RESUMEN
BACKGROUND AND AIM: Oxidative stress is associated with insulin resistance pathogenesis, insulin secretion deficiency, and complication onset. Fermented papaya preparation (FPP), a dietary supplement obtained by fermentation of the papaya fruit, may be used as an antioxidant in the prevention of diabetic complications. METHODS AND RESULTS: Platelets from 30 patients with type 2 diabetes mellitus (DM 2) and 15 healthy subjects were analyzed to evaluate the in vitro effects of FPP incubation. Na(+)/K(+)-adenosine triphosphatase (ATPase) activity, membrane fluidity, total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, and conjugated diene levels were determined. In vitro FPP incubation improved platelet function, by enhancing Na(+)/K(+)-ATPase activity and membrane fluidity, and ameliorated the antioxidant system functionality, through an increase in TAC and SOD activity and a parallel decrease in conjugated diene levels in patients with DM 2. CONCLUSION: Our data suggest that the incubation with FPP may have a protective effect on platelets from patients with DM 2, by preventing the progression of oxidative damage associated with diabetes and its complications.
Asunto(s)
Plaquetas/metabolismo , Carica , Diabetes Mellitus Tipo 2/sangre , Fermentación , Preparaciones de Plantas/farmacología , Antioxidantes/farmacología , Estudios de Casos y Controles , Femenino , Manipulación de Alimentos , Voluntarios Sanos , Humanos , Insulina/sangre , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Masculino , Persona de Mediana Edad , Estrés Oxidativo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
To evaluate the in vitro effects of resveratrol (RSV) incubation on platelets from compensated and decompensated diabetic patients in order to use it as an adjuvant therapy. The study was performed on 77 diabetic patients and divided into two phases: 29 compensated and 48 decompensated diabetic platelets were analyzed at recruitment (T0) and after in vitro RSV incubation (20 µg/ml) for 3 h at 37 °C (T1). Lipoperoxide and nitric oxide (NO) levels, superoxide dismutase (SOD) and Na(+)/K(+) ATPase activities, total antioxidant capacity (TAC), and membrane fluidity tested by anisotropy of fluorescent probes TMA-DPH and DPH were determined. In vitro RSV incubation counteracts oxidative damage associated with diabetes and its complications; it is able to improve platelet function through augmented membrane fluidity and Na(+)/K(+) ATPase activity; it enhances antioxidant systems' functionality by increasing NO levels, SOD activity, and TAC and by decreasing lipoperoxide levels in both compensated and decompensated patients. Such platelet functionality enhancement suggests a new method of secondary prevention of complications associated with platelet dysfunction. Being free from one of the major risks associated with many antidiabetic agents, it can be assumed that RSV utilization in the diabetic diet may have a preventive and protective role in the progression of diabetic oxidative damage.
