RESUMO
Coronary artery disease (CAD) is a life-threatening medical emergency which needs urgent medical attention. Percutaneous coronary intervention (PCI) is common and necessary for patients with CAD, but it has not completely evaluated in cases with repeated PCI. Therefore, the aim of this study was to examine the risk factors and prognosis in patients with CAD requiring repeated PCI. This is a prospective observational study. A total of 1126 patients with CAD requiring PCI took part in this study. Clinical parameters including baseline characteristics, hemodynamic data, location of vascular lesions, SYNTAX score, left ventricular ejection fraction, central pulse pressure (CPP), central aortic systolic pressure (CSP), risk factors, and invasive strategies were analyzed to identify the risk factors for patients requiring repeated PCI. We further analyzed the prognosis, including risk for myocardial infarction (MI), cardiovascular (CV) mortality, and all-cause mortality, in patients with repeated PCI. Among patients with PCI, 276 received repeated PCI. Patients in the repeated PCI group had a higher CPP (66.7 vs 62.5âmm Hg; Pâ=â0.006), CSP (139.9 vs 135.9âmm Hg; Pâ=â0.017), and male preponderance (Pâ=â0.012). Drugs including diuretics, beta-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs), and aspirin were all used more frequently in the repeated PCI group (all Pâ<â0.05). Freedom from MI was lower in the repeated PCI group than in the single PCI group (Pâ<â0.001). Logistic regression revealed that CPP, CSP, number of diseased vessels, male sex, usage of diuretics, BBs, ACEIs, and MI were all predictors for requiring repeated PCI (all Pâ<â0.05). In addition, CPP was a predictor for MI attack, CV mortality, and all-cause mortality in the repeated PCI group (Pâ=â0.010, Pâ=â0.041, Pâ=â0.004, respectively). Elevated CPP, CSP, male sex, multiple diseased vessels, and the usage of diuretics, BBs, ACEIs, and MI were predictors for repeated PCI. Most importantly, CPP was strongly associated with MI attack, CV mortality, and all-cause mortality, and could serve as a prognostic parameter for mortality in patients with CAD after performing repeated PCI.
Assuntos
Pressão Sanguínea , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Idoso , Glicemia , Fármacos Cardiovasculares/administração & dosagem , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Lipídeos/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
BACKGROUND: Hypertension control is of the utmost importance for reducing cardiovascular risk. In Taiwan, the hypertension control rate of the general population is low (25%). We investigated the factors affecting outpatient hypertension control to determine whether the low control rate stems from clinician unawareness or inadequate public education. METHODS: Hypertensive patients were recruited between 2003 and 2004 by 13 cardiologists and 9 non-cardiologists from 19 hospitals distributed across four geographical areas of Taiwan. Each clinician recruited 100 consecutive patients from outpatient clinics and reported their drug prescriptions, co-morbidities, and blood pressure (BP) levels. Data were analyzed using the chi square test and multivariate logistic regression analyses. RESULTS: Of the 2145 enrolled patients, 63% attained the BP goal of < 140/90 mmHg. BP control rates were higher in older patients, and in patients who were treated by cardiologists and at medical centers. The control rate of high risk co-morbidity patients (BP goal of < 130/80 mmHg) was 36%, which was significantly lower than the 62% control rate of low risk patients (BP goal of < 140/90 mmHg). Cardiologists achieved higher BP control rates (65% vs. 60%; p = 0.0039), and prescribed more combination regimens (p < 0.0001) and beta blockers than non-cardiologists. Overall, 63% of patients received combination therapy. Calcium channel blockers were the most commonly prescribed antihypertensive drugs, followed by beta blockers, angiotensin receptor blockers, diuretics, and angiotensin-converting enzyme inhibitors. CONCLUSIONS: Two-thirds of the entire study population received combination therapy, although BP control rate is still less than optimal in the high risk patients. Ultimately, a more aggressive strategy is strongly encouraged for patients considered to be at high risk. KEY WORDS: Combination therapy; Hypertension control rate; Prescribing habit.
