RESUMEN
The Czech Republic reported one of the highest incidence rate in cutaneous melanoma (CM) in Europe and because this incidence has been increasing, mainly among young people, the main goal of our study was to establish sun exposure behavior risk factors for CM formation and to evaluate whether the young generation of Czechs is exposed to a higher risk of CM than the older generation. A questionnaire-based case-control study was conducted. We obtained 978 completed questionnaires: 216 from patients with CM and 762 from healthy respondents. The healthy individuals were further divided to adolescents (n = 460) and older respondents (n = 302). Three logistic regression models were developed: 1. patients with CM vs. healthy older respondents, 2. adolescents vs. healthy older respondents, and 3. patients with CM vs. adolescents. The main risk factors for all three models were the number of sunburn episodes and the use of the sunscreen in the childhood. The most alarming results for adolescents included: all day sun exposure, including times of maximum risk (11 AM to 3 PM), inadequate use of sunscreen in adulthood, and frequent mountain holidays. Our results show that sun-safety in the young generation is satisfactory, when the responsibility for sun exposure behavior is in the hands of their parents; however, when children become adolescents, they become immune to sun-safety and risk prevention campaigns and their behavior becomes much more risky. Our results further suggest the sun-safety campaigns need to be modified in such a way as to have greater impact and influence on adolescent sun-risk behaviors.
Asunto(s)
Melanoma/epidemiología , Melanoma/etiología , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología , Quemadura Solar/complicaciones , Quemadura Solar/epidemiología , Luz Solar/efectos adversos , Adolescente , Conducta del Adolescente , Adulto , Estudios de Casos y Controles , Niño , República Checa/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Melanoma/prevención & control , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Neoplasias Cutáneas/prevención & control , Quemadura Solar/prevención & control , Protectores Solares/uso terapéutico , Encuestas y Cuestionarios , Adulto JovenRESUMEN
In hereditary HTG rats, basal systolic blood pressure using tail-cuff sphygmomanometry was significantly higher (122.1 +/- 2.1 mm Hg; n = 16) than that in NTG animals (107.1 +/- 1.52; n = 16). A low salt diet did not influence blood pressure in NTG rats during the consecutive 4 weekly periods. However, in the second week blood pressure in HTG rats rose significantly in both the control rats on a normal salt diet and those on a low salt diet (132.5 +/- 1.89, n = 8, and 132.6 +/- 1.93, n = 8). No further changes were registered in the third and fourth week in control HTG rats. On the other hand, blood pressure fell significantly in HTG rats on a low salt diet in the third week in comparison with the second week (119.5 +/- 3.2, n = 8), and it increased again in the fourth week (123.0 +/- 2.35, n = 8). Hormones in plasma were determined at the end of the experiment. Plasma levels of norepinephrine were not influenced by differences in salt intake and were significantly higher by about 45% in HTG than in NTG animals. The lowest concentration of corticosterone in plasma was found in control HTG rats (1.2 +/- 0.2 vs 4.6 +/- 0.8 micrograms/100 ml in control NTG rats). Nevertheless, corticosterone concentration increased in HTG rats on a low salt diet at comparable values found in NTG rats on a low salt diet (3.1 +/- 0.8 vs 4.3 +/- 1.5). Plasma renin activity and plasma aldosterone concentrations were not different in the NTG and HTG groups and were uninfluenced by the diets (Table 1). We conclude that the elevated blood pressure in HTG rats and its variations during the experiment may reflect more pronounced sympathetic activity in HTG rats rather than blood pressure dependency on different salt intake.
Asunto(s)
Presión Sanguínea , Hipertrigliceridemia/fisiopatología , Sodio en la Dieta/administración & dosificación , Aldosterona/sangre , Animales , Corticosterona/sangre , Hipertrigliceridemia/genética , Masculino , Norepinefrina/sangre , Ratas , Ratas Wistar , Renina/sangre , Sodio en la Dieta/farmacología , Triglicéridos/sangreRESUMEN
Nonobese, hereditary hypertriglyceridemic (HTG) rats provide an interesting model of hypertriglyceridemia, glucose intolerance, and hypertension. In age-matched 15 HTG and 16 control Wistar rats fed on a high sucrose diet (70 cal%) for 6 weeks, we measured insulin sensitivity in vivo and some parameters of sympatoadrenal system. Using euglycemic clamps with administration of 2-deoxy[1-3H]glucose, we found whole body insulin resistance and decreased glucose metabolic index Rg' in soleus muscle, epitrochlearis muscle, diaphragm, and white adipose tissue in HTG rats. We found higher levels of plasma epinephrine and higher excretion of vanilmandelic and homovanilic acids in HTG rats. The binding of [3H]-dihydroalprenol to the heart membrane fraction was similar in both groups, but the dissociation constant Kd was increased by 75% in the heart of HTG rats.
