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1.
Gene ; 256(1-2): 123-38, 2000 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-11054542

RESUMEN

The bone morphogenetic proteins 2 and 4 are known to be important in bone formation and are expressed in both the developing and adult mammalian bone. Understanding the regulation of these genes in osteoblasts may yield methods by which we can control expression to induce bone formation. We have isolated and characterized the human BMP-2 and BMP-4 promoters and report substantially more upstream sequence information than that which has been published. Human osteoblasts were found to have a single transcript initiation site that is conserved across species, rather than multiple start sites, as has previously been reported (Feng, J.Q., Harris, M.A., Ghosh-Choudhury, N., Feng, M., Mundy, G.R., Harris, S.E., 1994. Structure and sequence of mouse morphogenetic protein-2 gene (BMP-2): comparison of the structures and promoter regions of BMP-2 and BMP-4 genes. Biochim. Biophys. Acta 1218, 221-224; Heller, L.C., Li, Y., Abrams, K.L., Rogers, M.B., 1999. Transcriptional regulation of the Bmp2 gene. J. Biol. Chem. 274, 1394-1400; Sugiura, T., 1999. Cloning and functional characterization of the 5'-flanking region of the human bone morphogenetic protein-2 gene. Biochem. J. 338, 433-440). A series of promoter deletions for both human BMP-2 and BMP-4 fused to the luciferase reporter gene were analyzed thoroughly in human and murine osteoblastic cell lines. Several compounds and growth factors that stimulate general or osteogenic pathways were used to treat cells transfected with the promoter constructs. Retinoic acid compounds and the phorbol ester, PMA were found to stimulate BMP-2 and, to a lesser degree, BMP-4. The combination of all trans-RA and PMA caused a synergistic increase in BMP-2 promoter activity and endogenous mRNA. The RA stimulation appears to be an indirect effect on the BMP-2 promoter, as the most highly conserved RRE in the BMP-2 promoter was unable to functionally bind or compete for protein binding. Potential binding sites in both promoters for the bone-specific transcription factor, Cbfa-1, were found to specifically bind Cbfa-1 protein in osteoblast nuclear extracts; however, deletion of these sites did not significantly affect transcriptional activity of the promoters in osteoblasts. These data thus present new sequence and regulatory information for the human BMP-2 and BMP-4 promoters and clarify the human BMP-2 gene transcriptional start site in osteoblasts.


Asunto(s)
Proteínas Morfogenéticas Óseas/genética , Proteínas de Neoplasias , Regiones Promotoras Genéticas/genética , Factor de Crecimiento Transformador beta , Animales , Secuencia de Bases , Proteína Morfogenética Ósea 2 , Proteína Morfogenética Ósea 4 , Línea Celular , ADN/química , ADN/genética , Sinergismo Farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Datos de Secuencia Molecular , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes , Retinoides/farmacología , Análisis de Secuencia de ADN , Eliminación de Secuencia , Acetato de Tetradecanoilforbol/farmacología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética , Células Tumorales Cultivadas
2.
Int J Sport Nutr Exerc Metab ; 10(3): 340-59, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10997957

RESUMEN

The effects of androgen precursors, combined with herbal extracts designed to enhance testosterone formation and reduce conversion of androgens to estrogens was studied in young men. Subjects performed 3 days of resistance training per week for 8 weeks. Each day during Weeks 1, 2, 4, 5, 7, and 8, subjects consumed either placebo (PL; n = 10) or a supplement (ANDRO-6; n = 10), which contained daily doses of 300 mg androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 625 mg Chrysin, 300 mg Indole-3-carbinol, and 540 mg Saw palmetto. Serum androstenedione concentrations were higher in ANDRO-6 after 2, 5, and 8 weeks (p <.05), while serum concentrations of free and total testosterone were unchanged in both groups. Serum estradiol was elevated at Weeks 2, 5, and 8 in ANDRO-6 (p <.05), and serum estrone was elevated at Weeks 5 and 8 (p <.05). Muscle strength increased (p <.05) similarly from Weeks 0 to 4, and again from Weeks 4 to 8 in both treatment groups. The acute effect of one third of the daily dose of ANDRO-6 and PL was studied in 10 men (23 +/- 4 years). Serum androstenedione concentrations were elevated (p <.05) in ANDRO-6 from 150 to 360 min after ingestion, while serum free or total testosterone concentrations were unchanged. These data provide evidence that the addition of these herbal extracts to androstenedione does not result in increased serum testosterone concentrations, reduce the estrogenic effect of androstenedione, and does not augment the adaptations to resistance training.


Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Androstenodiona/farmacología , Deshidroepiandrosterona/farmacología , Fitoterapia , Testosterona/sangre , Adulto , Andrógenos , Androstenodiona/administración & dosificación , Antropometría , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , HDL-Colesterol/efectos de los fármacos , Deshidroepiandrosterona/administración & dosificación , Método Doble Ciego , Antagonistas de Estrógenos/administración & dosificación , Antagonistas de Estrógenos/farmacología , Flavonoides/administración & dosificación , Flavonoides/farmacología , Humanos , Indoles/administración & dosificación , Indoles/farmacología , Masculino , Músculo Esquelético/fisiología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Rosales , Serenoa , Levantamiento de Peso
3.
J Nutr ; 130(8): 1937-45, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10917905

RESUMEN

The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the effects of exercise on muscle size and strength. Although several reports in animals and humans indicate that HMB is safe, quantitative safety data in humans have not been reported definitively. The objective of this work was to summarize safety data collected in nine studies in which humans were fed 3 g HMB/d. The studies were from 3 to 8 wk in duration, included both males and females, young and old, exercising or nonexercising. Organ and tissue function was assessed by blood chemistry and hematology; subtle effects on emotional perception were measured with an emotional profile test (Circumplex), and tolerance of HMB was assessed with a battery of 32 health-related questions. HMB did not adversely affect any surrogate marker of tissue health and function. The Circumplex emotion profile indicated that HMB significantly decreased (improved) one indicator of negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward effects of HMB were indicated. Compared with the placebo, HMB supplementation resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4 mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular health could result in a decrease in the risk of heart attack and stroke. In conclusion, the objective data collected across nine experiments indicate that HMB can be taken safely as an ergogenic aid for exercise and that objective measures of health and perception of well-being are generally enhanced.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Suplementos Dietéticos , Valeratos/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Suplementos Dietéticos/efectos adversos , Evaluación de Medicamentos , Emociones/efectos de los fármacos , Ejercicio Físico , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Distribución Aleatoria , Factores de Riesgo , Valeratos/efectos adversos
4.
J Appl Physiol (1985) ; 87(6): 2274-83, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10601178

RESUMEN

This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 +/- 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min (P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 +/- 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo (n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly (P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly (P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.


Asunto(s)
Adaptación Fisiológica/efectos de los fármacos , Deshidroepiandrosterona/farmacología , Educación y Entrenamiento Físico , Testosterona/sangre , Levantamiento de Peso/fisiología , Administración Oral , Adulto , Antropometría , Dieta , Método Doble Ciego , Prueba de Tolerancia a la Glucosa , Histocitoquímica , Hormonas/sangre , Humanos , Insulina/sangre , Masculino , Músculo Esquelético/enzimología , Músculo Esquelético/fisiología
5.
JAMA ; 281(21): 2020-8, 1999 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-10359391