RESUMO
BACKGROUND: Hyperuricemia is thought to be associated with an increased risk of hypertension, impaired renal function and cardiovascular disease. Our aim is to study the prevalence of hyperuricemia and its association with antihypertensive treatment in Taiwanese hypertensive subjects. METHODS: We recruited 2145 hypertensive subjects from 19 hospitals in four areas of Taiwan. We assessed the prevalence of hyperuricemia and determined the independent risk factors for raised serum uric acid level by multiple logistic regression analyses. RESULTS: Compared to the general population, hypertensive subjects in Taiwan had a higher prevalence (mean 35% in males, 43% in females) of hyperuricemia; this prevalence being 1.5- and 1.7-fold higher in males and females respectively. Uric acid levels; gout and prevalence of hyperuricemia were found to be highest in the younger age group (20-39 years) and no regional differences were noted. The most important risk factors for hyperuricemia were impaired renal function and diuretic use. Serum uric acid values correlated significantly with four quintiles of serum creatinine (p<0.0001) independent of diuretic use. Diuretic users had a significantly elevated serum uric acid and serum creatinine values than non-users. Among the patients given diuretics, hyperuricemia occurred in 44% of those given thiazides, in 56% of those given loop diuretics, and in 57% of those given aldosterone receptor blockers. CONCLUSIONS: Diuretic usage and renal function status have a strong impact on the prevalence of hyperuricemia in Taiwanese hypertensive subjects. It is still unclear, however, whether diuretics induce renal failure through elevating serum uric acid levels.
Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hiperuricemia/induzido quimicamente , Hiperuricemia/epidemiologia , Idoso , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/sangue , Hiperuricemia/sangue , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Prevalência , Taiwan/epidemiologia , Resultado do Tratamento , Ácido Úrico/sangueRESUMO
BACKGROUND: Individuals with hypertension and hyperuricemia have an increased risk of coronary artery disease and cerebral vascular disease as compared to patients with normal uric acid levels. Our aim is to determine the prevalence of hyperuricemia in hypertensive patients in Taiwan, and whether serum uric acid (SUA) is associated with changes in renal function in patients with hypertension. METHODS: We studied 2145 hypertensive patients receiving medical treatment, assessed the prevalence of hyperuricemia, and determined the independent risk factors for SUA. Simple correlation and multiple regression analyses were applied to identify the independent risk factors for SUA increase. Logistic regression analysis was used to estimate the association between 4 quartiles of SUA level and correspondent serum creatinine (SCr) concentrations. RESULTS: Hypertensive subjects had a high prevalence of hyperuricemia (men, 35%; women, 43%). SUA was significantly associated with the independent risk factors of SCr, diuretic usage, and diabetes (inversely related) in both genders, whereas ß-blocker usage and body mass index were only associated in men. Multiple logistic regression models showed that in the non-diuretic user group the highest SUA quartile entailed >4 times greater risk for SCr elevation than the lowest. In the diuretic user group, a >2 times greater risk was noted. CONCLUSIONS: Hyperuricemia hypertensive subjects demonstrated a corresponding elevation of SUA and SCr irrespective of diuretic use. Elevation of SUA, in addition to SCr, may represent a progression of renal function impairment.
Assuntos
Creatinina/sangue , Diuréticos/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Ácido Úrico/sangue , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Ventricular tachyarrhythmias are life threatening cardiac arrhythmias and are the most common causes of sudden cardiac death. Greater post-infarction left ventricular remodeling has been shown to have a greater preponderance of ventricular arrhythmias. The hypothesis herein is that adverse structural and electrophysiological remodeling at non-infarcted regions after myocardial infarction constitutes the arrhythmogenic substrate responsible for clinically occurring ventricular arrhythmias leading to sudden cardiac death. Post-infarction patients with more severe left ventricular remodeling (regional hypertrophy) at sites remote to infarction scar might have the highest risk for sudden cardiac death due to lethal ventricular arrhythmias. In the hypertrophic non-infarcted zone, larger action potential duration and repolarization heterogeneity is not in self arrhythmogenic, but can predispose towards arrhythmia development under certain condition, such as transient myocardial ischemia. We should draw more attention to apparently "normal" non-infarction region for further understanding the mechanism of sudden cardiac death.
