Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.

Kinetics of Muscle Carnosine Decay after ß-Alanine Supplementation: A 16-wk Washout Study.

PURPOSE: This study aimed to describe the kinetics of carnosine washout in human skeletal muscle over 16 wk. METHODS: Carnosine washout kinetics were studied in 15 young, physically active omnivorous men randomly assigned to take 6.4 g·d-1 of ß-alanine (n = 11) or placebo (n = 4) for 8 wk. Muscle carnosine content (M-Carn) was determined before (PRE), immediately after (POST), and 4, 8, 12, and 16 wk after supplementation. High-intensity exercise tests were performed at these same time points. Linear and exponential models were fitted to the washout data, and the leave-one-out method was used to select the model with the best fit for M-Carn decay data. Repeated-measures correlation analysis was used to assess the association between changes in M-Carn and changes in performance. RESULTS: M-Carn increased from PRE to POST in the ß-alanine group only (+91.1% ± 29.1%; placebo, +0.04% ± 10.1%; P < 0.0001). M-Carn started to decrease after cessation of ß-alanine supplementation and continued to decrease until week 16 (POST4, +59% ± 40%; POST8, +35% ± 39%; POST12, +18% ± 32%; POST16, -3% ± 24% of PRE M-Carn). From week 12 onward, M-Carn was no longer statistically different from PRE. Both linear and exponential models displayed very similar fit and could be used to describe carnosine washout, although the linear model presented a slightly better fit. The decay in M-Carn was mirrored by a similar decay in high-intensity exercise tolerance; M-Carn was moderately and significantly correlated with total mechanical work done (r = 0.505; P = 0.032) and time to exhaustion (r = 0.72; P < 0.001). CONCLUSIONS: Carnosine washout takes 12-16 wk to complete, and it can be described either by linear or exponential curves. Changes in M-Carn seem to be mirrored by changes in high-intensity exercise tolerance. This information can be used to optimize ß-alanine supplementation strategies.

Bouts of exercise elicit discordant testosterone: cortisol ratios in runners and non-runners.

OBJECTIVE: The testosterone:cortisol ratio (T:C) is suggested to be used in order to examine whether physical exercise generates either a "catabolic environment" or an "anabolic environment". The present study aims to evaluate the acute time-course profile of cortisol and testosterone due to an episode of physical exercise. A biphasic profile in the T:C ratio response was hypothesized. MATERIALS AND METHODS: Morning sessions of treadmill running at two different intensities (Heart Rate at 65% and 80% of the maximum cardiac reserve) were performed by 6 male non-runners (NR) and 12 trained male runners (subdivided into trained runners T1 and T2). Cortisol and testosterone were measured in saliva. NR and T1 ran for 30 minutes at both intensities, and T2 ran for 46 minutes (± 4.1) at 65% and 42 minutes (± 3.5) at 80%. RESULTS: In the 80% heart rate target, both groups of runners showed the biphasic time-profile, while the non-runners group did not. However, at the 65% level, none of the groups presented the hypothesized biphasic response. CONCLUSIONS: A biphasic time-profile in the testosterone:cortisol ratio can be seen in short-bout, high intensity exercise (treadmill running) during the morning in men trained for this specific physical activity.

Heart rate variability changes as an indicator of decompression-related physiological stress.

Many aspects of the physiological stress related to the exposure to the hyperbaric environment have been studied, but no research has been made to evaluate the impacts of scuba diving on heart rate variability (HRV). We investigated the effects of a simulated dive to 557 KPa (45 meters of salt water) for a 30-minute bottom time on the frequency and time domains estimators of HRV. Electrocardiogram records were obtained with superficial electrodes for 30 minutes before the simulated dive and, subsequently, for one hour after the dive. Each of these time-series was then subdivided into non-overlapping windows of 256 consecutive R-R intervals. A control group was submitted to the same protocol, breathing the same gases used in the simulated dive, while not being exposed to the hyperbaric environment. In the control group we observed a significant increase in SDNN (the square root of the variance of the R-R intervals), RMSSD (the square root of the mean squared differences of successive R-R intervals), and in two bands (high and low) of the power spectrum of frequencies. The subjects in the simulated dive presented only an increase in the low-frequency estimator without any further relevant changes in other estimators of HRV. This study suggests that the low-frequency increase without concomitant high-frequency increase might be an indicator of the physiological stress caused by decompression and that such a dissimilarity in responses might be correlated to the dive-related impairment of the endothelial function.

