Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 11(1): 18250, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521870

RESUMO

There has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia-Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy.

2.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361003

RESUMO

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Benzilisoquinolinas/farmacologia , Dermatite Atópica/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/toxicidade , Células HaCaT/efeitos dos fármacos , Células HaCaT/metabolismo , Humanos , Interferon gama/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Toxins (Basel) ; 12(8)2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32722241

RESUMO

Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients.


Assuntos
Cresóis/metabolismo , Miócitos de Músculo Liso/metabolismo , Osteogênese , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/metabolismo , Ésteres do Ácido Sulfúrico/metabolismo , Uremia/metabolismo , Calcificação Vascular/metabolismo , Idoso , Idoso de 80 Anos ou mais , Artérias/citologia , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/cirurgia , Transdução de Sinais , Uremia/complicações , Calcificação Vascular/etiologia
4.
Arch Med Res ; 51(5): 388-396, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32409143

RESUMO

BACKGROUND AND AIMS: Heme oxygenase 1 (HO-1) is mainly regulated by the redox-sensitive transcription factor, namely nuclear factor erythroid 2-related factor 2 (Nrf2). We previously found a physically-made gold nanoparticle (GNP) can affect migration, adhesion, and proliferation of rat aortic vascular smooth muscle cells (VSMCs). This study was sought to investigate whether the GNP can affect HO-1 expression level in VSMCs. METHODS: Cellular fractionation, Western blotting, and immunofluorescence microscopy were used to determine Nrf2 translocation and phosphorylation. SiRNA interference was used to examine role of Nrf2 in GNP-induced HO-1 expression. RESULTS: The GNP concentration- and time-dependently enhanced HO-1 protein and mRNA expression; however, the mRNA induction was declined after 16 h treatment. The GNP treatment caused Nrf2 expression level and phosphorylation. In addition, it induced cytosolic Nrf2 translocation into nucleus. The HO-1 induction was inhibited by a ROS scavenger N-acetylcysteine (NAC), thiol-containing antioxidants (glutathione [GSH] and dithiothreitol [DTT]), JNK and p38 MAPK inhibitors, and nuclear transport inhibitor leptomycin. Meanwhile, the GNP-induced Nrf2 translocation (activation) was also reduced by NAC, JNK and p38 MAPK inhibitors, and nuclear transport inhibitor. Intriguingly, the GNP only enhanced activation of p38 MAPK but not JNK1/2. Finally, introduction of Nrf2 siRNA to cells to knockdown Nrf2 expression significantly inhibited GNP-induced HO-1 protein expression. CONCLUSIONS: This study elucidates the action mechanism that the naked physically-made GNP can enhance HO-1 expression in rat aortic VSMCs by inducing Nrf2 expression and phosphorylation and translocation into nucleus. The Nrf2 activation is mediated through a redox-related reaction and p38 MAPK activation.


Assuntos
Aorta/metabolismo , Ouro/química , Heme Oxigenase-1/metabolismo , Nanopartículas Metálicas/química , Músculo Liso Vascular/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Humanos , Ratos
5.
Front Med (Lausanne) ; 7: 102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32296707

RESUMO

Objective: Systemic hypoperfusion is intricately involved in neurohormone secretion, vascular calcification (VC) related impaired vasodilation, and luminal stenosis. We aimed to conduct a joint evaluation of vasopressin-neurophysin II-copeptin peptide (VP) and advanced aortic arch calcification (AAC) on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients. Methods: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed for different groups of VP and AAC in 167 MHD patients. The modification effect between higher VP and advanced AAC on mortality risk was examined using an interaction product term. Results: Interactions between VP and AAC with respect to all-cause and CV mortality were statistically significant. In multivariable analysis, higher VP predicted all-cause and CV mortality [aHR: 2.2 (95% confidence interval (CI): 1.1-4.5)] and 2.6 (95% CI: 1.1-4.6), respectively. Advanced AAC was associated with incremental risks of all-cause and CV mortality [aHR: 2.1 (95% CI: 1.1-4.0)and 2.5 (95% CI: 1.0-4.3), respectively]. Patients with combined higher VP (>101.5 ng/mL) and advanced AAC were at the greatest risk of all-cause and CV mortality [aHR: 4.7 (95% CI: 1.2-16.2)and 4.9 (95% CI: 1.1-18.9), respectively]. Conclusion: Combined VP and advanced AAC predict not only all-cause but also CV death in MHD patients, and a joint evaluation is more comprehensive than single marker. In light of hypoperfusion and ischemic events in vital organs, VP and AAC could act as more robust dual marker for prognostic assessment.