Assuntos
Potenciais de Ação/fisiologia , Arritmias Cardíacas/complicações , Morte Súbita Cardíaca/etiologia , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Morte Súbita Cardíaca/patologia , Cães , Estimulação Elétrica , Eletrocardiografia , Humanos , Fatores de RiscoRESUMO
Chitin is an abundant biopolymer composed of units of N-acetyl-D-glucosamine linked by ß-1,4 glycosidic bonds. Chitin is the main component of the shells of mollusks, the cell wall of fungi and yeast and of the exoskeleton of crustaceans and insects. The degradation of chitin is catalyzed by chitinases that occur in a wide range of organisms. Among them, the chitinases from microorganisms are extremely important for the degradation and recycling of the carbon and nitrogen trapped in the large amount of insoluble chitin in nature. Streptomyces sp. TH-11 was isolated from the sediment of the Tou-Chien River, Taiwan. The chitinolytic enzyme activities were detected using a rapid in-gel detection method from the cell-free preparation of the culture medium of TH-11. The chitinolytic enzyme activity during prolonged liquid culturing was also analyzed by direct measurement of the chitin consumption. Decomposition of the exoskeleton of shrimps was demonstrated using electron microscopy and atomic force microscopy.
Assuntos
Proteínas de Bactérias/fisiologia , Quitina/metabolismo , Quitinases/fisiologia , Streptomyces/enzimologia , Exoesqueleto/química , Exoesqueleto/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Quitinases/metabolismo , Microscopia de Força Atômica , Streptomyces/isolamento & purificação , Propriedades de SuperfícieRESUMO
A modified Coomassie Brilliant Blue G 250 staining method for detecting chitinolytic enzymes in chitin-containing polyacrylamide gel electrophoresis (PAGE) is presented. The staining formed achromatic zones at the locations of the migrated enzyme. Using Streptomyces griseus chitinase, we have demonstrated that our method is more sensitive and less complicated than the conventional Calcofluor white M2R staining.
Assuntos
Quitinases/análise , Quitinases/química , Corantes de Rosanilina/química , Eletroforese em Gel de Poliacrilamida/métodos , Ativação Enzimática , Peso Molecular , Coloração e Rotulagem/métodosRESUMO
AIMS: This study sought to compare the antihypertensive efficacy and tolerability of a fixed-dose combination with amlodipine/benazepril with that of amlodipine monotherapy in Chinese hypertensive subjects. RESULTS: This multicenter, double-blind, 8-week study randomized 111 patients to fixed-dose amlodipine besylate/benazepril HCl (2.5/5 mg/day titrated to 5/10 mg/day as needed at week 4 to reach goal blood pressure (BP) <140/90 mmHg) or amlodipine besylate monotherapy (5 mg/day titrated to 10 mg/day as needed). At week 8, patients randomized to combination therapy compared with monotherapy had a comparable BP control rate (56.0% vs. 46.2%; p = 0.32). Fixed-dose combination resulted in similar reductions in sitting systolic (SBP) and diastolic BP (DBP) compared with monotherapy (SBP: -19.3 +/- 12.5 vs. -20.9 +/- 13.3 mmHg; DBP: -9.2 +/- 10.4 vs. -11.3 +/-9.3 mmHg; both p=NS). Safety profiles did not differ between groups, but cough was more common in the combination group (11.0% vs. 0%; p = 0.013). CONCLUSIONS: In this group of patients, comparable antihypertensive effects were seen with the fixed-dose combination therapy, compared with amlodipine monotherapy. Both treatments appeared well tolerated in the studied population, but cough was more common in the fixed-dose combination group.
