RESUMEN
We examined correlations between the frequency of insulin resistance and the accumulation of coronary risk factors in residents of rural comities in Japanese, using simple criteria for determination of insulin resistance based on evaluation by the euglycaemic-hyperinsulinaemic glucose clamp (GC) method. The subjects were 376 men and 589 women living in two rural communities in Japan. We measured body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), HDL cholesterol (HDL), and homeostasis model assessment (HOMA-R). Correlations between HOMA-R and those parameters were examined. To assess the existence of insulin resistance in these subjects, we used a practical index based on the GC method. The subjects with value of HOMA-R >or= 1.73 have insulin resistance. In addition, the HOMA-R was divided into five quantiles based on the frequency distribution (0.60 or below, from 0.61 to 0.82, from 0.83 to 1.18, from 1.19 to 1.69, and 1.70 or higher), to examine the concentration of risk factors in each group. In total, 74 (19.6%) of the men and 119 (20.3%) of the women had insulin resistance (HOMA-R >or= 1.73). It was found that the higher the HOMA-R, the higher was the number of coronary risk factors, such as hypertension, obesity, hypertriglyceridaemia and hypo HDL cholesterolaemia. The number of coronary risk factors was particular high in subjects with HOMA-R >or= 1.70. HOMA-R in the case of no glucose loading is a useful and practical index for evaluation of insulin resistance and coronary risk factors in the epidemiological study.
Asunto(s)
Enfermedad de la Arteria Coronaria/etiología , Resistencia a la Insulina/fisiología , Adulto , Presión Sanguínea/fisiología , Índice de Masa Corporal , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Homeostasis , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Triglicéridos/sangreRESUMEN
We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, on insulin sensitivity including lipid metabolism in skeletal muscle. Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) or a fructose-rich chow (fructose-fed rats (FFRs)) for 6 weeks. FFRs were treated either with a vehicle or with 30 mg/kg per day of fenofibrate for the last 2 weeks. Insulin sensitivity (M-value) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Fatty acid-binding protein (FABP) in skeletal muscle was measured by ELISA, and the expression of FABP mRNA was analyzed by semi-quantitative RT-PCR. The serum and muscle triglyceride (sTG and mTG) levels and the activity of 3-hydroxyacyl-CoA dehydrogenase (HADH), a beta-oxidation enzyme, in muscle were also determined. FFRs showed a lower M-value and higher blood pressure, sTG and mTG than did the control group. The mTG was correlated positively with sTG and negatively with the M-value. Fenofibrate treatment for 2 weeks did not change blood pressure but significantly improved the M-value, sTG and mTG. FABP content and mRNA in the soleus muscle were significantly elevated in FFRs compared with those in the control group. Fenofibrate treatment further increased FABP. The HADH activity was comparable between the control group and FFRs, but significantly increased by fenofibrate treatment. These results suggest that fenofibrate improves insulin sensitivity not only by lowering serum lipids and subsequent influx of fatty acids into muscles but also by reducing intramuscular lipid content via further induction of FABP and stimulation of beta-oxidation in muscles.