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Antioxidantes/farmacología , Plaquetas/efectos de los fármacos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Estrés Oxidativo/efectos de los fármacos , Estilbenos/farmacología , Adulto , Anciano , Plaquetas/metabolismo , Células Cultivadas , Femenino , Humanos , Masculino , Fluidez de la Membrana/efectos de los fármacos , Persona de Mediana Edad , ResveratrolRESUMEN
BACKGROUND AND AIM: We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study. METHODS AND RESULTS: All subjects underwent a 75-g oral glucose tolerance test (OGTT) for the estimation of plasma levels of glucose and C-peptide, as well as fasting insulin and lipid profile. IR was arbitrarily defined as HOMA-IR value above the 75th centile of normal glucose tolerance (NGT) subjects. Overall MS prevalence (National Cholesterol Treatment Panel-Adult Treatment Panel (NCEP-ATPIII) criteria) was 33%, 19% in subjects with NGT, 42% in impaired fasting glucose (IFG), 34% in impaired glucose tolerance (IGT), 74% in IFG+IGT subjects, and 56% in newly diagnosed diabetic patients. Prevalence was slightly higher with IDF criteria. MS prevalence was >50% in subjects with 2h glucose >7.8mmoll(-1), independently of fasting plasma glucose. IR prevalence was higher in subjects with MS than in those without (63% vs. 23%; p<0.0001) and increased from 54% to 73% and 88% in the presence of three, four or five traits, respectively. IR occurred in 42% of subjects with non-diabetic alterations of glucose homeostasis, being the highest in those with IFG+IGT (IFG+IGT 53%, IFG 45%, IGT 38%; p<0.0001). Individuals with MS were more IR irrespective of glucose tolerance (p<0.0001) with no difference in insulinogenic index. Hypertriglyceridaemia (OR: 3.38; Confidence Interval, CI: 2.294.99), abdominal obesity (3.26; CI: 2.18-4.89), hyperglycaemia (3.02; CI: 1.80-5.07) and hypertension (1.69; CI: 1.12-2.55) were all associated with IR. CONCLUSIONS: These results show that in subjects with altered glucose tolerance (in particular IFG+IGT) MS prevalence is high and is generally associated to IR. Some combinations of traits of MS may significantly contribute to identify subjects with IR.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Síndrome Metabólico/fisiopatología , Adulto , Glucemia/análisis , Péptido C/metabolismo , Femenino , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Hiperglucemia/fisiopatología , Hipertensión/fisiopatología , Resistencia a la Insulina , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estado Prediabético , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: Although many studies have appeared about diabetes mellitus-associated periodontitis, few have compared periodontitis inflammatory markers between type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and information regarding this issue is scarce and contradictory. We evaluated the levels of plasma C-reactive protein and of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in gingival crevicular fluid in two groups of subjects affected by T1DM and T2DM, in order to identify possible differences between the two classes in the inflammatory mechanisms of diabetes mellitus-associated periodontitis. MATERIAL AND METHODS: Plasma C-reactive protein and gingival crevicular fluid IL-1ß, IL-6 and TNF-α were measured in periodontitis patients affected by type 1 (P-T1DM, n = 24) and type 2 diabetes mellitus (P-T2DM, n = 24). RESULTS: Gingival crevicular fluid levels of IL-1ß and TNF-α in P-T1DM subjects were significantly higher than in P-T2DM subjects. In P-T1DM subjects, we found significant negative correlations between the duration of diabetes mellitus and IL-1ß and between the duration of diabetes mellitus and TNF-α. CONCLUSION: This study shows that IL-1ß and TNF-α levels in periodontitis patients with T1DM are affected by the duration of diabetes mellitus.
Asunto(s)
Periodontitis Crónica/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Mediadores de Inflamación/análisis , Adulto , Anciano , Pérdida de Hueso Alveolar/clasificación , Antihipertensivos/uso terapéutico , Proteína C-Reactiva/análisis , Periodontitis Crónica/clasificación , Índice de Placa Dental , Líquido del Surco Gingival/química , Hemorragia Gingival/clasificación , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Interleucina-1beta/análisis , Interleucina-6/análisis , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/clasificación , Índice Periodontal , Bolsa Periodontal/clasificación , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Obesity is increasing in middle-aged adults and the elderly. This multifactorial phenomenon may have different causes, such as incorrect nutritional and dietary habits, psycho-social aspects and sedentary life-style. It is becoming a serious problem, due also to the world's ageing society. The aim of this study is to provide preliminary results on BMI, life-style and psycho-social aspects in a sample of Italian subjects, which also assesses the relationship between obesity and psychological health. We hypothesize that obesity is related to many factors, such as life-style, behavioral, socio-economic, and psychological aspects. The sample was made up of 107 obese and non-obese subjects, aged 50-74. All participants were given a multidimensional assessment, which included anthropometric, psycho-social and life-style evaluation. As per the protocol a structured life-style questionnaire designed to gather information on anthropometric measurements, socio-economic factors, physical activity, smoking, alcohol and food intake. The Symptom Checklist-90 (SCL-90) for the evaluation of a broad range of psychological problems and symptoms of psychopathology; the Binge Eating Scale (BES) for the assessment of disorders in the eating habits were administered. BMI was associated with age and education, socio-economic status and smoking in both genders. Psychological factors for obesity differed between overweight men and women. In conclusion, obesity and non-obesity appear as two different entities in some aspects. The increase in the prevalence of obesity in elderly subjects could lead to disability and age-related diseases. For this reason, greater insight of the factors related to the development of obesity is required to develop treatment strategies weight-loss prevention programs.
