Luís Fernando Bicudo Pereira Costa Rosa

Branched-chain amino acid supplementation and the immune response of long-distance athletes

OBJECTIVE Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. METHODS Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. RESULTS After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. CONCLUSIONS Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.

Cardiovascular adaptations in rats submitted to a resistance-training model

1. The present study sought to evaluate cardiovascular adaptations, such as blood pressure (BP), heart rate (HR) and cardiac hypertrophy, to resistance training (RT) in a rat model.

Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy

Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms—metabolic and neuroendocrine—we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

Alteração da relação testosterona: cortisol induzida pelo treinamento de força em mulheres

La razon entre testosterona y cortisol (T:C) es frecuentemente utilizada como indicador del nivel de stress impuesto por el ejercicio. Las alteraciones de las concentraciones de estas hormonas son las responsables por modular diversas respuestas inducidas por el entrenamiento, como son la hipertrofia y el aumento de la fuerza. El objetivo del presente estudio fue examinar la influencia del protocolo de entrenamiento de fuerza, conocido como series multiples (MS), sobre la ganancia de fuerza, la resistencia muscular localizada y la relacion entre las concentraciones de las hormonas catabolicas (cortisol) y anabolicas (testoterona). Para testar esta hipotesis, cinco jovenes del sexo feminino con un ano de experiencia en entrenamiento de fuerza fueron sometidas al protocolo MS. Las muestras de sangre fueron colectadas antes e imediatamente despues del ejercicio, en el primer dia y despues de ocho semanas de entrenamiento. Los tests de 1-RM y de repeticiones maximas fueron realizados tambien al inicio y al final despues de las ocho semanas del entrenamiento de fuerza. No fueron observadas alteraciones de la masa corporal, IMC, porcentaje de masa grasa, fuerza (1-RM) para los ejercicios supino, agachamiento y rosca directa. El numero de repeticiones maximas al 50% de 1-RM fue aumentando solamente apenas para el supino (p < 0,05). No se observo alteracion en la concentracion de la testosterona total. Con relacion a la concentracion plasmatica de cortisol despues de las ocho semanas de entrenamiento, en la situacion de reposo fue reducida (38% - p < 0,05). En consecuencia de la atenuacion de la secrecion de cortisol despues de ocho semanas de entrenamiento, la razon T:C presento elevacion del 20% de la situacion de reposo (p < 0,05). A pesar de no haber sido detectadas alteraciones funcionales en los tests de 1-RM de repeticiones maximas, el metodo MS indujo un cuadro hormonal favorable al anabolismo proteico.

Chronic supplementation of creatine and vitamins C and E increases survival and improves biochemical parameters after Doxorubicin treatment in rats.

1 Doxorubicin is an anti‐cancer drug with well‐described effects against a wide range of tumours. However, doxorubicin also exhibits dose‐dependent cytotoxicity. The purpose of the present study was to determine whether chronic supplementation of creatine or a mix of vitamins C and E could increase survival and improve plasma parameters 48 h after doxorubicin treatment. 2 Rats were divided into four groups: (i) saline (control); (ii) doxorubicin treated; (iii) a creatine (0.2 g/kg per day)‐supplemented group; and (iv) a vitamin C (250 mg/kg per day) and E (400 IU/kg per day)‐supplemented group. After 30 days supplementation of rats with either creatine or the vitamins, one dose of doxorubicin (15 mg/kg, i.p.) was administered. 3 There was no difference in weight loss among the groups until the 3rd day after doxorubicin treatment, but the creatine‐ and vitamin‐supplemented groups lived longer compared with the doxorubicin only treated group (6, 7 and 3 days, respectively). The doxorubicin‐treated group lost 13.4% bodyweight over 3 days, whereas the creatine‐ and vitamin‐supplemented groups lost approximately 35% 3 days after the administration of doxorubicin. Doxorubicin treatment resulted in an increase in alanine aminotransferase (ALT; P < 0.05), lactate dehydrogenase (LDH; P < 0.05), urea (P < 0.05) and creatinine (P < 0.05) compared with levels observed in the control group. Conversely, creatine supplementation promoted a partial return to control values for LDH (P < 0.05) and creatinine (P < 0.05), whereas the vitamin mix reversed the changes in ALT (P < 0.05), LDH (P < 0.05), urea (P < 0.05) and creatinine (P < 0.05). 4 In conclusion, the results of the present study indicate that the two supplementation protocols decreased the cytotoxic effects of doxorubicin and that a protective effect was more noticeable in animals supplemented with the mixture of vitamins C and E.