Assuntos
Anlodipino/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Benzazepinas/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , Idoso , Anlodipino/administração & dosagem , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: We compared the expression and distribution of atrial annexin VI between patients with atrial fibrillation (AF) or sinus rhythm (SR). METHODS: Atrial appendages were obtained during cardiac surgery from 20 patients with chronic AF and 34 matched controls in SR. The expression and distribution of annexin VI were analyzed using semiquantitative RT-PCR, Western blotting and immunoconfocal microscopy. RESULTS: In the AF group, compared to SR, the mRNA was reduced to <35% and the protein to <50% in amount (for each atrium, all p < 0.01). Immunoconfocal microscopy confirmed the downregulation of annexin VI protein in AF and demonstrated the colocalization of annexin VI with both Na(+)/Ca(2+) exchangers and L-type Ca(2+) channels in the sarcolemma, but not with ryanodine receptors in the sarcoplasmic reticulum. CONCLUSIONS: Atrial annexin VI, spatially colocalized with both Na(+)/Ca(2+) exchangers and L-type Ca(2+) channels in the myocyte membrane, is downregulated during chronic AF.
Assuntos
Anexina A6/metabolismo , Fibrilação Atrial/metabolismo , RNA Mensageiro/metabolismo , Actinas/metabolismo , Idoso , Biomarcadores/metabolismo , Western Blotting , Distribuição de Qui-Quadrado , Doença Crônica , Comorbidade , Regulação para Baixo , Feminino , Humanos , Masculino , Microscopia Confocal , Reação em Cadeia da Polimerase , Estatísticas não ParamétricasRESUMO
Benzene-1,2-, 1,3-, and 1,4-di-N-substituted carbamates (1-15) are synthesized as the conformationally constrained inhibitors of acetylcholinesterase and mimic gauche, eclipsed, and anti-conformations of acetylcholine, respectively. All carbamates 1-15 are characterized as the pseudo substrate inhibitors of acetylcholinesterase. For a series of geometric isomers, the inhibitory potencies are as follows: benzene-1,4-di-N-substituted carbamate (para compound) > benzene-1,3-di-N-substituted carbamate (meta compound) > benzene-1,2-di-N-substituted carbamate (ortho compound). Therefore, benzene-1,4-di-N-substituted carbamates (para compounds), with the angle of 180 degrees between two C(benzene)-O bonds, mimic the preferable anti C-O/C-N conformers of acetylcholine for the choline ethylene backbone in the acetylcholinesterase catalysis.
Assuntos
Acetilcolinesterase/metabolismo , Benzeno/química , Carbamatos/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Electrophorus/metabolismo , Acetilcolina/química , Animais , Benzeno/farmacologia , Carbamatos/farmacologia , Cinética , Análise dos Mínimos Quadrados , Conformação Molecular , Especificidade por Substrato/efeitos dos fármacosRESUMO
Atherosclerosis is the main underlying pathology of cardiovascular disease. Experimental studies in animal models provided early evidence of the antiatherosclerotic effects of nifedipine in reducing and reversing plaque formation and improving endothelial function. Over the past decade, clinical trials, including 'Intervention as a Goal in Hypertension Treatment', 'Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement', 'Evaluation of Nifedipine and Cerivastatin on Recovery of Coronary Endothelial Function' and 'A Coronary Disease Trial Investigating Outcome with Nifedipine Gastrointestinal System', have further demonstrated that nifedipine gastrointestinal therapeutic system can slow the progression of various markers of atherosclerosis, restore endothelial function, and reduce the incidence of coronary events and the need for coronary interventions. These results are reviewed here, along with the impact they have had on therapy guidelines for patients with hypertension and symptomatic stable angina.
