Exposición intermitente a altitud simulada y ejercicio para la recuperación del daño muscular: células madre circulantes y ajustes hemorreológicos en ratas entrenadas

[spa] La hipótesis general de este trabajo se basa en que un protocolo de hipoxia hipobárica intermitente (IHH) combinada con ejercicio aeróbico ligero en normoxia, puede tener un efecto beneficioso en la regeneración de musculatura esquelética dañada y contribuir a una recuperación más rápida en este tipo de lesiones. Sin embargo, el conocido efecto hematopoyético de la exposición a hipoxia y del ejercicio, y el consiguiente aumento de hematocrito, podrían afectar a la dinámica del aporte de oxígeno a los tejidos, por lo que se hace necesario conocer y estudiar los potenciales efectos de estos tratamientos sobre la hematología y la reología sanguínea. Además, se ha dedicado especial atención a la presencia de células madre circulantes (CD34+) y a la población de “side population” (SP) en médula ósea para obtener evidencias de su posible incidencia en la recuperación de la lesión muscular. El núcleo fundamental de esta tesis doctoral está compuesto por dos estudios que tienen como objetivos: 1. Determinar si la respuesta hematopoyética durante un programa IHH, podría provocar alteraciones en el comportamiento hemorreológico, generando efectos negativos en el suministro de oxígeno a los tejidos. 2. Cuantificar y contrastar los efectos de la IHH y el ejercicio en el aumento del número de células progenitoras en la circulación sanguínea periférica. 3. Determinar los efectos de la IHH combinada o no con el ejercicio aeróbico ligero en normoxia, genera cambios en la presencia de SP. 4. Establecer la dinámica temporal en las modificaciones de la concentración de células madre CD34+ y SP en los diferentes grupos de animales, según las diferentes condiciones experimentales. La muestra se obtuvo de ratas Sprague-Dawley que fueron estudiadas en dos estados basales (no entrenadas y entrenadas) y comparadas durante la fase de recuperación de una lesión por contracción excéntrica repetida (inducida a ratas entrenadas) los días 1, 3, 7 y 14 posteriores a la lesión muscular. Los tres grupos experimentales estudiados durante la recuperación de sus lesiones musculares fueron: ratas con recuperación pasiva (CTRL); ratas expuestas a IHH después del daño muscular (HYP); y ratas entrenadas que además de IHH, realizaron sesiones de ejercicio aeróbico ligero (EHYP). Los resultados obtenidos en los estudios, nos permiten extraer las siguientes conclusiones: 1. Después de dos semanas de tratamiento, la IHH en combinación con ejercicio aeróbico ligero en normoxia, muestra parámetros hemorreológicos alterados en comparación a las demás condiciones experimentales. 2. Aunque la respuesta eritropoyética provocada por la exposición IHH tiende a aumentar la viscosidad de la sangre en el grupo EHYP, otros parámetros microrreológicos tales como mayor elasticidad y menor tiempo de relajación pueden contribuir a compensar este aumento. 3. Los ajustes compensatorios reológicos pueden considerarse como positivos desde un punto de vista funcional, pues contribuyen a mantener la microcirculación normal y un suministro adecuado de oxígeno, nutrientes y agentes químicos a los tejidos durante su proceso de reparación después de daño sufrido en el músculo esquelético. 4. La tinción DyeCycle Violet se retiene selectivamente para las células CD34+, que permite la discriminación de los dos subconjuntos de células, denominadas internamente como CD34+/DCVhigh y CD34+/DCVlow, debido a una intensidad más brillante o atenuada de la tinción. 5. En el séptimo día de la recuperación después de una lesión muscular, el grupo EHYP aumentó claramente el número de progenitores CD34+/CD45neg y CD34+/CD45+. 6. El grupo HYP aunque no muestra un aumento en células progenitoras después de la lesión muscular, es altamente sensible a la expresión de células SP las primeras horas de exposición. 7. La exposición a IHH parece ser decisiva en la expresión de la población SP, aunque el estímulo inducido por el ejercicio mostró un efecto inverso sobre su cinética.[eng] The general hypothesis of this PhD dissertation document is based on the possible favorable effects of a protocol of intermittent hypobaric hypoxia (IHH) combined with light aerobic exercise in normoxia. We have tested if such IHH program can elicit a beneficial effect on the regeneration of skeletal muscle damage and contribute to a faster recovery in this type of injury. However, the well-known hematopoietic action of hypoxia exposure and exercise can alter the erythrocyte mass and even the circulatory dynamic at microcirculatory level. We have focused on the rheological properties of blood, presence of circulating stem cells and the dynamics of bone marrow side population (SP) cells. The core of this thesis is composed by two main studies whose general objective are: 1. To determine if the erythropoietic response elicited by intermittent hypobaric hypoxia exposure can alter blood rheology and thus affect in any way the oxygen delivery to tissues. 2. To outline if the IHH exposure can help to increase the number of peripheral blood circulating progenitor cells (CD34+) and bone marrow side population stem cells, in order to establish the usefulness of this intervention for skeletal muscle repair. Male Sprague-Dawley rats were studied in two basal states: untrained and trained and compared with trained rats that suffered skeletal muscle injury (down-hill running until exhaustion) at four stages (1, 3, 7 and 14 days) during damage recovery. Three experimental groups of wounded trained rats were studied: rats with passive recovery (CTRL); rats exposed to IHH after muscle damage (HYP); and, rats that, in addition to IHH, performed light aerobic exercise sessions (EHYP). The results obtained in this thesis allow us to conclude that the IHH in combination with light aerobic exercise in normoxia showed a higher erythropoietic effect, but without threatening the perfusion of damaged muscle because advantageous hemorheological adjustments. DyeCycle® Violet staining is selectively retained into CD34 + cells, thus allowing to the discrimination of two subsets of cells, internally referred as CD34+/DCVhigh and CD34+/DCVlow cells. Finally, IHH in combination with light aerobic exercise increased the number of CD34+/CD45neg and CD34+/CD45+ cells on the 7th day in EHYP group, although the exercise-induced stimulus showed a reverse effect on SP kinetics

