In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

To promote and support tendon healing, one viable strategy is the use or administration of growth factors at the wound/rupture site. Platelet derived growth factor-BB (PDGF-BB), together with other growth factors, is secreted by platelets after injury. PDGF-BB promotes mitogenesis and angiogenesis, which could accelerate tendon healing. Therefore, in vitro studies with PDGF-BB have been performed to determine its effect on tenocytes and tenoblasts. Moreover, accurate and sophisticated drug delivery devices, aiming for a sustained release of PDGF-BB, have been developed, either by using heparin-binding and fibrin-based matrices or different electrospinning techniques. In this review, the structure and composition, as well as the healing process of tendons, are described. Part A deals with in vitro studies. They focus on the multiple effects evoked by PDGF-BB on the cellular level. Moreover, they address strategies for the sustained delivery of PDGF-BB. Part B focuses on animal models used to test different delivery strategies for PDGF-BB, in the context of tendon reconstruction. These studies showed that dosage and timing of PDGF-BB application are the most important factors for deciding which delivery device should be applied for a specific tendon laceration

Paràmetres cardiorespiratoris durant l'exercici submàxim sota una exposició aguda a hipòxia hipobàrica i normobàrica

Set joves sans i en bona condició física foren sotmesos a dos tests de tolerància a la hipòxia a una altitud simulada de 3.000 m. El primer s’efectuà en una cambra hipobàrica i els segon en un tenda hipòxica. Es registraren diversos paràmetres cardiorespiratoris i la variabilitat de la freqüència cardíaca sota cada condició d’hipòxia. En comparació amb les condicions de normòxia, s’observà un decrement significatiu del 6 al 8% en la saturació de l’oxigen arterial (SpO2) en ambdues condicions d’hipòxia en repòs. L’exercici desencadenà descensos d’un 10% en SpO2 tot i l’increment del 27% del volum ventilatori minut. Tant els components de baixa (BF) com d’alta freqüència (AF) de la variabilitat del ritme cardíac van canviar significativament de la normòxia (BF: 37,1; AF: 62,9; BF/AF: 1,27) a la hipòxia hipobàrica (HH) (BF: 49,1; AF: 50,6; BF/AF: 1,96). Malgrat això, aquests canvis no s’apreciaren en condicions d’hipòxia normobàrica. Per tant, la variabilitat de la freqüència cardíaca té un comportament diferent en les dues condicions d’hipòxia, la qual cosa recolza la hipòtesi que l’hipòxia normobàrica i l’hipobàrica no suposen un estímul igual dels sistemes cardiovacular i respiratori. S’observà una correlació entre la modulació vagal i simpàtica en normòxia i l’SpO2 durant l’exercici en hipòxia hipobàrica (HH). Els subjectes amb major modulació simpàtica (BF%) en normòxia presenten major SpO2 durant l’exercici en HH (r = 0,808; p < 0,05) i els individus amb major modulació vagal (AF%) en normòxia tendeixen a SpO2 més baixa en exercici en HH (r = −0,636; p = 0,125). Sorgeix la possibilitat d’utilitzar aquesta correlació com a eina predictiva de la capacitat individual d’aclimatació a l’altitud

Androgen-regulated cardiac metabolism in aging men

The prevalence of cardiovascular mortality is higher in men than in age-matched premenopausal women. Gender differences are linked to circulating sex-related steroid hormone levels and their cardio-specific actions, which are critical factors involved in the prevalence and features of age-associated cardiovascular disease. In women, estrogens have been described as cardioprotective agents, while in men, testosterone is the main sex steroid hormone. The effects of testosterone as a metabolic regulator and cardioprotective agent in aging men are poorly understood. With advancing age, testosterone levels gradually decrease in men, an effect associated with increasing fat mass, decrease in lean body mass, dyslipidemia, insulin resistance and adjustment in energy substrate metabolism. Aging is associated with a decline in metabolism, characterized by modifications in cardiac function, excitation-contraction coupling, and lower efficacy to generate energy. Testosterone deficiency -as found in elderly men- rapidly becomes an epidemic condition, associated with prominent cardiometabolic disorders. Therefore, it is highly probable that senior men showing low testosterone levels will display symptoms of androgen deficiency, presenting an unfavorable metabolic profile and increased cardiovascular risk. Moreover, recent reports establish that testosterone replacement improves cardiomyocyte bioenergetics, increases glucose metabolism and reduces insulin resistance in elderly men. Thus, testosterone-related metabolic signaling and gene expression may constitute relevant therapeutic target for preventing, or treating, age- and gender-related cardiometabolic diseases in men. Here, we will discuss the impact of current evidence showing how cardiac metabolism is regulated by androgen levels in aging men.Fondo Nacional de Ciencia y Tecnología (FONDECYT) Grant 1151118 119040

Effects of oxygen supplementation on acute mountain sickness symptoms and functional capacity during a 2-kilometer walk test on chajnantor plateau (5050 meters, Northern Chile)