Asunto(s)
Índice de Masa Corporal , Ingestión de Energía/fisiología , Conductas Relacionadas con la Salud , Estilo de Vida , Evaluación Nutricional , Obesidad/psicología , Factores de Edad , Anciano , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Obesidad/prevención & control , Prevalencia , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
The polycystic ovary syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, has many features of metabolic syndrome and can be considered a metabolic disease. Approximately 50% of patients with PCOS are overweight or obese with abdominal fat accumulation. Some metabolic alterations and abdominal fat distribution have also been reported in lean women with PCOS. The aim of this study was to evaluate the effect, if any, of obesity on metabolic features, body composition and fat distribution in patients with PCOS. Body composition and abdominal fat distribution (evaluated by DEXA), waist circumference, blood pressure, lipid profile, glucose tolerance and homeostasis model assessment index were determined in 23 lean [mean age 23 +/- 5 yr, mean body mass index (BMI) 22 +/- 2 kg/m2] and 27 overweight-obese (mean age 21 +/- 5 yr, mean BMI 32 +/- 5 kg/m2) patients with PCOS and in 20 age- and weight-matched eumenorrhoic women. Patients exhibited slight but non-significant differences in metabolic parameters, waist circumference, blood pressure and total and abdominal fat content compared with weight-matched controls. None of the lean subjects suffered from metabolic syndrome according to the National Cholesterol Education Program--Adult Treatment Panel III (NCEP-ATPIII) criteria as opposed to 10 overweight-obese patients and three overweight-obese control subjects (37% and 33.3% of each subgroup, respectively). Our data do not show significant metabolic alterations in lean PCOS women. Results indicate that obesity seems to underpin the metabolic alterations exhibited by the overweight-obese patients. However, since women with PCOS are at increased cardiovascular risk, further studies are needed to evaluate metabolic alterations and body composition in these patients.
Asunto(s)
Composición Corporal/fisiología , Obesidad/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Tejido Adiposo/metabolismo , Adulto , Androstenodiona/sangre , Glucemia/metabolismo , Presión Sanguínea/fisiología , Colesterol/sangre , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Humanos , Insulina/sangre , Obesidad/sangre , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Testosterona/sangre , Triglicéridos/sangreRESUMEN
The renin-angiotensin-aldosterone system (RAAS) plays a well-recognized role in the regulation of BP and in salt and water balance. Since hypertension affects a considerable proportion of obese patients, circulating RAAS has been studied in obese subjects with and without hypertension, albeit with conflicting results. Furthermore, attention has recently focused on the expression of the components of the Renin-angiotensin system (RAS) in some organs, including adipose tissue where it seems to be involved in the regulation of growth and differentiation. The aim of our study was to investigate circulating RAAS and adipose tissue RAS in obese patients with and without hypertension and in matched controls. PRA, and plasma and urinary aldosterone levels were measured in 35 obese, 30 hypertensive obese patients and in 20 controls. In addition, the expression of angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1) genes was studied in sc adipose tissue from 8 obese, 6 hypertensive obese and 6 healthy subjects. As previously demonstrated in other studies, there were no significant differences in the levels of circulating RAAS components in the 3 groups. As regards local RAS, interestingly, we found that AT1 gene was significantly more expressed in sc adipose tissue from obese patients with hypertension than in those without hypertension and controls. By contrast, AGT levels were similar in the 3 groups. Our data do not support the hypothesis of an involvement of circulating RAAS in the development of obesity-related hypertension. On the other hand, local RAS seems to be differently regulated in sc adipose tissue from obese patients with hypertension with respect to normotensive obese patients and controls.