6.
J Formos Med Assoc ; 119(1 Pt 1): 59-68, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31023506

RESUMO

BACKGROUND/PURPOSE: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. METHODS: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. RESULTS: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. CONCLUSION: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Dronedarona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/efeitos adversos , Dronedarona/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Taiwan , Resultado do Tratamento
7.
J Clin Med ; 7(10)2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30249969

RESUMO

BACKGROUND: Interactions and joint effects of galectin-3 and vascular cell adhesion molecule 1 (VCAM-1) on risks of all-cause and cardiovascular (CV) mortality remain unclear in patients with maintenance hemodialysis (MHD). METHODS: Unadjusted and adjusted hazard ratios (aHRs) of mortality risks were analyzed between higher and lower concentration groups of serum galectin-3 and VCAM-1. The modification effect between serum galectin-3 and VCAM-1 on mortality risk was investigated using an interaction product term. RESULTS: During follow-up, galectin-3 and VCAM-1 were associated with incremental risks of all-cause mortality (aHR: 1.038 (95% confidence interval (CI): 1.001⁻1.077) and 1.002 (95% CI: 1.001⁻1.003), respectively). Nonetheless, VCAM-1 but not galectin-3 predicted CV mortality (aHR: 1.043 (95% CI: 0.993⁻1.096) and 1.002 (95% CI: 1.001⁻1.003), respectively). In the interaction analysis, patients with combined higher galectin-3 (>29.5 ng/mL) and VCAM-1 (>1546.9 ng/mL) were at the greatest risk of all-cause and CV mortality (aHR: 4.6 (95% CI: 1.6⁻13.4), and 4.2 (95% CI: 1.3⁻14.4), respectively). The interactions between galectin-3 and VCAM-1 with respect to all-cause and CV mortality were statistically significant (p < 0.01 and < 0.05, respectively). CONCLUSION: Galectin-3 and VCAM-1 could serve as a promising dual biomarker for prognostic assessment, considering their joint effects on pathogenesis of leukocyte trafficking and atherothrombosis.

8.
Int J Mol Sci ; 19(4)2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29642394

RESUMO

Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI) injury model in mice. Treatment with platonin (200 µg/kg) significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1ß. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.


Assuntos
Anti-Inflamatórios/uso terapêutico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Tiazóis/uso terapêutico , Animais , Caspases/genética , Caspases/metabolismo , Córtex Cerebral/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Força da Mão , Interleucinas/genética , Interleucinas/metabolismo , Locomoção , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
J Clin Nurs ; 23(13-14): 2063-73, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24372795

RESUMO

AIMS AND OBJECTIVES: To evaluate the effectiveness of an accessibility-enhanced multimedia informational educational programme in reducing anxiety and increasing satisfaction with the information and materials received by patients undergoing cardiac catheterisation. BACKGROUND: Cardiac catheterisation is one of the most anxiety-provoking invasive procedures for patients. However, informational education using multimedia to inform patients undergoing cardiac catheterisation has not been extensively explored. DESIGN: A randomised experimental design with three-cohort prospective comparisons. METHODS: In total, 123 consecutive patients were randomly assigned to one of three groups: regular education; (group 1), accessibility-enhanced multimedia informational education (group 2) and instructional digital videodisc education (group 3). Anxiety was measured with Spielberger's State Anxiety Inventory, which was administered at four time intervals: before education (T0), immediately after education (T1), before cardiac catheterisation (T2) and one day after cardiac catheterisation (T3). A satisfaction questionnaire was administrated one day after cardiac catheterisation. Data were collected from May 2009-September 2010 and analysed using descriptive statistics, chi-squared tests, one-way analysis of variance, Scheffe's post hoc test and generalised estimating equations. RESULTS: All patients experienced moderate anxiety at T0 to low anxiety at T3. Accessibility-enhanced multimedia informational education patients had significantly lower anxiety levels and felt the most satisfied with the information and materials received compared with patients in groups 1 and 3. A statistically significant difference in anxiety levels was only found at T2 among the three groups (p = 0·004). CONCLUSIONS: The findings demonstrate that the accessibility-enhanced multimedia informational education was the most effective informational educational module for informing patients about their upcoming cardiac catheterisation, to reduce anxiety and improve satisfaction with the information and materials received compared with the regular education and instructional digital videodisc education. RELEVANCE TO CLINICAL PRACTICE: As the accessibility-enhanced multimedia informational education reduced patient anxiety and improved satisfaction with the information and materials received, it can be adapted to complement patient education in future regular cardiac care.


