Cleaved Caspase-3 Response to Acute Resistance Exercise in Young and Old Men and Women : Relationship to Muscle Glycogen Content and 5'-AMP-Activated Protein Kinase (AMPK) Activity

In addition to suppressing protein synthesis and activating protein degradation in skeletal muscle and other cell types, 5'-AMP-activated protein kinase (AMPK) is known to stimulate nuclear apoptosis in non-muscle cells through cleaved (activated) caspase-3, one of the final steps in the apoptosis cascade. Although it is unknown whether AMPK stimulates caspase-3 cleavage or nuclear apoptosis in skeletal muscle cells in vivo, AMPK activity and nuclear apoptosis are elevated at rest in aged rat skeletal muscle. AMPK phosphorylation and activity are also higher in old vs. young rats and humans in response to overload or resistance exercise. Furthermore, older individuals display lower muscle glycogen content, a condition known to accentuate AMPK activity at rest and during aerobic exercise. We hypothesized that skeletal muscle cleaved caspase-3 content would be higher after acute resistance exercise in older versus younger individuals. Seven young (21.7 ± 2.1 yrs) and 11 old (67.0 ± 8.6 yrs) subjects performed an acute bout of leg extension resistance exercise. Muscle biopsies were obtained pre-exercise (PRE), immediately post-exercise (0P), 1-hour post-exercise (1P), and 2-hours post-exercise (2P). Glycogen content was measured in muscle samples, as were the phosphorylations (via western blot) of AMPK and acetyl-CoA carboxylase (ACC; a marker of AMPK activity). Procaspase-3 and cleaved (activated) caspase-3 contents were also assessed via western blot. AMPK phosphorylation was significantly (p < 0.05) increased in old, but not young, subjects immediately post-exercise. In both age groups, AMPK activity (assessed by ACC phosphorylation) was elevated vs. PRE at the 0P and 1P time points, and cleaved caspase-3 content was elevated vs. PRE at the 0P, 1P, and 2P time points. However, there was no effect of exercise on procaspase-3 content in either age group, and no differences between age groups in AMPK activity, procaspase-3 content, or cleaved caspase-3 content at any time point. There were significant, or close to significant, relationships between glycogen content and AMPK activity at time points PRE, 0P, and 1P regardless of age. However, no significant correlations between AMPK activity and cleaved caspase-3 content were observed at any time point. In summary, these data indicate that cleaved caspase-3 (e.g., caspase-3 activity) increases in response to acute resistance exercise in both young and old subjects. However, exercise-induced AMPK activation may not be the mechanism by which this occurs.  M.S

Studies on the Variability of Human Basal Metabolic Rate

The studies presented in this thesis examine some of the factors responsible for variation in basal metabolic rate (BMR, defined as the energy expended by an individual lying quietly at rest in a thermoneutral environment, at least 12 hours postabsorptive). They are particularly concerned with the parts played by differences in body composition and cellular metabolic activity, under the influence of thyroid hormones and catechloamines, in explaining variability in BMR. In the great majority of people, and certainly most of those living in an industrialised society, BMR accounts for the largest part of daily energy expenditure, often making up more than two thirds of the total. Study of the factors that effect BMR is therefore central to our understanding of the causes of variation in daily energy needs. The first study undertaken sought to explore some of the general relationships between BMR and body composition in a group of 97 healthy women. BMR was measured using the Douglas bag technique, and body composition assessed by measurements of weight, height, body fat content (skinfold and densitometry estimates), circumferences and diameters. Differences in BMR between the women were found to be large (CV = 11.8%, standard deviation 159 kcal/day) and could be best explained by differences in FFM, accounting for 45 % of the total variance. The relationship between BMR and FFM was unaffected by body fatness or age. However, at a given FFM considerable variation in the BMR of individual women was evident. Moreover, for the purposes of predicting an individual's BMR, FFM was found to be no better than body weight. Simple differences in the weight of the FFM therefore, could only partially explain the variation in BMR between the women. A further observation from the study was that BMR expressed per kg body weight or per kg FFM tended to decline form light to heavy individuals. This finding has implications for the use of FFM as a metabolic reference standard, and it is suggested that it may relate to differences in the composition of the FFM. The role of the catecholamines was considered in a study which investigated the effect of B-adrenergic blockade on basal metabolic rate. The BMRs (measured using a ventilated hood system) of a group of 18 patients receiving beta blocker drugs in the treatment of cardiovascular disorders were compared to those of 28 healthy control subjects. In relation to the FFM (estimated from skinfold thicknesses) the BMRs of the B-blocker patients were found to 8% lower than that of the controls, equivalent to 136 kcal/day. The study revealed a potentially important side effect of this widely prescribed group of drugs and moreover, suggested that BMR has an adrenergically mediated component. A further study was undertaken with the aim of elucidating the causes of the marked variation in BMR relative to the FFM observed in the initial investigation. Two groups of women characterised by particularly high or low BMRs in relation to their FFM were selected for further study. Repeat measurements of BMR suggested that part of the differences between the groups, and by extension the initial study also, resulted from within-subject variation in BMR. Error in measurement of the FFM (estimated by skinfolds, total body water and densitometry) was found to be small and its potential contribution considered minor. It was estimated that genuine inter-individual variation in BMR in relation to the FFM was in the region of 100 kcal/day. Thyroid hormone levels were found to be significantly greater in the high BMR group than in the low and it was postulated that these differences were likely to be responsible for at least part of the variance in BMR relative to FFM. Thyroid status did not however, provide the complete explanation, a residual standard deviation approximately 70 kcal/day remained. It was considered likely that differences in the composition of the FFM were involved in explaining the remaining variance. Urinary catecholamine levels were comparable in both groups, however the possibility that differences in an adrenergically mediated process may have contributed to the differences in BMR could not be ruled out. Traditionally, differences in BMR have been ascribed to differences in body size, age, sex, race, climate and nutritional status. The studies presented in this thesis suggest however, that that these may have a common basis in that they relate to differences in one or both of the major determinants of BMR; to differences in body composition - primarily to the mass of fat-free tissue and to the relative proportions of its component parts - and to hormonally induced metabolic activity of the tissues