Asunto(s)
Tejido Adiposo/metabolismo , Hipertensión/complicaciones , Hipertensión/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Sistema Renina-Angiotensina/fisiología , Adulto , Aldosterona/metabolismo , Angiotensinógeno/genética , Sangre/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Receptor de Angiotensina Tipo 1 , Receptores de Angiotensina/genética , Valores de Referencia , Renina/sangreRESUMEN
The aim of this study was to evaluate body composition and metabolic features in women with nonhypersecretory adrenal cortical incidentaloma (AI) and women with Cushing's syndrome (CS) compared with healthy control (C) women matched for age, menopausal status, and body mass index. We examined 15 females with CS, 22 with AI, and 20 C. We evaluated anthropometric, hormonal, and metabolic parameters in all subjects. Body composition was measured by dual-energy x-ray absorptiometry for total body (TB); in addition, abdominal fat was measured between L2 and L4 vertebrae. Women with CS and AI were overweight; waist to hip ratio mean values showed that women with CS and AI had a central fat distribution. TB fat was significantly higher in CS than in C women, however, AI women also had high fat values. Abdominal fat was significantly more increased in CS than in AI and C women. Eighty percent of CS women and 50% of AI women were hypertensive. High density lipoprotein cholesterol levels were lower and triglyceride levels were higher in CS and AI women than in C. The area under the curve for glucose after oral glucose tolerance test was significantly higher in CS and AI than in C. AI had urinary free cortisol values slightly higher than C and than the normal range. In conclusion, these data indicate that AI are at an intermediate state between normal and pathological. These alterations suggest that a subtle cortisol hypersecretion is probably present in AI and it may be the factor promoting alterations of body composition and metabolic parameters.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/metabolismo , Composición Corporal/fisiología , Síndrome de Cushing/metabolismo , Absorciometría de Fotón , Tejido Adiposo/metabolismo , Adulto , Envejecimiento/metabolismo , Presión Sanguínea/fisiología , Índice de Masa Corporal , Glándulas Endocrinas/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Metabolismo de los Lípidos , Menopausia/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Ácido Úrico/metabolismoRESUMEN
Decreased levels of nitric oxide (NO) may contribute to impaired endothelium-dependent vasodilatation in essential hypertension. Moreover, in hypertension, major platelets aggregation and endothelial adhesion, and increased atherogenetic risks are also present. Nitric oxide produced by platelet NO synthase, which is similar to endothelial NO synthase, inhibits platelets aggregation by increasing cytoplasmic cyclic GMP levels and contributes in a major way to the antithrombogenic properties of endothelium. The aim of this study was to investigate platelet NO production and cytosolic Ca2+ levels in patients with essential hypertension and in healthy subjects. We studied NO production in 36 subjects (21 patients had essential hypertension and 15 subjects were normotensive); NO synthase activity was evaluated by measuring nitrite levels by the Griess reaction in the supernatant of sonicated platelets. Cytosolic Ca2+ levels were measured in intact platelets using the fluorescent probe Fura 2-AM. Nitric oxide levels in platelets were found higher in normotensive than in hypertensive patients (P < .0001). Nitric oxide levels in hypertensive women were significantly higher than in hypertensive men (P < .001). Hypertensive women and men had lower levels of nitrite than normotensive women and men (P < .001 and P < .002, respectively). Platelet cytosolic Ca2+ levels were higher in hypertensive patients than in normotensive subjects (P < .001). An inverse correlation was found between platelet cytosolic Ca2+ and NO levels (r = 0.74, P < .002). These data confirm the link between hypertension and altered platelets function and suggest a role for NO in cardiovascular events. Moreover, the higher levels of nitric oxide in child-bearing age women than in men further support the protective effect of estrogens on cardiovascular diseases.