Objective.—The aim of this study was to test the hypothesis that administration of low-flow oxygen will improve physical performance in subjects unacclimatized to altitude. We evaluated the effects of oxygen supplementation on functional capacity and acute mountain sickness (AMS) symptoms in young, healthy male and female subjects who performed a 2-km fast walk test following rapid ascent to the Chajnantor plateau (5050 m above sea level) in Northern Chile. Methods.—The participants were randomly distributed into 2 groups according to oxygen supplementation levels: 1 or 3 L O2·min 1. Within each group, males and females were evaluated separately. A preliminary walk test was carried out at sea level on a 100-m long, flat track with 10 U-turns. For the first walk at altitude, subjects carried the supplementary oxygen system but did not breathe the oxygen. Subjects received oxygen through a facemask the following day during the second test. The nights prior to altitude tests were spent at 2400 m in San Pedro de Atacama. Results.—Supplementary oxygen administration during a 2-km walk test significantly improved walking times at 5050 m. We also observed a significant improvement in AMS symptoms. As expected, however, performance was poorer at altitude compared to test values at sea level, despite supplementary oxygen administration. Conclusions.—Our findings demonstrate the beneficial effects of supplementary oxygen administration on physical capacity, reducing the incidence of AMS and, thus, improving health and safety conditions for high altitude workers following rapid ascent, when adequate acclimatization is not possible

Parámetros cardiorrespiratorios durante ejercicio submáximo en hipoxia aguda hipobárica y normobárica

Siete jóvenes sanos y en buena condición física realizaron dos pruebas de tolerancia a hipoxia a una altitud simulada de 3.000 m. La primera fue en cámara hipobárica, mientras que la segunda se efectuó en una tienda hipóxica. Se registraron varios parámetros cardiorrespiratorios y la variabilidad de la frecuencia cardiaca. En comparación con las condiciones de normoxia, se observó un decremento significativo del 6% al 8% en la saturación de oxígeno arterial (SpO2) en reposo en ambas condiciones de hipoxia. El ejercicio desencadenó descensos de un 10% en SpO2 pese a un incremento del 27% del volumen minuto ventilatorio. Tanto los componentes de baja (LF) como alta frecuencia (HF) de la variabilidad del ritmo cardiaco cambiaron significativamente en hipoxia hipobárica (LF: 49,1, HF: 50,6, LF/HF: 1,96) respecto a normoxia (LF: 37,1, HF: 62,9, LF/HF: 1,27). Estos cambios no se apreciaron en condiciones de hipoxia normobárica, lo cual apoya la hipótesis de que la hipoxia hipobárica y normobárica no suponen igual estímulo para los sistemas respiratorio y cardiovascular. Se ha observado una correlación entre la modulación vagal y simpática en normoxia y la SpO2 durante ejercicio en cámara hipobárica. Los sujetos con mayor modulación simpática (LF%) en normoxia presentan mayor SpO2 en ejercicio en la cámara (r=0,808, p<0,05) y los individuos con mayor modulación vagal (HF%) en normoxia tienden a SpO2 más bajas en ejercicio en hipobaria (r=−0,636, p=0,125). Surge la posibilidad de utilizar esta asociación como herramienta predictiva de la capacidad individual de aclimatación a la altura

Vitamin D insufficiency is associated with metabolic risk factors in women with polycystic ovary syndrome

Seven healthy young men were submitted twice to a hypoxia tolerance test at a simulated altitude (3000m). Their first acute exposure was in a hypobaric chamber; and the second, in a hypoxic tent. Cardiorespiratory parameters and heart rate variability measurements were obtained under each hypoxic condition. A significant decrease of 6% to 8% compared to normal oxygen conditions was observed in arterial oxygen saturation (SpO2) in both hypoxic conditions at rest; whereas exercise led to decreases of 10% in SpO2 despite an increase of 27% in respiratory minute volume. The low frequency (LF) and high frequency (HF) components of heart rate variability significantly changed from normoxia (LF: 37.1, HF: 62.9, LF/HF: 1.27) to hypobaric hypoxia (HH) (LF: 49.1, HF: 50.6, LF/HF: 1.96). However, these changes were not observed under normobaric hypoxia. Thus, heart rate variability behaved differently in the two hypoxic conditions, supporting the hypothesis that normobaric hypoxia and hypobaric

Acute psychological stress increases serum circulating cell-free mitochondrial DNA

Intrinsic biological mechanisms transduce psychological stress into physiological adaptation that requires energy, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, exposure to psychological stress increases serum circulating cell-free mtDNA (ccf-mtDNA) levels. Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibited a 2-3-fold increase in ccf-mtDNA, with no change in ccf-nuclear DNA levels, establishing the magnitude and specificity for ccf-mtDNA reactivity. In cell-based studies, we show that glucocorticoid signaling – a consequence of psychological stress in humans – is sufficient to induce mtDNA extrusion in a time frame consistent with stress-induced ccf-mtDNA increase. Collectively, these findings provide evidence that acute psychological stress induces ccf-mtDNA and implicate neuroendocrine signaling as a potential trigger for ccf-mtDNA release. Further controlled work is needed to confirm that observed increases in ccf-mtDNA result from stress exposure and to determine the functional significance of this effect