Asunto(s)
Hipertrigliceridemia/fisiopatología , Resistencia a la Insulina , Receptores Adrenérgicos beta/fisiología , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Presión Sanguínea , Dihidroalprenolol/metabolismo , Epinefrina/sangre , Glucosa/metabolismo , Técnica de Clampeo de la Glucosa , Ácido Homovanílico/orina , Hipertrigliceridemia/genética , Insulina/sangre , Masculino , Músculos/metabolismo , Ratas , Ratas Wistar , Ácido Vanilmandélico/orinaRESUMEN
Palmitate and glucose oxidation were investigated in isolated hemidiaphragm of rats in which hypertriglyceridemia was induced by dietary fructose. Palmitate oxidation was increased, and glucose oxidation was reduced, in fructose-fed rats, as compared with glucose-fed controls. Glucose incorporation into muscle glycogen was similar in both dietary groups.
Asunto(s)
Glucosa/metabolismo , Hiperlipidemias/metabolismo , Músculos/metabolismo , Palmitatos/metabolismo , Ácidos Palmíticos/metabolismo , Triglicéridos/sangre , Animales , Diafragma/metabolismo , Carbohidratos de la Dieta , Femenino , Fructosa , Hiperlipidemias/inducido químicamente , RatasRESUMEN
Insulin was covalently attached to two terpolymers of N-(2-hydroxypropyl) methacrylamide, N-methacryloyldiglycine and a) R-(-)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside or b) S-(+)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside. The mitogenic effect of both conjugates on vascular smooth muscle cell proliferation was investigated. The results indicated that insulin bound to both carriers with pendant N-acetylglucosaminyl groups possesses hypoglycemic activity but not the mitogenic effect of native insulin. This study shows that for these insulin conjugates, the effect does not depend on the steric configuration of the sugar-containing monomer units incorporated in the terpolymer. A hypothesis is developed that some competition is taking place between N-acetylglucosaminyl groups on the polymeric insulin carrier and the same moieties in the insulin receptor expressed on the surface of smooth muscle cells leading to a lack of mitogenic activity.
Asunto(s)
Insulina/administración & dosificación , Mitógenos/farmacología , Músculo Liso Vascular/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , División Celular/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/farmacología , Masculino , Músculo Liso Vascular/citología , Polímeros/administración & dosificación , Ratas , Ratas Sprague-Dawley , Ratas WistarRESUMEN
The effects of polyunsaturated fatty acids of the omega-3 family (PUFA n-3), (addition of fish oil), on the molecular composition of cholesteryl esters and triglycerides in plasma and liver perfusate of rats were studied. Rats fed a diet rich in saturated fatty acids (addition of lard) served as controls. Supplemention with PUFA n-3 not only decreases the plasma concentrations of free cholesterol, cholesteryl esters, and triglycerides, it also significantly alters the plasma composition of cholesteryl esters and triglycerides. Analyses of liver perfusate indicate a decrease in triglycerides secretion by in vitro perfused liver and reciprocal changes in relative contents of cholesteryl esters fractions with C(16) and C(20) acyl chains. This finding may be a result of chain-shortening of long-chain fatty acids probably in peroxisomal beta-oxidative system. Alterations in plasma cholesteryl esters and triglycerides composition of the fish oil group could be affected further by additional factors such as increased plasma cholesterol esterification activity and presence of triglyceride species of intestinal origin.
RESUMEN
Glucose tolerance and in vivo incorporation of glucose into liver glycogen were investigated in rats fed high carbohydrate diets containing glucose or fructose as the sole carbohydrate source. As compared with control glucose-adapted rats, a slight deterioration of the glucose tolerance was observed in fructose-adapted rats. The possivle cause of the deteriorated glucose tolerance in fructose-adapted rats seems to be among others reduced glucose incorporation into liver glycogen and a smaller depression of endogenous glucose production by exogenous glucose.
Asunto(s)
Carbohidratos de la Dieta/metabolismo , Fructosa , Glucosa/metabolismo , Glucógeno Hepático/biosíntesis , Adaptación Fisiológica , Animales , Glucemia/análisis , Femenino , Fructosa/metabolismo , Prueba de Tolerancia a la Glucosa , RatasRESUMEN
The effect of the type of dietary carbohydrate on oral glucose tolerance and on in vivo incorporation of labeled glucose or fructose into liver and muscle glycogen in the rat were investigated. The intake of fructose or sucrose reduced, as compared with starch or glucose, glucose incorporation into liver glycogen and caused a slight deterioration of the glucose tolerance. These effects were observed already when 50% of the total dietary carbohydrate was substituted by fructose or sucrose. The incorporation of labeled glucose into muscle glycogen was not affected by the type of dietary carbohydrate. Specific radioactivity of liver and muscle glycogen and the concentration of muscle glycogen after administration of labeled fructose were higher in fructose-adapted than in glucose-adapted rats.