Exercise prevents the effects of experimental arthritis on the metabolism and function of immune cells

Active lymphocytes (LY) and macrophages (MΦ) are involved in the pathophysiology of rheumatoid arthritis (RA). Due to its anti‐inflammatory effect, physical exercise may be beneficial in RA by acting on the immune system (IS). Thus, female Wistar rats with type II collagen‐induced arthritis (CIA) were submitted to swimming training (6 weeks, 5 days/week, 60 min/day) and some biochemical and immune parameters, such as the metabolism of glucose and glutamine and function of LY and MΦ, were evaluated. In addition, plasma levels of some hormones and of interleukin‐2 (IL‐2) were also determined. Results demonstrate that CIA increased lymphocyte proliferation (1.9‐ and 1.7‐fold, respectively, in response to concanavalin A (ConA) and lipopolysaccharide (LPS)), as well as macrophage H2O2 production (1.6‐fold), in comparison to control. Exercise training prevented the activation of immune cells, induced by CIA, and established a pattern of substrate utilization similar to that described as normal for these cells. Exercise also promoted an elevation of plasma levels of corticosterone (22.2%), progesterone (1.7‐fold) and IL‐2 (2.6‐fold). Our data suggest that chronic exercise is able to counterbalance the effects of CIA on cells of the IS, reinforcing the proposal that the benefits of exercise may not be restricted to aerobic capacity and/or strength improvement. Copyright

Efeito do treinamento físico de nataçäo sobre o sistema cardiovascular de ratos normotensos

Uma das principais adaptacoes ao treinamento fisico (TF) aerobio e a bradicardia de repouso, observada tanto em humanos (Goldsmith, Bigger, Steinman & Fleiss, 1992, 1992; Kenney, 1985; Puig, Freitas, Carvalho, Puga, Ramos, Fernandes, Costa & Freitas, 1993; Katona, McLean, Dighton & Guz, 1982) como em animais de experimentacao (Bolter, Hughson & Critz, 1973; Negrao, Moreira, Santos, Farah & Krieger, 1992; Brum, 1995; Kalil, 1997). No entanto, a evolucao da frequencia cardiaca (FC) e da pressao arterial (PA) durante o periodo de TF e o curso temporal para que a bradicardia de repouso ocorra ainda nao estao totalmente esclarecidos. Foram estudados 16 ratos Wistar machos. Oito foram treinados (T) durante 8 semanas, utilizando um protocolo de natacao de baixa intensidade e oito foram mantidos sedentarios (S). A PA sistolica e a FC foram registradas batimento-a-batimento, duas vezes por semana durante o periodo de TF atraves de um esfigmomanometro de cauda...Resting bradycardia is considered to be a good marker of exercise training (ET) adaptation. However, the time course to heart rate (HR) and blood pressure (BP) responses occur during the exercise training period has not been clarified yet. Therefore, we studied 16 male normotensive Wistar rats. Eight rats were exercise trained (T) for 8 weeks, at a low intensity swimming protocol and 8 were kept sedentary (S). Systolic blood pressure and heart rate were measured two times per week during ET period by caudal measurements. The signal was recorded on a beat-to-beat basis (AT/CODAS) at a frequency of 100 Hz for 30 min in quiet and conscious rats. After ET, an arterial cannula was implanted for direct BP measurements and resting HR was studied using subcutaneously implanted electrodes. After BP and HR measurements, the rats were sacrificed and cardiac chambers were weighed in order to evaluate the cardiac hypertrophy. Maximal citrate synthase activity was measured in the soleus muscle to evaluate the oxidative muscle adaptation. Blood pressure was not changed by swimming training in normotensive rats. As expected, the resting HR was lower in T than in S rats (355±16 vs. 330±20 bpm). We observed increased left ventricle weight/body weight ratio in T rats (1.95 vs. 2.20 g/gBW) which represented 13% of left ventricle hypertrophy in T rats. The maximal citrate synthase activity increased 52% in the T rats. It was concluded that the swimming training for rats is a good experimental model to study the cardiovascular adaptations to dynamic exercise training

Effects of dietary restriction or swimming on lymphocytes and macrophages functionality from old rats