Total body nitrogen by prompt neutron activation analysis using californium-252

Many diseases are accompanied by wasting with a consequent loss of protein. The establishment of nutritional status in such patient groups would enable the efficacy of management regimens to be evaluated. The nutritional model adopted will be a compromise between its useful complexity and the practicality of measuring each compartment. The advantages of the four compartment model (protein, water, minerals and fat) adopted for this thesis, over simpler two compartment (fat and fat free mass) models are discussed.Protein is related to nitrogen by the universally accepted multiplicative factor of 6.25. Prompt neutron activation analysis (NAA) (1AN(n,fc)15"N} has been shown to be superior to delayed NAA {1AN(n,2n)l3N} for the measurement of protein. These advantages are in respect of : specificity of reaction product; number of interfering reactions; uniformity of combined activation/detection sensitivity; radiation dose for a given precision and cost of apparatus. Furthermore, only the prompt technique is feasible for studies involving the critically ill. Additionally, radio-isotopic neutron sources can be used and the advantages of Californium-252 (252Cf) over alternative sources are discussed. The disadvantage of the prompt technique is the high count rate at the detectors, caused by the simultaneous irradiation and detection of the subject.A consequence of the high count rate during the protein measurement is pulse pile-up, which leads to spectrum distortion and has been identified as the principal contributor to the nitrogen background. Consideration has been given to the characteristics of the pulse processing system to minimise this pile-up. The combination of source and detector shielding materials has been determined empirically by minimising the nitrogen background. Comparison has been made of alternative unilateral and bilateral irradiation/detection geometries for prompt NAA and the latter chosen for construction of clinical apparatus. The apparatus enables the in-vivo measurement of total body protein by prompt NAA using 2S2Cf with a precision of ±3%, from a 40 minute scan for a whole body dose equivalent of 0.18mSv.Techniques for predicting the nitrogen background from a subject spectrum are presented. Calibration of the apparatus to convert a nitrogen:hydrogen counts ratio to a mass ratio and the continued requirement for recalibration as the 252Cf decays is discussed. The prompt technique requires total body nitrogen to be calculated from the nitrogen:hydrogen mass ratio by the independent estimate of total body hydrogen. A circularity in the relationships used enables this estimate to be made by measuring total body water by an isotope dilution technique. Finally, data-from a study on normal subjects is presented and prediction equations generated for total body nitrogen based on anthropometrics. The results are compared with findings from other centres

Comparación metodológica del análisis de la composición corporal antropometría, bioimpedancia y excreción de creatinina

La estimación de la composición corporal proporciona información adecuada para la realización de estudios de crecimiento, nutrición y práctica deportiva. En la actualidad para efectuar este tipo de trabajos existen diversos procedimientos por lo que dada la heterogeneidad los investigadores se planteen dudas respecto a que material, técnica y ecuación emplear a la hora de abordar esta clase de análisis. Para intentar responder en parte a estas cuestiones y establecer unas recomendaciones básicas se plantea el presente trabajo. El objetivo principal es comparar tres técnicas a partir de una muestra de 204 mujeres y 78 varones de 18 a 25 años de edad. Los resultados indican que el método gráfico elaborado por Bland y Altman (1986) permite extraer información detallada sobre la concordancia entre técnicas o ecuaciones. En antropometría el método desarrollado por Drinkwater y Ross (1980), basado en la táctica Phantom, y la ecuación de pliegues de Yuhasz (1974) estiman adecuadamente la composición corporal, mientras que la fórmula de Durnin y Womersley (1974) sobrestima el porcentaje de grasa. El análisis basado en bioimpedancia aunque tienen ventajas sobre otros métodos presenta la limitación de que es altamente dependiente de las ecuaciones de regresión utilizadas. Las expresiones más concordantes con antropometría de acuerdo al análisis Bland y Altman (1986) son: Deurenberg et al.1 (1991), Deurenberg et al.2 (1990b), Lukaski y Bolonchuk1 (1988), Lukaski y Bolonchuk2 (1988) y Segal et al. (1988). Por último, para predecir adecuadamente la masa muscular a partir de la excreción de creatinina en orina se deben controlar numerosos factores y en consecuencia los resultados derivados de su aplicación son menos óptimos que lo inicialmente planteado

