RESUMEN
The purpose of the present study was to evaluate the impact of a lifestyle intervention programme, combined with a daily low-glycaemic index meal replacement, on body-weight and glycaemic control in subjects with impaired glucose regulation (IGR). Subjects with IGR were randomly assigned to an intervention group (n 46) and a control group (n 42). Both groups received health counselling at baseline. The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study, and follow-up visits performed monthly until the end of the 1-year study. Outcome measurements included changes in plasma glucose, glycated Hb (HbA1c), plasma lipids, body weight, blood pressure and body composition (such as body fat mass and visceral fat area). The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group (-1·8 (SEM 0·35) v. -0·6 (SEM 0·40) 2·5 kg, P<0·05). The 2 h plasma glucose concentration decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group (P<0·05) compared with their baseline, respectively. A 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose (P<0·01). The incidence of normal glucose regulation (NGR) in the two groups was significantly different (P=0·001). In conclusion, the combination of regular contact, lifestyle advice and meal replacement is beneficial in promoting IGR to NGR.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Dieta para Diabéticos , Dieta Reductora , Trastornos del Metabolismo de la Glucosa/terapia , Estilo de Vida , Obesidad/terapia , Anciano , Bebidas , Índice de Masa Corporal , Desayuno , China , Terapia Combinada , Diabetes Mellitus Tipo 2/etiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Trastornos del Metabolismo de la Glucosa/complicaciones , Trastornos del Metabolismo de la Glucosa/dietoterapia , Trastornos del Metabolismo de la Glucosa/fisiopatología , Índice Glucémico , Promoción de la Salud , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Obesidad/fisiopatología , Educación del Paciente como Asunto , Pérdida de PesoRESUMEN
BACKGROUND: Accumulating evidence implicates leukocyte telomere length (LTL) shortening as a potential risk predictor for cardiovascular disease. Arterial stiffness chronicles the cumulative burden of cardiovascular disease risk factors. Therefore, the capacity of LTL to predict arterial stiffness was examined. METHODS: A total of 275 unrelated Chinese males: 163 patients with coronary artery disease (CAD) and 112 healthy controls, 40-73 years of age were included in this study. The relative telomere length of leukocytes was determined by a real-time fluorescence quantitative polymerase chain reaction (PCR). Large artery stiffness was measured with carotid-femoral pulse wave velocity (PWV). RESULTS: The relative telomere length (T/S) ratio was significantly shorter in patients with CAD (0.79 +/- 0.26) than in control subjects (1.08 +/- 0.22) (p<0.001). The correlation between LTL and PWV in patients with CAD was stronger than that in the controls (r= -0.467, r(2)=0.227, p<0.001 for patients with CAD versus r= -0.223; r(2)=0.050; p=0.018 for controls). The log(e)-transformed T/S ratio was inversely correlated with age (r= -0.345; p<0.001), PWV (r= -0.326; p<0.001) and C-reactive protein ( r= -0.133; p=0.027). CONCLUSIONS: The data show an association of leukocyte telomere length shortening with increased arterial stiffness and cardiovascular burden, suggesting that telomere length is a biomarker of large artery elasticity and CAD. Further studies are warranted to study the role of LTL dynamics in the pathogenesis of atherosclerosis.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Vasos Coronarios/patología , Telómero/genética , Adulto , Anciano , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/diagnóstico por imagen , Elasticidad , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Valores de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , UltrasonografíaRESUMEN
Alzheimer's disease (AD) is an age-related neurodegenerative disease and characterized by dementia, memory decline, loss of learning and cognitive disorder. The main pathological features of AD are the deposition of amyloid plaques and the formation of neurofibrillary tangles (NFTs) in the brain. The current anti-AD drugs have shown unsatisfactory therapeutic results. Due to the complications and unclear pathogenesis, AD is still irreversible and incurable. Among several hypotheses proposed by the academic community, the amyloid cascade is widely recognized by scholars and supported by a large amount of evidences. However, controversy over pathogenic factors has also been ongoing. Increasing evidence has shown that amyloid-ß (Aß) and especially amyloid-ß oligomers (AßOs) are highly neurotoxic and pathogenic agents that damage neurons, mediate various receptors in the downstream pathways, and ultimately lead to learning and cognitive dysfunction. However, efforts in developing inhibitors of Aß or amyloid-ß precursor protein (APP) have all failed to yield good clinical results. More recently, it has been demonstrated that sigma receptors, including sigma-1 and sigma-2 subtypes, may play critical roles in the regulation of binding and metabolism of AßOs in neuron cells and the pathophysiology of AD. Thus, sigma receptor ligands are being recognized as promising therapeutic agents for treating or ameliorating AD. This article will review the pathophysiology of AD and highlight the sigma ligands that display the capability of preventing or even reversing Aß- and AßOs-induced neurotoxicity and blocking the signal transduction caused by AßOs.