Beta-hydroxy-beta-methylbutyrate associated with low-intensity exercise training improves skeletal muscle regeneration through the IGF-Akt pathway.

The effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation associated with exercise training at different intensities and frequencies on skeletal muscle regeneration of muscle-injured rats was investigated. Male Wistar rats were divided into sedentary and trained groups. The sedentary groups were subdivided into non-injured (SED-Ct), non-injured supplemented with HMB (SED-Ct-HMB), injured (SED), and injured with HMB (SED-HMB), and the trained groups were injured, supplemented with HMB, and then divided into training three times a week without load (HT3) or with load (HT3L) and training five times a week without load (HT5) and with load (HT5L). The rats received a daily dose of HMB associated with 60 min of swimming with or without 5% body mass load for 14 days. On the 15th day, cryoinjury was performed in the right tibialis anterior muscle (TA), and 48 h later, supplementation and training continued for 15 days. After the last session, the TA was dissected and a cross-sectional area (CSA) of muscle fibers was used to determine the percentage of CSA fibers and connective tissue (%CT), as well as the total and phosphorylated protein contents. SED-HMB showed increased CSA and decreased %CT and TGF-ß when compared to SED. HT3 showed increased CSA and reduced %CT accompanied by increased IGF-1/Akt, myogenin, and MuRF1, and decreased TGF-ß. The CSA of HT5L also increased, but at the cost of a higher %CT compared to the other groups. Our results demonstrated that HMB associated with training without load and with lower frequency per week may be a valuable strategy for skeletal muscle regeneration.

Beta-hydroxy-beta-methylbutyrate associated with low-intensity exercise training improves skeletal muscle regeneration through the IGF-Akt pathway

The effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation associated with exercise training at different intensities and frequencies on skeletal muscle regeneration of muscle-injured rats was investigated. Male Wistar rats were divided into sedentary and trained groups. The sedentary groups were subdivided into non-injured (SED-Ct), non-injured supplemented with HMB (SED-Ct-HMB), injured (SED), and injured with HMB (SED-HMB), and the trained groups were injured, supplemented with HMB, and then divided into training three times a week without load (HT3) or with load (HT3L) and training five times a week without load (HT5) and with load (HT5L). The rats received a daily dose of HMB associated with 60 min of swimming with or without 5% body mass load for 14 days. On the 15th day, cryoinjury was performed in the right tibialis anterior muscle (TA), and 48 h later, supplementation and training continued for 15 days. After the last session, the TA was dissected and a cross-sectional area (CSA) of muscle fibers was used to determine the percentage of CSA fibers and connective tissue (%CT), as well as the total and phosphorylated protein contents. SED-HMB showed increased CSA and decreased %CT and TGF-β when compared to SED. HT3 showed increased CSA and reduced %CT accompanied by increased IGF-1/Akt, myogenin, and MuRF1, and decreased TGF-β. The CSA of HT5L also increased, but at the cost of a higher %CT compared to the other groups. Our results demonstrated that HMB associated with training without load and with lower frequency per week may be a valuable strategy for skeletal muscle regeneration.

Evaluation of skeletal muscle regeneration in experimental model after malnutrition / Avaliação da regeneração do músculo esquelético em modelo experimental após desnutrição

Abstract The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-β1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.

Resumo O objetivo do presente estudo foi analisar a regeneração muscular após criolesão no músculo tibial anterior de ratos jovens desnutridos e recuperados. Foram utilizados 40 ratos da linhagem Wistar, divididos em 2 grupos: ratos nutridos receberam dieta normoproteica (14% de caseína) por 90 dias; e ratos desnutridos e recuperado submetidos a duas fases nutricionais pós-desmame, correspondendo a 45 dias de desnutrição com dieta hipoproteica (6% caseína), seguida por 45 dias de dieta normoproteica (14% caseína). Ao completar a fase de recuperação, todos os animais foram submetidos à criolesão no músculo tibial anterior direito e a eutanasia ocorreu 7, 14 e 21 dias após a lesão. A quantidade de tecido conjuntivo e a área de inflamação 14 dias pós-lesão foi maior no grupo desnutrido, recuperado e lesado (MRI – malnourished, recovered and injured group) (p < 0,05). A área de secção transversa (AST) das fibras regeneradas do grupo MRI foi menor (p < 0,05). O conteúdo das proteínas MyoD e Miogenina foi maior no grupo nutridos e lesados. A citocina TGF-β1 não apresentou diferença entre os grupos. O protocolo proposto foi eficaz para demonstrar alterações no processo de regeneração do músculo tibial anterior de ratos jovens, atrasando o reparo muscular mesmo após a recuperação nutricional.

