RESUMO
BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.
Assuntos
Antivirais , Composição Corporal , Hepatite C Crônica , Músculo Esquelético , Sarcopenia , Humanos , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Longitudinais , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Idoso , Sarcopenia/tratamento farmacológico , Composição Corporal/efeitos dos fármacos , Força da Mão , Força Muscular/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologiaRESUMO
La sarcopenia asociada a la edad es una condición clínica caracterizada por una disminución en la fuerza, calidad y cantidad de masa muscular así como también en la función muscular. Un biomarcador se define como una característica que es medible objetivamente y evaluable como indicador de un proceso biológico normal, patológico o respuesta terapéutica a una intervención farmacológica. Los marcadores bioquímicos propuestos para el estudio de la sarcopenia pueden ser categorizados en dos grupos. El primero de ellos evalúa el estatus musculoesquelético; este panel de marcadores está formado por miostatina/folistatina, procolágeno aminoterminal tipo III e índice de sarcopenia. El segundo grupo de marcadores bioquímicos evalúa factores causales, para lo cual se sugiere medir el factor de crecimiento insulino-símil tipo 1 (IGF-1), dehidroepiandrosterona (DHEAS), cortisol, facto-res inflamatorios [proteína C reactiva (PCR), interleuquina 6 (IL-6) y factor de necrosis tu-moral (TNF-a)]. Las recomendaciones realiza-das están basadas en la evidencia científica disponible en la actualidad y la disponibilidad de la metodología apropiada para cada uno de los biomarcadores. (AU)
Sarcopenia is a progressive and generalized skeletal muscle disorder defined by decrease in the strength, quality and quantity of muscle mass as well as in muscle function. A biomarker is defined as a feature objectively measured and evaluated as an indicator of a normal biologic process, a pathogenic process or a pharmacologic response to therapeutic intervention. The biochemical markers proposed for the study of sarcopenia may be classified in two groups. The first group evaluates the musculoskeletal status, made up by myostatin/follistatin, N-terminal Type III Procollagen and the sarcopenia index. The second evaluates causal factors, where the measurement of the following is suggested: hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate (DHEAS), cortisol, inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)]. The recommendations made are based on scientific evidence currently available and the appropriate methodology availability for each biomarker. (AU)
Assuntos
Humanos , Biomarcadores/metabolismo , Sarcopenia/tratamento farmacológico , Músculos/efeitos dos fármacos , Hormônios Esteroides Gonadais/análise , Pró-Colágeno , Creatinina , Hormônios Peptídicos/análise , Folistatina/farmacologia , Adipocinas/farmacologia , Miostatina/farmacologia , Sarcopenia/diagnóstico , Músculos/metabolismoRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic and systemic inflammation. Besides, it is known that RA patients may present several comorbidities, such as sarcopenia, a condition where patients present both muscle mass and muscle quality impairment. RA treatment is mostly pharmacological and consists in controlling systemic inflammation and disease activity. Despite that, the effect of pharmacological treatment on sarcopenia is not well characterized. OBJECTIVE: To summarize the effects of disease-modifying anti-rheumatic drugs (DMARDs) on skeletal muscle tissue in rheumatoid arthritis (RA) patients. METHODS: A systematic review of randomized clinical trials and observational studies was conducted using MEDLINE, Embase, Cochrane Library, and Web of Science. We selected studies with rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs (DMARDs) that analyzed muscle mass parameters such as lean mass and appendicular lean mass. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Standardized mean difference (SMD) and 95% confidence intervals (CI) were set. A meta-analysis of observational studies was performed using the R software, and we considered significant statistics when p < 0.05. RESULTS: Nine studies were included in this systematic review. In the meta-analysis, DMARD treatment had no positive difference (p = 0.60) in lean mass. In the same way, in the appendicular lean mass parameter, our results showed that DMARDs did not have changes between baseline and post-treatment analysis (p = 0.93). CONCLUSION: There is no evidence of a significant effect of DMARD therapy, either synthetic or biological, on muscle mass. However, this association should be investigated with more studies.
Assuntos
Antirreumáticos , Artrite Reumatoide , Sarcopenia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Inflamação/tratamento farmacológico , Músculo Esquelético , Sarcopenia/induzido quimicamente , Sarcopenia/tratamento farmacológicoRESUMO
BACKGROUND: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-κB) signaling and attenuates the severity of some muscle diseases. OBJECTIVE: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber´s diameter in a murine model of sarcopenia by aging. METHODS: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber´s diameter were measured. RESULTS: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber´s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber´s diameter. CONCLUSION: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber´s diameter are potentiated.