RESUMEN

CONTEXT: Androstenedione, a precursor to testosterone, is marketed to increase blood testosterone concentrations as a natural alternative to anabolic steroid use. However, whether androstenedione actually increases blood testosterone levels or produces anabolic androgenic effects is not known. OBJECTIVES: To determine if short- and long-term oral androstenedione supplementation in men increases serum testosterone levels and skeletal muscle fiber size and strength and to examine its effect on blood lipids and markers of liver function. DESIGN AND SETTING: Eight-week randomized controlled trial conducted between February and June 1998. PARTICIPANTS: Thirty healthy, normotestosterogenic men (aged 19-29 years) not taking any nutritional supplements or androgenic-anabolic steroids or engaged in resistance training. INTERVENTIONS: Twenty subjects performed 8 weeks of whole-body resistance training. During weeks 1, 2, 4, 5, 7, and 8, the men were randomized to either androstenedione, 300 mg/d (n = 10), or placebo (n = 10). The effect of a single 100-mg androstenedione dose on serum testosterone and estrogen concentrations was determined in 10 men. MAIN OUTCOME MEASURES: Changes in serum testosterone and estrogen concentrations, muscle strength, muscle fiber cross-sectional area, body composition, blood lipids, and liver transaminase activities based on assessments before and after short- and long-term androstenedione administration. RESULTS: Serum free and total testosterone concentrations were not affected by short- or long-term androstenedione administration. Serum estradiol concentration (mean [SEM]) was higher (P<.05) in the androstenedione group after 2 (310 [20] pmol/L), 5 (300 [30] pmol/L), and 8 (280 [20] pmol/L) weeks compared with presupplementation values (220 [20] pmol/L). The serum estrone concentration was significantly higher (P<.05) after 2 (153 [12] pmol/L) and 5 (142 [15] pmol/L) weeks of androstenedione supplementation compared with baseline (106 [11] pmol/L). Knee extension strength increased significantly (P<.05) and similarly in the placebo (770 [55] N vs 1095 [52] N) and androstenedione (717 [46] N vs 1024 [57] N) groups. The increase of the mean cross-sectional area of type 2 muscle fibers was also similar in androstenedione (4703 [471] vs 5307 [604] mm2; P<.05) and placebo (5271 [485] vs 5728 [451] mm2; P<.05) groups. The significant (P<.05) increases in lean body mass and decreases in fat mass were also not different in the androstenedione and placebo groups. In the androstenedione group, the serum high-density lipoprotein cholesterol concentration was reduced after 2 weeks (1.09 [0.08] mmol/L [42 (3) mg/dL] vs 0.96 [0.08] mmol/L [37 (3) mg/dL]; P<.05) and remained low after 5 and 8 weeks of training and supplementation. CONCLUSIONS: Androstenedione supplementation does not increase serum testosterone concentrations or enhance skeletal muscle adaptations to resistance training in normotestosterogenic young men and may result in adverse health consequences.


Asunto(s)
Androstenodiona/farmacología , Ejercicio Físico/fisiología , Músculo Esquelético/efectos de los fármacos , Testosterona/sangre , Administración Oral , Adulto , Análisis de Varianza , Androstenodiona/administración & dosificación , Androstenodiona/metabolismo , Biopsia con Aguja , Composición Corporal , Suplementos Dietéticos , Método Doble Ciego , Estrógenos/sangre , Humanos , Lípidos/sangre , Pruebas de Función Hepática , Masculino , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Evaluación Nutricional , Transaminasas/metabolismo
6.
Int J Sport Nutr ; 9(1): 13-23, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10036338

RESUMEN

Previous investigations have reported that soluble fiber reduces the plasma glucose and insulin changes after an oral glucose load. To improve the palatability of a soluble-fiber feeding, this study addressed how a combined, soluble fiber (delivered in capsule form) and a preexercise CHO feeding would affect metabolic responses during exercise. On 3 different days, participants ingested a placebo (CON), 75 g liquid CHO (GLU), or 75 g liquid CHO with 14.5 g encapsulated guar gum (FIB) 45 min before cycling for 60 min at 70% VO2 peak. Peak concentrations of plasma glucose and insulin were similar and significantly greater than CON preexercise (p < 05). Similarities in carbohydrate reliance were observed in GLU and FIB. Muscle glycogen use did not differ significantly among trials. These results demonstrate that encapsulated soluble fiber delivered with liquid CHO feeding does not affect plasma glucose, insulin, or muscle glycogen utilization during exercise.


Asunto(s)
Carbohidratos de la Dieta/metabolismo , Fibras de la Dieta/administración & dosificación , Esfuerzo Físico/fisiología , Adulto , Análisis de Varianza , Glucemia/análisis , Cápsulas , Prueba de Esfuerzo , Ácidos Grasos no Esterificados/sangre , Galactanos/administración & dosificación , Glucosa/metabolismo , Glucógeno/análisis , Humanos , Insulina/sangre , Lactatos/sangre , Masculino , Mananos/administración & dosificación , Músculo Esquelético/metabolismo , Consumo de Oxígeno/fisiología , Placebos , Gomas de Plantas , Respiración , Solubilidad
7.
J Appl Physiol (1985) ; 85(4): 1329-36, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9760324