Assuntos
Adaptação Psicológica , Cateterismo Cardíaco/psicologia , Educação em Saúde , Multimídia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/enfermagem , Feminino , Acesso aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
10.
Int Immunopharmacol ; 15(2): 333-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23337882

RESUMO

BACKGROUND: Sorafenib, a multi-kinase inhibitor approved for treatment of advanced renal cell carcinoma and other malignancies, has been shown as a modulator for dendritic cells. This study was designed to examine the effects of sorafenib on macrophages, the major ontogeny of innate immunity. MATERIALS AND METHODS: Macrophages were derived from sorted CD14(+) monocytes of human peripheral blood mononuclear cells. Cell viability and surface antigens were examined by trypan blue analysis. Autophagy was characterized by light microscopy and transmission electron microscopy for morphology, Western blotting for microtubule associated light chain protein 3B (LC-3B) I lipidation, and acridine orange staining for acidic component vacuoles. Soluble factors contained in culture medium and serum were measured by ELISA. RESULTS: We found that sorafenib inhibited the viability of macrophages accompanied by morphological changes characteristic of autophagy. This autophagy-inducing effect was validated by LC3B-I lipidation and autophagosome accumulation. The surface antigen expression and the function of activated macrophages were inhibited by sorafenib, including the expression of co-stimulatory molecule CD80, phagocytosis, and the production of reactive oxygen species. The secretion of IL-10, but not IL-6, TNF-α nor TGF-ß, was reduced by sorafenib. CONCLUSION: Sorafenib, in addition to being a cancer targeted therapeutic agent, can induce autophagy and modulate the function of human macrophages.


Assuntos
Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antígeno B7-1/genética , Antígeno B7-1/metabolismo , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/imunologia , Regulação para Baixo , Humanos , Imunidade Inata/efeitos dos fármacos , Imunossupressão , Receptores de Lipopolissacarídeos/metabolismo , Macrófagos/imunologia , Terapia de Alvo Molecular , Niacinamida/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe
11.
Transplantation ; 95(6): 791-800, 2013 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-23354299

RESUMO

BACKGROUND: Sorafenib, a multikinase inhibitor approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, has been reported inhibitory on the function of dendritic cells. This study was aimed to determine the effects of sorafenib on inducing autophagy and immunomodulatory activity and its implication on graft rejection. METHODS: Cell viability and surface antigens were examined by 7-amino-actinomycin D and flow cytometric analysis. Autophagy was characterized using light microscopy and transmission electron microscopy for morphology, Western blotting for LC3B-I lipidation and mammalian target of rapamycin signaling molecules, and immunofluorescence staining for endogenous LC3B, GFP-LC3 transfection, and acidic component vacuoles. Skin allograft in mice was used as an experimental transplantation rejection model. Soluble factors contained in culture medium and serum were measured by enzyme-linked immunosorbent assay. RESULTS: We found that sorafenib inhibited the viability of dendritic cells accompanied by morphologic changes characteristic of autophagy and immature differentiation. This autophagic effect induced by sorafenib was validated by LC3B-I lipidation and autophagosome accumulation. Sorafenib treatment was associated with the down-regulation of phosphorylated mammalian target of rapamycin and its downstream substrate p70S6K. We next performed skin graft model to testify the role of sorafenib-induced immature and autophagic dendritic cells. Intriguingly, sorafenib prolonged the survival of skin allograft without major toxicity. Blockade of autophagic flux by chloroquine partially diminished the protective effect of sorafenib, indicating an autophagy-related mechanism in vivo. CONCLUSION: This study suggests that sorafenib, in addition to being an anticancer agent, may have potential to be developed as a new category of immunosuppressant drugs acting via autophagy induction of dendritic cells.


Assuntos
Autofagia/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Mieloides/efeitos dos fármacos , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Transplante de Pele/métodos , Animais , Antígenos/metabolismo , Sobrevivência Celular , Dactinomicina/análogos & derivados , Dactinomicina/farmacologia , Ensaio de Imunoadsorção Enzimática/métodos , Citometria de Fluxo/métodos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Camundongos , Microscopia de Fluorescência/métodos , Niacinamida/farmacologia , Sorafenibe , Transplante Homólogo
12.
Acta Pharmacol Sin ; 33(1): 49-56, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22212430

