RESUMEN

ParaSHIFT agents have shown promise in detecting chemical targets in biological systems by magnetic resonance, but few studies have used transition metal complexes for this purpose. Here we report our investigations into CoMe6trenCl (tren = tris(2-aminoethyl)amine) as a paraSHIFT agent. The paramagnetic region of the 1H NMR spectrum shows characteristic spectral profiles in the presence of fluoride, acetate, lactate and citrate in aqueous solution. These distinctive NMR shifts of each anion are maintained even in mixtures of anions.

RESUMEN

OBJECTIVE: Cassava, a major carbohydrate source in Africa, contains potentially diabetogenic chemicals, although its consumption is not associated with incident diabetes. As it is not known whether cassava intake impairs residual beta-cell function in patients with type 2 diabetes (T2D), our study compared the metabolic phenotypes of diet- and/or oral antidiabetic drug (OAD)-treated T2D patients in South Kivu (Democratic Republic of the Congo) with [Cassava (+); n=147] and without [Cassava (-); n=46] self-reported cassava consumption. DESIGN & METHODS: A total of 193 patients [male:female (%) 37:63; mean +/-1 SD age: 56+/-11 years] were interviewed to determine the frequency and distribution of eight major dietary carbohydrate (CHO) sources (cassava, plantain, rice, maize, bread, sorghum, potatoes and legumes). Fasting glucose, insulin and lipid levels were obtained after an overnight fast and OAD discontinuation. Cassava (+) and Cassava (-) groups were compared for HOMA indices of insulin sensitivity (S), beta-cell function (B), hyperbolic product (B x S) and B x S loss rate (B x S LR). RESULTS: Diabetes duration was 6+/-7 years, age at diabetes diagnosis was 51+/-11 years and BMI was 25+/-5 kg/m(2). Cassava intake was reported by 76% of patients, and amounted to 29+/-11% of their daily CHO intake. The Cassava (-) group ate more plantain, maize, bread and potatoes, and less sorghum. Age, gender and age at diabetes diagnosis did not differ between Cassava (+) and (-) patients, nor did BMI, fat mass, waist circumference, lipid profile and metabolic syndrome prevalence. HOMA indices of S, B, B x S and B x S LR did not differ significantly between groups-Cassava (+) vs (-): S, 114+/-56% vs 114+/-60%; B, 34+/-30% vs 39+/-32%; B x S, 38+/-35% vs 40+/-31%; and B x S LR, 1.19+/-0.84% vs 1.09+/-0.65% per year-nor did the glucose-lowering modalities. CONCLUSION: Cassava consumption in South Kivu is not associated with changes in T2D phenotype or in the glucose homoeostasis determinants S, B, B x S and B x S LR. Cassava consumption does not accelerate beta-cell function loss in such a population, whose markedly compromised glucose homoeostasis renders them vulnerable to environmentally acquired beta-cell impairment.

Asunto(s)

Diabetes Mellitus Tipo 2/metabolismo , Dieta , Manihot , Adulto , Anciano , Análisis de Varianza , Metabolismo de los Hidratos de Carbono/fisiología , Estudios Transversales , República Democrática del Congo/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/fisiología , Masculino , Persona de Mediana Edad , Fenotipo

RESUMEN

OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients. DESIGN: A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (-600 kcal/day; < or =30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase. SUBJECTS: Patients with body mass index (BMI) 27-40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1-6.7 mmol/l). MEASUREMENTS: Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments. RESULTS: Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was-6.8% in the orlistat group and -3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of > or =5% (64 vs 39%) or > or =10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (-11.9% vs -4.0%; P<0.001) and LDL-C (-17.6 vs -7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (> or =1 event in 64 vs 38% of patients). CONCLUSION: Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia.