RESUMEN

To investigate the impact of fluid composition on rehydration effectiveness, 30 subjects (15 men and 15 women) were studied during 2 h of rehydration after a 2.5% body weight loss. In a randomized crossover design, subjects rehydrated with water (H2O), chicken broth (CB: 109.5 mmol/l Na, 25.3 mmol/l K), a carbohydrate-electrolyte drink (CE: 16.0 mmol/l Na, 3.3 mmol/l K), and chicken noodle soup (Soup: 333.8 mmol/l Na, 13.7 mmol/l K). Subjects ingested 175 ml at the start of rehydration and 20 min later; H2O was given every 20 min thereafter for a total volume equal to body weight loss during dehydration. At the end of the rehydration period, plasma volume was not significantly different from predehydration values in the CB (-1.6 +/- 1.1%) and Soup (-1.4 +/- 0.9%) trials. In contrast, plasma volume remained significantly (P < 0.01) below predehydration values in the H2O (-5.6 +/- 1.1%) and CE (-4.2 +/- 1.0%) trials after the rehydration period. Urine volume was greater in the CE (310 +/- 30 ml) than in the CB (188 +/- 20 ml) trial. Urine osmolality was higher in the CB and Soup trials than in the CE trial. Urinary sodium concentration was higher in the Soup and CB trials than in the CE and H2O trials. These results provide evidence that the inclusion of sodium in rehydration beverages, as well as consumption of a sodium-containing liquid meal, increases fluid retention and improves plasma volume restoration.


Asunto(s)
Ingestión de Líquidos/fisiología , Ingestión de Alimentos/fisiología , Sodio en la Dieta , Equilibrio Hidroelectrolítico/fisiología , Adulto , Animales , Bebidas , Pollos , Estudios Cruzados , Femenino , Humanos , Masculino , Carne , Periodo Posprandial/fisiología , Potasio en la Dieta , Agua
8.
Int J Sports Med ; 18(5): 347-53, 1997 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9298774

RESUMEN

The purpose of the present study was to determine if common indexes of exercise intensity, assessed with land-based exercise, could be applied to swimming. Consequently, the heart rate (HR) and oxygen uptake (VO2) responses to submaximal and maximal treadmill running (TR) and free swimming (SW) in 11 fitness swimmers were assessed to determine if the responses to TR could be used to predict those of SW. A maximal graded exercise test using a discontinuous protocol was used for TR, while four graded submaximal 200 yd swims and one 400 yd maximal swim was used for SW. Rest periods were similar for each mode. Significantly lower (p < 0.05) peak values were found in SW compared to TR for both HR (174 +/- 3 vs 183 +/- 3 bt x min(-1)) and VO2 (3.58 +/- 0.18 vs 3.97 +/- 0.22 L x min(-1)), SW vs TR; +/- SE, respectively. However, regression analyses of submaximal HR vs VO2 for each subject revealed similar slopes for TR and SW (30.5 +/- 1.7 vs 29.9 +/- 3.5 bt x L(-1), p > 0.05) and similar intercepts (67.3 +/- 2.6 vs 66.5 +/- 11.5 bt x min(-1), p > 0.05). At the VO2 equivalent to 50% treadmill VO2max, the heart rate predicted from SW did not differ significantly from TR (118 +/- 5 vs 124 +/- 1 bt x min(-1), p > 0.05). This was also true at 85% treadmill VO2max (171 +/- 4 vs 166 +/- 3 bt x min(-1), SW vs TR, respectively; p > 0.05). These data suggest that peak heart rate and oxygen uptake appear to be mode specific, but exercising at a given submaximal oxygen uptake will elicit a similar heart rate regardless of the mode. Thus, target heart rate ranges designed for land-based exercise appear to be appropriate for fitness swimmers during swimming.


Asunto(s)
Frecuencia Cardíaca/fisiología , Carrera/fisiología , Natación/fisiología , Adulto , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Consumo de Oxígeno , Análisis de Regresión
9.
Int J Sport Nutr ; 7(4): 298-309, 1997 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9407256

RESUMEN

The purpose of this study was to determine if amino acid supplementation influences blood and muscle lactate response to exercise and the time course of the metabolic adaptations to training. Two groups of untrained males (n = 7 each) were given (double-blind) a daily supplement (2.9 g.day-1) containing a mixture of leucine, isoleucine, valine, glutamine, and carnitine (EXP) or 3 g.day-1 of lactose (CON). Following 7 days of supplementation there was no significant change in VO2peak, time to exhaustion (TTX) at 120% VO2peak, or muscle and blood lactate in either EXP or CON. Subjects then initiated 6 weeks of combined aerobic and anaerobic training on a Monark cycle ergometer. It was found that amino acid supplementation had no effect on either blood or muscle lactate accumulation during exercise, while supplementation resulted in a faster adaptation in buffer capacity. Performance during intense exercise was not improved with amino acid supplementation.