Asunto(s)
Glucemia , Carbohidratos de la Dieta , Glucógeno/biosíntesis , Músculos/metabolismo , Animales , Glucemia/análisis , Carbohidratos de la Dieta/administración & dosificación , Femenino , Fructosa , Prueba de Tolerancia a la Glucosa , Glucógeno Hepático/biosíntesis , Ratas , Almidón , SacarosaRESUMEN
Hypertriglyceridemia was demonstrated in untreated hypertensive patients as well as in animals with genetic and experimental hypertension. The main purpose of the present study was to evaluate the possibility to use the hereditary hypertriglyceridemic (HTG) nonobese rats in hypertensive research. Direct measurement of blood pressure demonstrated significantly higher systolic, diastolic and mean arterial pressures in HTG rats in comparison with control Wistar rats. There was significant positive correlation between blood pressure and plasma triglyceride concentration (r = 0.585, n = 40, p less than 0.001). In addition, there were significantly increased plasma norepinephrine and epinephrine concentrations in HTG rats, suggesting that the stimulation of sympathetic nervous system could be one of the pathogenetic mechanisms involved in the increase of blood pressure of HTG rats.
Asunto(s)
Diabetes Mellitus/genética , Modelos Animales de Enfermedad , Hiperlipoproteinemia Tipo IV/genética , Hipertensión/genética , Animales , Glucemia/análisis , Presión Sanguínea , Peso Corporal , Epinefrina/sangre , Prueba de Tolerancia a la Glucosa , Hiperlipoproteinemia Tipo IV/sangre , Hiperlipoproteinemia Tipo IV/fisiopatología , Insulina/sangre , Masculino , Modelos Genéticos , Norepinefrina/sangre , Ratas , Ratas Endogámicas , Triglicéridos/sangreRESUMEN
The electrodeposition of cadmium and copper on a special graphite disk electrode has been performed at controlled potential. The electrode with the deposit has been inserted into the graphite atomizer HGA-400 by an adapted automatic sampler for the final determination by ET-ASS. The sensitivity of determination has been 0.371 (microg l(-1))(-1) for cadmium and 0.025 (microg l(-1))(-1) for copper for 2 min electrodeposition and increased linearly with the time of deposition. The limit of detection (3s(bl)) has been 7.9 ng l(-1) Cd(2+) and 0.11 microg l(-1) Cu(2+) for 2 min deposition and it has been improved with increased time of electrodeposition. The technique has been applied to the determination of both metals in seawater and to speciation in the presence of EDTA complexing agent.
RESUMEN
The resistance to insulin (insulin resistance, IR) is a common feature and a possible link between such frequent disorders as non-insulin dependent diabetes mellitus (NIDDM), hypertension and obesity. Pharmacological amelioration of IR and understanding its pathophysiology are therefore essential for successful management of these disorders. In this review, we will discuss the mechanisms of action of thiazolidinediones (TDs), a new family of insulin-sensitizing agents. Experimental studies of various models of IR and an increasing number of clinical studies have shown that TDs normalize a wide range of metabolic abnormalities associated with IR. By improving insulin sensitivity in skeletal muscles, the adipose tissue and hepatocytes, TDs reduce fasting hyperglycaemia and insulinaemia. Furthermore, TDs markedly influence lipid metabolism--they decrease plasma triglyceride, free fatty acid and LDL-cholesterol levels, and increase plasma HDL-cholesterol concentrations. Although TDs do not stimulate insulin secretion, they improve the secretory response of beta cells to insulin secretagogues. TDs act at various levels of glucose and lipid metabolism--ameliorate some defects in the signalling cascade distal to the insulin receptor and improve glucose uptake in insulin-resistant tissues via increased expression of glucose transporters GLUT1 and GLUT4. TDs also activate glycolysis in hepatocytes, oppose intracellular actions of cyclic AMP, and increase intracellular magnesium levels. TDs bind to peroxisome proliferator activating receptors gamma (PPAR gamma), members of the steroid/thyroid hormone nuclear receptor superfamily of transcription factors involved in adipocyte differentiation and glucose and lipid homeostasis. Activation of PPAR gamma results in the expression of adipocyte-specific genes and differentiation of various cell types in mature adipocytes capable of active glucose uptake and energy storage in the form of lipids. Furthermore, TDs inhibit the pathophysiological effects exerted by tumour-necrosis factor (TNF alpha), a cytokine involved in the pathogenesis of IR. These effects are most likely also mediated by stimulation of PPAR gamma. In mature adipocytes, PPAR gamma stimulation inhibits stearoyl-CoA desaturase 1 (SCD1) enzyme activity resulting in a change of cell membrane fatty acid composition. Apart from their metabolic actions, TDs modulate cardiovascular function and morphology independently of the insulin-sensitizing effects. TDs decrease blood pressure in various models of hypertension as well as in hypertensive insulin-resistant