Effects of Creatine Supplementation on the Myostatin Pathway and Myosin Heavy Chain Isoforms in Different Skeletal Muscles of Resistance-Trained Rats.

Creatine has been used to maximize resistance training effects on skeletal muscles, including muscle hypertrophy and fiber type changes. This study aimed to evaluate the impact of creatine supplementation on the myostatin pathway and myosin heavy chain (MyHC) isoforms in the slow- and fast-twitch muscles of resistance-trained rats. Twenty-eight male Wistar rats were divided into four groups: a sedentary control (Cc), sedentary creatine supplementation (Cr), resistance training (Tc), and resistance training combined with creatine supplementation (Tcr). Cc and Tc received standard commercial chow; Cr and Tcr received a 2% creatine-supplemented diet. Tc and Tcr performed a resistance training protocol on a ladder for 12 weeks. Morphology, MyHC isoforms, myostatin, follistatin, and ActRIIB protein expressions were analyzed in soleus and white gastrocnemius portion samples. The results were analyzed using two-way ANOVA and Tukey's test. Tc and Tcr exhibited higher performance than their control counterparts. Resistance training increased the ratio between muscle and body weight, the cross-sectional area, as well as the interstitial collagen fraction. Resistance training alone increased MyHC IIx and follistatin while reducing myostatin (p < 0.001) and ActRIIB (p = 0.040) expressions in the gastrocnemius. Resistance training induced skeletal muscle hypertrophy and interstitial remodeling, which are more evident in the gastrocnemius muscle. The effects were not impacted by creatine supplementation.

Influence of CReatine supplementation on mUScle mass and strength after stroke (ICaRUS Stroke Trial): study protocol for a randomized controlled trial.

BACKGROUND: Stroke is a leading cause of mortality and disability, and its sequelae are associated with inadequate food intake which can lead to sarcopenia. The aim of this study is to verify the effectiveness of creatine supplementation on functional capacity, strength, and changes in muscle mass during hospitalization for stroke compared to usual care. An exploratory subanalysis will be performed to assess the inflammatory profiles of all participants, in addition to a follow-up 90 days after stroke, to verify functional capacity, muscle strength, mortality, and quality of life. METHODS: Randomized, double-blind, unicenter, parallel-group trial including individuals with ischemic stroke in the acute phase. The duration of the trial for the individual subject will be approximately 90 days, and each subject will attend a maximum of three visits. Clinical, biochemical, anthropometric, body composition, muscle strength, functional capacity, degree of dependence, and quality of life assessments will be performed. Thirty participants will be divided into two groups: intervention (patients will intake one sachet containing 10g of creatine twice a day) and control (patients will intake one sachet containing 10g of placebo [maltodextrin] twice a day). Both groups will receive supplementation with powdered milk protein serum isolate to achieve the goal of 1.5g of protein/kg of body weight/day and daily physiotherapy according to the current rehabilitation guidelines for patients with stroke. Supplementation will be offered during the 7-day hospitalization. The primary outcomes will be functional capacity, strength, and changes in muscle mass after the intervention as assessed by the Modified Rankin Scale, Timed Up and Go test, handgrip strength, 30-s chair stand test, muscle ultrasonography, electrical bioimpedance, and identification of muscle degradation markers by D3-methylhistidine. Follow-up will be performed 90 days after stroke to verify functional capacity, muscle strength, mortality, and quality of life. DISCUSSION: The older population has specific nutrient needs, especially for muscle mass and function maintenance. Considering that stroke is a potentially disabling event that can lead the affected individual to present with numerous sequelae, it is crucial to study the mechanisms of muscle mass loss and understand how adequate supplementation can help these patients to better recover. TRIAL REGISTRATION: The Brazilian Clinical Trials Registry (ReBEC) RBR-9q7gg4 . Registered on 21 January 2019.

The evident and the hidden factors of vitamin D status in older people during COVID-19 pandemic.

Purpose: Considering the COVID-19 pandemic, vitamin D is a target of research and speculation. Lockdown or home isolation reduces sunlight exposition and increases the risk of vitamin D deficiency. Special attention is needed for older people at risk of both severe forms of COVID-19 and vitamin D deficiency. This review aims to highlight the association of vitamin D and COVID-19 in two instances, the direct influence of vitamin D on the immune system, and the indirect risks for other vitamin D deficiency-related diseases, such as musculoskeletal properties in older persons. Methods: We performed a narrative review. Results: Whether vitamin D deficiency is associated with COVID-19 poor prognosis, and if vitamin D supplementation may improve the post-infection outcomes is still unclear. In any case, the pandemic generates indirect burden, such as the sequence: home isolation, low sunlight exposition, vitamin D deficiency, and fragility fractures. Conclusion: Therefore, it is time to debate how to optimize vitamin D status in older people, especially during the COVID-19 pandemic.

