RESUMEN
The skeletal muscle plays an important role in maintaining body temperature, which is mediated by thermogenesis and glucose or lipid metabolism. Mangalica is a native Hungarian pig that has cold tolerance and can live in grazing environments throughout the year. We evaluated the morphological and genetic aspects of Mangalica using muscle tissues to elucidate the mechanisms underlying the tolerance to seasonal effects in grazing environments. The muscle tissues in each season were analysed using morphological evaluation and electron microscopy. The cross-sectional area of skeletal muscle cells in summer was significantly larger than that in winter. The thickness of myofibrils in summer was significantly higher than in winter. The thickness of the Z-line in winter was significantly higher than in summer. The expression of MYH4 and GLUT4 was significantly lower in winter than in summer. The result of ATPase staining indicated significantly increase the muscle fibre ratio of type 1 in winter than that in summer. These findings indicate that the muscle fibre in Mangalica shifts from fast-twitch to slow-twitch fibre, and the metabolic physiology of the muscle was adapted to the cold environment. This study demonstrates that Mangalica gained tolerance to both seasonal heat and cold stresses that are caused by significant changes in ambient temperature in a year because of changes in their muscle fibre type and metabolic function. This study may contribute to elucidating the mechanism of thermogenetic adaptation in cold and heat environments among mammals.
Asunto(s)
Frío , Músculo Esquelético , Animales , Porcinos , Estaciones del Año , MamíferosRESUMEN
Subclinical Cushing's syndrome (SCS), a subtle cortisol hypersecretion from an adrenal tumor, may be a common adrenal disease. However, the cardiovascular prognosis and the optimal surgical and conservative treatment in SCS remain elusive. The present study was undertaken to evaluate the prevalence of cardiovascular risk factors in 16 SCS cases, their relationships to cortisol secretory activities, and the clinical outcome after surgical and medical treatment. The prevalence of hypertension, impaired glucose tolerance (IGT), diabetes mellitus (DM), dyslipidemia and obesity in our SCS cases were 56%, 50%, 50%, and 19%, respectively, and 75% of cases were associated with two or more cardiovascular risk factors. In our series, 24-h urinary free-cortisol excretion showed a significant positive correlation with HbA1c and a negative correlation with high-density lipoprotein-cholesterol, but no correlation with age, body mass index, blood pressure or glycemic and lipid profile was found. Eight cases underwent unilateral adrenalectomy (operated (OP) group); the remaining eight cases were a conservative-treatment group (non-OP group). The number of cardiovascular risk factors decreased significantly in the OP group, but not in the non-OP group. In terms of differential changes in risk factors between the groups, more significant improvements of hypertension, dyslipidemia and IGT/DM were observed in the OP group than in the non-OP group. In conclusion, the present study showed the increased prevalence of cardiovascular risk factors in SCS patients with mild hypercortisolism related to impaired glucose/lipid metabolism. Adrenalectomy decreased accumulated cardiovascular risk factors in certain SCS patients, suggesting the possible involvement of mild hypercortisolism in the development of cardiovascular risk factors in SCS.
Asunto(s)
Adrenalectomía/estadística & datos numéricos , Síndrome de Cushing/epidemiología , Hipertensión/epidemiología , Adulto , Anciano , Síndrome de Cushing/cirugía , Síndrome de Cushing/terapia , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Estudios de Seguimiento , Intolerancia a la Glucosa/epidemiología , Humanos , Hidrocortisona/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Salusins, which are derived from the prosalusin precursor molecule, regulate hemodynamics, mitogenesis and atherogenesis. The preprosalusin gene is ubiquitously expressed, while the salusin-beta peptide is present in systemic endocrine cells and the neuroendocrine system. However, the regulatory mechanisms for the preprosalusin gene and prosalusin expression remain to be investigated. Real-time quantitative RT-PCR and salusin-alpha radioimmunoassay revealed that the neuroblastoma cell line, SK-N-SH, exhibited marked upregulation of preprosalusin mRNA and salusin-alpha-like immunoreactivity (LI) when incubated under 2% serum condition. However, SK-N-SH cells released a limited amount of salusin-alpha-LI into the culture supernatant. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay after extraction of proteins from the conditioned media using an octyl-silica column did not reveal a component that co-eluted with authentic salusin-alpha. Western blotting of the nuclear extracts from SK-N-SH showed the expression of prosalusin and its cleaved fragments, but not authentic salusin-alpha. Addition of Jak-2 inhibitors to growing SK-N-SH cells cultured under 10% serum condition resulted in increased salusin-alpha-LI expression. Suppression of Jak-2 mRNA using siRNAs upregulated intracellular salusin-alpha-LI, as detected by immunofluorescence. In summary, the preprosalusin gene and prosalusin protein are expressed in a neuroblastoma cell line and upregulated by reduced serum. The Jak-2 pathway may be involved in the regulation of salusin expression.