Asunto(s)

Fármacos Antiobesidad/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Lactonas/uso terapéutico , Obesidad/tratamiento farmacológico , Adolescente , Adulto , Anciano , Fármacos Antiobesidad/administración & dosificación , Bélgica , Colesterol/sangre , LDL-Colesterol/sangre , Dieta Reductora , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/dietoterapia , Lactonas/administración & dosificación , Lipasa/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Orlistat , Resultado del Tratamiento , Pérdida de Peso

RESUMEN

OBJECTIVE: To examine associations between sociodemographic, dietary factors and physical activity and the prevalence of obesity in the Belgian general population. DESIGN: Base-line data from the Belgian Interuniversity Research on Nutrition and Health (BIRNH) study (1979-1984). SUBJECTS: A total of 5837 men and 5243 women aged 25-74y were included in the analysis. The sample was considered representative of the Belgian population. MEASUREMENTS: Using the body mass index (BMI) as the criterion, obesity was defined as a BMI> or =30 kg/m2. Nutritional data were assessed by a 24 h food record. Physical activity level (PAL) was calculated by dividing total caloric intake by an estimation of basal metabolic rate (BMR, predicted from gender, weight and age). Age-adjusted odds ratios (OR) of the prevalence of obesity were estimated by multilogistic regression analysis. RESULTS: Prevalence of obesity was 12.1% in men and 18.4% in women. In both sexes, prevalence of obesity increased gradually in each 10-year age category (P<0.0001) and steeply decreased with level of education. Comparing lowest (Q1) to highest quartile (Q4), after adjustment for age, prevalence of obesity decreased with total carbohydrate intake, as well as total sugar intake in both sexes, and increased with total fat intake only in men. Obesity increased with a high fat to sugar ratio (men: OR(Q4/Q1) = 1.56; confidence interval (CI): 1.25-1.93; women: OR(Q4/Q1) = 1.45; CI: 1.17-1.80). PAL was inversely and very strongly associated with obesity (men: OR(Q4/Q1) = 0.20; CI: 0.15-0.26; women: OR(Q4/Q1) = 0.18; CI: 0.14-0.23). The same associations were observed with the mean BMI. CONCLUSION: This study indicates that prevalence of obesity is particularly high in Belgium. Low level of education and reduced physical activity, increased fat intake and especially elevated fat to sugar ratio appear to be powerful determinants of obesity in this Belgian population.

Asunto(s)

Estado Nutricional , Obesidad/epidemiología , Adulto , Anciano , Metabolismo Basal , Bélgica/epidemiología , Índice de Masa Corporal , Ingestión de Energía , Ejercicio Físico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores Socioeconómicos

RESUMEN

While the prevalence of hypertension is clearly increased among the overweight persons, the pathophysiological mechanisms underlying this frequent association of obesity and hypertension are still poorly understood. The expansion of extracellular volume, inducing hypervolaemia and increased cardiac output, represents the characteristic haemodynamic feature of the obesity-related hypertension. The maintenance of hypervolemia in the face of elevated blood pressure, indicates a resetting of pressor natriuresis toward higher blood pressure. The development of hypertension also indicates an increase in peripheral vascular resistance, thus the lack of physiological adaptation of peripheral resistance to increased cardiac output. The mechanisms underlying these changes in renal function and vascular reactivity can no longer be attributed to hyperinsulinaemia as such, but might be related to insulin resistance responsible for the enhancement in pressor activity of noradrenaline and angiotensin II. This increased reactivity to pressor factors may be due to an inadequate nitric oxide generation by vascular endothelium and to increased sodium and calcium concentration in vascular smooth muscle cells. The role of increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement of tubular sodium reabsorption, it could be related to histological changes within the renal medulla, leading to compression of tubules and vasa recta, hence a more efficient sodium reabsorption. As to the therapeutic approach, the low-energy sodium-restricted diet associated with increased physical activity, represents the cornerstones of treatment for the obesity-related hypertension. If this approach fails, the pharmacological treatment becomes necessary, and the use of the converting enzyme inhibitors seems to be the most appropriate choice of drug therapy for hypertensive obese patients.

