p = 0.002), and the MET value of the treadmill exercise test was significantly higher (9.93 ± 1.18 METs vs. 9.31 ± 1.52 METs, p = 0.037) in the CDDP group. Discussion: CDDP decreases the incidence of AMS and enhances exercise tolerance greater than placebo after high-altitude exposure. CDDP decreases the heart rate and myocardial oxygen consumption, increases the levels of hemoglobin, hematocrit, and antioxidant factors, and decreases the levels of inflammatory factors, which may explain the roles of CDDP in improving the adaptation to high-altitude exposure.


Assuntos
Doença da Altitude , Medicamentos de Ervas Chinesas , Aclimatação , Altitude , Doença da Altitude/tratamento farmacológico , Doença da Altitude/prevenção & controle , Canfanos , Frequência Cardíaca , Humanos , Panax notoginseng , Salvia miltiorrhiza
4.
Am J Med ; 133(10): 1195-1202.e2, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32289310

RESUMO

BACKGROUND: The mobile atrial fibrillation application (mAFA-II) randomized trial reported that a holistic management strategy supported by mobile health reduced atrial fibrillation-related adverse outcomes. The present study aimed to assess whether regular reassessment of bleeding risk using the Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratio, Elderly, Drugs or alcohol (HAS-BLED) score would improve bleeding outcomes and oral anticoagulant (OAC) uptake. METHODS: Bleeding risk (HAS-BLED score) was monitored prospectively using mAFA, and calculated as 30 days, days 31-60, days 61-180, and days 181-365. Clinical events and OAC changes in relation to the dynamic monitoring were analyzed. RESULTS: We studied 1793 patients with atrial fibrillation (mean, standard deviation, age 64 years, 24 years, 32.5% female). Comparing baseline and 12 months, the proportion of atrial fibrillation patients with HAS-BLED ≥3 decreased (11.8% vs 8.5%, P = .008), with changes in use of concomitant nonsteroidal antiinflammatory drugs/antiplatelets, renal dysfunction, and labile international normalized ratio contributing to the decreased proportions of patients with HAS-BLED ≥3 (P < .05). Among 1077 (60%) patients who had 4 bleeding risk assessments, incident bleeding events decreased significantly from days 1-30 to days 181-365 (1.2% to 0.2%, respectively, P < .001). Total OAC usage increased from 63.4% to 70.2% (Ptrend < .001). Compared with atrial fibrillation patients receiving usual care (n = 1136), bleeding events were significantly lower in atrial fibrillation patients with dynamic monitoring of their bleeding risk (mAFA vs usual care, 2.1%, 4.3%, P = .004). OAC use decreased significantly by 25% among AF patients receiving usual care, when comparing baseline to 12 months (P < .001). CONCLUSION: Dynamic risk monitoring using the HAS-BLED score, together with holistic App-based management using mAFA-II reduced bleeding events, addressed modifiable bleeding risks, and increased uptake of OACs.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Sistemas de Apoio a Decisões Clínicas , Hemorragia/epidemiologia , Aplicativos Móveis , Acidente Vascular Cerebral/prevenção & controle , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Fibrilação Atrial/complicações , Monitoramento de Medicamentos , Feminino , Hemorragia/induzido quimicamente , Humanos , Hipertensão/epidemiologia , Coeficiente Internacional Normatizado , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Insuficiência Renal/epidemiologia , Medição de Risco , Acidente Vascular Cerebral/etiologia , Adulto Jovem
5.
J Am Coll Cardiol ; 75(13): 1523-1534, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32241367