Envejecimiento y Enfermedad: Innovaciones Terapéuticas: XIX Curso de Actualización para Postgraduados en Farmacia

El envejecimiento de la población, con sus consecuencias médicas, sociales, económicas y políticas, constituye uno de los fenómenos más relevantes de nuestra época. Y gracias al desarrollo socio-económico que en los últimos años han experimentado los países desarrollados, se ha mejorado la calidad de vida y las condiciones sociales de las personas mayores. A medida que avanza la edad, todos los órganos sufren cambios que, si se desarrollan de una forma que podríamos considerar fisiológica, suponen un proceso armónico de envejecimiento. Sin embargo, como la posibilidad de enfermar se incrementa con la edad, las patologías asociadas al envejecimiento constituyen uno de los capítulos más importantes de la patología humana. El deterioro de los sistemas cardiocirculatorio, respiratorio, osteoarticular y de los órganos de los sentidos, junto con las enfermedades del sistema nervioso central, amenazan con mayor frecuencia la calidad de vida de los ancianos. De las demencias seniles, la enfermedad de Alzheimer es quizás la que provoca un deterioro mayor, con un alto coste humano, social y económico. El cuidado de la salud de los ancianos requiere estrategias preventivas mediante una alimentación correcta, un conocimiento de las enfermedades que les aquejan, y un tratamiento farmacológico eficaz. No se puede olvidar que las personas ancianas son las que más medicamentos consumen, siendo particularmente sensibles a los efectos indeseables que pueden originar. Por otra parte, la gestión y uso correcto de productos sanitarios y accesorios debe ser objeto de interés para los profesionales que los atienden, entre los que se encuentra el farmacéutico. Este curso aborda algunos conocimientos y actitudes que deben traducirse en una mejor comprensión y atención de un sector tan importante de la sociedad, como son las personas mayores

Cineantropometría: composición corporal y somatotipo de futbolistas que desarrollan su actividad física en equipos de la Comunidad Autónoma de Madrid

Definimos Cineantropometría como el estudio del tamaño, forma, proporcionalidad, composición, maduración biológica y función corporal; con objeto de entender el proceso del crecimiento, el ejercicio, el rendimiento deportivo y la nutrición. OBJETIVOS: Estudio controlado, transversal, no randomizado, de tipo observacional y analítico cineantropométrico. MATERIAL Y METODO: Utilizamos el protocolo de medidas establecido por la Sociedad Internacional para el Avance de la Cineantropometría (I.S.A.K.) y aceptadas por el Grupo Español de Cineantropometría. RESULTADOS: La talla media de todos los jugadores estudiados es de 176.64 cm; peso 77.01Kg, porcentaje de grasa derecho 8.04% e izquierdo 8.10%, masa ósea derecha 11.72Kg e izquierda 11.59Kg, masa muscular derecha 38.46Kg e izquierda 38.55Kg, peso residual 18.56Kg, somatotipo derecho e izquierdo Endo - Mesomorfo. CONCLUSIONES: 1. La homogeneidad interpoblacional aparece como un rasgo característico general de los jugadores de fútbol investigados, patente cuando los analizamos por categoría profesional, pero existe cierta heterogeneidad al distinguirlos en base a su posición en el terreno de juego. 2. La heterogeneidad intrapoblacional aparece como rasgo específico manifestado en los porteros, futbolistas que muestran una tipología propia cuando se analizan por su posición en el terreno de juego, desarrollando un morfotipo característico, siendo los futbolistas más altos y pesados. 3. La talla es superior en los jugadores de fútbol profesionales, lo que no corresponde a un mayor peso. Los futbolistas de la 2ªB división son los deportistas más bajos y asimismo los más ligeros. 4. Los jugadores de fútbol más altos y más pesados son los porteros no profesionales, y los delanteros de la 2ªB división los más bajos y livianos. 5. Los somatotipos no valoran la asimetría, pero registran información de la diferencia entre el lado derecho y el izquierdo en estudios particulares. 6. La heterogeneidad intragrupo reafirma nuestro objetivo de estudiar a los jugadores de fútbol como dos hemimitades independientes. La variabilidad entre el hemicuerpo derecho e izquierdo expuesta en las conclusiones precedentes no cuestiona en ningún momento la aceptación universalmente aprobada y base del método científico utilizado en la presente investigación de considerar las mediciones realizadas en el lado derecho equivalentes al futbolista en su conjunto