Asunto(s)

Hipertensión/fisiopatología , Hipertensión/terapia , Obesidad/fisiopatología , Obesidad/terapia , Animales , Humanos , Hipertensión/etiología , Riñón/fisiopatología , Obesidad/complicaciones , Resistencia Vascular , Desequilibrio Hidroelectrolítico/etiología

RESUMEN

This review evaluates the benefits and potential health risks of the currently used drugs that are approved for the pharmacological treatment of obesity. Analysis of several long term clinical trials indicates that all of these drugs are efficient in reducing excess bodyweight, and that the majority of them allow the maintenance of the reduced bodyweight for at least 1 year. However, the loss of bodyweight attributable to these drugs is in general rather modest, approaching only 0.2 kg per week during the first 6 months of treatment, and at least a partial regain of bodyweight occurs when these drugs are used for periods longer than 1 year. All of these drugs induce several adverse effects. Although most of these adverse effects are mild and transient, the prolonged use of adrenergic or serotonergic anorectic drugs, or their use as combination treatment, may induce serious and potentially life-threatening complications, such as primary pulmonary hypertension or valvular heart disease. The adrenergic appetite-suppressing drugs are not recommended for the treatment of obesity, since their safety has never been evaluated in long term clinical trials, and because of their stimulatory effects on the cardiovascular and nervous systems. The serotonergic drugs, such as fenfluramine and dexfenfluramine, have been the most widely used during the past decade; however, both these compounds have recently been withdrawn from the market, since their use was associated with serious cardiovascular complications. The safety of the prolonged therapeutic use of newer compounds such as sibutramine and orlistat has not yet been demonstrated. Therefore, none of the currently available anti-obesity medications meets the criteria of an 'ideal anti-obesity drug' and, if prescribed, these medications should be used with caution and only under careful medical supervision. Since obesity is recognised as a chronic health-threatening condition, and since classical behavioural therapeutic approaches lack long term efficacy, there is clearly a need for an efficient pharmacological treatment offering an acceptable safety profile. Such a treatment is not available at present. Development of new agents and a more careful assessment of the safety of currently available drugs are needed.

Asunto(s)

Fármacos Antiobesidad/uso terapéutico , Obesidad/tratamiento farmacológico , Fármacos Antiobesidad/efectos adversos , Sistema Cardiovascular/efectos de los fármacos , Humanos , Medición de Riesgo

RESUMEN

OBJECTIVE: To assess trends in average body mass index (BMI) and the prevalence of obesity between 1977 and 1992, in middle-aged Belgian men at work. SUBJECTS: A subsample of men at work, aged 40-54 y extracted from the base-line data from four independent prospective studies, each representing a period (Physical Fitness Study (1977-1978), Belgian Interuniversity Research on Nutrition and Health (BIRNH) (1979-1984), Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases (MONICA) (1986-1991) and ORCA (1992-1993)). DESIGN: Linear regression of the average body mass index (kg/m2) and logistic regression of the prevalence of obesity (BMI > or = 30kg/m2). Independent variables taken into account in multivariate analysis were: age, educational level, marital status and region. RESULTS: In this subsample of Belgian men at work, aged 40-54 y, prevalence of obesity increased from 9.2% in 1977-1978 to 14.5% in 1992-1993. This rise was present in each five-year age group, in both regions and in all educational groups, but strongest in the lowest educated. After adjustment for sociodemographic covariables, it was estimated that with regard to 1977-1978, the proportion of men with a BMI > or = 30 kg/m2 doubled over the 15-year period (odds ratio OR (95% confidence intervals, 95% CI)): 1.98 (1.40; 2.80). CONCLUSION: Keeping in mind that the trends have been calculated from data from four different studies, presenting some shortcomings, prevalence of obesity has increased between 1977-1992 in men aged 40-54 y at work. This rise is particularly pronounced in the lower educated groups.