RESUMO

BACKGROUND: Current management of patients with atrial fibrillation (AF) is limited by low detection of AF, non-adherence to guidelines, and lack of consideration of patients' preferences, thus highlighting the need for a more holistic and integrated approach to AF management. OBJECTIVE: The objective of this study was to determine whether a mobile health (mHealth) technology-supported AF integrated management strategy would reduce AF-related adverse events, compared with usual care. METHODS: This is a cluster randomized trial of patients with AF older than 18 years of age who were enrolled in 40 cities in China. Recruitment began on June 1, 2018 and follow-up ended on August 16, 2019. Patients with AF were randomized to receive usual care, or integrated care based on a mobile AF Application (mAFA) incorporating the ABC (Atrial Fibrillation Better Care) Pathway: A, Avoid stroke; B, Better symptom management; and C, Cardiovascular and other comorbidity risk reduction. The primary composite outcome was a composite of stroke/thromboembolism, all-cause death, and rehospitalization. Rehospitalization alone was a secondary outcome. Cardiovascular events were assessed using Cox proportional hazard modeling after adjusting for baseline risk. RESULTS: There were 1,646 patients allocated to mAFA intervention (mean age, 67.0 years; 38.0% female) with mean follow-up of 262 days, whereas 1,678 patients were allocated to usual care (mean age, 70.0 years; 38.0% female) with mean follow-up of 291 days. Rates of the composite outcome of 'ischemic stroke/systemic thromboembolism, death, and rehospitalization' were lower with the mAFA intervention compared with usual care (1.9% vs. 6.0%; hazard ratio [HR]: 0.39; 95% confidence interval [CI]: 0.22 to 0.67; p < 0.001). Rates of rehospitalization were lower with the mAFA intervention (1.2% vs. 4.5%; HR: 0.32; 95% CI: 0.17 to 0.60; p < 0.001). Subgroup analyses by sex, age, AF type, risk score, and comorbidities demonstrated consistently lower HRs for the composite outcome for patients receiving the mAFA intervention compared with usual care (all p < 0.05). CONCLUSIONS: An integrated care approach to holistic AF care, supported by mHealth technology, reduces the risks of rehospitalization and clinical adverse events. (Mobile Health [mHealth] technology integrating atrial fibrillation screening and ABC management approach trial; ChiCTR-OOC-17014138).


Assuntos
Fibrilação Atrial/terapia , Telemedicina/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , China/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
6.
BMJ Open ; 9(7): e026362, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31320346

RESUMO

INTRODUCTION: Successful ST-segment elevation myocardial infarction (STEMI) management is time-sensitive and is based on prompt reperfusion mainly to reduce patient mortality. It has evolved from a single hospital care to an integrated regional network approach over the last decades. This prospective study, named the China STEMI Care Project (CSCAP), aims to show how implementation of different types of integrated regional STEMI care networks can improve the reperfusion treatment rate, shorten the total duration of myocardial ischaemia and lead to mortality reduction step by step. METHODS AND ANALYSIS: The CSCAP is a prospective, multicentre registry study of three phases. A total of 18 provinces, 4 municipalities and 2 autonomous regions in China were included. Patients who meet the third universal definition of myocardial infarction and the Chinese STEMI diagnosis and treatment guidelines are enrolled. Phase 1 (CSCAP-1) focuses on the in-hospital process optimisation of primary percutaneous coronary intervention (PPCI) hospitals, phase 2 (CSCAP-2) focuses on the PPCI hospital-based regional STEMI care network construction together with emergency medical services and adjacent non-PPCI hospitals, while phase 3 (CSCAP-3) focuses on the whole-city STEMI care network construction by promoting chest pain centre accreditation. Systematic data collection, key performance index assessment and subsequent improvement are implemented throughout the project to continuously improve the quality of STEMI care. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Ethics Committee of Peking University First Hospital. Ranking reports of quality of care will be generated available to all participant affiliations. Results will be disseminated via peer-reviewed scientific journals and presentations at congresses. TRIAL REGISTRATION NUMBER: NCT03821012.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Melhoria de Qualidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , China , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Sistema de Registros
7.
Int J Clin Pract ; 73(7): e13352, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31002434