Although aging compromises the functionality of macrophages (MΦ) and lymphocytes (LY), and dietary restriction (DR) and exercise partially counterbalance immunosenescence, it is unknown what effects of both strategies have on the functionality of these immune cells. Rats were randomly distributed into adult control (AD), older group (OLD), older submitted to 50% of DR (DR) and older submitted to swimming (EX) (n = 10 in each group). The function of immune cells (proliferative index, phagocytic capacity and H2O2 production), the weight and protein content of lymphoid organs (thymus and spleen), plasma glutamine concentration, interleukins (IL-1, IL-2, IL-6) and, immunoglobulins (IgA and IgG) were analysed. There was an increase of 74% in body weight in aged animals as compared with the AD group, while body weight reduced 19% in the DR as compared with the OLD group. Swimming training stimulated MΦ phagocytosis, while the EX group presented a decrease of the proliferative capacity of LY from the mesenteric lymph nodes (44% and 62%, respectively), when stimulated with ConA and LPS as compared with the old rats. These data demonstrated that DR and exercise affects differentially MΦ and LY function.

EFFECT OF EXERCISE ON GLUTAMINE SYNTHESIS AND TRANSPORT IN SKELETAL MUSCLE FROM RATS

1 Reductions in plasma glutamine are observed after prolonged exercise. Three hypotheses can explain such a decrease: (i) high demand by the liver and kidney; (ii) impaired release from muscles; and (iii) decreased synthesis in skeletal muscle. The present study investigated the effects of exercise on glutamine synthesis and transport in rat skeletal muscle. 2 Rats were divided into three groups: (i) sedentary (SED; n = 12); (ii) rats killed 1 h after the last exercise bout (EX‐1; n = 15); and (iii) rats killed 24 h after the last exercise bout (EX‐24; n = 15). Rats in the trained groups swam 1 h/day, 5 days/week for 6 weeks with a load equivalent to 5.5% of their bodyweight. 3 Plasma glutamine and insulin were lower and corticosterone was higher in EX‐1 compared with SED rats (P < 0.05 and P < 0.01, respectively). Twenty‐four hours after exercise (EX‐24), plasma glutamine was restored to levels seen in SED rats, whereas insulin levels were higher (P < 0.001) and costicosterone levels were lower (P < 0.01) than in EX‐1. In the soleus, ammonia levels were lower in EX‐1 than in SED rats (P < 0.001). After 24 h, glutamine, glutamate and ammonia levels were lower in EX‐24 than in SED and EX‐1 rats (P < 0.001). Soleus glutamine synthetase (GS) activity was increased in EX‐1 and was decreased in EX‐24 compared with SED rats (both P < 0.001). 4 The decrease in plasma glutamine concentration in EX‐1 is not mediated by GS or glutamine transport in skeletal muscle. However, 24 h after exercise, lower GS may contribute to the decrease in glutamine concentration in muscle.

Alteration of testosterone: cortisol ratio induced by resistance training in women

La razon entre testosterona y cortisol (T:C) es frecuentemente utilizada como indicador del nivel de stress impuesto por el ejercicio. Las alteraciones de las concentraciones de estas hormonas son las responsables por modular diversas respuestas inducidas por el entrenamiento, como son la hipertrofia y el aumento de la fuerza. El objetivo del presente estudio fue examinar la influencia del protocolo de entrenamiento de fuerza, conocido como series multiples (MS), sobre la ganancia de fuerza, la resistencia muscular localizada y la relacion entre las concentraciones de las hormonas catabolicas (cortisol) y anabolicas (testoterona). Para testar esta hipotesis, cinco jovenes del sexo feminino con un ano de experiencia en entrenamiento de fuerza fueron sometidas al protocolo MS. Las muestras de sangre fueron colectadas antes e imediatamente despues del ejercicio, en el primer dia y despues de ocho semanas de entrenamiento. Los tests de 1-RM y de repeticiones maximas fueron realizados tambien al inicio y al final despues de las ocho semanas del entrenamiento de fuerza. No fueron observadas alteraciones de la masa corporal, IMC, porcentaje de masa grasa, fuerza (1-RM) para los ejercicios supino, agachamiento y rosca directa. El numero de repeticiones maximas al 50% de 1-RM fue aumentando solamente apenas para el supino (p < 0,05). No se observo alteracion en la concentracion de la testosterona total. Con relacion a la concentracion plasmatica de cortisol despues de las ocho semanas de entrenamiento, en la situacion de reposo fue reducida (38% - p < 0,05). En consecuencia de la atenuacion de la secrecion de cortisol despues de ocho semanas de entrenamiento, la razon T:C presento elevacion del 20% de la situacion de reposo (p < 0,05). A pesar de no haber sido detectadas alteraciones funcionales en los tests de 1-RM de repeticiones maximas, el metodo MS indujo un cuadro hormonal favorable al anabolismo proteico.