Asunto(s)

Índice de Masa Corporal , Obesidad/epidemiología , Adulto , Anciano , Bélgica/epidemiología , Escolaridad , Humanos , Masculino , Estado Civil , Persona de Mediana Edad , Análisis de Regresión , Trabajo

RESUMEN

The mechanisms underlying the reduction in blood pressure that occurs with a severe energy-restricted diet were evaluated in 12 obese subjects during 8 days on a very-low-calorie diet (1.67 MJ/d) with a constant intake of 17 mmol sodium per day. The relationship between changes in blood pressure, sodium balance, plasma volume, renin-aldosterone and sympathetic nervous system activities, plasma C-terminus and N-terminus of the atrial natriuretic factor (ANF) prohormone, brain natriuretic peptide (BNP), and endothelin-1 (ET-1) concentrations was investigated. A negative sodium balance was present throughout the diet and was associated with a moderate reduction in plasma volume, a marked activation of the renin-aldosterone system, and a concomitant reduction in C- and N-terminal ANF prohormone levels. Moreover, the postural changes in N-terminal proANF and ANF secretion documented before the diet, disappeared after 8 days of dieting, in contrast to a greater postural stimulation of aldosterone and renin. A negative correlation was found between the changes of C- and N-terminal ANF prohormone levels and those of aldosterone. Urinary catecholamine excretion, BNP, and ET-1 remained unchanged. These results indicate that the decrease in blood pressure occurring during severe caloric restriction was essentially due to the reduction in the effective blood volume, as reflected by the stimulation of the renin-aldosterone system and the decrease in ANF levels. The lack of any changes in catecholamine excretion and endothelin levels suggests that peripheral vascular resistance did not change significantly in these circumstances.

Asunto(s)

Presión Sanguínea/fisiología , Privación de Alimentos/fisiología , Hormonas/metabolismo , Obesidad/fisiopatología , Adolescente , Adulto , Aldosterona/sangre , Factor Natriurético Atrial/sangre , Nitrógeno de la Urea Sanguínea , Peso Corporal/fisiología , Catecolaminas/orina , Creatinina/sangre , Interpretación Estadística de Datos , Dieta Reductora , Electrólitos/sangre , Endotelina-1/sangre , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hidrocortisona/sangre , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico , Proteínas del Tejido Nervioso/sangre , Obesidad/sangre , Obesidad/orina , Volumen Plasmático/fisiología , Renina/sangre , Sodio/sangre , Inanición/fisiopatología , Ácido Úrico/sangre

RESUMEN

Since severe obesity is frequently associated with serious metabolic, cardiovascular and psychological co-morbid conditions, and given the usually unsuccessful results of conservative therapeutic approaches, surgical treatment based on gastric restriction procedures is increasingly recognized as a treatment of choice for morbidly obese persons. Among several surgical approaches designed to promote a substantial loss of weight, two gastric restriction procedures, i.e. the vertical banded gastroplasty and the gastric bypass, have been increasingly used during the past years. Both techniques induce an impressive loss of weight, and are surprisingly well tolerated, even by severely obese persons. The usual 50-75% reduction of initial weight excess, is followed by a clear-cut reduction, or even disappearance of, obesity-related co-morbidity, such as hypertension, diabetes mellitus or sleep apnea syndrome. While serious peri- and postoperative risks are very limited, the intractable vomiting occurring after gastroplasty, and potential sequelae related to iron and calcium malabsorption after the gastric bypass, represent much more frequent complications of the surgical treatment of obesity. There is also a tendency towards a late regain of weight, but the benefit in terms of improvement in the obesity-associated co-morbidity is in general maintained despite this partial increase in weight. Gastric procedures are, therefore, an effective treatment of severe obesity and of its co-morbid conditions. However, careful medical and nutritional supervision is necessary during the follow-up after surgery, to prevent potential nutritional or digestive complications.