Asunto(s)
Adaptación Fisiológica , Aminoácidos/administración & dosificación , Ciclismo , Ejercicio Físico/fisiología , Resistencia Física , Adulto , Humanos , Concentración de Iones de Hidrógeno , Cinética , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Lactosa/administración & dosificación , Masculino , Músculo Esquelético/metabolismo , Consumo de Oxígeno , Factores de Tiempo
10.
Biochem Mol Med ; 55(2): 122-30, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7582869

RESUMEN

We sought evidence for precursors of the leukocyte integrin subunits alpha M and alpha X among unicellular eukaryotes such as Saccharomyces cerevisiae. Chromatography of cytosolic extracts of Saccharomyces cerevisiae on an affinity matrix coupled to BU-15, a monoclonal antibody that recognizes alpha X, revealed a band of M(r) > 205 kDa under nonreducing conditions. Screening a lambda gt11 library of S. cerevisiae DNA with BU-15 (anti-alpha X) and anti-Mo1 (anti-alpha M) led to the isolation of a 3.7-kb EcoRI fragment containing the 3' end of an open reading frame sufficient to encode a polypeptide in excess of 118 kDa. On the basis of Southern blotting at high stringency, this gene was present in S. cerevisiae, but not in other yeast species such as Candida glabrata. Analysis of the derived amino acid sequence demonstrated > 98% identity with the S. cerevisiae protein Uso1p, a myosin-like polypeptide found exclusively in the cytosol. The C-terminal 1016 aa, expressed from the 3.7-kb EcoRI fragment in Escherichia coli as a beta-galactosidase fusion protein, bound iC3b, a ligand for the I-domain in alpha M and alpha X, and were recognized by Mn41, a monoclonal antibody specific for the alpha M I-domain. Antigenic and functional conservation of an I-domain in S. cerevisiae suggests that this domain may be a prototype for integrin-like proteins in other primitive eukaryotes.


Asunto(s)
Integrinas/genética , Saccharomyces cerevisiae/genética , Secuencia de Aminoácidos , Animales , Genes Fúngicos , Integrinas/inmunología , Integrinas/fisiología , Datos de Secuencia Molecular , Conejos
11.
J Appl Physiol (1985) ; 78(1): 17-22, 1995 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7713807

RESUMEN

The purposes of this study were 1) to investigate glucose tolerance and insulin action immediately after exercise and 2) to determine how long the improved glucose homeostatic mechanisms observed 12-16 h after exercise persist. Nine (seven men, two women) moderately trained middle-aged (51 +/- 3 yr) subjects performed 45 min of exercise at 73 +/- 2% of peak O2 uptake for 5 days, followed by 7 days of inactivity. Oral glucose tolerance tests (OGTT; 75 g) were performed immediately postexercise (IPE; approximately 30 min) after the final exercise bout and 1, 3, 5, and 7 days after exercise. The incremental area under the plasma glucose curve was markedly higher IPE (355 +/- 82 mM.min) compared with those on days 1 (136 +/- 57 mM.min; P < 0.05) and 3 (173 +/- 62 mM.min; P < 0.05). The glucose area was significantly higher on days 5 (213 +/- 80 mM.min) and 7 (225 +/- 84 mM.min) compared with those on days 1 and 3 (P < 0.05). The incremental insulin area IPE (3,729 +/- 1,104 microU.ml-1.min) was 43% higher compared with that on day 1 (2,603 +/- 635 microU.ml-1.min; P < 0.05) and 66% higher compared with that on day 3 (2,240 +/- 517 microU.ml-1.min; P < 0.05). The insulin area increased to 3,616 +/- 617 microU.ml-1.min after 5 days of inactivity (P < 0.05). An additional 48 h of inactivity did not result in any further increase in the plasma insulin response.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Glucemia/metabolismo , Ejercicio Físico/fisiología , Insulina/sangre , Adulto , Anciano , Composición Corporal/fisiología , Dieta , Ácidos Grasos no Esterificados/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/fisiología
12.
Eur J Pharmacol ; 269(3): R5-7, 1994 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-7895767