Euterpe oleracea Mart. (Açai) Supplementation Attenuates Acute Doxorubicin-Induced Cardiotoxicity in Rats.

BACKGROUND/AIMS: Doxorubicin, a chemotherapy drug used successfully for years, could induce cardiotoxicity. Euterpe oleracea Mart. (açai) is a fruit high in antioxidant properties. The aim of this study was to evaluate doxorubicin-induced cardiotoxicity prevention after açai administration. METHODS: A total of 64 male Wistar rats were allocated into 4 groups: control (C), açai (A), doxorubicin (D) and açai-doxorubicin (DA). Rats received regular chow (C and D groups) or chow supplemented with açai 5% (A and DA groups) for 4 weeks. Subsequently, rats received doxorubicin 20 mg/kg (D and DA groups) or saline (C and A groups). Euthanasia was performed 48 hours after doxorubicin injection. Left ventricular function was evaluated by echocardiography in vivo and by isolated heart study ex vivo. Oxidative stress, myocardial metabolism and nitric oxide metabolite were evaluated by spectrophotometry, MMP-2 activity by zymography and caspase-3 and Bcl-2 protein expression by Western blot. RESULTS: Doxorubicin induced decreases in body weight, food and water ingestion. We observed decreases in left ventricular fractional shortening in rats treated with doxorubicin. Additionally, the same rats showed lower +dP/dt and -dP/dt during isolated heart study than those who did not receive doxorubicin. Doxorubicin injection increased caspase-3 protein expression, myocardium lipid hydroperoxide concentration, MMP-2 activity, phosphofructokinase and lactate dehydrogenase activity, and decreased ß-hydroxyacyl-CoA dehydrogenase, pyruvate dehydrogenase, citrate synthase, complex I, complex II and ATP synthase activity in myocardium. Açai supplementation improved left ventricular fractional shortening, decreased myocardium lipid hydroperoxide concentration, MMP-2 activity, and improved ß-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, citrate synthase, complex II and ATP synthase enzymatic activities. We did not observe differences in nitric oxide metabolite concentrations between groups. CONCLUSION: Doxorubicin induced left ventricular dysfunction, increases in oxidative stress, changes in myocardium metabolism and MMP-2 activation. Açai supplementation was able to prevent these alterations.

Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação / Echocardiography in thalassemic patients on blood transfusions and chelation without heart failure

FUNDAMENTO: Pacientes com talassemia major (TM) apresentam hemólise crônica e necessitam de transfusões sanguíneas egularmente que podem causar cardiomiopatia por sobrecarga de ferro e insuficiência cardíaca crônica. A hemocromatose é caracterizada por acúmulo excessivo de ferro nos tecidos; acometimento do coração é a principal causa de óbito em pacientes com talassemia. OBJETIVO: Avaliar as estruturas e a função cardíaca por meio de ecocardiografia com Doppler convencional e Doppler tecidual em pacientes com TM, sem evidência clínica de insuficiência cardíaca. MÉTODOS: Trata-se de estudo observacional prospectivo de 18 pacientes com TM que recebem transfusão sanguínea regularmente. Para avaliar, separadamente, os efeitos da anemia e da transfusão sanguínea, dois grupos controles pareados por gênero, idade, peso e altura foram incluídos: um com indivíduos saudáveis (Saudável, n = 18) e outro com pacientes com anemia por deficiência de ferro (Anemia, n = 18). Análise estatística foi realizada utilizando ANOVA seguida pelo teste de Tukey ou Kruskal-Wallis e teste de Dunn. RESULTADOS: As seguintes variáveis ecocardiográficas apresentaram valores significativamente mais elevados no grupo TM do que nos grupos Anemia e Saudável: índice de volume do átrio esquerdo (Saudável: 16,4 ± 6,08; Anemia: 17,9 ± 7,02; TM: 24,1 ± 8,30 cm/m); razão E/Em septal mitral (Saudável: 6,55 ± 1,60; Anemia: 6,74 ± 0,74; TM: 8,10 ± 1,31) e duração do fluxo reverso em veias pulmonares [Saudável: 74,0 (59,0-74,0); Anemia: 70,5 (67,0-74,0); TM: 111 (87,0-120) ms]. Arazão E/A mitral foi maior no grupo TM do que no grupo Anemia (Saudável: 1,80 ± 0,40; Anemia: 1,80 ± 0,24; TM: 2,03 ± 0,34). Não foram encontradas diferenças entre os grupos em variáveis estruturais do ventrículo esquerdo e em índices de função sistólica. CONCLUSÃO: A ecocardiografia com Doppler convencional e o Doppler tecidual permite que alterações na função diastólica do ventrículo esquerdo sejam identificadas em pacientes assintomáticos com talassemia major.

BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.

Influence of rutin treatment on biochemical alterations in experimental diabetes.

Dietary antioxidant compounds such as flavonoids may offer some protection against early-stage diabetes mellitus and its complications. Abnormalities in both glucose metabolism and lipid profile constitute one of the most common complications in diabetes mellitus. The present study aimed to evaluate the effect of rutin, through biochemical parameters, on experimental streptozotocin (STZ)-induced diabetes in rats. Male Wistar rats were divided into four groups: untreated controls (GI); normal rats receiving rutin (GII); untreated diabetics (GIII); diabetic rats receiving rutin (GIV). STZ was injected at a single dose of 60 mg kg(-1) to induce diabetes mellitus. The diabetes resulted in increased serum glucose, cholesterol, triacylglycerols and lipoproteins (LDL and VLDL-cholesterol) but decresed serum HDL-cholesterol and insulin. Rutin (50 mg kg(-1)) reduced (p<0.05) blood glucose and improved the lipid profile in STZ-induced diabetic rats. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities were significantly augmented in serum of STZ-diabetic rats, while these activities were diminished in hepatic and cardiac tissues compared with the control group. Rutin prevents changes in the activities of ALT, AST and LDH in the serum, liver and heart, indicating the protective effect of rutin against the hepatic and cardiac toxicity caused by STZ. Rutin was associated with markedly decreased hepatic and cardiac levels of tryacylglycerols and elevated glycogen. These results suggest that rutin can improve hyperglycemia and dyslipidemia while inhibiting the progression of liver and heart dysfunction in STZ-induced diabetic rats.

Terapia nutricional como coadjuvante no tratamento do paciente com insuficiência cardíaca / Nutrition support as part of the treatment in chronic heart failure patients

Entre as complicações decorrentes da insuficiência cardíaca encontra-se a desnutrição energético-protéica, que ocorre nos estágios avançados da doença. Recentemente, foi observado que a desnutrição energético-protéica constitui importante fator preditivo de redução da sobrevida nos doentes com insuficiência cardíaca, independentemente de variáveis importantes, como idade, classe funcional da insuficiência cardíaca e fração de ejeção. Nesta revisão, primeiramente, serão apresentados a definição de desnutrição energético-protéica na insuficiência cardíaca e os dados sobre a epidemiologia dessa condição. A seguir, serão discutidos os mecanismos para o desenvolvimento de desnutrição nos pacientes e as implicações clínicas da desnutrição energético-protéica, assim como suas conseqüências sobre o próprio coração. Finalmente, serão abordadas as diretrizes para a terapia nutricional e o tratamento de pacientes com desnutrição energético-protéica associada à insuficiência cardíaca.

Ventricular remodeling induced by retinoic acid supplementation in adult rats.

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.

Esclerose sistêmica difusa com hipertensão pulmonar isolada: relato de caso / Diffuse systemic sclerosis with isolated pulmonary hypertension: a case report

A esclerose sistêmica (ES) é uma doença incomum, caracterizada por alterações vasculares e fibrose em pele e vários órgãos. O envolvimento pulmonar é freqüente na ES; entretanto, hipertensão pulmonar (HP) na ausência de fibrose intersticial é raramente observada. Os autores descrevem um caso de ES difusa com HP isolada em paciente do sexo feminino, de 49 anos. O diagnóstico de HP pôde ser sugerido pelo exame físico e confirmado por ecodopplercardiograma, que permitiu estimar a pressão sistólica em artéria pulmonar em 80mmHg. Tratamento foi iniciado com nifedipina; entretanto, devido a efeitos colaterais da droga, não foi possível o aumento da dose além de 30mg ao dia; nesta dosagem, a nifedipina não acarretou redução da pressão arterial pulmonar