Asunto(s)
Plaquetas/metabolismo , Calcio/sangre , Hipertensión/sangre , Óxido Nítrico/sangre , Adulto , Citosol/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/sangre , Nitritos/sangre , Concentración Osmolar , Valores de Referencia , Caracteres SexualesRESUMEN
Recent clinical and experimental data have radically modified the concept of adipose tissue as one solely devoted to energy storage and release. Adipose tissue is a target organ for glucocorticoids. Several studies of the function of the hypothalamic-pituitary-adrenal axis in obese subjects have failed to reach conclusive results. An innovative finding is that adipose tissue produces cortisol from its inactive precursor, cortisone. Identification of leptin, a hormone synthesised by adipose tissue, has ushered in the modern view that it is a true endocrine organ. Leptin is produced by subcutaneous and to a lesser extent by visceral adipose tissue. It has a central role in body weight and especially fat stores regulation, but is also involved in several complex functions, including the physiological processes associated with puberty. Angiotensinogen (AGT), another hormone synthesised in abundance by adipose tissue, is produced in larger amounts by visceral than subcutaneous fat. In addition, in man and animals adipose tissue appears to possess the whole renin-angiotensin system (RAS), suggesting that angiotensin II, the final effector of the system, is locally produced. The function of adipose RAS is not well known; besides participating, together with other hormones and substances, in adipocyte differentiation and fat tissue growth, it could be involved in the pathogenesis of the complications of obesity. All these findings have opened interesting prospects and are expected to yield further stimulating insights into the physiopathology of the adipose organ.
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Tejido Adiposo/metabolismo , Glucocorticoides/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Angiotensinógeno/metabolismo , Femenino , Humanos , Leptina/metabolismo , Masculino , Obesidad/metabolismoRESUMEN
Incidentally discovered adrenal masses, or adrenal incidentalomas, have become a common clinical problem owing to wide application of radiologic imaging techniques. This definition encompasses a heterogeneous spectrum of pathologic entities, including primary adrenocortical and medullary tumors, benign or malignant lesions, hormonally active or inactive lesions, metastases, and infections. Once an adrenal mass is detected, the clinician needs to address two crucial questions: is the mass malignant, and is it hormonally active? This article provides an overview of the diagnostic clinical approach and management of the adrenal incidentaloma. Mass size is the most reliable variable to distinguish benign and malignant adrenal masses. Adrenalectomy should be recommended for masses greater than 4.0 cm because of the increased risk of malignancy. Adrenal scintigraphy has proved useful in discriminating between benign and malignant lesions. Finally, fine-needle aspiration biopsy is an important tool in the evaluation of oncological patients and it may be useful in establishing the presence of metastatic disease. The majority of adrenal incidentalomas are non-hypersecretory cortical adenomas but an endocrine evaluation can lead to the identification of a significant number of cases with subclinical Cushing's syndrome (5-15%), pheochromocytoma (1.5-13%) and aldosteronoma (0-7%). The first step of hormonal screening should include an overnight low dose dexamethasone suppression test, the measure of urinary catecholamines or metanephrines, serum potassium and, in hypertensive patients, upright plasma aldosterone/plasma renin activity ratio. Dehydroepiandrosterone sulfate measurement may show evidence of adrenal androgen excess.
Asunto(s)
Adenoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Adenoma/fisiopatología , Neoplasias de las Glándulas Suprarrenales/fisiopatología , Síndrome de Cushing/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Hiperaldosteronismo/diagnóstico , Incidencia , Masculino , Feocromocitoma/diagnósticoRESUMEN
Recently, the genes of components of the renin-angiotensin system (RAS), namely angiotensinogen (AGT), angiotensin converting enzyme and angiotensin II receptor have been described in adipose tissue. In animal models the angiotensinogen in adipose tissue has been implicated in the pathogenesis of metabolic alterations and hypertension associated with obesity. The aim of our study was to evaluate the AGT gene expression both in visceral and subcutaneous adipose tissue in obese patients and lean subjects. AGT mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR) using specific primers. AGT mRNA was expressed at variable levels in obese patients. It was significantly greater in visceral than in subcutaneous adipose tissue. Positive and significant correlation was found between the expression of AGT in visceral adipose tissue and BMI. These data suggest that angiotensinogen may be determinant of fat distribution and may be involved in the plurimetabolic syndrome of central obesity.