Asunto(s)

Obesidad Mórbida/cirugía , Dieta , Derivación Gástrica , Gastroplastia , Humanos , Fenómenos Fisiológicos de la Nutrición , Pérdida de Peso

RESUMEN

Weight reduction is essential in the management of most non-insulin-dependent diabetics, but this therapeutical goal is difficult to obtain. In this double-blind parallel study, 82 non-insulin-dependent diabetics, moderately obese (BMI = 30 - 39 kg/m2), were given for an 8-week period either placebo (P) or fluoxetine (F), a specific serotonin reuptake inhibitor, in addition to their usual antidiabetic treatment. Thirty-nine of them received 60 mg fluoxetine a day and 43 were given the placebo. At admission, both groups had similar weight excess, metabolic control and serum lipid values. In comparison with the P-treated subjects, those treated with fluoxetine (F) lost more weight after 3 weeks (-1.9 vs. -0.7 kg, p < -0.0009) and after 8 weeks (-3.1 vs. -0.9 kg, p < 0.0007). Fasting blood glucose decreased in group F after 3 weeks (-1.5 vs -0.4 mmol/L, p < 0.003) and after 8 weeks (-1.7 vs. -0.02 mmol/L, p < 0.0004). HbAlc decreased from 8.5% to 7.7% in group F and from 8.6% to 8.3% in group P (p = 0.057). Mean triglyceride level was also reduced in group F after 8 weeks (p = 0.042). Fasting C-peptide did not change in either group, but fasting insulin values decreased in group F after 3 weeks (p < 0.02) and after 8 weeks (p < 0.05). The insulin/C-peptide molar ratio decreased significantly in group F after 3 weeks (p < 0.04) and after 8 weeks (p < 0.05) in comparison with group P. The drug was generally well tolerated and no major side effects were reported. In conclusion, the addition of fluoxetine to the usual oral hypoglycemic agent therapy might be beneficial in obese non-insulin-dependent diabetics, at least on a short-term basis.

Asunto(s)

Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Fluoxetina/uso terapéutico , Obesidad , Adolescente , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Método Doble Ciego , Fluoxetina/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Insulina/sangre , Lípidos/sangre , Persona de Mediana Edad , Placebos , Triglicéridos/sangre , Pérdida de Peso

RESUMEN

Although several reports suggest that pharmacologic amounts of glucagon may promote natriuresis, the influence of a physiological or even pathophysiological increase in circulating glucagon levels on kidney function has never been convincingly demonstrated. The present study was therefore undertaken to determine whether a moderate increase in plasma glucagon concentration of blood perfusing the kidney may influence kidney function and promote urinary sodium excretion. To this end, glucagon was infused directly into one renal artery of anesthetized dogs at a rate of 1 ng x kg(-1) x min(-1), calculated to increase glucagon concentration in the blood perfusing the kidney within the pathophysiologic range and thus to levels seen in some catabolic states such as poorly controlled diabetes or starvation. The contralateral kidney was infused with saline only. The estimated concentration of glucagon in blood perfusing the hormone-infused kidney increased with glucagon infusion from 227 pg x mL(-1) during the control period to mean of 779 pg x mL(-1). There was a significant increase in glucagon extraction by this kidney, from 33% in baseline conditions to 61% upon intrarenal infusion of the hormone, and hence venous glucagon levels were only slightly higher than in the contralateral kidney. Despite a more than threefold increase in glucagon levels in blood perfusing the hormone-infused kidney versus the contralateral kidney, this experimentally induced hyperglucagonemia was without influence on renal plasma flow (RFP), glomerular filtration rate (GFR), renal vascular resistance, renal uptake of oxygen and energy-providing substrates. Excretion of Na+, K+, Cl-, and PO4(3-) was likewise unaffected. These results indicate that hyperglucagonemia, at least of a magnitude comparable to that seen in starvation or diabetic decompensation, is devoid of any detectable direct influence on renal hemodynamics or tubular function.

Asunto(s)

Glucagón/farmacología , Riñón/efectos de los fármacos , Sodio/metabolismo , Animales , AMP Cíclico/orina , Perros , Femenino , Glucagón/metabolismo , Hemodinámica/efectos de los fármacos , Riñón/metabolismo , Masculino