RESUMEN

Cloned human metabotropic glutamate receptors, mGlu1 alpha and mGlu5 alpha, were functionally expressed in Xenopus oocytes. Cyclothiazide dose-dependently inhibited glutamate-stimulated human mGlu1 alpha responses (IC50 = 18 microM) in a non-competitive manner. In contrast, cyclothiazide slightly potentiated glutamate-stimulated human mGlu5 alpha responses. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8- methyl-endioxyl-5H-2,3-benzodiazepinehydrochloride) did not alter glutamate-stimulated human mGlu1 alpha or human mGlu5 alpha responses, either in the presence or absence of cyclothiazide. Thus, human metabotropic glutamate receptors coupled to phosphoinositide stimulation appear to contain sites sensitive to cyclothiazide but insensitive to GYKI 52466.


Asunto(s)
Ansiolíticos , Benzotiadiazinas/farmacología , Fosfatidilinositoles/metabolismo , Receptores de Glutamato Metabotrópico/efectos de los fármacos , Inhibidores de los Simportadores del Cloruro de Sodio/farmacología , Animales , Benzodiazepinas/metabolismo , Benzodiazepinas/farmacología , Benzotiadiazinas/metabolismo , Sitios de Unión , Diuréticos , Relación Dosis-Respuesta a Droga , Electrofisiología , Antagonistas de Aminoácidos Excitadores/metabolismo , Antagonistas de Aminoácidos Excitadores/farmacología , Humanos , Hidrólisis , Oocitos , Receptores de Glutamato Metabotrópico/metabolismo , Inhibidores de los Simportadores del Cloruro de Sodio/metabolismo , Xenopus laevis
13.
Eur J Pharmacol ; 266(1): R1-2, 1994 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-7511109

RESUMEN

Cloned human AMPA/kainate subunits were functionally expressed in Xenopus oocytes. Cyclothiazide potentiated kainate-evoked currents by 682 +/- 122% (mean +/- S.E.M., n = 5), 1396 +/- 55% (n = 4), and 690 +/- 40% (n = 14) in oocytes expressing GluR1, GluR2, and GluR1 + GluR2 receptors, respectively. AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate)-induced currents were also potentiated by cyclothiazide. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8-methylendioxyl-5H-2,3-benzod++ + iazepine hydrochloride) attenuated cyclothiazide potentiation in all cases. Thus, modulatory sites for cyclothiazide and GYKI 52466 exist on individual human AMPA/kainate receptor subunits. Additionally, kainate appears to act as a desensitizing partial agonist at human GluR1 and GluR2 receptor subunits.


Asunto(s)
Ansiolíticos , Benzotiadiazinas/farmacología , Receptores AMPA/efectos de los fármacos , Receptores de Ácido Kaínico/efectos de los fármacos , Animales , Benzodiazepinas/farmacología , Clonación Molecular , Humanos , Ácido Kaínico/farmacología , Oocitos , Receptores AMPA/metabolismo , Receptores de Glutamato/efectos de los fármacos , Receptores de Glutamato/metabolismo , Receptores de Ácido Kaínico/metabolismo , Xenopus laevis , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología
14.
J Appl Physiol (1985) ; 75(5): 2151-6, 1993 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8307872

RESUMEN

The effects of an exhaustive bout of eccentric exercise on insulin secretion and action were determined using the hyperglycemic clamp technique. Clamps were performed on eight healthy men after 7 days of inactivity and approximately 36 h after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10 repetitions of combined knee extensions and flexions for each leg at a mean torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was maintained near this level for 120 min. Arterialized blood samples were obtained from a heated hand vein to determine plasma glucose and insulin concentrations. Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50-fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811 U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response during the early phase (0-10 min) of the hyperglycemic clamp was higher after eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/- 23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not altered after eccentric exercise. Peak plasma C-peptide concentrations were higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric exercise had no significant effect on whole body glucose disposal or glucose disposal rate adjusted for prevailing plasma insulin concentration. These data provide evidence that a single bout of eccentric exercise causes an increase in pancreatic beta-cell insulin secretion in response to hyperglycemia.


