Variations of sex hormone-binding globulin in thyroid dysfunction.

With the aim of understanding the variations of the levels of sex hormone-binding globulin (SHBG) in thyroid dysfunction, we studied the influence of factors that also modify SHBG, such as menopausal status, age, and body mass index (BMI) in women with hypothyroidism and hyperthyroidism, both overt and subclinical. Statistical analysis was performed by means of analysis of variance (ANOVA), stepwise multiple regression, and partial correlation. The ANOVA showed a significant statistical difference among the means of SHBG of all groups (p<0.01). The difference was due to the group that included hyperthyroid women. Multiple regression analysis showed that the main factors influencing SHBG were BMI and age, except for the hyperthyroid group, where the most important independent variables were triiodothyronine (T3) and thyroxine (T4). Partial correlation controlling the effect of BMI and age showed no association between SHBG and the other variables in all groups except for the subclinical hyperthyroid and hyperthyroid, where we found a significant association between SHBG and T4 and T3. The premenopausal or postmenopausal status did not modify SHBG levels. When the patients are taken as a whole, BMI, age, T4, and T3 all have an association with SHBG levels according to the multiple regression analysis.

Pharmacokinetics of metronidazole in horses after intravenous, rectal and oral administration.

Metronidazole pharmacokinetics in horses was studied after intravenous (i.v.), rectal (p.r.) and oral (p.o.) administration at 20 mg/kg using a triple crossover study design. Metronidazole mean+/-SD half-life was 196+/-39, 212+/-30 and 240+/-65 min after i.v., p.r. and p.o. administration, respectively. The metronidazole clearance was 2.8 (mL/min/kg) and the volume of distribution at steady state was 0.68 L/kg. The pharmacokinetic parameters calculated for metronidazole after administration of the drug by the various routes showed that bioavailability (74+/-18 vs. 30+/-9%) and maximum serum concentration (22+/-8 vs. 9+/-2 microg /mL) were significantly higher after p.o. administration compared with p.r. administration. There were no significant differences in mean absorption time (45+/-69 vs. 66+/-18 min) and the time to reach maximum serum concentration (65+/-36 vs. 58+/-18 min). The results indicated that p.r. administration of metronidazole to horses, although inferior to p.o. administration in terms of bioavailability, provides an alternative route of administration when p.o. administration cannot be used.

Effect of insulin on LHRH release by perifused hypothalamic fragments.

Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle's, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 microliters/min). When glucose was absent (in the presence of insulin 10 mU/l), LHRH release was reduced, peak levels being < 5 pg/100 microliters. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 microliters (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/l) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/100 microliters (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release.

Diet only or diet and sulfonylureas in mild type II diabetes (NIDDM)? Pathophysiologic and therapeutic implications.

UNLABELLED: Plasma glucose, insulin and C-peptide responses to a test meal were studied in 7 nonobese patients with type II diabetes mellitus (NIDDM) treated with diet alone and after 6 months of gliclazide therapy, as well as in 6 matched controls. The glycemic levels were significantly higher (p less than 0.05) in patients under diet alone than in controls and after gliclazide treatment (peak: 12.8 +/- 1.0; 7.9 +/- 0.4 and 10.0 +/- 0.5 mmol/l, respectively; means +/- SEM). Diet and gliclazide treated patients showed a reduced B-cell response during the first hour after the meal as indicated by insulin and C-peptide values and areas (insulin areas 0-60 min: controls 57.9 +/- 10.9; p less than 0.01 vs diet alone 14.2 +/- 2.7 and vs gliclazide 22.1 +/- 2.8 microU/ml/min). The hypoinsulinemic phase lasted from 20 to 60 min before gliclazide, and from 20 to 45 min after gliclazide. The first significant C-peptide increase, detected at 10 min in controls and at 30 min under diet alone, was advanced to 15 min after gliclazide treatment. IN CONCLUSION: patients with mild, diet-treated NIDDM show a sluggish and attenuated B-cell response to a physiologic challenge (test meal); this secretory impairment is present even after a complete post-prandial glycemic normalization, supporting the idea of a persistent defect. Nevertheless, the slight improvement observed in insulin secretion after gliclazide treatment may be promoting, at least partially, the normalization of prandial hyperglycemia. The benefits of this normalization in diabetic patients previously controlled by diet only await further investigation.