RESUMO

AIM: To investigate the signaling pathways involved in thrombin-induced connective tissue growth factor (CTGF) expression in rat vascular smooth muscle cells (VSMCs). METHODS: Experiments were preformed on primary rat aortic smooth muscle cells (RASMCs) and a rat VSMC line (A10). CTGF protein levels were measured using Western blotting. Luciferase reporter genes and dominant negative mutants (DNs) were used to investigate the signaling pathways mediating the induction of CTGF expression by thrombin. RESULTS: Thrombin (0.3-3.0 U/mL) caused a concentration- and time-dependent increase in CTGF expression in both RASMCs and A10 cells. Pretreating A10 cells with the protease-activated receptor 1 (PAR-1) antagonist SCH79797 (0.1 µmol/L) significantly blocked thrombin-induced CTGF expression, while the PAR-4 antagonist tcY-NH(2) (30 µmol/L) had no effect. The PAR-1 agonist SFLLRN-NH(2) (300 µmol/L) induced CTGF expression, while the PAR-4 agonist GYPGQV-NH(2) (300 µmol/L) had no effect. Thrombin (1 U/mL) caused time-dependent phosphorylation of c-Jun N-terminal kinase (JNK). Pretreating with the JNK inhibitor SP600125 (3-30 µmol/L) or transfection with DNs of JNK1/2 significantly attenuated thrombin-induced CTGF expression. Thrombin (0.3-3.0 U/mL) increased activator protein-1 (AP-1)-luciferase activity, which was inhibited by the JNK inhibitor SP600125. The AP-1 inhibitor curcumin (1-10 µmol/L) concentration-dependently attenuated thrombin-induced CTGF expression. CONCLUSION: Thrombin acts on PAR-1 to activate the JNK signaling pathway, which in turn initiates AP-1 activation and ultimately induces CTGF expression in VSMCs.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Receptor PAR-1/metabolismo , Trombina/farmacologia , Fator de Transcrição AP-1/metabolismo , Animais , Linhagem Celular , Fator de Crescimento do Tecido Conjuntivo/genética , Hemostáticos/farmacologia , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/fisiologia , Ratos , Receptor PAR-1/agonistas , Receptor PAR-1/antagonistas & inibidores , Receptor PAR-1/genética , Receptores de Trombina/agonistas , Receptores de Trombina/antagonistas & inibidores , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Transcrição AP-1/genética
13.
Circ J ; 75(7): 1592-600, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21576830

RESUMO

BACKGROUND: Atrial fibrosis is a feature of structural remodeling in atrial fibrillation (AF). Connective tissue growth factor (CTGF) is a potent profibrotic factor, but its role of CTGF in AF is not yet fully understood. METHODS AND RESULTS: Right atrial appendages were obtained from 20 patients who underwent cardiac surgery (10 with sinus rhythm, 10 with AF). The mRNA level, protein level and immunohistochemical staining of CTGF were significantly increased in AF patients. In a porcine AF model, tissue angiotensin II (Ang II) and CTGF levels were significantly upregulated in both atria. In perfused rat hearts, Ang II stimulation increased CTGF expression, which could be inhibited by Ang II type I receptor antagonist. In a cell culture system, both atrial fibroblasts and myocytes were responsible for the increased CTGF expression under Ang II treatment. Ang II type I receptor antagonist could inhibit the Ang II-induced CTGF expression. Treating with recombinant CTGF, atrial fibroblasts expressed an increased level of collagen I. Furthermore, the CTGF level was highly correlated with tissue Ang II content in AF pigs. CONCLUSIONS: AF patients and animals exhibited a significantly increased expression of CTGF. Ang II stimulation upregulated CTGF expression in both atrial fibroblasts and myocytes. Ang II-induced CTGF expression might be involved in atrial substrate remodeling.


Assuntos
Angiotensina II/farmacologia , Fibrilação Atrial/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Idoso , Idoso de 80 Anos ou mais , Angiotensina II/metabolismo , Animais , Fibrilação Atrial/patologia , Fibrilação Atrial/fisiopatologia , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Suínos
14.
Heart Rhythm ; 8(7): 961-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21315847

RESUMO

BACKGROUND: The biatrial substrate properties in patients with paroxysmal atrial fibrillation (AF) originating from the pulmonary veins (PVs) and superior vena cava (SVC) are not available. OBJECTIVE: The purpose of this study is to characterize the differences of biatrial substrate properties in patients with different types of AF. METHODS: A total of 36 patients with paroxysmal AF originating from the PV (PV-AF) and 9 patients with paroxysmal AF initiating from the SVC (SVC-AF) were included. Regional electrogram voltage, conduction velocity (CV), and spectral analysis to identify the AF nest were performed to characterize the biatrial, PVs, and SVC substrate. RESULTS: In the left atrial (LA) body, the bipolar voltage, total activation time, CV, and dominant frequency (DF) were similar between the PV-AF and SVC-AF. However, in the PV regions, the electrogram voltage, CV, and DF were decreased in the PV-AF. The proportions of AF nest in the LA body (72.2% vs. 22.2%, P = .008) and PV regions (100% vs. 22.2%, P <.001) were higher in PV-AF compared with SVC-AF, respectively. On the other hand, lower bipolar voltage, longer total activation time, and slower CV of RA body were recognized in the SVC-AF as compared with the PV-AF. In the SVC, lower bipolar voltage, slower CV, higher DF, and higher proportions of AF nest in SVC (16.7% vs. 66.7%, P = .002) were identified in SVC-AF. CONCLUSION: These most-remodeled substrates in different types of paroxysmal AF indicated the importance of the atrial substrate in the vicinity of the arrhythmogenic thoracic veins.