Asunto(s)
Fenofibrato/farmacología , Hipolipemiantes/farmacología , Insulina/sangre , Lípidos/sangre , Músculo Esquelético/metabolismo , Proteínas de Neoplasias , Proteínas del Tejido Nervioso , 3-Hidroxiacil-CoA Deshidrogenasas/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Animales , Proteínas Portadoras/análisis , Citosol/química , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Fructosa , Técnica de Clampeo de la Glucosa , Masculino , Músculo Esquelético/química , Ratas , Ratas Sprague-Dawley , Triglicéridos/análisisRESUMEN
INTRODUCTION: A sensitive and simple enzymatic cycling method is described for the quantitation of myo-inositol in biological samples. METHODS: The method involves the use of a sensitive and simple enzymatic cycling method is described for the quantitation of myo-inositol in biological samples. The method involves use of thio-NAD(+), NADH and thermostable myo-inositol dehydrogenase (IDH; EC. 1.1.1.18) and measurement of the increase in absorbance at 405 nm of thio-NADH at 37 degrees C. RESULTS: The calibration curve for myo-inositol was linear (r=1.00) between 10 and 400 micromol/l. Analytical recoveries of exogenous myo-inositol added to serum and urine were 100-105% and 98-103%, respectively. Within-run and between-run coefficient of variation (CV) were 0.6-2.1% and 1.1-3.0%, respectively. This method was free from interference by hemoglobin, bilirubin, ascorbate, chyle, various sugars, sugar alcohol and myo-inositol phosphates. With the use of myo-inositol as a standard solution, the serum myo-inositol concentration (mean+/-SD) was significantly greater in patients with diabetes mellitus (DM) without nephropathy (73.0+/-13.8 micromol/l, n=7) than in healthy individuals without DM (61.0+/-12.4 micromol/l, n=20). The urinary myo-inositol concentration was also significantly greater in patients with DM without nephropathy (793.3+/-870.3 micromol/l, n=7) than in healthy individuals without DM (76.0+/-63.0 micromol/l, n=13). CONCLUSIONS: This new method is simple, sensitive and enables quantitative analysis of myo-inositol.
Asunto(s)
Bioquímica/métodos , Diabetes Mellitus Tipo 2/metabolismo , Inositol/análisis , Deshidrogenasas del Alcohol de Azúcar/metabolismo , Anciano , Bacillus/enzimología , Femenino , Glucosa/química , Humanos , Inositol/metabolismo , Masculino , NAD/metabolismo , Valores de Referencia , Sensibilidad y Especificidad , Deshidrogenasas del Alcohol de Azúcar/aislamiento & purificaciónRESUMEN
The aim of this study was to examine the roles of muscle fiber composition, capillary density and muscle blood flow in insulin resistance (IR) and the effect of cilnidipine, a calcium channel blocker in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow or fructose-rich chow for 6 weeks. For the last 2 weeks, the rats were treated by gavage with a vehicle (Control and FFR groups) or with cilnidipine (FFR+Cil group). Blood pressure (BP) and insulin sensitivity were assessed in the sixth week. Muscle fiber composition, capillary density and blood flow in the soleus muscle were evaluated. BP of FFR was significantly higher than that of the controls. Cilnidipine significantly lowered BP in FFR. Insulin sensitivity was significantly lower in FFR than in the controls. Cilnidipine significantly improved IR in FFR. The composite ratio of type I fibers in the soleus muscle was significantly lower in FFR than in the controls, but that of type II fibers was significantly higher in FFR. Treatment with cilnidipine resulted in recovery of this ratio to that of the controls. Insulin sensitivity was found to be significantly correlated with the composite ratio of either type I fibers or type II fibers. There were no intergroup differences in capillary density. Muscle blood flow in the FFR+Cil group was higher than that in the Control or FFR groups. These results suggest that muscle fiber composition is linked to IR and that cilnidipine may improve IR in FFR either by modulating muscle fiber composition or by increasing muscle blood flow.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Fructosa/farmacología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/citología , Animales , Capilares/efectos de los fármacos , Técnica de Clampeo de la Glucosa , Resistencia a la Insulina , Masculino , Fibras Musculares de Contracción Rápida/citología , Fibras Musculares de Contracción Lenta/citología , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
Liddle's syndrome is a rare form of autosomal-dominant salt-sensitive hypertension. Constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel (ENaC) is essential for salt-sensitive hypertension. Recently, several DNA analysis studies have indicated that there is a mutation of C-terminus of either the beta or y subunit. We sequenced the C-termini of the beta and -gamma subunits of the ENaC in a Japanese family with hypertension and hypopotassemia without excess minerarocorticoids, clinically diagnosed as Liddle's syndrome. The mutation of the ENaC of this family was beta R564X. Since such case seem to be rare in the literature, detailed data are shown in this report.