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Neuronas/metabolismo , Receptores sigma/agonistas , Receptores sigma/metabolismo , Enfermedad de Alzheimer/fisiopatología , Animales , Humanos , Ligandos , Enfermedades Neuroinflamatorias/metabolismo , Presenilinas/metabolismo , Proteínas tau/metabolismo , Receptor Sigma-1RESUMEN
Sigma-2 receptor plays key roles in promoting tumor cell apoptosis, enhancing efficacy of anti-tumor drugs, blocking signal transduction controlled by Aß oligomers, regulating Ca2+ homeostasis and protecting nerve cells. Studies indicated that sigma-2 receptor may be closely coupled with ROS, LDL, mTOR, RAS, PLC/PKC, lysosomal autophagy and mitochondrial super oxidative stress. In addition, the high expression of this receptor in proliferating cells and nerve cells indicates that sigma-2 receptor is an ideal molecular target for imaging and therapeutic development for cancer, Alzheimer's disease, schizophrenia and traumatic brain injury. Various sigma-2 agonists have shown promising anticancer activities, while sigma-2 antagonists have displayed neuroprotection and inhibition of Aß oligomers in the brain of Alzheimer's disease patients. Thus, both sigma-2 agonists and antagonists are potentially useful therapeutics for the management of cancer and neurodegenerative disorders.
Asunto(s)
Enfermedad de Alzheimer , Preparaciones Farmacéuticas , Receptores sigma , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides , Encéfalo/metabolismo , Humanos , Receptores sigma/metabolismoRESUMEN
Sigma-2 receptor (σ2R/TMEM97) has been implicated to play important roles in multiple cellular dysfunctions, such as cell neoplastic proliferation, neuro-inflammation, neurodegeneration, etc. Selective σ2 ligands are believed to be promising pharmacological tools to regulate or diagnose various disorders. As an ongoing effort of discovery of new and selective σ2 ligands, we have synthesized a series of tetrahydroisoquinolino-2-alkyl phenone analogs and identified that 10 of them have moderate to potent affinity and selectivity for σ2R/TMEM97. Especially, 4 analogs showed Ki values ranging from 0.38 to 5.1 nM for σ2R/TMEM97 with no or low affinity for sigma-1 receptor (σ1R). Functional assays indicated that these 4 most potent analogs had no effects on intracellular calcium concentration and were classified as putative σ2R/TMEM97 antagonists according to current understanding. The σ2R/TMEM97 has been suggested to play important roles in the central nervous system. Based on published pharmacological and clinical results from several regarded σ2R/TMEM97 antagonists, these analogs may potentially be useful for the treatment of various neurodegenerative diseases.
Asunto(s)
Proteínas de la Membrana/antagonistas & inhibidores , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/química , Receptores sigma/antagonistas & inhibidores , Tetrahidroisoquinolinas/química , Calcio/metabolismo , Evaluación Preclínica de Medicamentos , Humanos , Ligandos , Células MCF-7 , Fármacos Neuroprotectores/farmacología , Relación Estructura-Actividad , Tetrahidroisoquinolinas/farmacología , Receptor Sigma-1RESUMEN
Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardiomyocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP +45 polymorphism of the adiponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The genotypes of adiponectin gene polymorphisms were detected by the polymerase chain reaction (PCR) method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects. The integrated backscatter score (IBS) was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group ((2.69±1.0) µg/ml vs. (4.21±2.89) µg/ml, respectively, P<0.001). The serum levels of type-I procollagen carboxyl end peptide (PICP) and type-III procollagen ammonia cardinal extremity peptide (PIIINP) in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium (r=0.46 and 0.61, respectively, P<0.05 for both). The serum levels of PICP and PIIINP were significantly different among the three genotypes of SNP +45 (P<0.01). Logistic regression analyses showed that sex and genotype (GG+GT) were the major risk factors of myocardial fibrosis in hypertensive patients (OR=5.343 and 3.278, respectively, P<0.05). These data suggest that lower levels of adiponectin and SNP +45 polymorphism of the adiponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.