Farmacologia de la Insulinorresistencia: Situacion actual y perspectivas / Insulin Resistance Pharmacology: Current Situation and Perspectives

El proposito de este trabajo es revisar las estrategias farmacologicas especificamente destinadasa disminuir la insulinoresistencia. Se plantean cuatro objetivos, siendo el primero la inhibicion de la produccion hepatica de glucosa. Aqui se incluye a la metformina, biguanida que reduce la gluconeogenesis desde lactato y aumenta la actividad de la AMPK (enzima que estimula la oxidacion de acidos grasos no esterificados y disminuye la gluconeogenesis y sintesis de colesterol), Tambien se encuentran el BAY-27-9955 y NNC-25-2504L (antagonistas del glucagon) y los inhibidores de la glucogeno fosforilasa hepatoica, glucogenosintasa-kinasa-3, piruvato-deshidrogena-kinasa, fructosa-1,6-difosfatasa y glucosa-6-fosfatasa. Los insulinosensibilizadores, segundo objetivo, incluyen a tiazolidinodionas (agonistas PPARgamma) que aumentan la exposicion de GLUT 4, lipogenesis y disminuyen la glucogenesis. y a drogas en desarrollo: nuevos agonistas PPAR, activadores RxR, agosnistas Beta3 e inhibidores de la PTB-1B. El tercer objetivo son los modificadores del metabolismo lipidico, y contiene a los inhibidores de la 11Beta-HSD1. Los activadores del receptor insulinico, dependientes e independientes de insulina, constituyen el cuarto objetivo. La importancia del desarrollo de nuevos farmacos radica en que el control de la insulinorresistencia retrasaria la aparicion de diabetes 2 e implicaria un menor riesgo cardiovascular

Prueba de tolbutamida y respuesta terapéutica a los hipoglucemiantes orales / Talbutamide test and therapeutic response to oral hypoglycemic agents

Es de interés fisiopatológico y clínico disponer, en el estudio de los diabéticos no insulinodependientes o tipo 2, de una prueba pronóstica del fracaso secundario o sulfodrogas. En este trabajo se estudia la respuesta glucémica e insulinémica a la tolbutamida administrada en forma aguda, intentado identificar a aquellos pacientes que requerirán insulinoterapia en algún momento de la evolución de su diabetes. Se estudiaron 30 diabéticos tipo 2 con 10,1 ñ 1,4 años de evolución y con + 11½ de desviación del peso corporal mediante la administración de 1 g de tolbutamida endovenosa al tiempo de su primera consulta. Estos pacientes fueron luego seguidos longitudinalmente durante 2 a 3 años. Con la prueba de tolbutamida se comprobó un descenso glucémico similar en todo el grupo. La variación insulinémica permitió identificar dos grupos de pacientes. Uno de ellos (grupo A de 18 pacientes) presentó un ascesno de insulina de 24,8 ñ 4,7 micronUl/ml y el otro (grupo B de 12 pacientes) presentó un ascenso de insulina de 1,5 ñ 0,7 micronUl/ml, que fue significativamente menor

Cambios clínicos, bioquímicos e inmunológicos obtenidos en pacientes tratados con insulina porcina biobras / Clinical, biochemical and immunological changes in patientstreated with porcine insulin Biobras

Se estudiaron los cambios ocurridos a nivel clínico, bioquímico e inmunológico en pacientes diabéticos insulinodependientes (adultos y niños) tratados con insulina NPH de origen porcino (Biobras) durante 90 días y se loscomparó con los obtenidos previamente en esos mismos pacientes tratados con otras insulinas disponibles en el mercado nacional. Los resultados obtenidos no mostraron cambios importantes en el corto plazo en ninguno de los parámetros estudiados, lo que sugiere que la insulina Biobras presenta características apropiadas para el tratamiento del diabético insulinodependiente. Ello brinda al paciente, junto con una correcta alimentación, una actividad física apropiada y el permanente soporte educativo, otra alternativa de elección para el tratamiento insulínico de esta enfermedad metabólica