Asunto(s)
Epitelio/química , Hipertensión/genética , Canales de Sodio/sangre , Canales de Sodio/genética , Aldosterona/sangre , Aldosterona/genética , Alcalosis/sangre , Alcalosis/genética , Secuencia de Bases , Análisis de los Gases de la Sangre , Bloqueadores de los Canales de Calcio/uso terapéutico , Análisis Mutacional de ADN , Diagnóstico Diferencial , Diuréticos/uso terapéutico , Salud de la Familia , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipopotasemia/diagnóstico , Hipopotasemia/tratamiento farmacológico , Hipopotasemia/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutagénesis/genética , Mutación Puntual/genética , Potasio/sangre , Potasio/orina , Renina/genética , Renina/metabolismo , Espironolactona/uso terapéutico , Síndrome , Triantereno/uso terapéuticoRESUMEN
The aim of this study was to determine the effect of Jiang-Tang-Ke-Li (JTKL), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 weeks. For the last 2 weeks of the 6-week period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or JTKL (3.24 g/kg/day; FFR+JT), and then an euglycemic hyperinsulinemic glucose clamp technique was performed to estimate insulin sensitivity. Systolic blood pressure was measured each week of the 6-week period. At the end of the glucose clamp, the soleus and extensor digitorum longus (EDL) muscles were dissected out for determination of the role of tumor necrosis factor (TNF)-alpha by an ELISA assay. Systolic blood pressures in the FFR groups were significantly higher than that in the control group, although there was no effect on systolic blood pressure for the last 2 weeks of treatment with JTKL. The average rate of glucose infusion during the glucose clamp, as an index of insulin sensitivity (M value), was significantly lower in the FFR than in the control rats, and treatment with JTKL for 2 weeks significantly increased the M value to that of control. TNF-alpha levels were significantly higher in the soleus and EDL muscles of the FFR (480+/-46 and 570+/-45 pg/g wet tissue in the soleus and EDL muscles, respectively) than in those of the control rats (177+/-34 and 206+/-33 pg/g wet tissue in the soleus and EDL muscles, respectively; p<0.01). Treatment with JTKL for 2 weeks significantly lowered TNF-alpha levels to the control levels (189+/-22 and 239+/-92 pg/g wet tissue in the soleus and EDL muscles, respectively). The results suggest that the Chinese medicine JTKL improves insulin resistance and modulates TNF-alpha in the soleus and EDL muscles in hypertensive and insulin-resistant fructose-fed rats.
Asunto(s)
Medicamentos Herbarios Chinos , Resistencia a la Insulina , Animales , Glucemia , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Ayuno , Fructosa/farmacología , Técnica de Clampeo de la Glucosa , Frecuencia Cardíaca , Hipertensión/tratamiento farmacológico , Insulina/sangre , Masculino , Músculo Esquelético/química , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Studies reveals that plasma leptin levels (LEP) in females are higher than those in males, and that LEP in hypertensive subjects are higher than those in BMI-matched normotensive subjects. To investigate the relationships among LEP, blood pressure (BP) and insulin sensitivity, we studied these relationships in 133 Japanese males and 263 females. LEP were positively correlated with BP, body mass index, body fat mass (FM) and homeostasis model assessment (HOMA). Regression analysis in which age and FM were adjusted showed LEP were associated with BP and HOMA. Even with adjustment by age, FM and HOMA, LEP were still positively correlated BP in males. LEP in insulin-resistant hypertensives was significantly higher than those in insulin-sensitive hypertensives, in insulin-sensitive normotensives and in insulin-resistant normotensives in males. However, in females, a significantly higher LEP was observed in insulin-resistant subjects than in insulin-sensitive subjects regardless of hypertension. These data suggest that it would be sexual difference in the relationships among hyperleptinemia, hyperinsulinemia and hypertension.