Assuntos
Diterpenos , Doenças Musculares , Sarcopenia , Angiotensina I/farmacologia , Angiotensina I/uso terapêutico , Animais , Diterpenos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , Fragmentos de Peptídeos , Sarcopenia/tratamento farmacológico , Sarcopenia/patologiaRESUMO
The epidemiological profile of people living with HIV (PLWH) has expressively changed since the introduction of antiretroviral therapy (ART), from a high mortality rate to a profile similar to those living with chronic diseases. Despite the advances and effectiveness of ART, there are still various challenges to overcome, and we highlight the increased risk of sarcopenia in PLWH. This review study aims to (i) explore the pathophysiological background of sarcopenia in PLWH under the different existing ART and (ii) develop a mini-systematic review searching epidemiological studies investigating sarcopenia prevalence in PLWH. As our main findings: we established the risk of sarcopenia development, under a sequential path involving HIV, ART, immune activation, low-grade systemic inflammation, metabolic disorders, and changes in protein synthesis and breakdown in skeletal muscle tissue; some ART drugs, mainly reverse transcriptase inhibitors and protease inhibitors, contribute to critical metabolic changes, lowering the autophagy, increasing mitochondrial dysfunction and insulin resistance, which favor the development of inflammation and muscle protein breakdown. There is still insufficient data to discuss the effects of the new generation drugs, namely integrase inhibitors and fusion inhibitors, on skeletal muscle. More studies are needed to better clarify these relationships.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Sarcopenia , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Inibidores da Transcriptase Reversa , Sarcopenia/tratamento farmacológico , Sarcopenia/epidemiologiaRESUMO
INTRODUCTION: Metabolic and hormonal disorders resulting from chronic liver diseases culminate in increased proteolysis and decreased protein synthesis, which contributes to the development and progression of malnutrition and, consequently, sarcopenia. Nutritional management of sarcopenia in liver cirrhosis is a continuously evolving field and data on essential amino acid supplementation in chronic liver diseases is scarce. AREAS COVERED: This review encompasses the current literature on oral amino acids supplementation in patients with chronic liver disease or patients with liver cirrhosis to try to elucidate the possible effects of L-branched-chain amino acids and isolated L-leucine as a therapeutic approach to malnutrition and sarcopenia. EXPERT COMMENTARY: To ensure an optimal nutritional status and to reduce sarcopenia, it is necessary to assess nutritional status in all patients with liver cirrhosis and to apply nutritional interventions accordingly. The supply of calories, proteins, and essential amino acids is necessary for the maintenance of muscle mass and function. Although supplementation of L-branched-chain amino acids plays an important role in liver disease, L-leucine has been described as the main amino acid involved in protein turnover, reducing proteolysis, and stimulating protein synthesis.
Assuntos
Aminoácidos de Cadeia Ramificada/uso terapêutico , Leucina/uso terapêutico , Hepatopatias/tratamento farmacológico , Desnutrição/tratamento farmacológico , Sarcopenia/tratamento farmacológico , Administração Oral , Aminoácidos de Cadeia Ramificada/administração & dosagem , Doença Crônica , Suplementos Nutricionais , Progressão da Doença , Leucina/administração & dosagem , Hepatopatias/complicações , Desnutrição/etiologia , Proteólise/efeitos dos fármacos , Sarcopenia/etiologiaRESUMO
BACKGROUND: Nutritional interventions may have positive effects on sarcopenia and body composition. OBJECTIVE: to evaluate the effectiveness of extra virgin olive oil (EVOO) consumption and a healthy traditional Brazilian diet (DieTBra) on improving sarcopenia indicators and reducing total body fat in severe obesity. METHODS: A randomized controlled trial registered at ClinicalTrials.gov (NCT02463435) conducted with 111 severely obese participants randomized into three treatment groups-(1) EVOO (52 mL/day), (2) DieTBra, (3) DieTBra + EVOO (52 mL/day)-for 12 weeks. Body composition was assessed by dual-energy X-ray absorptiometry and sarcopenia by walking speed and handgrip strength. RESULTS: Significant reductions in total body fat (p = 0.041) and body weight (p = 0.003) were observed in the DieTBra group. In the DietBra + olive oil group there was also a significant reduction in body weight (0.001) compared to the olive oil-only group. ANCOVA analyses showed reductions in total body fat in the DieTBra (p = 0.016) and DieTBra + olive oil (p = 0.004) groups. Individuals in the DieTBra group had significant improvements in their walking speed (p = 0.042) and handgrip strength (p = 0.044). CONCLUSIONS: DieTBra contributes to improvements in handgrip strength, walking speed, and total body fat in severely obese adults. The major study was registered at ClinicalTrials.gov (NCT02463435).