RESUMO

BACKGROUND: Current management of patients with atrial fibrillation (AF) is limited by low detection of AF, non-adherence to guidelines and lack of consideration of patient's preferences, thus highlighting the need for a holistic and integrated approach to AF management. This study aims to determine whether a mHealth technology-supported AF integrated management strategy will reduce AF-related adverse events. METHODS/DESIGN: The mAFA II trial is a prospective, cluster randomised controlled trial. The 40 sites will be randomised to mAFA-integrated care intervention or usual care arms. Prior to randomisation, study sites will be paired to be matched in size and the proportion of study eligible patients. All AF patients aged over 18 years old with CHA2 DS2 -VASc score ≥ 2 will be enrolled. Assuming a composite adverse event rate of 10% pre-intervention, reduced to 5% after intervention, we aim to recruit 3660 patients assuming a 10% loss to follow-up. The primary study endpoint is a composite of stroke/thromboembolism, all-cause death and rehospitalisation. Ancillary analyses would determine patient-related outcome measures, health economics and cost effectiveness, as well as an embedded qualitative study. DISCUSSION: The mAFA II trial will provide evidence for an integrated care approach to holistic AF care, supported by mobile health technology to improve screening, patient involvement and optimisation of management.


Assuntos
Fibrilação Atrial/terapia , Prestação Integrada de Cuidados de Saúde , Participação do Paciente , Telemedicina , Adolescente , Adulto , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/economia , China , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Projetos de Pesquisa
8.
J Diabetes ; 11(3): 204-213, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30070032

RESUMO

BACKGROUND: The RESOLUTE-DIABETES CHINA study was specifically designed to investigate the safety and efficacy of Resolute zotarolimus-eluting stents (ZES; Medtronic, Santa Rosa, CA, USA) in the treatment of diabetic coronary lesions in the Chinese population. METHODS: In all, 945 patients with de novo native coronary lesions and type 2 diabetes mellitus were recruited at 32 cardiac centers across the Chinese mainland and were implanted with Resolute ZES. The primary endpoint was target vessel failure (TVF); secondary endpoints were clinical outcomes, namely all-cause death, stroke, bleeding, target lesion revascularization (TLR), target vessel revascularization (TVR), non-TVR, and stent thrombosis (ST). The follow-up period for all endpoints was 12 months after the procedure. RESULTS: In all, 933 patients (98.73%) had clinical follow-up at 12 months. The rate of TVF was 11.60%, whereas the rate of occurrence of secondary endpoints was 5.47%, with four patients (0.43%) having subacute or late ST. There were no significant differences in TVF rates comparing patients with different HbA1c levels or receiving different glucose control treatments (all P > 0.05). Patients with multivessel lesions had higher TVF rates (95% confidence intervals) than those with single-vessel lesions (16.76% [12.10%-22.97%) vs 9.72% [7.79%-12.11%], respectively; P = 0.006). There were no significant differences in TVF rates in patients with or without small vessels, bifurcated lesions, or chronic total occlusions (all P > 0.05). [Correction added on 17 January 2019, after first online publication: in the second sentence of Results section, "TLF" was changed to "TVF".]. CONCLUSIONS: Resolute ZES may perform well in the Chinese diabetic population, especially in those with poor glucose control, complex lesions, and certain unfavorable clinical features. Further studies are needed to determine why ZES perform well in this population.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Stents Farmacológicos , Sirolimo/análogos & derivados , Doença da Artéria Coronariana/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Segurança , Sirolimo/uso terapêutico , Resultado do Tratamento
9.
J Pineal Res ; 65(3): e12503, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29770487

