RESUMEN
Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28-0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.
Asunto(s)
Cardiomiopatías/tratamiento farmacológico , Infecciones por Enterovirus/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Selenio/administración & dosificación , Adulto , Cardiomiopatías/fisiopatología , Enfermedad Crónica , Suplementos Dietéticos , Electrocardiografía/métodos , Infecciones por Enterovirus/fisiopatología , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVE: To observe ten-year prognosis of patients with latent Keshan disease (KD) and to determine its associated risk factors. METHODS: A total of 448 patients with newly diagnosed latent KD were monitored and followed up for 10 years. Their ECG abnormalities were classified as major or minor using the Minnesota Code. COX proportional hazards regression models were established to identify risk factors associated with the development of chronic KD. RESULTS: A final sample of 414 cases was included in analyses, with an average of (112.9 ± 17.5) months of follow-up. At the end of follow-up, 92 (22. 2%) patients developed chronic KD. Older age (> 15 years), male, family history of KD, smoking, lower level of blood selenium (< 60 µg/L), major ECG abnormalities, and 18.5 kg/m² ≤ body mass index (BMI) 23.9 kg/m² were associated with higher cumulative incidence of chronic KD. The COX regression models showed that major ECG abnormalities, BMI, selenium deficiency, hypertension, and ventricular premature complex (VPC) abnormalities contributed to increased risk of chronic KD. A positive linear correlation (r = 0.719, P < 0.01) between GPx activity and blood selenium concentration was found. CONCLUSION: Major ECG abnormalities, BMI, selenium deficiency, hypertension and VPC abnormalities are associated with the development of chronic KD.
Asunto(s)
Cardiomiopatías/diagnóstico , Infecciones por Enterovirus/diagnóstico , Índice de Masa Corporal , Enfermedad Crónica , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión , Incidencia , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Selenio/deficienciaRESUMEN
Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.
Asunto(s)
Cardiomiopatías/genética , Infecciones por Enterovirus/genética , Genes Mitocondriales , Factores de Transcripción/genética , Transcripción Genética , Adulto , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Factores de Transcripción/metabolismo , Regulación hacia ArribaRESUMEN
The objective of this study is to investigate the relationship between single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor-α (TNF-α) and Fas genes and Kashin-Beck disease (KBD) in Shaanxi province, Northwest in China. Blood samples of 388 residents were collected from 14 KBD villages in Linyou and Yongshou counties, Shaanxi, Northern of China. One hundred eighty-six cases with KBD and 202 cases of health in KBD areas were diagnosed by "Diagnosis Criterion of Kashin-Beck disease in China (WS/T207- 2010)". The TNF-α -308G/A, TNF-α -238G/A, and Fas -670A/G SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in combination with sequence analysis in KBD and healthy control groups. The genotypes and allele frequencies distribution of these SNPs were then analyzed. TNF-α -308A allele frequency in KBD patients were significantly higher than that in healthy controls. Although TNF-α -238 genotypes and allele frequencies were not significantly different between KBD patients and the healthy controls, GA genotype and A allele frequency in KBD patients were higher than those in healthy controls. The TNF-α -308G/A SNPs were associated with the susceptibility of KBD.
Asunto(s)
Enfermedad de Kashin-Beck/genética , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/genética , Receptor fas/genética , Adolescente , Adulto , Anciano , Alelos , Pueblo Asiatico/genética , Niño , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: To investigate the effect of a traditional Chinese medicine compound (CTMC) on chronic heart failure (CHF) in guinea-pigs. METHODS: The CHF of guinea-pigs were induced by repeated injection of hyodemic isoproterenol. The hemodynamics, organ (heart, lung, liver and kidney)/body weight ratio, pathological changes, and serum cTn-I and CK-MB were measured to determine the effectiveness of the traditional Chinese medicine treatement. RESULTS: The LVDP and LVEDP were decreased and the absolute value of + dp/dt(max) and - dp/ dt(max) were increased by the administration of 10 mg/kg, 20 mg/kg and 30 mg/kg of the compound tablets. The effect increased with doses. The traditional Chinese medicine also decreased the area of myocardial necrosis and the degree of injury to myocardiacyte. The intervention group had lower serum cTn-I and CK-MB levels than the controls. CONCLUSION: The compound tablets can improve the left ventricular diastolic function of CHF and reduce the myocardial damage in a dose-dependent manner.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Fitoterapia , Función Ventricular Izquierda/efectos de los fármacos , Animales , Cardiotónicos/uso terapéutico , Enfermedad Crónica , Femenino , Cobayas , Insuficiencia Cardíaca/fisiopatología , Masculino , Distribución AleatoriaRESUMEN
The purpose of the current study was to investigate the changes of serum proteome and discover potential biomarkers for Kashin-Beck disease (KBD) using surface-enhanced laser desorption ionization mass spectrometry (SELDI-TOF MS). The serum protein profiles from 102 cases (36 KBD patients, 16 controls in KBD areas, 33 controls in non-KBD areas, and 17 osteoarthritis controls) were detected by SELDI-TOF MS and weak cation-exchange protein chip. Differently expressed peaks in KBD were identified by comparing the data among the four groups using the nonparametric Mann-Whitney test with Bonferroni correction at a significance level of 0.05. Then, those 102 cases were used to generate a classification tree as the training set, and an additional 34 cases were collected as the test set. A classification tree was generated by Biomarker Patterns Software (Ciphergen). Multiple protein changes were detected in the KBD group, including three potential biomarkers (15 886, 5336, 6113 m/z). A classification tree with three distinct proteins was generated. The classification tree was able to distinguish the KBD patients from the controls with 88.89% specificity and 86.36% sensitivity. The study demonstrates that marked serum proteomic changes exist in KBD. The proteins represented by the differently expressed peaks are candidate biomarkers for KBD.