Asunto(s)
Ejercicio Físico/fisiología , Insulina/metabolismo , Adulto , Glucemia/metabolismo , Composición Corporal/fisiología , Péptido C/metabolismo , Creatina Quinasa/metabolismo , Dieta , Glucógeno/metabolismo , Humanos , Hiperglucemia/metabolismo , Insulina/sangre , Secreción de Insulina , Masculino , Músculos/metabolismo , Consumo de Oxígeno/fisiología , Carrera
15.
Biol Sport ; 10(2): 73-80, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-34404962

RESUMEN

The purpose of this study was to investigate the effect of menstrual cycle phase on the insulin/glucose relationship at rest and response to sub-maximal exercise. Eight eumenorrheic women completed exercise sessions (60 min, 70% V̇O2max) in the follicular (day 7±2) and luteal (day 20±2) phases of their cycles. At 45 min before each exercise session the subject consumend an oral glucose load (OGL) of 1 gkg-1 body weight in a 400 ml solution. Blood samples were obtained before the OGL (-45 min) immediately before exercise, and at 15 min intervals until the end of exercise (60 min). Results indicated that serum glucose and insulin increased (P<0.01) due to the OGL and decreased (P<0.01) due to exercise. No significant phase differences were observed for the glucose responses: however, insulin levels were greater immediately before exercise in the luteal than follicular phase (47.2±5.8 vs. 39.3±5.1 U·ml-1, respectively). The insulin-to-glucose ratio (I/G) was calculated and also showed significant changes. The I/G ratio was greater in the luteal than in the follicular phase at 0 min (6.5±0.4 vs. 5.3±0.6 mU·mmol-1, respectively). These data would suggest that in eumenorrheic women the menstrual cycle impacts the insulin/glucose relationship at rest, but has no effect during exercise. Whether the mechanism of the resting effect is due to changes in pancreatic and/or target tissue functions in unclear.

16.
Int J Sport Nutr ; 2(4): 307-16, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1299500

RESUMEN

Eleven subjects performed a graded exercise test after 1 week of protein supplementation (PRO) or glucose polymer placebo (CON), randomly assigned in a double blind fashion. The exercise consisted of 3-min graded exercise bouts separated by 10 min of active recovery at zero pedal resistance. Subjects then performed a 30-sec Wingate test (WIN) to assess performance during supramaximal exercise. Blood samples were obtained in the last 15 sec of each exercise and recovery period. PRO resulted in a decrease in blood lactate following 120% VO2max and WIN, an increase in blood alanine at all time points, and lower postexercise muscle lactate and glycogen. Resting muscle GPT activity was 47% higher during the PRO trial. Mean power output during the WIN did not differ between PRO and CON. The WIN fatigue index was not significantly different between PRO and CON. The increased alanine may reflect increased transamination of pyruvate, thereby reducing the accumulation of lactate, which in turn had a marginal effect on performance during supramaximal exercise.


Asunto(s)
Proteínas en la Dieta/administración & dosificación , Ejercicio Físico/fisiología , Lactatos/metabolismo , Alanina/sangre , Método Doble Ciego , Femenino , Glucógeno/metabolismo , Humanos , Lactatos/sangre , Ácido Láctico , Masculino , Músculos/metabolismo , Consumo de Oxígeno
17.
Int J Sports Med ; 12(1): 62-5, 1991 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1903130

RESUMEN

The purpose of this study was to determine the effect of a reduced ventilatory frequency (Vf) on blood gases and acid-base changes during three intensities of cycling exercise. VO2max and lactate threshold workload (LaT) of six subjects were assessed on a Monark ergometer. Experimental rides were performed 1) with no restriction on Vf (NB) and 2) with a prescribed Vf of 10/min (CFB). Each exercise period consisted of 8 min at 10% of VO2max below the LaT (WI), followed immediately by 8 min at LaT (WII), followed immediately by 8 min at 10% of VO2max above LaT (WIII). Blood was taken from a heated fingertip at the end of each load and analyzed for lactate concentration, pH, PO2, and PCO2. Respiratory exchange was monitored continuously using open circuit indirect calorimetry. Minute ventilation (VE) was significantly reduced by CFB at all three workloads. The reduced VE resulted in lower (p less than 0.05) blood PO2 at each workload (p less than 0.05), however, neither blood lactate nor VO2 were significantly different between CFB and NB for the three loads. Blood [H+] was significantly higher in CFB than NB at all three loads with the greatest difference between trials at WIII (NB: 37.93 +/- 0.68 nM: CFB: 44.77 +/- 1.02 nM). This was accounted for by a significantly higher PCO2 during CFB in WII and WIII (WII, NB: 33.0 +/- 1.4 mmHg, CFB: 35.7 +/- 2.7 mmHg; WIII, NB: 31.2 +/- 1.7 mmHg, CFB: 38.9 +/- 2.4 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Equilibrio Ácido-Base , Dióxido de Carbono/sangre , Ejercicio Físico/fisiología , Oxígeno/sangre , Respiración/fisiología , Adulto , Umbral Anaerobio , Análisis de Varianza , Femenino , Humanos , Lactatos/sangre , Ácido Láctico , Masculino , Consumo de Oxígeno
18.
Med Sci Sports Exerc ; 21(5): 576-80, 1989 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-2691818