RESUMO

The molecular features of necroptosis in cardiac ischemia-reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR-mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms, and microvascular perfusion defects. However, administration of melatonin prevented Ripk3 activation and provided a pro-survival advantage for the endothelial system in the context of cardiac IR injury, similar to the results obtained via genetic ablation of Ripk3. Functional investigations clearly illustrated that activated Ripk3 upregulated PGAM5 expression, and the latter increased CypD phosphorylation, which obligated endothelial cells to undergo necroptosis via augmenting mPTP (mitochondrial permeability transition pore) opening. Interestingly, melatonin supplementation suppressed mPTP opening and interrupted endothelial necroptosis via blocking the Ripk3-PGAM5-CypD signal pathways. Taken together, our studies identified the Ripk3-PGAM5-CypD-mPTP axis as a new pathway responsible for reperfusion-mediated microvascular damage via initiating endothelial necroptosis. In contrast, melatonin treatment inhibited the Ripk3-PGAM5-CypD-mPTP cascade and thus reduced cellular necroptosis, conferring a protective advantage to the endothelial system in IR stress. These findings establish a new paradigm in microvascular IR injury and update the concept for cell death management handled by melatonin under the burden of reperfusion attack.


Assuntos
Vasos Coronários/metabolismo , Ciclofilinas/metabolismo , Melatonina/farmacologia , Microvasos/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fosfoproteínas Fosfatases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Vasos Coronários/patologia , Peptidil-Prolil Isomerase F , Ciclofilinas/genética , Camundongos , Camundongos Knockout , Microvasos/patologia , Proteínas de Transporte da Membrana Mitocondrial/genética , Poro de Transição de Permeabilidade Mitocondrial , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Fosfoproteínas Fosfatases/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
10.
Cell Signal ; 47: 88-100, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29601906

RESUMO

Melatonin and its metabolites have been demonstrated to modulate the glucose, dyslipidemia and other metabolic disorders. This study aimed to explore a novel mechanism responsible for diabetic cardiomyopathy development, and also validated whether melatonin played a protective role in repairing damaged heart in the diabetes setting. Our data demonstrated that spleen tyrosine kinase (Syk) was activated by chronic high-glucose stimulus and contributed to the development of diabetic cardiomyopathy. However, genetic ablation of Syk or supplementation of melatonin to inhibit Syk activation improved diabetic myocardial function, reduced cardiac fibrosis and preserved cardiomyocytes viability. Mechanistically, activated Syk repressed the expression and activity of mitochondrial complex I (COX-1), unfortunately evoking mitochondrial and/or cellular ROS overproduction. Subsequently, excessive superoxide facilitated SERCA peroxidation which failed to re-uptake the cytoplasmic calcium back into endoplasmic reticulum (ER), leading to cellular calcium overload. Finally, activated oxidative stress and calcium overload collectively promoted the high-glucose-induced cardiomyocytes death via caspase-9-related mitochondrial apoptosis and caspase-12-involved ER apoptosis, respectively. Interestingly, inhibition of Syk via Syk genetic ablation or melatonin administration blocked Syk/COX-1/SERCA signalling pathways, and thus abolished mitochondrial- and ER-mediated cardiomyocyte death in the setting of diabetes. Based on these results, we suggest a novel pathway by which high-glucose stimulus induces diabetic cardiomyopathy is possibly through an activation of Syk/COX-1/SERCA axis which could be abrogated by melatonin treatment.


Assuntos
Complexo I de Transporte de Elétrons/metabolismo , Melatonina/farmacologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinase Syk/genética , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Caspase 9/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Glucose/farmacologia , Melatonina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Quinase Syk/deficiência , Quinase Syk/metabolismo , Troponina T/metabolismo
11.
Am J Clin Nutr ; 105(3): 564-570, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28122783

RESUMO

Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P = 0.01).Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials.gov as NCT00794885.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus , Angiopatias Diabéticas/prevenção & controle , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Hipertensão/complicações , Acidente Vascular Cerebral/prevenção & controle , Idoso , China/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Angiopatias Diabéticas/sangue , Método Duplo-Cego , Jejum , Feminino , Ácido Fólico/sangue , Humanos , Hiperglicemia/complicações , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Complexo Vitamínico B/sangue , Complexo Vitamínico B/uso terapêutico
12.
Free Radic Biol Med ; 77: 363-75, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25452142