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Regulación de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neuroblastoma/metabolismo , Precursores de Proteínas/metabolismo , Western Blotting , Línea Celular , Cromatografía Líquida de Alta Presión , Medios de Cultivo , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Precursores de Proteínas/genética , RadioinmunoensayoRESUMEN
Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age- and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, low-density lipoprotein cholesterol (LDL-C), hemoglobin HA(1C), fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.
Asunto(s)
Acromegalia/fisiopatología , Acromegalia/cirugía , Endotelio Vascular/fisiopatología , Adulto , Velocidad del Flujo Sanguíneo , Arteria Braquial , Arterias Carótidas/patología , LDL-Colesterol/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Frecuencia Cardíaca , Hormona de Crecimiento Humana/sangre , Humanos , Resistencia a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Análisis de Regresión , Túnica Íntima/patología , VasodilataciónRESUMEN
AIM: Endothelial dysfunction is considered an early event in the development of atherosclerosis. The present study was undertaken to determine whether the accumulation of cardiovascular risk factors and insulin resistance are associated with endothelial function in diabetic patients. METHODS: 101 patients with type 2 diabetes without macroangiopathy stratified by the number of cardiovascular risk factors (dyslipidemia, hypertension, obesity) and 9 normal control subjects were studied for vascular endothelial functions by measuring flow-mediated vasodilation (FMD) using a high-resolution ultrasound method, brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (IMT), and the ankle-brachial index (ABI). RESULTS: FMD negatively correlated with baPWV and carotid IMT, and positively correlated with ABI. FMD was significantly lower in diabetic patients associated with 3 other risk factors than in those with diabetes alone. In subjects with fasting plasma glucose < or = 140mg/dL, FMD showed significant negative correlations with fasting insulin levels and homeostasis model assessment (HOMA)-R. Multivariate analysis revealed that insulin resistance as represented by HOMA-R and systolic blood pressure showed a significant association with impaired FMD. CONCLUSION: The present results suggest that the accumulation of cardiovascular risk factors is associated with endothelial dysfunction in diabetic patients, and that insulin resistance as well as high blood pressure could play a pathogenic role in the development of endothelial dysfunction.
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Diabetes Mellitus Tipo 2/patología , Endotelio Vascular/fisiopatología , Resistencia a la Insulina , Adulto , Anciano , Enfermedades Cardiovasculares , Estudios de Casos y Controles , Femenino , Homeostasis , Humanos , Hipertensión , Masculino , Persona de Mediana Edad , Factores de Riesgo , VasodilataciónRESUMEN
PURPOSE: To report the association of HLA antigens with keratoconus in Japanese patients. DESIGN: Observational consecutive case series. METHODS: In 90 consecutive Japanese keratoconus patients, HLA class I (HLA-A, -B, -C) and class II (HLA-DR, -DQ) were analyzed. RESULTS: Compared with control frequencies, based on mean gene frequencies for the Japanese population, higher frequencies of HLA-A26, B40, and DR9 antigens were found in patients whose conditions were diagnosed before 20 years of age (chi(2) = 6.45, P =.01; chi(2) = 6.78, P =.01; chi(2) =3.99, P =.05, respectively), but were not found in patients whose conditions were diagnosed later in life. Men were significantly younger at diagnosis than were women. No obvious relation was found between HLA antigens and other clinical data. CONCLUSION: HLA-A26, B40, and DR9, which were found relatively frequently in the ancient Japanese population, seem to be associated with keratoconus in younger individuals.