RESUMEN

Nine male collegiate swimmers (EXP) were studied 8 d before (PRE) and 1 d after (POST) shaving the hair from their arms, legs, and exposed trunk. A control group (CON, N = 4) of their teammates was also tested at these times but did not remove body hair. In PRE and POST, distance per stroke (SL), VO2, heart rate (HR), and post-swim blood lactate concentration (BL) were measured during a 365.8 m breaststroke swim at approximately 90% effort. Subjects also performed a tethered breaststroke swim with retarding forces of 6.27, 7.75, and 9.26 kg. The EXP group experienced a significant (P less than 0.05) reduction in BL (mean +/- SE: 8.48 +/- 0.78 to 6.74 +/- 0.74 mmol.l-1), a decreased VO2 (3.60 +/- 0.15 to 3.27 +/- 0.14 l.min-1), an increase in SL (2.07 +/- 0.08 to 2.31 +/- 0.10 m.stroke-1), and an insignificant (P = 0.08) decline in HR (174 +/- 5 to 168 +/- 4 beats.min-1) during the free swim. The CON group showed no changes in BL, SL, or HR. During the tethered swim, there were no significant PRE-POST differences in VO2, HR, or BL for either group. In a separate group of swimmers (nine who shaved body hair and nine controls), removing body hair significantly reduced the rate of velocity decay during a prone glide after a maximal underwater leg push-off. It is concluded that removing body hair reduces active drag, thereby decreasing the physiological cost of swimming.


Asunto(s)
Eficiencia/fisiología , Remoción del Cabello , Lactatos/sangre , Consumo de Oxígeno/fisiología , Natación , Adulto , Ensayos Clínicos como Asunto , Humanos , Ácido Láctico , Masculino
19.
Int J Sports Med ; 10(4): 264-9, 1989 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-2606593

RESUMEN

Six eumenorrheic females (age = 26.3 +/- 2.4 yrs; X +/- SE) exercised until exhaustion (EE; 70% VO2max) at the midluteal (LP, 7-8 days after ovulation) and midfollicular (FP, days 7-8) phases of their menstrual cycles. Phases were confirmed by estradiol and progesterone concentrations. Each EE test was preceded by a depletion exercise bout (DE; 90 min, 60% VO2max and 4 x 1 min, 100% VO2max) and 3 days of rest/diet control. Muscle biopsies 1% (vastus lateralis) were taken post-DE, pre-EE, and post-EE and then analyzed for glycogen content. There was a strong tendency (P less than 0.07) for EE duration to be greater during LP (139.2 +/- 14.9 min) than FP (126 +/- 17.5 min). Glycogen repletion (pre-EE minus post-DE) following DE was greater (P = 0.05) during the LP than FP (88.2 +/- 4.7 vs 72.8 +/- 5.7 mumol/g w. w. muscle). However, EE glycogen utilization (pre-EE minus post-EE/EE time) did not differ between phases (LP = 0.41 +/- 0.08 mumol/g w. w. muscle/min vs FP = 0.33 +/- 0.11 mumol/g w. w. muscle/min; P = 0.17). The results suggest that exercise performance and muscle glycogen content are enhanced during the LP of the menstrual cycle. These findings imply athletic performance may be affected by the phases of the menstrual cycle.


Asunto(s)
Ejercicio Físico , Glucógeno/metabolismo , Ciclo Menstrual , Músculos/metabolismo , Adulto , Estradiol/sangre , Prueba de Esfuerzo , Ácidos Grasos no Esterificados/sangre , Femenino , Frecuencia Cardíaca , Humanos , Lactatos/sangre , Ácido Láctico , Consumo de Oxígeno , Progesterona/sangre
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