Bouts of exercise elicit discordant testosterone: cortisol ratios in runners and non-runners

ABSTRACT Objective: The testosterone:cortisol ratio (T:C) is suggested to be used in order to examine whether physical exercise generates either a "catabolic environment" or an "anabolic environment". The present study aims to evaluate the acute time-course profile of cortisol and testosterone due to an episode of physical exercise. A biphasic profile in the T:C ratio response was hypothesized. Materials and methods: Morning sessions of treadmill running at two different intensities (Heart Rate at 65% and 80% of the maximum cardiac reserve) were performed by 6 male non-runners (NR) and 12 trained male runners (subdivided into trained runners T1 and T2). Cortisol and testosterone were measured in saliva. NR and T1 ran for 30 minutes at both intensities, and T2 ran for 46 minutes (± 4.1) at 65% and 42 minutes (± 3.5) at 80%. Results: In the 80% heart rate target, both groups of runners showed the biphasic time-profile, while the non-runners group did not. However, at the 65% level, none of the groups presented the hypothesized biphasic response. Conclusions: A biphasic time-profile in the testosterone:cortisol ratio can be seen in short-bout, high intensity exercise (treadmill running) during the morning in men trained for this specific physical activity.

Descripción histológica de la substancia cortical dorsal en la parte media de la diáfisis del metacarpiano III en yegua mestiza / Histological description of the dorsal cortical bone in the midle diaphysis of the metacarpial III in the mixed mare

El hueso es el unicó tejido capaz de adaptarse estructural y geométricamente ante presiones impuestas sobre él. Durante la vida, el hueso es afectado por procesos externos e internos. Los externos producen cambios en sus medidas y forma. Los internos remodelan su arquitectura interna. Además, los huesos son afectados por factores que incluyen edad, sexo, especie, origen y contenido de minerales. Las variaciones estructurales en la organización microscópica del tejido óseo ocurren de manera constante y consistente mediante el crecimiento y la remodelación por parte de cada especie animal. El objetivo del presente trabajo fue estudiar la estructura microscópica inorgánica del cuadrante dorsal del metacarpiano III en la parte media de la diáfisis en distintos grupos etarios. Se estudió la substancia cortical dorsal de los huesos metarcapianos III izquierdos provenientes de 30 yeguas mestizas, con edades entre 2 y 5 años. Extraídos los huesos se los liberó de los tejidos blandos. El cuadrante dorsal fue muestreado, en la parte media de la diáfisis. Posteriormente, se realizó el pulido en forma manual. Las muestras fueron observadas al microscopio de luz polarizada. Se observaron diferencias histológica en los diferentes grupos etarios. Se concluyó que se producen variaciones microscópicas de la subtancia cortical dorsal del metarcapiano III en la parte media de la diáfisis, en el transcurso de 4 años

Contaminación ambiental y parasitosis en el área del Gran Buenos Aires / Environment contamination and parasitosis in Gran Buenos Aires

Se estudió el grado de parasitosis intestinal en una población del Gran Buenos Aires, donde están representadas las cinco clases sociales de Grafar. Las aguas de consumo presentaban contaminación ya que excedían la concentración máxima permitida de nitratos y nitritos (40 mg/l), pudiendo vehiculizar bacterias, parásitos y virus. Las parasitosis se analizaron mediante los clásicos métodos directos. La población se dividió en dos grupos: A: clase social alta, media alta y media; B: clase media baja y baja. Los dos grupos extraían las aguas de consumo del mismo acuífero. Se obtuvieron los siguientes resultados: Grupo A: de 2.620 casos, el 79% estaba parasitado: 56% por Giardia lamblia, 19% por Enterobius vermicularis, 4% por otros parásitos y 21% negativos. El mayor porcentaje de giardiasis se observó en el subgrupo de lactantes y preescolares, disminuyendo en los escolares y adultos. La oxyuriasis fue máxima en el subgrupo de escolares. En el grupo B se estudiaron 320 niños (0 a 13 años), el 70% estaba parasitado: 35% por Giardia lamblia, 29% por Enterobius vermicularis, 6% por otros parásitos y 30% negativos. Se destaca la alta incidencia de giardiasis en todos los grupos estudiados, parásito que al interferir en la absorción de nutrientes coloca a la población, de todos los niveles socioeconómicos en situación de riesgo nutricional