RESUMEN

A 33-year-old woman with AIDS was treated with somatostatin (continuous infusion 6 mg/day) for intractable diarrhoea. Improvement was insufficient and the dose was increased to 12 mg/day 5 days later. Hyperosmolar non-ketotic coma occurred two days later (blood glucose 53 mmol/l, bicarbonate 8 mmol/l, pH of arterial blood 7.2). Search for urinary ketones was negative. Klebsiella pneumonia was isolated in the urine sample. Somatostatin was withdrawn and the patient improved with parenteral nutrition and intravenous insulin. Glucose tolerance was verified after recovery and was normal. Somatostatin is known to impair glucose tolerance and as shown in this case should also be recognized as a cause of hyperosmolar non-ketotic coma. Increasing use of somatostatin, particularly in HIV patients often given other hyperglycaemia inducing drugs such as didanosine, pentamidine, dapsone, and phenytoin should be accompanied with careful monitoring of blood glucose levels.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/complicaciones , Diarrea/tratamiento farmacológico , Antagonistas de Hormonas/efectos adversos , Coma Hiperglucémico Hiperosmolar no Cetósico/inducido químicamente , Somatostatina/efectos adversos , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Antibacterianos , Diarrea/etiología , Quimioterapia Combinada/uso terapéutico , Femenino , Antagonistas de Hormonas/administración & dosificación , Antagonistas de Hormonas/uso terapéutico , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Somatostatina/administración & dosificación , Somatostatina/uso terapéutico , Infecciones Urinarias/complicaciones , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología

RESUMEN

To evaluate the benefit of gastric surgery in terms of improvement in health risk factors, the loss of weight and its long-term maintenance, 28 non-diabetic morbidly obese subjects were followed during three to five years after vertical banded gastroplasty. Aside from a rapid and sustained loss of weight averaging nearly 75% reduction of weight excess, there occurred a concomitant improvement in glucose tolerance with 50% reduction in fasting insulinaemia and correction of hypertension. The improvement in cardiovascular risk factors also included the drop in plasma triglycerides associated with an increase in HDL-cholesterol, while uricaemia decreased to low normal levels. Gastric procedures are therefore an effective treatment of severe obesity and of its comorbid conditions, but they should be followed by careful medical and nutritional monitoring to prevent any possible digestive or nutritional complications.

Asunto(s)

Gastroplastia/normas , Obesidad Mórbida/cirugía , Adulto , Bélgica/epidemiología , Glucemia/análisis , Presión Sanguínea/fisiología , Peso Corporal/fisiología , HDL-Colesterol/sangre , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Obesidad Mórbida/sangre , Obesidad Mórbida/epidemiología , Obesidad Mórbida/fisiopatología , Triglicéridos/sangre , Pérdida de Peso/fisiología

Asunto(s)

Hipertensión/terapia , Obesidad/complicaciones , Femenino , Hemodinámica/fisiología , Humanos , Hipertensión/etiología , Hipertensión/fisiopatología , Insulina/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Sodio/metabolismo

Asunto(s)

Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Fenómenos Fisiológicos de la Nutrición , Enfermedades Cardiovasculares/fisiopatología , Humanos , Factores de Riesgo

RESUMEN

To examine the effect of ketone body utilization on sympathetic nervous system (SNS) activity, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed diets enriched with D(-)3-hydroxybutyrate (3OHB), the naturally occurring isomer of hydroxybutyrate. Isoenergetic substitution of 3OHB for chow for 4 days increased cardiac [3H]NE turnover (P < .025), with a slightly less marked (P < .06) effect in IBAT. When [3H]NE turnover was measured in rats fed chow diets supplemented with 3OHB or sucrose and compared with that in animals fed chow alone, [3H]NE turnover rates in heart and IBAT were similar in the ketone-supplemented and chow-fed groups. Animals fed the sucrose-supplemented chow displayed lower rates of [3H]NE turnover in IBAT than rates found in those given the 3OHB-containing chow (-36%, P < .025 in IBAT). In addition, the stimulatory effect on SNS activity of a 4-day exposure to a sucrose-enriched diet after 2 days of fasting was significantly enhanced by concomitant ketone ingestion. Fractional NE turnover in IBAT was increased from 9.3% +/- 1.3%/h in control rats to 14.2% +/- 0.9%/h in rats refed with 3OHB (P < .005). These observations indicate that increased ketone body utilization does not suppress SNS activity and may stimulate it in a manner quantitatively similar to that seen with carbohydrate or fat ingestion.

