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.

Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina / Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin. / Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina.

BACKGROUND: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. OBJECTIVE: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. METHODS: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. RESULTS: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid ß-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. CONCLUSION: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

FUNDAMENTO: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. OBJETIVOS: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. MÉTODOS: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. RESULTADOS: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na ß-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. CONCLUSÃO: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

The relationship between Vitamin D status and exacerbation in COPD patients- a literature review.

OBJECTIVE: To investigate the relationship between Vitamin D and exacerbation in COPD patients. METHODS: The PubMed database was searched for articles published from 2012 onwards using search terms related to Vitamin D and exacerbation in COPD patients. Meta-analysis, clinical trials, observational studies, and human studies were included. Non-English articles or articles with full text unavailable were excluded; a total of 15 articles were selected. RESULTS: The association between exacerbation frequency and Vitamin D levels in observational studies remains controversial, however, meta-analysis revealed a negative association between serum Vitamin D and exacerbation. Also, two clinical trials showed that Vitamin D3 supplementation in COPD patients reduced the risk of moderate and severe exacerbation. Vitamin D binding protein (VDBP) polymorphisms seem to affect patient exacerbation susceptibility. CONCLUSIONS: Few studies in literature have data related to diet, 25-hydroxyVitamin D [25(OH)D] and polymorphism in COPD exacerbation. One clinical trial indicates Vitamin D supplementation plays a role in COPD patients with hypovitaminosis D in preventing exacerbations. Further studies are needed to elucidate the role of Vitamin D in this population and to establish the best marker for Vitamin D, which patient subgroups will benefit, and the best supplement dosage without leading to toxicity.

Aldosterone is not involved in the ventricular remodeling process induced by tobacco smoke exposure.

BACKGROUND/AIMS: Renin-angiotensin-aldosterone system blockade with a mineralocorticoid-receptor antagonist has not yet been studied in exposure to tobacco smoke (TS) models. Thus, this study investigated the role of spironolactone on cardiac remodeling induced by exposure to tobacco smoke. METHODS: Male Wistar rats were divided into 4 groups: a control group (group C, n=11); a group with 2 months of cigarette smoke exposure (group TS-C, n=13); a group that received spironolactone 20 mg/kg of diet/day and no cigarette smoke exposure (group TS-S, n=13); and a group with 2 months of cigarette smoke exposure and spironolactone supplementation (group S, n=12). The rats were observed for a period of 60 days, during which morphological, biochemical and functional analyses were performed. RESULTS: There was no difference in invasive mean arterial pressure among the groups. There were no interactions between tobacco smoke exposure and spironolactone in the morphological and functional analysis. However, in the echocardiographic analysis, the TS groups had left chamber enlargement, higher left ventricular mass index and higher isovolumetric relaxation time corrected by heart rate compared with the non-TS groups. In vitro left ventricular diastolic function also worsened in the TS groups and was not influenced by spironolactone. In addition, there were no differences in myocardial levels of IFN-γ, TNF-α, IL-10, ICAM-1 and GLUT4 [TS: OR 0.52, 95%CI (-0.007; 0.11); Spironolactone: OR -0.01, 95%CI (-0.07;0.05)]. CONCLUSION: Our data do not support the participation of aldosterone in the ventricular remodeling process induced by exposed to cigarette smoke.