Asunto(s)
Hiperinsulinismo/complicaciones , Hipertensión/complicaciones , Leptina/sangre , Vigilancia de la Población , Adulto , Presión Sanguínea , Índice de Masa Corporal , Femenino , Humanos , Hiperinsulinismo/sangre , Hipertensión/sangre , Insulina/sangre , Resistencia a la Insulina , Japón , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
Recent studies have shown that not only an enhanced renin-angiotensin system, but also relative volume retention might contribute to hypertension even in the early phase of a two-kidney, one-clip hypertensive model. To evaluate the role of renal depressor and natriuretic systems in the development of high blood pressure in the early phase of this model, we measured urinary excretion of kallikrein(uKAL), prostaglandin E2(uPGE2), and dopamine(uDA) in male Sprague-Dawley rats instrumented with a 0.2 mm diameter clip on the left renal artery(2K1C) and compared the results with those of sham-operated rats(sham). We also measured ouabain-like factor(OLF) in the plasma(pOLF) and urine(uOLF) in both groups. In 2K1C, systolic blood pressure(SBP) progressively increased and plasma renin activity was higher than the sham in the 3rd week. UDA and uPGE2 were not different between these groups, but uKAL attenuated in 2K1C in the 1st and 3rd week compared to the sham. There was a negative correlation between %delta SBP and %delta uKAL. On the other hand, uOLF increased in 2K1C in the 1st, 2nd and 3rd week compared to the sham. There was a positive correlation between SBP and uOLF. And pOLF was higher in 2K1C than in the sham. Furthermore there was a negative correlation between %delta uKAL and %delta uOLF. These results indicated that even in the early phase, suppression of the renal kallikrein-kinin system would contribute to high blood pressure in part, and OLF might play a compensatory role against the impaired natriuretic system in the kidney. However, OLF might contribute to blood pressure elevation through vasoconstriction in 2K1C.
Asunto(s)
Digoxina , Hipertensión/etiología , Animales , Presión Sanguínea , Cardenólidos , Dinoprostona , Modelos Animales de Enfermedad , Dopamina/orina , Hipertensión/fisiopatología , Sistema Calicreína-Quinina/fisiología , Calicreínas/orina , Riñón/fisiopatología , Masculino , Natriuresis , Ratas , Ratas Sprague-Dawley , Saponinas/sangre , Saponinas/orina , VasoconstricciónRESUMEN
OBJECTIVE: The aim of this study was to determine the role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle tissue in insulin resistance and hypertension and the effect of anti-hypertensive medicine on skeletal muscle TNF-alpha in fructose-induced insulin-resistant and hypertensive rats (fructose-fed rats: FFR). DESIGN AND METHODS: Six-week-old male Sprague-Dawley rats were fed either normal rat chow or fructose-rich chow. For the last 2 weeks of a 6-week period of either diet, the rats were treated with a vehicle (control or FFR); temocapril, an angiotensin converting enzyme inhibitor (ACEI); or CS-866, an angiotensin II type 1 receptor blocker (ARB). The euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity (M value). TNF-alpha levels in soleus and extensor digitorum longus (EDL) muscles and epididymal fat pads were measured. We also measured the TNF-alpha concentration in an incubated medium secreted from soleus muscle strips with or without angiotensin II. RESULTS: TNF-alpha levels were significantly higher in the soleus and EDL muscles, but not in the epididymal fat, in the FFRs compared with the control rats. Temocapril and CS-866 lowered systolic blood pressure, improved insulin resistance, and reduced TNF-alpha in both skeletal muscles. There were significant negative correlations between M values and TNF-alpha levels in both soleus and EDL muscles. Also, the soleus muscle strip incubation with 10(-7) mol/l angiotensin II increased TNF-alpha secreted into the incubation medium compared to the incubation without angiotensin II. These results suggest that skeletal muscle TNF-alpha is linked to insulin resistance and hypertension and that angiotensin II may be one of the factors that regulate skeletal muscle TNF-alpha.