Asunto(s)
Tejido Adiposo/metabolismo , Angiotensinógeno/genética , Expresión Génica , Obesidad/metabolismo , Tejido Adiposo/química , Humanos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Na+,K(+)-ATPase activity was evaluated in relation to membrane composition and molecular organization in erythrocyte membranes from obese patients by the amphyphylic molecule 6-dodecanoyl-2-dimethylamino-naphthalene (Laurdan). Its possible relationship with fat distribution and hyperinsulinaemia was also investigated. DESIGN: Subjects were 10 obese men (OM), 12 women with subcutaneous obesity (FSO), 10 women with abdominal obesity (FAO) and 41 healthy lean subjects, 26 women (FC) and 15 men (MC). An oral glucose tolerance test was administered to all subjects to evaluate insulin secretion and glucose tolerance. RESULTS: Na+,K(+)-ATPase activity was increased in all obese patients. Values were higher in FSO and FAO than in FC (with FAO greater than FSO) and in OM than in MC. The erythrocyte membrane cholesterol-to-phospholipid ratio was increased in obese patients and was significantly different in FSO patients compared with FC. The erythrocyte membrane protein-to-phospholipid ratio was also increased in all obese subjects, reaching statistical significance only in FSO vs. FC. The liquid crystalline phase, as tested by Laurdan generalized polarization (GP), was decreased in obese patients, indicating the presence of greater molecular environmental order; all patients groups showed lower GP values than control subjects, but only FAO reached statistical significance compared with FC. There was no evident correlation between membrane Na+,K(+)-ATPase activity and insulin levels, nor did membrane composition and properties show any evident relationship with insulin levels. CONCLUSION: Both increased Na+,K(+)-ATPase activity and altered fluidity and lipid composition were observed in the erythrocyte membrane of all obese patients. These findings are in line with previous observations by our group and indicate that the changes in Na+,K(+)-ATPase activity observed in obese patients could be related to changes in plasma membrane organization and composition.
Asunto(s)
Membrana Eritrocítica/metabolismo , Obesidad/metabolismo , Adulto , Colesterol/metabolismo , Membrana Eritrocítica/enzimología , Femenino , Humanos , Masculino , Obesidad/enzimología , Fosfolípidos/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Increased 5 alpha-reductase activity has been found in hair follicles of hirsute women, suggesting a pathogenetic role. The aim of the present study was to evaluate the effect of finasteride in the treatment of idiopathic hirsutism. Twenty-seven women with idiopathic hirsutism, aged 16-35 years, were treated for 6 months with finasteride, 5 mg once daily. Fourteen patients were on finasteride alone (group A), while the remaining received in addition an oral contraceptive (group B). Clinical, hormonal and biochemical evaluation were performed before, and after 3 and 6 months of treatment. Clinical evaluation was repeated 6 months after drug discontinuation in seven patients. Treatment was well tolerated by all patients; no side effects or adverse reactions were reported. A significant improvement of hirsutism was obtained by finasteride; clinical score observed at the 6th month of therapy was reduced from 11.71 +/- 2.23 to 7.92 +/- 1.81 (p < 0.05) and from 14.92 +/- 6.13 to 9.3 +/- 2.75 (p < 0.05) in group A and B, respectively. Clinical score in seven patients was still 8.61 +/- 2.28 (p < 0.05) 6 months after the end of therapy. Finasteride treatment alone (group A) induced a slight increase, though not significant, in serum androgens; DHT and SHBG did not change. In group B (finasteride plus oral contraceptive) total testosterone and free testosterone showed no significant decrease; after 6 months of therapy DHT was reduced significantly, while SHBG levels were increased. These data demonstrate that 5 alpha-reductase inhibition may be an effective treatment in women suffering from idiopathic hirsutism. This approach may be attractive due to the absence of adverse reactions, although the necessity of an adequate contraception should be kept in mind.