Evaluation of skeletal muscle regeneration in experimental model after malnutrition / Avaliação da regeneração do músculo esquelético em modelo experimental após desnutrição

The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-β1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.(AU)

O objetivo do presente estudo foi analisar a regeneração muscular após criolesão no músculo tibial anterior de ratos jovens desnutridos e recuperados. Foram utilizados 40 ratos da linhagem Wistar, divididos em 2 grupos: ratos nutridos receberam dieta normoproteica (14% de caseína) por 90 dias; e ratos desnutridos e recuperado submetidos a duas fases nutricionais pós-desmame, correspondendo a 45 dias de desnutrição com dieta hipoproteica (6% caseína), seguida por 45 dias de dieta normoproteica (14% caseína). Ao completar a fase de recuperação, todos os animais foram submetidos à criolesão no músculo tibial anterior direito e a eutanasia ocorreu 7, 14 e 21 dias após a lesão. A quantidade de tecido conjuntivo e a área de inflamação 14 dias pós-lesão foi maior no grupo desnutrido, recuperado e lesado (MRI malnourished, recovered and injured group) (p < 0,05). A área de secção transversa (AST) das fibras regeneradas do grupo MRI foi menor (p < 0,05). O conteúdo das proteínas MyoD e Miogenina foi maior no grupo nutridos e lesados. A citocina TGF-β1 não apresentou diferença entre os grupos. O protocolo proposto foi eficaz para demonstrar alterações no processo de regeneração do músculo tibial anterior de ratos jovens, atrasando o reparo muscular mesmo após a recuperação nutricional.(AU)

Evaluation of skeletal muscle regeneration in experimental model after malnutrition.

The aim of this study was to analyze muscle regeneration after cryoinjury in the tibialis anterior muscle of young rats that were malnourished and then recovered. Forty Wistar rats were divided into a nourished group that received a normal protein diet (14% casein) for 90 days and a malnourished and recovered rats group (MR) that was submitted to 45 days of malnutrition with a hypoproteic diet (6% casein) followed by 45 days of a normal protein diet (14% casein). After the recovery period, all of the animals underwent cryoinjury in the right tibialis anterior muscle and euthanasia after 7, 14 and 21 days. The amount of connective tissue and the inflammation area was higher in the malnutrition recovered injury MR group (MRI) at 14 days post-injury (p < 0.05). Additionally, the cross-sectional area (CSA) of the regenerated fibers was decreased in the MRI (p < 0.05). The MyoD and myogenin protein levels were higher in the nourished injury group. Similar levels of TGF-ß1 were found between groups. The proposed malnutrition protocol was effective in showing delayed changes in the regeneration process of the tibialis anterior muscle of young rats. Furthermore, we observed a delay in muscle repair even after nutritional recovery.

Nasal administration of salmon calcitonin for prevention of glucocorticoid-induced osteoporosis in children with nephrosis.

To determine the effect of intranasal administration of salmon calcitonin on glucocorticoid-induced osteoporosis in children with nephrosis, we gave 100 U of calcitonin intranasally on alternate days with 1 alpha-hydroxyvitamin D3 to five children, 8 to 12 years of age, with frequently relapsing nephrosis. Four patients with osteoporosis, 10 to 14 years of age, were treated only with 1 alpha-hydroxyvitamin D3 and served as control subjects. Both groups were treated with an almost equal amount of glucocorticoids previously and during this study period. Bone mineral content of the spine was measured by a quantitative computed tomographic technique. The bone mineral content was preserved in both cortical and spongeous areas of the vertebrae during the 16-month period in the calcitonin-treated group but was decreased significantly in the control group. Urinary hydroxyproline and calcium excretion decreased significantly in the calcitonin-treated group. The serum calcium and phosphorus concentrations and the parathyroid function did not change significantly in either group. We conclude that calcitonin suppressed bone resorption and might be useful for the long-term treatment of osteoporosis, in combination with 1 alpha-hydroxyvitamin D3, in children with nephrosis requiring long-term glucocorticoid therapy.