Asunto(s)

Hidroxibutiratos/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Ácido 3-Hidroxibutírico , Tejido Adiposo Pardo/metabolismo , Animales , Dieta , Ayuno , Alimentos , Hidroxibutiratos/administración & dosificación , Hidroxibutiratos/química , Masculino , Miocardio/metabolismo , Norepinefrina/metabolismo , Ratas , Ratas Endogámicas , Estereoisomerismo , Sacarosa/administración & dosificación , Sacarosa/farmacología

RESUMEN

The purpose of the present study was to assess whether a moderate increase in ketonemia interferes with renal uptake of energy-providing substrates, and whether it may promote natriuresis similar to that occurring spontaneously during the early phase of starvation. To this end, the sodium salt of D(-)3-hydroxybutyrate (3OHB) was infused to 10 anesthetized dogs at a rate of 20 mumol/kg.min-1 over 135 minutes. To allow comparison, an equivalent amount of sodium was infused as sodium bicarbonate to 10 other dogs (to induce an alkalinization similar to that resulting from the utilization of the sodium salt of 3OHB), while 10 additional dogs received an equimolar infusion of NaCl to provide reference values. Before 3OHB or bicarbonate infusion, lactate represented the major fuel taken up by the kidney (28 +/- 3 mumol/100 g kidney.min-1 on average). While small but significant amounts of 3OHB were taken up by the kidney in control conditions (0.7 +/- 0.1 mumol/100 g.min-1; P < .05), there was no significant uptake of free fatty acids (FFA) or glucose. Upon 3OHB infusion, which increased plasma 3OHB levels to 1.7 mmol/L, the renal uptake of this substrate increased to 25 +/- 3 mumol/100 g.min-1, in proportion to renal 3OHB availability (r = .73, P < .001). Despite an increase in arterial lactate levels that occurred during 3OHB infusion, renal lactate uptake and the extraction ratio of this substrate were decreased (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Cuerpos Cetónicos/metabolismo , Túbulos Renales/metabolismo , Riñón/metabolismo , Lactatos/metabolismo , Sodio/metabolismo , Ácido 3-Hidroxibutírico , Absorción , Análisis de Varianza , Animales , Bicarbonatos/metabolismo , Perros , Femenino , Concentración de Iones de Hidrógeno , Hidroxibutiratos/metabolismo , Ácido Láctico , Masculino , Consumo de Oxígeno , Bicarbonato de Sodio

RESUMEN

To evaluate the role of dietary polyamines in maturation of the rat small intestine, spermine was given orally twice daily to suckling pups from day 10 to day 14 postpartum at different doses: 0, 0.2, 0.5, 1, 2.5, and 5 mumol/dose. Compared to saline treated controls, spermine (5 mumol) produced significant increases in mucosal mass parameters (+12 to +57%, P < 0.05), induced prematurely an adult pattern of microvillous enzymes, and enhanced, respectively, by 19- and 3.5-fold (P < 0.01 vs controls) the concentration of the secretory component of p-immunoglobulins in villous and crypt cells. The response of microvillous enzymes (lactase, sucrase, maltase, and aminopeptidase) to spermine was dose-dependent and -specific since oral administration of arginine (5 mumol) or ornithine (5 mumol) was without effect. Intestinal changes were found to be significant (P < 0.05) for doses of spermine exceeding 1 mumol/day, which is in the range of the amount of polyamines provided by solid pellets at weaning (0.4 mumol/g). However, intestinal changes were undetectable at the physiological amounts of polyamines consumed by pups from rat milk during the suckling period (less than 0.3 mumol/day). Consistent with a direct effect of spermine on the intestinal cell, the cytosolic activity of ornithine decarboxylase was depressed by 27-fold (P < 0.005 vs controls) in the jejunum, while inhibition of ornithine decarboxylase by alpha-difluoromethylornithine did markedly decrease but did not suppress the cell response to spermine. Alternately, plasma corticosteronemia, which was virtually absent by day 14 in controls, ranged between 1.4 and 4.6 micrograms/dl in 60% (N = 9) of the spermine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Dieta , Mucosa Intestinal/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Poliaminas/farmacología , Animales , Animales Lactantes , Relación Dosis-Respuesta a Droga , Mucosa Intestinal/enzimología , Mucosa Intestinal/crecimiento & desarrollo , Intestino Delgado/enzimología , Intestino Delgado/crecimiento & desarrollo , Microvellosidades/efectos de los fármacos , Microvellosidades/enzimología , Ornitina Descarboxilasa/efectos de los fármacos , Ornitina Descarboxilasa/metabolismo , Ratas , Ratas Wistar , Componente Secretorio/efectos de los fármacos , Componente Secretorio/metabolismo , Cloruro de Sodio/farmacología , Espermina/farmacología , Destete