Asunto(s)
Inhibidores Enzimáticos/uso terapéutico , Finasterida/uso terapéutico , Hirsutismo/tratamiento farmacológico , Oxidorreductasas/antagonistas & inhibidores , Adolescente , Adulto , Colestenona 5 alfa-Reductasa , Dihidrotestosterona/sangre , Femenino , Finasterida/efectos adversos , Humanos , Globulina de Unión a Hormona Sexual/metabolismoRESUMEN
Impaired cellular uptake and utilization of glucose is the hallmark of non-insulin-dependent-diabetes (NIDDM). We have developed a quantitative assay to probe the expression of glucose-transporter genes in tissues derived from patients with NIDDM. Using the polymerase chain reaction (PCR), we assessed levels of expression of the insulin responsive glucose transporter GLUT-4 in adipose tissue of patients with NIDDM and in obese patients. We report that expression of GLUT-4 is reduced in NIDDM and in obesity associated with hyperinsulinemia and insulin resistance. These results suggest that reduction of GLUT-4 levels in the adipose cell plays an important role in the pathogenesis of insulin resistance, an early feature of NIDDM.
Asunto(s)
Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Transporte de Monosacáridos/genética , Proteínas Musculares , Obesidad/metabolismo , ARN Mensajero/análisis , Tejido Adiposo/química , Tejido Adiposo/fisiología , Secuencia de Bases , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Expresión Génica , Transportador de Glucosa de Tipo 4 , Humanos , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteínas de Transporte de Monosacáridos/metabolismo , Obesidad/genética , Obesidad/fisiopatología , Oligonucleótidos/análisis , Oligonucleótidos/química , Oligonucleótidos/genética , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/genéticaRESUMEN
It is well known that TSH is the main factor responsible for thyrocyte proliferation and growth. Recent studies have shown that other growth factors, including transforming growth factor-beta 1 (TGF-beta 1), have an important role in the control of thyrocyte proliferation and differentiation. The aim of the study was to evaluate the expression of the TGF-beta 1 gene in thyroid follicular adenoma (FA) by Northern analysis, and its protein localization by immunohistochemistry. Surgically removed thyroid tissue from 56 patients with thyroid FA was screened for the study. Normal thyroid tissue from 4 patients with papillary carcinoma was used as a control. Sixteen FA (8 with a "cold" and 8 with a "hot" scintiscan pattern) having homogeneous histological characteristics were subsequently selected. FA showed greater TGF-beta 1 gene expression than control tissue. There was not a statistically significant difference between "cold" and "hot" FA. Immunohistochemistry analysis showed that TGF-beta 1 was located in various histological structures of the adenomas (thyrocytes, endothelium, perinervium and connective tissue); on the other hand, perinodular and control tissue did not show appreciable TGF-beta 1 protein. Our data suggest that TGF-beta 1 may be involved in the pathogenesis of FA. The different TGF-beta 1 distribution in thyrocytes, endothelium, perinervium and connective tissue in FA suggests that TGF-beta 1 may be variably expressed during the natural history of FA. Since no significant difference in TGF-beta 1 gene expression between "hot" and "cold" adenomas was found, it appears that other factors are involved in their functional differentiation.