RESUMO

Adipose-derived mesenchymal stem cells (ADMSCs)-based therapy is a promising modality for the treatment of myocardial infarction in the future. However, the majority of transplanted cells are readily lost after transplantation because of hypoxia and oxidative stress. An efficient means to enhance the ability of ADMSCs to survive under pathologic conditions is required. In our study, we explored the effects of exendin-4 (Ex-4) on ADMSCs apoptosis in vitro induced by hydrogen peroxide, focusing in particular on mitochondrial apoptotic pathways and PI3K/Akt-secreted frizzled-related protein 2 (Sfrp2) survival signaling. We demonstrated that ADMSCs subjected to H2O2 for 12h exhibited impaired mitochondrial function and higher apoptotic rate. However, Ex-4 (1-20 nM) preconditioning for 12h could protect ADMSCs against H2O2-mediated apoptosis in a dose-dependent manner. Furthermore, Ex-4 pretreatment upregulated the levels of superoxide dismutase and glutathione as well as downregulating the production of reactive oxygen species and malondialdehyde. Western blots revealed that increased antiapoptotic proteins Bcl-2 and c-IAP1/2 as well as decreased proapoptotic proteins Bax and cytochrome c appeared in ADMSCs with Ex-4 incubation, which inhibited the caspase-9-involved mitochondrial apoptosis pathways with evidence showing inactivation of caspase-9/3 and preservation of mitochondrial membrane potential. Furthermore, we illustrated that Ex-4 enhanced Akt phosphorylation, which increased the expression of Sfrp2. Notably, blockade of the PI3K/Akt pathway or knockdown of Sfrp2 with siRNA obviously abolished the protective effects of Ex-4 on mitochondrial function and ADMSCs apoptosis under H2O2. In summary, this study confirmed that H2O2 induced ADMSCs apoptosis through mitochondria-dependent cell death pathways, and Ex-4 preconditioning may reduce such apoptosis of ADMSCs through the PI3K/Akt-Sfrp2 pathways.


Assuntos
Apoptose/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Células-Tronco Mesenquimais/fisiologia , Peptídeos/farmacologia , Peçonhas/farmacologia , Animais , Sobrevivência Celular , Avaliação Pré-Clínica de Medicamentos , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1 , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Receptores de Glucagon/metabolismo , Transdução de Sinais
13.
Zhonghua Yi Xue Za Zhi ; 94(30): 2346-9, 2014 Aug 13.
Artigo em Chinês | MEDLINE | ID: mdl-25399975

RESUMO

OBJECTIVE: To observe the myocardial protective effect of Danhong Injection evaluated by velocity vector imaging (VVI) in patients with unstable angina pectoris after percutaneous coronary intervention (PCI) and elucidate its possible mechanism. METHODS: A total of 120 patients were randomized into Danhong (DG, n = 60) or control (CG, n = 60) groups. The patients in CG group received regular medication according to the guidelines while those in DG group regular medication plus Danhong Injection before and after PCI. During PCI, 40 ml Danhong Injection was administrated intravenously. The levels of CK-MB and cTnT were tested before and 24 hours after PCI. And VVI was performed before and 24 hours after PCI. RESULTS: After treatment with Danhong injection, the serum level of MB isoenzyme of creatine kinase (CK-MB) and cardiac troponin T (cTnT) in DG were lower than those in CG (18.19 ± 10.23 vs 25.12 ± 11.91,0.079 ± 0.007 vs 0.132 ± 0.011, P < 0.05). Meanwhile, strain and strain rate of interventricular septum apex, anterior apex, inferior basement and inferior middle segment were better in DG than those in CG (26.01 ± 7.94 vs 23.25 ± 6.68, 20.91 ± 7.55 vs 18.79 ± 8.45, 18.10 ± 7.31 vs 16.89 ± 6.05, 21.16 ± 6.42 vs 18.37 ± 6.54, P < 0.05; 1.93 ± 0.79 vs 1.69 ± 0.63, 1.86 ± 0.72 vs 1.63 ± 0.68, 1.51 ± 0.80 vs 1.25 ± 0.54, 1.50 ± 0.45 vs 1.33 ± 0.32, P < 0.05 respectively). CONCLUSION: Peri-procedual Danhong injection can ameliorate myocardial injury and improve segmental systolic function.