Asunto(s)
Fructosa/farmacología , Hipertensión/metabolismo , Resistencia a la Insulina/fisiología , Músculo Esquelético/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Tejido Adiposo/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Glucemia , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Peso Corporal , Epidídimo/metabolismo , Técnica de Clampeo de la Glucosa , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Imidazoles/farmacología , Masculino , Olmesartán Medoxomilo , Ratas , Ratas Sprague-Dawley , Tetrazoles/farmacología , Tiazepinas/farmacologíaRESUMEN
A noninvasive method for the diagnosis of cardiac calcinosis, a life-threatening complication in hemodialysis patients with end-stage renal disease (ESRD), has not, as yet, been firmly established. We tested whether whole body scanning with 99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis. In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females, aged 40-81, mean 63 +/- 8 years) with cardiovascular disease [mitral annular calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects, respectively, but was absent in controls. Positive cardiac uptake was related to cardiac calcified complications (mobile intracardiac calcinosis, myocardial calcinosis and mitral annular calcification) and the duration of hemodialysis (p = 0.015). While it was statistically insignificant, subjects showing MDP uptake were elder and had higher serum Ca or Ca x P product and lower intact parathyroid hormone levels. These results suggest that cardiac calcinosis in ESRD patients can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP.
Asunto(s)
Calcinosis/diagnóstico por imagen , Calcinosis/etiología , Cardiomiopatías/diagnóstico por imagen , Radiofármacos , Diálisis Renal/efectos adversos , Medronato de Tecnecio Tc 99m , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Radiofármacos/efectos adversos , Radiofármacos/farmacocinética , Medronato de Tecnecio Tc 99m/efectos adversos , Medronato de Tecnecio Tc 99m/farmacocinética , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-induced insulin-resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angiotensin-converting enzyme inhibitor (FFR+ACE), temocapril (1 mg/kg/ day) or an angiotensin II receptor antagonist (FFR+AT), CS-866 (0.3 mg/kg/day), by gavage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp, the soleus muscle was dissected for determination of the muscle fiber composition by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both temocapril and CS-866 significantly lowered the blood pressure of the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR rats compared to the controls (15.4 +/- 0.4, 10.9 +/- 0.6 mg/kg/min, for control and FFR, respectively, P < .01). Both temocapril and CS-866 partially improved the M values compared to FFR (13.2 +/- 0.7, 12.8 +/- 0.5 mg/kg/min, for FFR+ACE, FFR+AT, respectively, P < .01 compared with FFR, P < .05 compared with control). The composite ratio of type I fibers of the soleus muscle was decreased significantly in the FFR rats compared with the controls (82% +/- 2%, 75% +/- 2%, for control and FFR, respectively, P < .01), and both temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% +/- 1%, 80% +/- 1% for FFR+ACE and FFR+AT, respectively). The M value was significantly correlated with the composition of type I and type II fibers. These results suggest that the fiber composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber composition in a hypertensive and insulin-resistant animal model, fructose-fed rats, to the same extent.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Fructosa/administración & dosificación , Resistencia a la Insulina , Animales , Antihipertensivos/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Ayuno , Glucosa/farmacología , Técnica de Clampeo de la Glucosa , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Hipertensión/fisiopatología , Imidazoles/farmacología , Magnesio/administración & dosificación , Magnesio/sangre , Masculino , Fibras Musculares de Contracción Rápida/química , Fibras Musculares de Contracción Rápida/efectos de los fármacos , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares de Contracción Lenta/química , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Músculo Esquelético/química , Músculo Esquelético/efectos de los fármacos , Olmesartán Medoxomilo , Ratas , Ratas Sprague-Dawley , Tetrazoles/farmacología , Tiazepinas/farmacologíaRESUMEN