A semiquantitative scoring tool to evaluate eccentric exercise-induced muscle damage in trained rats

Unaccustomed eccentric exercise is a welldocumented cause of exercise-induced muscle damage. However, in trained subjects muscle injury involves only light or moderate tissue damage. Since trained rats are widely used as a model for skeletal muscle injury, here we propose a semiquantitative scoring tool to evaluate muscle damage in trained rats. Twenty male Sprague-Dawley rats were trained for two weeks following a two-week preconditioning period, and randomly divided into two groups: control rats (CTL; n=5) and rats with eccentric exercise-induced muscle damage (INJ; n=15). Injured rats were sacrificed at three time points: 1, 3 and 7 days post injury (n=5 each). Transverse sections from the right soleus were cut (10 μm) and stained with haematoxylineosin. Samples were evaluated by two groups of observers (four researchers experienced in skeletal muscle histopathology and four inexperienced) using the proposed tool, which consisted of six items organised in three domains: abnormal fibre morphology, necrotic/(re) degenerating fibres (muscle fibre domain), endomysial and perimysial infiltration (inflammatory state domain) and endomysium and perimysium distension (interstitial compartment domain). We observed the expected time course in the six evaluated items. Furthermore, agreement among observers was evaluated by measuring the Intraclass Correlation Coefficient (ICC). Within the experienced group, items from the muscle fibre and interstitial compartment domains showed good agreement and the two items from the infiltration compartment domain showed excellent agreement. In conclusion, the proposed tool allowed quick and correct evaluation of light to moderate muscle damage in trained rats with good agreement between observers

Diferencias morfológicas y de condición física en futbolistas adolescentes según posición de juego: una revisión sistemática