Assuntos
Miocárdio , Intervenção Coronária Percutânea , Angina Instável , Biomarcadores , Creatina Quinase , Medicamentos de Ervas Chinesas , Humanos
14.
Clin Nutr ; 33(4): 603-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24461473

RESUMO

BACKGROUND & AIMS: There is a growing amount of data and a continuing controversy over the effect of folic acid supplementation with and without vitamin B6 on revascularization risk. METHODS: We conducted a meta-analysis based on up-to-date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of revascularization using a random-effects model. Total revascularization was defined as any arterial revascularization. Restenosis was defined as stenosis of more than 50 percent of the luminal diameter. RESULTS: Overall, folic acid supplementation had no significant effect on coronary revascularization (9 trials, n = 27,418, RR = 0.99; 95%CI:0.88-1.11, P = 0.88), coronary artery bypass grafting (CABG) (5 trials, n = 10,703, 0.90; 0.79-1.03, P = 0.11), percutaneous coronary intervention (PCI) (5 trials, n = 10,703, 1.05; 0.89-1.23, P = 0.59), coronary restenosis (3 trials, n = 926, 1.05; 0.89-1.23, P = 0.59) or total revascularization (7 trials, n = 29,314, 1.06; 95%CI: 0.99-1.13, P = 0.10). However, a greater beneficial effect was observed for coronary revascularization among those trials with a moderate dose of vitamin B6 (5-10 mg/d; RR: 0.47; 95%CI: 0.28-0.80, P = 0.005), but not in trials without vitamin B6 or with a high dose of vitamin B6. And a non-significant greater total revascularization risk was observed in trials with a higher folic acid dose (>2 mg/d, RR = 1.11; 95%CI: 0.98-1.25, P = 0.09; ≥5 mg/d, RR = 1.98; 95%CI: 0.93-4.20, P = 0.08). CONCLUSIONS: Our analyses indicate that folic acid supplementation has no significant effect on coronary revascularization, CABG, PCI, coronary restenosis or total revascularization. However, a combination of folic acid and moderate vitamin B6 may be beneficial in reducing coronary revascularization risk.


Assuntos
Reestenose Coronária/prevenção & controle , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Vitamina B 6/administração & dosagem , Ponte de Artéria Coronária/métodos , Bases de Dados Factuais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
15.
Zhongguo Zhong Yao Za Zhi ; 39(19): 3782-7, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25612440

RESUMO

Using the absorbent resin, silica gel and ODS column chromatography as well as semi-preparative HPLC, ten compounds were isolated from 70% ethanol extract of tubers of Dioscorea zingiberensis C. H. Wright, and their structures were elucidated as trigoneoside XIIIa (1), parvifloside (2), trigoneoside IVa (3), deltoside (4), protobioside (5), lilioglycoside k (6), zingiberensis newsaponin I (7), deltonin (8), prosapogenin A of dioscin (9), and trillin (10) on the basis of NMR and MS spectral data analysis. Among these compounds, 1, 3, 5 and 6 were isolated from this plant for the first time. In the screening test on platelet aggregation, compounds 7 and 8 exhibited induction effect on platelet aggregation, while compound 9 exhibited significant inhibitory effect on platelet aggregation in vitro.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Saponinas/farmacologia , Animais , Dioscorea/química , Medicamentos de Ervas Chinesas/química , Masculino , Espectrometria de Massas , Estrutura Molecular , Ratos , Ratos Wistar , Saponinas/química
16.
Zhonghua Xin Xue Guan Bing Za Zhi ; 41(6): 480-3, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24113039