Assuntos
Fibrilação Atrial/fisiopatologia , Função Atrial/fisiologia , Taquicardia Paroxística/fisiopatologia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Mapeamento Potencial de Superfície Corporal/métodos , Ablação por Cateter/métodos , Feminino , Seguimentos , Sistema de Condução Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Taquicardia Paroxística/diagnóstico , Taquicardia Paroxística/cirurgia
15.
J Clin Pharmacol ; 47(3): 397-403, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17322151

RESUMO

The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD-mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down-regulation of SOD-mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT(1) receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Hipertensão/tratamento farmacológico , Superóxido Dismutase/genética , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Adulto , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Northern Blotting , Tontura/induzido quimicamente , Método Duplo-Cego , Exantema/induzido quimicamente , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismo , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Resultado do Tratamento , Valina/efeitos adversos , Valina/farmacologia , Valina/uso terapêutico , Valsartana
16.
Acta Paediatr Taiwan ; 45(1): 41-4, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15264706

RESUMO

Ventricular tachycardia occurring in apparently normal heart is rare in children. A 9-year-old boy presented with recurrent palpitations and syncope was found to have idiopathic ventricular tachycardia with a right bundle branch block morphology and left axis deviation. Pace mapping and activation mapping were used to localize the site of ventricular tachycardia origin. Radiofrequency catheter ablation successfully abolished this arrhythmia at a site of the midportion of the inferoseptal region of the left ventricle. This boy was free of tachycardia over follow-up of 2 years.


Assuntos
Ablação por Cateter , Taquicardia Ventricular/cirurgia , Criança , Eletrocardiografia , Serviços Médicos de Emergência , Humanos , Masculino , Radiografia , Taquicardia Ventricular/diagnóstico por imagem , Resultado do Tratamento , Disfunção Ventricular Esquerda/cirurgia
17.
Cardiology ; 99(4): 182-9, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12845244

RESUMO

Since 1992, the Brugada syndrome has been increasingly recognized worldwide, although its incidence and distribution remain unclear. In Asia, several cases have been reported in Japan, Thailand, Singapore, and Vietnam. However, little information is available from the Chinese population. Since June 1997, we have identified 10 patients with the diagnosis of the Brugada syndrome from six hospitals in Taiwan. All patients were male with the mean age of 46 +/- 7 years (range 36-61). They all had a normal chemistry profile, coronary angiography and echocardiography. Clinical presentations varied from seizure and syncope to sudden cardiac death. MRI and ultrafast CT of the heart did not show any abnormalities. Sustained ventricular tachycardia/ventricular fibrillation (VF) was induced in 7 of 8 patients who underwent an electrophysiologic study. The pharmacological provocation test was positive in 4 of 5 patients. One of the 4 patients who had a genetic study showed SCN5A gene mutation. An implantable cardioverter defibrillator (ICD) was implanted in 8 patients. During a mean follow-up of 29 +/- 17 months (range 2-54), 3 of 8 patients who had an ICD received appropriate ICD discharges after implantation. These 3 patients who were subsequently treated with antiarrhythmic agents have had no further recurrent ICD discharges. Two patients who refused ICD implantation are alive and well without taking antiarrhythmic agents. Our study showed that the clinical characteristics of our patients are similar to those described in the literature and that ICD is an effective treatment modality for patients with recurrent VF. However, antiarrhythmic agents may be beneficial for suppressing arrhythmia recurrences in selected patients.


Assuntos
Taquicardia Ventricular/etnologia , Taquicardia Ventricular/fisiopatologia , Adulto , Antiarrítmicos/uso terapêutico , Cateterismo Cardíaco , China/etnologia , Angiografia Coronária , Ecocardiografia Doppler , Eletrocardiografia Ambulatorial , Exercício Físico , Teste de Esforço , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Procainamida/uso terapêutico , Síndrome , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Taiwan , Fibrilação Ventricular/etnologia , Fibrilação Ventricular/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...