The aim of this study was to determine the effect of Tang-Shen-Jiao-Nang (TSJN), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 wk. For the last 2 or 4 wk of a 6-wk period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or TSJN (800 mg/kg/d; FFR+TS), and then we performed the euglycemic hyperinsulinemic glucose clamp technique to estimate insulin sensitivity. Systolic blood pressure was measured weekly for 6 wk. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Systolic blood pressure was elevated at 2 wk after the start of the fructose-rich chow feeding and persisted thereafter throughout the study. Systolic blood pressure during the glucose clamp in the FFR group was significantly higher than that in the control group. Although there was no effect on systolic blood pressure in rats treated with TSJN for the last 2 wk of their 6-wk diet, those treated with TSJN for the last 4 wk of their 6-wk diet had lower systolic blood pressure than did the rats in the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the controls (10.9 +/- 0.6 and 15.4 +/- 0.4, mg/kg/min, for FFR and controls, respectively; p< 0.01). Treatment with TSJN for 2 wk significantly improved the M value compared to that of the control level (15.1 +/- 0.5 mg/kg/min). The composite ratio of type I fibers in the soleus muscle was significantly decreased in the FFR compared to controls (75.0 +/- 1.7 and 81.7 +/- 1.5%, for FFR and controls, respectively; p< 0.01), and treatment with TSJN for 2 wk led to a recovery composite ratio of type I fiber to the same level as that of the control group (78.7 +/- 1.7% in FFR + TS). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r= 0.45, p < 0.01, for type II fibers, r= -0.44, p< 0.05). These results suggest that the Chinese medicine TSJN may improve insulin resistance, lower the systolic blood pressure, and modulate muscle fiber composition in hypertensive and insulin-resistant fructose-fed rats.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Fructosa , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Resistencia a la Insulina/fisiología , Animales , Glucemia/análisis , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Ayuno/sangre , Técnica de Clampeo de la Glucosa , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Fibras Musculares Esqueléticas/clasificación , Fibras Musculares Esqueléticas/ultraestructura , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.
Asunto(s)
Calcio/metabolismo , Enfermedades Cardiovasculares/etiología , Hidroxicolecalciferoles/efectos adversos , Hipoparatiroidismo/complicaciones , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Adulto , Anciano , Anciano de 80 o más Años , Calcinosis/etiología , Calcinosis/metabolismo , Enfermedades Cardiovasculares/metabolismo , Femenino , Humanos , Hipercalcemia/complicaciones , Hipercalcemia/etiología , Hipoparatiroidismo/etiología , Hipoparatiroidismo/metabolismo , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Diálisis Renal/efectos adversosRESUMEN
New spectrophotometer was designed for the simultaneous assay of copper and iron using flow injection analysis and moreover, new 50 mm light path cells were equipped in the spectrophotometer to enhance the sensitivity. Both copper and iron at 2-10 ppb level were determined simultaneously and rapidly using water soluble reagent, 5-Br-PSAA. Determination limits were 1 ppb for copper and 1 ppb for iron. Relative standard deviations were about 1%.
RESUMEN
Blood serine protease inhibitors are becoming better understood and increasingly applied in blood clotting, cancer and other diseases. Reptiles are suitable models for blood coagulation and related processes, moreover, caiman is a good comparative model of a non-poisonous reptile. Recently, we reported the purification of a kininogen, the presence of proteases involved in blood clotting, and a serine protease inhibitor in Caiman crocodilus yacare plasma. In this paper, we described the partial sequence of an inhibitor (CcTI). The inhibitor is an 80-kDa protein, and it inactivates trypsin and chymotrypsin the hydrolysis of specific chromogenic substrates and in the degradation of gelatin. The inhibitor is member of Kazal-type inhibitor family and consists of several domains, its putative reactive site is Arg-His.