Assuntos
Dieta , Obesidade Mórbida/tratamento farmacológico , Azeite de Oliva/farmacologia , Sarcopenia/tratamento farmacológico , Absorciometria de Fóton , Adolescente , Adulto , Composição Corporal , Brasil , Feminino , Força da Mão , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Velocidade de Caminhada , Adulto JovemRESUMO
BACKGROUND: Sarcopenia is characterized by the loss of muscle mass and strength (muscle atrophy) because of aging or chronic diseases, such as chronic liver disease (CLD). Different mechanisms are involved in skeletal muscle atrophy, including decreased muscle fibre diameter and myosin heavy chain levels and increased ubiquitin-proteasome pathway activity, oxidative stress and myonuclear apoptosis. We recently found that all these mechanisms, except myonuclear apoptosis, which was not evaluated in the previous study, were involved in muscle atrophy associated with hepatotoxin 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLD. OBJECTIVE: In the present study, we evaluated the involvement of myonuclear apoptosis in CLD-associated sarcopenia and the effect of N-acetyl cysteine (NAC) treatment on muscle strength and apoptosis, using a DDC-supplemented diet-fed mouse model. METHODS: Four-month-old male C57BL6 mice were fed with a standard or DDCsupplemented diet for six weeks in the absence or presence of NAC treatment. RESULTS: Our results showed that NAC attenuated the decrease in muscle fibre diameter and muscle strength associated with CLD-induced muscle wasting in gastrocnemius (GA) muscle of DDC-supplemented diet-fed mice. In addition, in GA muscle of the mice fed with DDC-supplemented diet-induced CLD showed increased myonuclear apoptosis compared with the GA muscle of the control diet-fed mice, as evidenced by increased apoptotic nuclei number, caspase-8 and caspase-9 expression, enzymatic activity of caspase-3 and BAX/BCL-2 ratio. NAC treatment inhibited all the mechanisms associated with myonuclear apoptosis in the GA muscle. CONCLUSION: To our knowledge, this is the first study which reports the redox regulation of muscle strength and myonuclear apoptosis in CLD-induced sarcopenia.
Assuntos
Acetilcisteína/farmacologia , Doença Hepática Terminal/tratamento farmacológico , Atrofia Muscular/tratamento farmacológico , Sarcopenia/tratamento farmacológico , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Doença Hepática Terminal/induzido quimicamente , Doença Hepática Terminal/complicações , Doença Hepática Terminal/patologia , Humanos , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Estresse Oxidativo/efeitos dos fármacos , Piridinas/toxicidade , Sarcopenia/etiologia , Sarcopenia/metabolismo , Sarcopenia/patologiaRESUMO
En las últimas décadas se está presentando un incremento de la población adulta mayor en todo el mundo y sobre todo en los países latinoamericanos, los cuales no están preparados para enfrentar a este aumento poblacional, ya que este grupo presenta problemas frecuentes de incapacidad funcional para la realización de las actividades de la vida diaria y muchas veces presentando problemas de morbimortalidad incrementada. No debemos olvidar, que la capacidad de vivir independientemente es crucial para la calidad de vida en todas las edades y este estado de independencia a su vez, depende del buen estado físico y mental, así como del psicológico y de las condiciones socio-económicas de la persona...(AU)
In recent decades there has been an increase in the older adult population throughout the world and especially in Latin American countries, which are not prepared to face this population increase, since this group presents frequent problems of functional disability for carrying out activities of daily living and often presenting problems of increased morbidity and mortality. We must not forget that the ability to live independently is crucial for the quality of life in all ages and this state of independence, in turn, depends on the good physical and mental state, as well as the psychological and socio-economic conditions of the person ... (AU)
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso/fisiologia , Sarcopenia/diagnóstico , Fragilidade/prevenção & controle , População , Qualidade de Vida , Biomarcadores , Indicadores de Morbimortalidade , Fatores de Risco , Sarcopenia/tratamento farmacológicoRESUMO
In the present study we have compared the effects of leucine supplementation and its metabolite ß-hydroxy-ß-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.