Introduction: The aim of this systematic review was to analyze the studies that evaluate morphological and physical fitness differences in young soccer players according to playing position.Material and Methods: For its elaboration, the PRISMA-P protocol was followed, the PubMed/MEDLINE database was used, and the Downs & Black methodological quality assessment was applied. Six studies met all the selection criteria, adding 784 soccer players (229 defenders [DF]; 271 midfielders [MF], 168 forwards [FW] and 69 goalkeepers [GK]) with a mean age of 16.2 years.Results: The analyzed studies indicate, that GK and DF have a height, body weight, endomorphic component and body fat higher than MF and FW, except for one study that reports higher values for body weight in FW and DF with respect to MF. In relation to physical fitness, the maximum squat exhibited higher values for FW compared to MF; cardiorespiratory fitness was higher in DF and MF when compared with GK and abdominal muscle resistance was greater in MF compared to DF. Conclusion: The GK and DF show greater height, body weight and body fat than the MF and FW. While physical fitness indicates that FW show greater lower body strength, MF and DF achieve greater cardiorespiratory fitness and MF present greater abdominal muscle resistance when young soccer players are analyzed according to playing position.Introducción: El objetivo de la presente revisión sistemática fue analizar los estudios que evalúan las diferencias morfológicas y de condición física en futbolistas adolescentes según posición de juego.Material y métodos: Para su elaboración se siguió el protocolo PRISMA-P, se utilizó la base de datos PubMed/MEDLINE y se aplicó la evaluación de calidad metodológica de Downs & Black. Seis estudios cumplieron con todos los criterios de selección, sumando 784 futbolistas (229 defensas [DF]; 271 mediocampistas [MC], 168 delanteros [DL] y 69 porteros [PT]) con una edad media de 16,2 años. Resultados: Los estudios analizados indican que los PT y DF poseen una altura, peso corporal, componente endomórfico y grasa corporal mayor que MC y DL, excepto un estudio que reporta valores más altos para peso corporal en DL y DF respecto a MC. En relación a la condición física, la sentadilla máxima exhibió valores más elevados para DL respecto a MC; la capacidad cardiorrespiratoria fue superior en DF y MC al compararlos con PT y la resistencia muscular abdominal fue mayor en MC respecto a DF. Conclusión: Los PT y DF ostentan mayor altura, peso corporal y grasa corporal que los MC y DL. Mientras que la condición física, indica que los DL demuestran mayor fuerza del tren inferior, los MC y DF consiguen mayor capacidad cardiorrespiratoria y los MC presentan mayor resistencia muscular abdominal cuando se analizan futbolistas adolescentes según posición de juego

Fatiga, el enemigo del movimiento en altura. VFC una opción viable de detección.

The move allows us to perform our daily life as normal under perfectly known parameters, however, there are circumstances where the locomotive is fully exposed to complex situations beyond the control of human beings, is the case of hypobaric hypoxia. Under hypoxic conditions the movement faces the constant threat of physical and mental fatigue, decreasing the chances of well executed movements, which often puts the risk to the individual and their environment. The control of motor actions based on heart rate variability, is shown to be an effective method for prevention and early indicators of fatigue, contributing to enhance the action of the individual psychomotor geographical height, proposing itself as a simple and low-cost motor control in hypobaric hypoxic.El movimiento nos permite diariamente realizar nuestra vida de manera normal bajo parámetros perfectamente conocidos. Sin embargo, existen circunstancias en donde el aparato locomotor se ve expuesto a situaciones completamente complejas y ajenas a la voluntad del ser humano, es el caso de la hipoxia hipobárica. Bajo condiciones hipóxicas el movimiento enfrenta la constante amenaza de fatiga física y mental, disminuyendo las posibilidades de movimientos bien ejecutados, que muchas veces ponen el riesgo al individuo y su entorno. El control de acciones motrices en base a la variabilidad de frecuencia cardiaca, muestra ser un método eficaz de prevención y anticipación de indicadores de fatiga, contribuyendo a mejorar la acción psicomotriz del individuo en altura geográfica, proponiéndose como un sistema simple y de bajo costo en el control motriz en hipóxica hipobárica

Redox modifications in synaptic components as biomarkers of cognitive status, in brain aging and disease

Aging is a natural process that includes several changes that gradually make organisms degenerate and die. Harman's theory proposes that aging is a consequence of the progressive accumulation of oxidative modifications mediated by reactive oxygen/nitrogen species, which plays an essential role in the development and progression of many neurodegenerative diseases. This review will focus on how abnormal redox modifications induced by age impair the functionality of neuronal redox-sensitive proteins involved in axonal elongation and guidance, synaptic plasticity, and intercellular communication. We will discuss post-transcriptional regulation of gene expression by microRNAs as a mechanism that controls the neuronal redox state. Finally, we will discuss how some brain-permeant antioxidants from the diet have a beneficial effect on cognition. Taken together, the evidence revised here indicates that oxidative-driven modifications of specific proteins and changes in microRNA expression may be useful biomarkers for aging and neurodegenerative diseases. Also, some specific antioxidant therapies have undoubtedly beneficial neuroprotective effects when administered in the correct doses, in the ideal formulation combination, and during the appropriate therapeutic window. The use of some antioxidants is, therefore, still poorly explored for the treatment of neurodegenerative diseases such as Alzheimer's disease.DIUV - CIDI 5/06 Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT 11150776 1170446 MAG1895 MAG1995 ANID/FONDAP 15150012 Chilean State Universities Network grant 1656-175