RESUMO

OBJECTIVE: To investigate the anticoagulant efficacy and safety of argatroban for patients undergoing elective percutaneous coronary intervention (PCI). METHODS: A total of 300 consecutive patients with coronary heart disease undergoing elective PCI were enrolled and randomized into heparin group (100 U/kg via artery sheaths, n = 150) and argatroban group (200 µg/kg bolus, followed by 350 µg·kg(-1)·h(-1) i.v. infusion, n = 150). The primary efficacy endpoint was the activated clotting time (ACT) results (10 min and 60 min after anticoagulant administration and at the point at the end of PCI). The additional dosage of heparin or argatroban was given if the ACT value during PCI procedure < 250 s. Activated partial thromboplastin time (APTT) was also measured at pre-procedure, 10 min after anticoagulant injection and 60 min after PCI. The primary safety endpoint was thrombosis and hemorrhagic events during PCI procedure and hospital stay. RESULTS: All patients in the two groups attained the target ACT ( ≥ 250 s), and ACT in heparin group was significantly prolonged [(343.32 ± 44.70) s vs. (289.60 ± 20.88) s, P < 0.01], at 10 min after anticoagulation injection. ACT was similar between the two groups at 60 min after anticoagulation injection [(291.26 ± 46.79) s vs. (288.40 ± 21.61) s, P > 0.05]. The ACT value in argatroban group was similar at 10 min and 60 min after injection (P > 0.05). Supplemental anticoagulant was needed for 13 (8.7%) patients in heparin group and 2 (1.3%) patients in argatroban group because of ACT under 250 s (P < 0.05) . At the end of PCI procedure, ACT in heparin group was significantly shorter than in argatroban group [(247.16 ± 41.38)s vs. (278.65 ± 20.51) s, P < 0.01]. APTT in heparin group was significantly prolonged than in argatroban group not only at 10 min point [(182.16 ± 4.37) s vs. (81.69 ± 21.49) s, P < 0.01] after anticoagulant injection but also at the point of 60 min after PCI procedure[(169.13 ± 6.35)s vs. (56.21 ± 15.68) s, P < 0.01]. There was no thrombus event in two groups and no bleeding event in argatroban group, and there was three bleeding events in heparin group [2.0% (3/150) vs.0, P > 0.05]. CONCLUSION: Argatroban is an effective and safe anticoagulation agent during elective PCI procedure, anticoagulant efficacy and risk of bleeding side effects of argatroban are similar to heparin.


Assuntos
Intervenção Coronária Percutânea , Ácidos Pipecólicos/uso terapêutico , Adulto , Anticoagulantes/uso terapêutico , Arginina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sulfonamidas , Resultado do Tratamento
17.
Clin J Am Soc Nephrol ; 6(3): 482-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21088292

RESUMO

BACKGROUND AND OBJECTIVES: The efficacy of folic acid therapy to lower homocysteine (Hcy) levels in an effort to reduce cardiovascular disease (CVD) risk in patients with ESRD or advanced chronic kidney disease (ACKD; creatinine clearance, <30 ml/min) remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This meta-analysis included 3886 patients with ESRD/ACKD from seven qualified randomized trials using folic acid therapy and with CVD reported as one of the end points. RESULTS: When pooling the seven trials, folic acid therapy reduced the risk of CVD by 15% (RR, 0.85; 95% CI, 0.76 to 0.96; P = 0.009). A greater beneficial effect was observed among those trials with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02), a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no or partial folic acid fortification (RR, 0.80; 95% CI, 0.65 to 0.99; P = 0.04). The beneficial effect also was seen when Hcy levels decreased >20%, even in the presence of folic acid fortification (RR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. CONCLUSIONS: Folic acid therapy can reduce CVD risk in patients with ESRD/ACKD by 15%. A greater beneficial effect was observed among those trials with no or partial folic acid fortification or a decrease in Hcy level >20% regardless of folic acid fortification.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Nefropatias/terapia , Falência Renal Crônica/terapia , Diálise Renal , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Medicina Baseada em Evidências , Feminino , Homocisteína/sangue , Humanos , Nefropatias/sangue , Nefropatias/complicações , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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