Assuntos
Aterosclerose/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Nifedipino/administração & dosagem , Animais , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Humanos , Nifedipino/efeitos adversos , Nifedipino/farmacocinéticaRESUMO
1,2-Ethylene-di-N-n-propylcarbamate (1) is characterized as an essential activator of Pseudomonas species lipase while 1,2-ethylene-di-N-n-butyl-, t-butyl-, n-heptyl-, and n-octyl-carbamates (2-5) are characterized as the pseudo substrate inhibitors of the enzyme in the presence of the detergent taurocholate or triton X-100. The inhibition and activation reactions are more sensitive in taurocholate than in triton X-100. From CD studies, the enzyme changes conformations in the presence of the detergent and further alters conformations by addition of the carbamate activator or inhibitor into the enzyme-detergent adduct. Therefore, this study suggests that the conformational change of lipase during interfacial activation is a continuous process to expose the active site of the enzyme to substrate. From 600 MHz (1)H NMR studies, the conformations of the alpha- and beta-methylene moieties of the activator 1,2-ethylene-di-N-n-propylcarbamate in the presence of substrate change after adding taurocholate into the mixture, and the conformations of the beta-methylene moieties of the inhibitor 1,2-ethylene-di-N-n-butylcarbamate in the presence of substrate alter after adding taurocholate into the mixture.
Assuntos
Carbamatos/farmacologia , Detergentes/química , Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Lipase/metabolismo , Pseudomonas/enzimologia , Ativação Enzimática , Ressonância Magnética Nuclear BiomolecularRESUMO
Since there is evidence for estrogen and estrogen-like compounds to have beneficial effect on the pathogenesis of hepatocellular carcinoma (HCC), this study was designed to investigative the apoptotic and anti-proliferative effects of these compounds on the human hepatoma Hep3B cell line. The Hep3B cells were treated with 17beta-estradiol (E2), diethylstilbestrol (DES), tamoxifen, and genistein. After treatments of these compounds at the concentration of 10(-6) or 10(-8) M, the Hep3B cells were demonstrated to have significant DNA fragmentation, nucleus condensation, cytochrome-c leaking from the mitochondria and caspase-3 activation by DAPI and Western blotting. The cells were also observed to have declined proliferative potential by MTT assay, arrested cell cycle by flow-cytometry measurements. However, the cytochrome-c leaking from the mitochondria induced by E2 and E2-like compounds was blocked totally by ICI 182,780 treatment. These finding suggest that estrogen and the estrogen-like compounds may induce anti-proliferative and apoptotic effects in Hep3B cells, and the E2 and the E2-like compounds mediated apoptotic effect was estrogen receptor dependent. Among the drugs tested, E2, E2 agonists (DES and genistein) and partial antagonist (tamoxifen), all showed the stronger anti-tumor potential.
Assuntos
Dietilestilbestrol/farmacologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Estrogênios não Esteroides/farmacologia , Genisteína/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Fígado/efeitos dos fármacosRESUMO
Epidemiologic studies reported that the prevalence of hereditary non-polyposis colon cancer (HNPCC) in male is about 1.5-fold higher than that in female. Decreases in circulatory estradiol (E2) have been reported to downregulate the expression of E2 receptor (ER) and significantly increase the risk of colorectal cancer. Patients that received E2 replacement therapy were found to have a reduction in the incidence of colon adenoma and carcinoma. Furthermore, significant decreases in the expression of ER have been found in colorectal cancer specimens. These data strongly suggest the protective roles of E2 and ER against colorectal cancer. However, the mechanisms remain unexplored. LoVo cells were transient transfected to overexpress ER-beta, DNA fragmentation and caspase activity assay were performed to evaluate apoptotic effects. Western blotting was used to evaluate protein levels, and luciferase activity assay to measure the TNF-alpha promoter activity. Our data clearly demonstrated that E2 and ER-beta alone could upregulate p21 and p27 proteins, which further activate caspase-8 and caspase-9 to induce apoptosis in LoVo cell, and the ER-beta. effects were enhanced by E2. However, overexpressed ER-beta did not influence the expression and promoter activity of TNF-alpha. In addition, E2 and overexpressed ER-beta downregulated the beta-catenin proteins which cause the downregulation of its target genes, cyclin D1 and Rb, to inhibit the cell cycle and cell proliferation. The results indicate that overexpressed ER-beta may induce LoVo cell apoptosis and anti-proliferation by increasing p53 signaling in a ligand-dependent manner, and without hTNF-alpha involvement. Efforts aiming at enhancing ER-beta expression and/or activity may prove to be an attractive alternative therapy against colorectal cancer.
Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Receptor beta de Estrogênio/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Receptor beta de Estrogênio/genética , Humanos , Ligantes , Proteínas Recombinantes/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Serum iron overload or iron deficiency appears to be associated with atherosclerosis and ischemic myocardial damage. Roles of low or high serum iron in patients with ischemic heart diseases are still controversial. METHODS: Serum samples for biochemical and immunologic analyses were collected from the 73 normal subjects and the 90 patients with ischemic heart disease (IHD), the latter of which were selected from 142 patients and classified by low, normal and high serum iron. RESULTS: Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high sensitive C-Reactive protein (hsCRP), and interleukin-10 (IL-10) were increased and insulin-like growth factor (IGF)-I was decreased in IHD patients with low serum iron, whereas these parameters were not changed in IHD patients with normal or high serum iron, compared with normal subjects. Total bilirubin was increased in IHD patients with high serum iron but was not changed in IHD patients with low or normal serum iron, compared with normal subjects. CONCLUSION: The IHD patients with low serum iron were associated with a pro-inflammatory state, such as increased TNF-alpha, IL-6, and hsCRP; increased anti-inflammatory activities, such as increased IL-10; decreased cardiac protective factor, such as decreased IGF-I. These findings may imply that IHD patients with low serum irons were associated with less cardiac protection and more pro-inflammatory states than normal subjects or IHD patients with either normal or high serum iron.
Assuntos
Fator de Crescimento Insulin-Like I/análise , Ferro/sangue , Isquemia Miocárdica/sangue , Isquemia Miocárdica/patologia , Idoso , Antioxidantes/metabolismo , Biomarcadores , Proteína C-Reativa/metabolismo , Feminino , Hormônio do Crescimento/sangue , Humanos , Inflamação/sangue , Inflamação/patologia , Mediadores da Inflamação/sangue , Interleucina-6/metabolismo , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Epidemiologic studies reported that the prevalence of hereditary non-polyposis colon cancer (HNPCC) in male is about 1.5-fold higher than that in female. Decreases in circulatory estrogen (E(2)) have been reported to downregulate the expression of E(2) receptor (ER) and significantly increase the risk of colorectal cancer. Patients that received E(2) replacement therapy were found to have a reduction in the incidence of colon adenoma and carcinoma. Furthermore, significant decreases in the expression of ER have been found in colorectal cancer specimens. Evidences strongly suggest the protective roles of E(2) and ER against colorectal cancer. However, the mechanisms of ERalpha effects on colorectal cancer cells remained un-clear. LoVo cells were transient transfected to overexpress ERalpha, DNA fragmentation and the activated caspases measurements were performed to evaluate apoptotic effects. Western blotting was used to evaluate protein levels, and luciferase activity assay to measure the Htnf-a promoter activity. The results clearly demonstrated that overexpressed ERalpha with or without E(2) (10(-8) M) treatment could activate caspase -8, -9, and 3 and induce DNA fragmentation in LoVo cell. At the same time, overexpressed ERalpha plus E(2) significantly increases the expression and promoter activity of hTNF-alpha, and the DNA fragmentation effect induced by E(2) plus ERalpha were reduced by the addition of hTNF antibody (0.1 ng(ml). In addition, E(2) plus ERalpha significantly upregulated p21 and p27 levels and downregulated the beta-catenin and its target genes, cyclin D1 and Rb, which regulate the cell cycle and cell proliferation. The results indicate that E(2) plus overexpressed ERalpha induce LoVo cell apoptosis might mediate through the increase of hTNF-alpha gene expression, which in turn activate caspase-8, -9 and caspase-3 and lead to the DNA fragmentation and apoptosis. E(2) plus ERalpha also showed the downregulation of beta-catenin signalings implicating the suppression of proliferation and metastasis of colorectal cells. Efforts aiming at enhancing ERalpha expression and(or activity may be proved to be an alternative therapy against colorectal cancer.