RESUMEN

To test the ability of ketone bodies to inhibit myocardial fatty acid oxidation in vivo, the myocardial clearance kinetics of [1-11C]palmitate was assessed with positron emission tomography in six fasted volunteers and six instrumented dogs, studied repeatedly before and during infusion of 3-hydroxybutyrate (17 mumol.kg-1 x min-1). With the use of multiexponential fitting of tissue time-activity curves, the size, half time (T1/2), and index of the early rapid phase of 11C myocardial clearance, reflecting palmitate oxidation, were calculated. In humans, the relative size (-28%, P < 0.001) and index (-37%, P < 0.01) of the early rapid phase decreased significantly during infusion of 3-hydroxybutyrate, consistent with decreased fatty acid oxidation. Paradoxically, T1/2 decreased from 10.1 +/- 1.6 to 7.4 +/- 1.1 min (P < 0.01). To elucidate possible mechanisms, multiple coronary arteriovenous samples were obtained from the dogs to assess the efflux of oxidized and nonmetabolized tracer. Infusion of 3-hydroxybutyrate resulted in decreased myocardial [11C]CO2 production (-40%, P < 0.05) and reduced palmitate retention (-38%, P < 0.05). In three dogs, the arteriovenous difference in radiolabeled palmitate became negative 10 min after injection, indicating backdiffusion of nonmetabolized tracer from the myocardium. Thus a steady-state infusion of 3-hydroxybutyrate, resulting in physiological plasma levels, alters [1-11C]palmitate kinetics in vivo by decreasing myocardial long-chain fatty acid oxidation and by increasing backdiffusion of nonmetabolized tracer.

Asunto(s)

Cuerpos Cetónicos/metabolismo , Miocardio/metabolismo , Ácidos Palmíticos/metabolismo , Ácido 3-Hidroxibutírico , Adulto , Animales , Unión Competitiva , Dióxido de Carbono/metabolismo , Radioisótopos de Carbono , Perros , Ácidos Grasos/metabolismo , Femenino , Humanos , Hidroxibutiratos/sangre , Hidroxibutiratos/farmacología , Cuerpos Cetónicos/farmacología , Cinética , Masculino , Oxidación-Reducción , Ácido Palmítico , Tomografía Computarizada de Emisión

RESUMEN

A double-blind placebo-controlled trial was conducted, involving 97 obese diabetic and glucose intolerant patients receiving either 60 mg fluoxetine daily (47 patients) or a placebo (50 patients); a similar calorie-restricted diet was prescribed to all patients. Weight loss was significantly higher in the fluoxetine-treated patients, whose diabetic status improved. Drop-out rate was not significantly different for both groups of patients.

Asunto(s)

Diabetes Mellitus/tratamiento farmacológico , Fluoxetina/uso terapéutico , Hiperglucemia/fisiopatología , Obesidad/tratamiento farmacológico , Glucemia/metabolismo , Diabetes Mellitus/sangre , Diabetes Mellitus/fisiopatología , Método Doble Ciego , Femenino , Fluoxetina/efectos adversos , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Hiperglucemia/sangre , Insulina/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/fisiopatología , Placebos , Pérdida de Peso