Asunto(s)
Caimanes y Cocodrilos/sangre , Proteínas Sanguíneas/química , Inhibidores de Serina Proteinasa/química , Secuencia de Aminoácidos , Animales , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Inhibidores de Serina Proteinasa/sangre , Inhibidor de Tripsina Pancreática de Kazal/sangreRESUMEN
It is well-known that angiotensin converting enzyme (ACE) inhibitor not only decreases blood pressure (BP) but also improves insulin sensitivity. To elucidate the mechanisms of these actions of ACE inhibitor, we evaluated its effect on both BP and insulin sensitivity (M-value) as estimated by the glucose clamp technique in essential hypertensives in comparison with the effect of angiotensin receptor (AT) antagonist. We also evaluated the effect of ACE inhibitor on BP, M-value and muscle fiber composition in fructose-fed rats (FFR) as an insulin-resistant hypertensive model with or without treatment with Hoe 140 (kinin receptor antagonist). In essential hypertensives, both ACE inhibitor and AT antagonist decreased BP and improved insulin sensitivity to the same extent. In FFR, ACE inhibitor also decreased BP and improved insulin sensitivity. Moreover, Hoe 140 showed no effect on these actions of ACE inhibitor. The composite ratio of type I fiber of soleus muscle was decreased significantly in FFR compared to control and ACE inhibitor produced a recovery of the composite ratio of type I fiber to the same as control. These results suggested that muscle fiber composition of skeletal muscle is linked to insulin resistance, and that ACE inhibitor may modulate muscle fiber composition through its vasodilative effect in hypertension. These results also suggest that for vasodilation, it is more important to inhibit angiotensin II than to block degradation of kinins or to improve insulin sensitivity by ACE inhibitor.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Resistencia a la Insulina/fisiología , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Animales , Presión Sanguínea/efectos de los fármacos , Dieta , Fructosa/administración & dosificación , Técnica de Clampeo de la Glucosa , Humanos , Hipertensión/sangre , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/efectos de los fármacos , Músculo Esquelético/química , Músculo Esquelético/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Angiotensina/fisiologíaRESUMEN
Cardiac calcinosis is a common complication of end stage renal disease. A newly observed risk of thromboembolism is reported in four patients with mobile cardiac calcinosis, treated with long term dialysis. Rapidly growing mobile calcification was confirmed by echocardiography. Each patient had an imbalance in serum calcium x inorganic phosphate (Ca x P product >/= 50); this imbalance could not be treated due to the sudden death of the patient or the need for surgical resection to prevent recurrent cerebral thromboembolism. Histological examination revealed intracardiac calcinosis in three cases, and each case showed haemodialysis hypoparathyroidism (intact PTH < 160 pg/ml). Thromboembolism in such cases is rare, however it indicates a need for cautious echocardiographic monitoring in end stage renal disease in patients with an uncontrolled Ca x P product.
Asunto(s)
Calcinosis/complicaciones , Cardiomiopatías/complicaciones , Fallo Renal Crónico/complicaciones , Tromboembolia/etiología , Anciano , Calcinosis/diagnóstico , Ecocardiografía Transesofágica , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Renal , Factores de RiesgoRESUMEN
1. In order to investigate the changes of reduced urinary free dopamine excretion (uDA) in heart failure, 15 patients with symptomatic mitral stenosis were investigated on their uDA, endogenous creatinine (Cr) clearance, urinary excretion of sodium (UNaV), fractional excretion of sodium (FENa), plasma noradrenaline (pNA) and plasma L-dopa concentration before and early after percutaneous transvenous mitral commissurotomy (PTMC) by the clearance study. The delivery of L-dopa to renal proximal tubules (plasma L-dopa x Cr clearance), and the conversion ratio of plasma L-dopa to urinary dopamine in the kidney [uDA/(plasma L-dopa x Cr clearance)] were also estimated. 2. After successful PTMC, uDA, UNaV and FENa showed a significant but incomplete improvement and the changes of uDA were correlated positively with those of cardiac index (CI) (r = 0.665, P < 0.01), not with changes of pulmonary wedge pressure. While plasma L-dopa and plasma L-dopa x Cr clearance improved, uDA/(plasma L-dopa x Cr clearance) was not significantly changed early after PTMC. 3. From these results, it was suggested that reduced uDA tended to increase incompletely in relation with functional recovery of heart, and that increased plasma L-dopa and a delivery of L-dopa to renal proximal tubules have some positive role on urinary dopamine excretion, at least, early after PTMC.