patients, and inhibit proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMC) induced by growth factors. These processes are considered to be crucial in the development of vascular remodelling, atherosclerosis and diabetic organ complications. TDs induce vasodilation by blockade of Ca2+ mobilisation from intracellular stores and by inhibition of extracellular calcium uptake via L-channels. Furthermore, TDs interfere with pressor systems (catecholamines, renin-angiotensin system) and enhance endothelium-dependent vasodilation. A key role of TDs effects in vascular remodelling is played by inhibition of the mitogen-activated protein (MAP) kinase pathway. This signalling pathway is important for VSMC growth and migration in response to stimulation with tyrosine-kinase dependent growth factors. In addition to the vasoprotective mechanisms mentioned above, troglitazone, the latest representative of this pharmacological group, possesses antioxidant actions comparable to vitamin E. In summary, TDs have the unique ability to attack mechanisms responsible for metabolic alterations as well as for vascular abnormalities characteristic for IR. Therefore, TDs represent a powerful research tool in attempts to find a common denominator underlying the pathophysiology of the metabolic syndrome X. A recently reported link between MAP kinase signalling pathway and PPAR gamma
Asunto(s)
Angina Microvascular/etiología , Tiazoles/farmacología , Tiazolidinedionas , Antioxidantes , Vasos Sanguíneos/efectos de los fármacos , Cromanos/farmacología , Cromanos/uso terapéutico , Humanos , Hipoglucemiantes , Resistencia a la Insulina , Tiazoles/uso terapéutico , Troglitazona , VasodilatadoresRESUMEN
Glucose tolerance, insulin secretion and in vitro insulin action were examined in streptozotocin-induced diabetic rats following pancreatic islet allotransplantation treated with combination of oral cyclosporine A (10 mg/kg) and hydrocortisone (1.5 mg/kg) intramuscularly. 1400 pure islets from multiple donors were implanted either into the portal vein (n = 10) or under the renal capsule (n = 11). Ten sham-operated non-diabetic animals receiving the same immunosuppressive therapy, 8 healthy animals without any treatment and 10 diabetic animals without immunosuppression following islet transplantation were used as controls. In all transplanted animals blood glucose was normalized by day 3 after transplantation with lower levels in those transplanted intraportally (p < 0.05). Non-immunosuppressed animals rejected the graft after 6.5 +/- 1.2 days after transplantation, immunosuppressed animals in both groups remained normoglycaemic till the end of the experiment on day 28. Oral glucose tolerance tests and insulin levels on days 10 and 28 improved dramatically. No differences in glucose and insulin levels between intraportal and subcapsular groups were found. Post-load glucose levels in immunosuppressed non-transplanted animals were higher on day 28 than before treatment and were also higher than in the healthy non-treated group (p < 0.05). In vitro insulin action determined by the incorporation of labelled glucose into adipose tissue was impaired only in animals in which islets were transplanted into the liver (p < 0.05 vs other groups). In conclusion, therapy with cyclosporine A and hydrocortisone prevents allogeneic islet rejection in rats during a short-term experiment. Although glucose tolerance is not completely normalized following transplantation, slight impairment is also demonstrable in healthy animals on the same drug therapy.
Asunto(s)
Antiinflamatorios/farmacología , Ciclosporina/farmacología , Glucosa/metabolismo , Hidrocortisona/farmacología , Inmunosupresores/farmacología , Trasplante de Islotes Pancreáticos , Animales , Glucemia , Radioisótopos de Carbono , Creatinina/sangre , Ciclosporina/sangre , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/cirugía , Modelos Animales de Enfermedad , Quimioterapia Combinada , Ayuno , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Secreción de Insulina , Riñón/citología , Metabolismo de los Lípidos , Hígado/irrigación sanguínea , Hígado/citología , Vena Porta/citología , Ratas , Ratas WistarRESUMEN
The effect of particle size on bioavailability of 9 different formulations with cyclosporine A was studied. A common feature of all the formulations was the ability to form submicron dispersions under dilution. The composition of individual formulations was chosen in such a way that they were based on same or similar excipients. For each formulation, pharmacokinetic study was carried out in beagle dogs. On groups of 10 dogs, the average AUC was evaluated. Particle size of formulations under dilution in water was measured by laser scattering method. According to the results of particle size measurement, the formulations were sorted out into groups of similar particle size distribution by use of two methods of multivariate statistical analysis. The average AUC within groups and between-groups was compared, and the effect of particle size on bioavailability was evaluated.