Assuntos
Apoptose , Neoplasias do Colo/patologia , Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , beta Catenina/metabolismo , Proteína da Polipose Adenomatosa do Colo/metabolismo , Caspases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Fragmentação do DNA , Regulação para Baixo/genética , Receptor alfa de Estrogênio/genética , Estrogênios/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/efeitos dos fármacos , Transfecção , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/genética , Proteínas Wnt/metabolismo , beta Catenina/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Hypertension is very prevalent in the Chinese population in Taiwan. Chinese people frequently experience bothersome cough when receiving angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II (AT(1)) receptor antagonists are thus relatively more frequently used in this context. In this trial we studied the effectiveness of a new AT(1) receptor antagonist, olmesartan, in the treatment of Chinese patients with mild-to-moderate essential hypertension. PATIENTS AND METHODS: The present study was a double-blind, randomised, multicentre trial to compare the efficacy and safety profiles of two AT(1) receptor antagonists, olmesartan and losartan, in the treatment of Chinese patients with mild-to-moderate essential hypertension. 126 adults were randomised to receive either once-daily olmesartan 20mg or once-daily losartan 50mg for 12 weeks. There were 49 evaluable patients in the olmesartan group and 57 in the losartan group. RESULTS: At baseline, neither diastolic (DBP) nor systolic (SBP) blood pressures were significantly different between the two study groups. Trough blood pressures were measured and recorded for the evaluation of treatment effect. After drug treatment for 4, 8 and 12 weeks, SBP and DBP values were significantly decreased in both groups of patients. However, both SBP and DBP were significantly lower in the olmesartan group than in the losartan group after treatment. At the end of treatment, DBP values were 87.0 +/- 8.6mm Hg versus 91.6 +/- 8.7mm Hg (p < 0.001) and SBP values were 129.5 +/- 12.6mm Hg versus 135.4 +/- 12.1mm Hg (p < 0.001) in the olmesartan and losartan groups, respectively. After 4 weeks of treatment, the reduction in BP values was larger in the olmesartan group than in the losartan group (decreases in DBP of 12.1 +/- 8.4mm Hg vs 7.2 +/- 6.8mm Hg [p < 0.005] and in SBP of 15.1 +/- 13.0mm Hg vs 10.3 +/- 10.1mm Hg [p < 0.05] for the olmesartan and losartan groups, respectively). Patients treated with either drug experienced only mild adverse reactions, such as dizziness, cough, headache and neck pain, all of which occurred at low frequencies. There were no significant changes in laboratory parameters. CONCLUSION: Both olmesartan and losartan are effective and safe in the treatment of Chinese patients with mild-to-moderate essential hypertension. Olmesartan 20mg once daily is more potent and has a more rapid antihypertensive effect than losartan 50mg once daily in the treatment of mild-to-moderate hypertension in Chinese patients.
RESUMO
AIMS: This study aimed to assess whether enalapril could improve cardioversion outcome and facilitate sinus rhythm maintenance after conversion of chronic atrial fibrillation (AF). METHODS AND RESULTS: Patients with chronic AF for more than 3 months were assigned to receive either amiodarone (200mg orally 3 times a day; group I: n=75) or the same dosage of amiodarone plus enalapril (10mg twice a day; group II: n=70) 4 weeks before scheduled external cardioversion. The end-point was the time to first recurrence of AF. In 125 patients (86.2%), AF was converted to sinus rhythm. Group II had a trend to a trend to a lower rate of immediate recurrence of AF than group I did (4.3% vs 14.7%, P=0.067). Kaplan-Meier analysis demonstrated a higher probability of group II remaining in sinus rhythm at 4 weeks (84.3% vs 61.3%, P=0.002) and at the median follow-up period of 270 days (74.3% vs 57.3%, P=0.021) than in group II. CONCLUSIONS: The addition of enalapril to amiodarone decreased the rate of immediate and subacute arrhythmia recurrences and facilitated subsequent long-term maintenance of sinus rhythm after cardioversion of persistent AF.