Effect of Confinement on Anxiety Symptoms and Sleep Quality during the COVID-19 Pandemic

Confinement during the COVID-19 pandemic has significantly impacted lifestyles worldwide. The aim of this study was to evaluate the effect of confinement on anxiety symptoms and sleep quality in people living in extreme southern latitudes. The Beck Anxiety Inventory (BAI) and the Pittsburgh Sleep Quality Index (PSQI) were administered to 617 people, 74.2% of whom were women. The sample was grouped according to confinement: the zone of confinement (CZ) (46.5%) and the zone of partial confinement (PZ) (53.5%). In addition, the sample was further categorized into four age subgroups (18–25 years; 26–40 years; 41–50 years; over 50 years). Higher levels of anxiety and worse sleep quality were found in the CZ group than in the PZ group. Women had higher levels of anxiety and worse sleep quality than men. A significant bidirectional relationship between anxiety and sleep quality was observed, even after controlling for sex. This study demonstrated that women and young adults were more vulnerable to the effects of confinement on anxiety symptoms and sleep quality in populations at southern latitudes

A three-criteria performance score for rats exercising on a running treadmill.

In this study, we propose a novel three-criteria performance score to semiquantitatively classify the running style, the degree of involvement and compliance and the validity of electric shock count for rats exercising on a treadmill. Each score criterion has several style-marks that are based on the observational registry of male Sprague-Dawley rats running for 4-7 weeks. Each mark was given a score value that was averaged throughout a session-registry and resulting in a session score for each criterion, ranging from "0" score for a hypothetical "worst runner", to score "1" for a hypothetical "perfect runner" rat. We found significant differences throughout a training program, thus providing evidence of sufficient sensitivity of this score to reflect the individual evolution of performance improvement in exercise capacity due to training. We hypothesize that this score could be correlated with other physiological or metabolic parameters, thus refining research results and further helping researchers to reduce the number of experimental subjects

A three-criteria performance score for rats exercising on a running treadmill

In this study, we propose a novel three-criteria performance score to semiquantitatively classify the running style, the degree of involvement and compliance and the validity of electric shock count for rats exercising on a treadmill. Each score criterion has several style-marks that are based on the observational registry of male Sprague-Dawley rats running for 4-7 weeks. Each mark was given a score value that was averaged throughout a session-registry and resulting in a session score for each criterion, ranging from '0' score for a hypothetical 'worst runner', to score '1' for a hypothetical 'perfect runner' rat. We found significant differences throughout a training program, thus providing evidence of sufficient sensitivity of this score to reflect the individual evolution of performance improvement in exercise capacity due to training. We hypothesize that this score could be correlated with other physiological or metabolic parameters, thus refining research results and further helping researchers to reduce the number of experimental subjects

Factors Associated with Poor Health-Related Quality of Life in Physically Active Older People

This study aimed to associate morphological variables and physical fitness with health-related quality of life (HRQoL) in physically active older people. A cross-sectional study was carried out that evaluated 470 older people (89.57% female) with a mean age of 70.13 ± 6.57 years, residing in two regions of Chile. Morphological variables (body weight, bipedal height, waist circumference, body mass index, and waist to height ratio), physical fitness through the Senior Fitness Test protocol, and HRQoL using the SF-36 questionnaire were obtained. Logistic regression analysis was used to identify risk factors between morphological variables and physical fitness associated with HRQoL. The main results indicated that overweight (OR = 1.52; p = 0.034), a waist circumference with risk (OR = 1.56; p = 0.021), poor performance in the back scratch tests (OR = 1.02; p = 0.008) and timed up-and-go (OR = 1.19; p = 0.040) increased the probability of having a low general HRQoL. Also, the low performance of chair stand and arm curl tests was associated with poor physical and social dimensions of HRQoL (p < 0.05). In conclusion, a low HRQoL in physically active older people is associated with both morphological and physical fitness factors

Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD), in trained rats, of two recovery protocols based on: 1) intermittent hypobaric hypoxia (IHH) and 2) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7 and 14 days after an EEIMD protocol. The following treatments were applied one day after the EEIMD: passive normobaric recovery (PNR), four-hour daily exposure to passive IHH at 4000m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity had reduced 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1Îą and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1 and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser36)/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author