Asunto(s)
Adenoma/metabolismo , Neoplasias de la Tiroides/metabolismo , Factor de Crecimiento Transformador beta/análisis , Adulto , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Neoplásico/análisis , Factor de Crecimiento Transformador beta/genéticaRESUMEN
Six women with acne and six women with hirsutism were treated with the GnRH analog [D-Ser(Bu(t))6] LHRH-(1-9)ethylamide (Buserelin) for 6 months (nasal spray, 1,200 micrograms/day) to suppress ovarian steroidogenesis. All women were eumenorrheic and did not demonstrate any adrenal or ovarian dysfunction. During treatment, ovarian steroids, LH and FSH decreased, while DHEA-S showed minor modifications; the clinical score for both acne and hirsutism showed a significant reduction. Moreover, acne and hirsutism were still well controlled 6 months after therapy. Gonadal function resumed in all patients after discontinuation of therapy. Three patients suffered from hot flashes from the 4th month. These data demonstrate that suppression of ovarian steroid secretion might be an efficient treatment in women suffering from acne or idiopathic hirsutism, indicating that ovarian steroids may have a key-role in the pathogenesis of these conditions.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Buserelina/uso terapéutico , Hormonas Esteroides Gonadales/sangre , Gonadotropinas Hipofisarias/sangre , Hirsutismo/tratamiento farmacológico , Acné Vulgar/sangre , Adulto , Femenino , Hirsutismo/sangre , Humanos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Diabetic patients present alterations in the activity of a number of enzymes of the plasma membrane. The aim of this study was to verify if the modifications of the enzymatic activities in diabetes mellitus are associated with structural alterations of the cellular membrane. By means of the freeze-fracturing technique, we studied the structure of erythrocyte membranes from 15 insulin-dependent diabetic patients (24-43 years) and 15 age-matched healthy subjects (26-47 years). The kinetic properties of the Na+/K(+)-ATPase of the same membranes were also investigated. The Na+/K(+)-ATPase of the erythrocyte plasma membrane shows an uncompetitive inhibition in the diabetic subjects. As for the freeze-fracturing results, the intramembrane particles of the erythrocyte membranes from diabetic patients appear more clustered with respect to those obtained from controls. The uncompetitive inhibition of the enzyme suggests the presence of conformational modifications of the protein. This hypothesis is supported by the freeze-fracture results which indicate that the integral protein constituents of the membrane in diabetes tend to aggregate. Modifications of the interactions between the enzymatic subunits and the membrane lipid environment might be at the basis of the Na+/K(+)-ATPase alteration in diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Membrana Eritrocítica/fisiología , Membrana Eritrocítica/ultraestructura , Adulto , Diabetes Mellitus Tipo 1/enzimología , Membrana Eritrocítica/enzimología , Humanos , Cinética , Proteínas de la Membrana/sangre , Proteínas de la Membrana/fisiología , Persona de Mediana Edad , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
The pathogenesis of plasma membrane alterations present in diabetes mellitus is unclear. To add new insights to the question, platelet membrane properties were evaluated in 16 women presenting impaired glucose tolerance at the 28-29th week of gestation (GDM) and in 8 women with insulin-dependent diabetes mellitus (IDDM). 15 healthy pregnant women (HPW) and 21 healthy non-pregnant (HNPW) women were the control group for GDM and IDDM, respectively. Pregnancy (HPW vs. HNPW) provoked an increase in Ca(2+)-ATPase activity and a decrease in membrane fluidity; in contrast, Na+/K(+)-ATPase, intracellular free Ca2+ concentrations, membrane cholesterol and phospholipid content did not vary. Both GDM and IDDM showed lower Na+/K(+)-ATPase activity and higher Ca2+ concentration, compared to HPW and HNPW, respectively, whereas Ca(2+)-ATPase activity was higher only in IDDM; furthermore, membrane fluidity was lower in GDM and higher in IDDM. Finally, GDM showed higher membrane cholesterol content. Both GDM and IDDM showed a very good metabolic control so that variations reported cannot be due to hyperglycemia; it is tempting to suggest that membrane variations are present before the clinical metabolic alteration. Furthermore, both GDM and IDDM were on insulin therapy, therefore: (i) insulin may be the pathogenetic factor of higher intracellular free Ca2+ concentrations and lower Na+/K(+)-ATPase activity since they both varied accordingly in GDM and IDDM, but not of (ii) changes in Ca(2+)-ATPase, membrane fluidity and cholesterol content which did not vary accordingly in GDM and IDDM.