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Abstract Background Rheumatoid arthritis is an autoimmune inflammatory disease that often leads patients to muscle impairment and physical disability. This study aimed to evaluate changes in the activity of proteasome system in skeletal muscles of mice with collagen-induced arthritis (CIA) and treated with etanercept or methotrexate. Methods Male DBA1/J mice were divided into four groups (n = 8 each): CIA-Vehicle (treated with saline), CIA-ETN (treated with etanercept, 5.5 mg/kg), CIA-MTX (treated with methotrexate, 35 mg/kg) and CO (healthy control group). Mice were treated two times a week for 6 weeks. Clinical score and hind paw edema were measured. Muscles were weighted after euthanasia and used to quantify proteasome activity, gene (MuRF-1, PMSα4, PSMβ5, PMSβ6, PSMβ7, PSMβ8, PSMβ9, and PSMβ10), and protein (PSMβ1, PSMβ5, PSMβ1i, PSMβ5i) expression of proteasome subunits. Results Both treatments slowed disease development, but only CIA-ETN maintained muscle weight compared to CIA-MTX and CIA-Vehicle groups. Etanercept treatment showed caspase-like activity of 26S proteasome similar to CO group, while CIA-Vehicle and CIA-MTX had higher activity compared to CO group (p: 0.0057). MuRF-1 mRNA expression was decreased after etanercept administration compared to CIA-Vehicle and CO groups (p: 0.002, p: 0.007, respectively). PSMβ8 and PSMβ9 mRNA levels were increased in CIA-Vehicle and CIA-MTX compared to CO group, while CIA-ETN presented no difference from CO. PMSβ6 mRNA expression was higher in CIA-Vehicle and CIA-MTX groups than in CO group. Protein levels of the PSMβ5 subunit were increased in CO group compared to CIA-Vehicle; after both etanercept and methotrexate treatments, PSMβ5 expression was higher than in CIA-Vehicle group and did not differ from CO group expression (p: 0.0025, p: 0.001, respectively). The inflammation-induced subunit β1 (LMP2) was enhanced after methotrexate treatment compared to CO group (p: 0.043). Conclusions The results of CIA-Vehicle show that arthritis increases muscle proteasome activation by enhanced caspase-like activity of 26S proteasome and increased PSMβ8 and PSMβ9 mRNA levels. Etanercept treatment was able to maintain the muscle weight and to modulate proteasome so that its activity and gene expression were compared to CO after TNF inhibition. The protein expression of inflammation-induced proteasome subunit was increased in muscle of CIA-MTX group but not following etanercept treatment. Thus, anti-TNF treatment may be an interesting approach to attenuate the arthritis-related muscle wasting.
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Abstract Introduction/objectives: Clinical evidence of skeletal muscle involvement is not uncommon in systemic lupus erythematosus (SLE). Because of the poor understanding of signaling pathways involved in SLE muscle wasting, the aim of this study was to evaluate the effects of vitamin D supplementation on skeletal muscle in mice with pristane-induced lupus. Methods: Balb/c mice with lupus-like disease induced by pristane injection were randomized into three groups: pristane-induced lupus (PIL; n = 10), pristane-induced lupus + vitamin D supplementation (PIL + VD; n = 10) and healthy controls (CO; n = 8). Physical function was evaluated on days 0, 60, 120 and 180. The tibialis anterior and gastrocnemius muscles were collected to evaluate myofiber cross-sectional area (CSA) and protein expression. Results: The PIL + VD group showed lower muscle strength compared to the CO and PIL groups at different time points. PIL mice showed similar myofiber CSA compared to CO and PIL + VD groups. LC3-II expression was higher in PIL compared to CO and PIL + VD groups. MyoD expression was higher in PIL mice compared to PIL + VD, while myostatin expression was higher in PIL + VD than PIL group. Myogenin expression levels were decreased in the PIL + VD group compared with the CO group. The Akt, p62 and MuRF expressions and mobility assessment showed no significance. Conclusions: Changes in skeletal muscle in PIL model happen before CSA reduction, possibly due to autophagy degradation, and treatment with Vitamin D has a impact on physical function by decreasing muscle strength and time of fatigue.. Vitamin D supplementation has a potential role modulating physical parameters and signaling pathways in muscle during pristane-induced lupus model.
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Abstract Our objective was to adjust and validate predictive equations for appendicular skeletal muscle mass (ASM) in patients with Rheumatoid Arthritis (RA). Whole-body DXA data in 90 RA patients were used for measurement of ASM (kg). The prediction equation anthropometric for muscle mass proposed by Lee et al was used to generate estimates of ASM. Appendicular skeletal muscle mass index (ASMI, kg/m2) was calculated. Frequency analysis, Paired student's t-test, Linear regression, Pearson correlation, Intraclass correlation coefficients, and Bland-Altman scatter were performed. The statistical significance considered was p<0.05. Lee's equation was overestimated by 30% when compared with ASMI by DXA. When stratified by nutritional status, Lee's equation overestimated the ASMI by 30% in overweight patients and by 50% in obese patients when compared with DXA (p<0.05). These adjusted equations estimated values for ASMI were closer to those obtained by DXA than those estimated by the original Lee's equation (p<0.05). This greater concordance was confirmed by the observed interclass correlation coefficients and by Bland-Altman scatter graphs. In conclusion, the prediction of muscle mass in RA patients may be performed with equations that consider the nutritional status of patients.
Resumo Nosso objetivo foi ajustar e validar equações preditivas para massa muscular esquelética apendicular (ASM) em pacientes com Artrite Reumatoide (AR). Dados de DXA de corpo inteiro em 90 pacientes com AR foram usados para medição de ASM (kg). A equação de predição antropométrica de massa muscular proposta por Lee et al foi utilizada para gerar estimativas de ASM. Índice de massa muscular esquelética apendicular (ASMI, kg / m2) foi calculada. Análise de frequência, Teste t de Student pareado, Regressão linear, Correlação de Pearson, Coeficientes de correlação intraclasse e Dispersão de Bland-Altman foram realizados. A significância estatística considerada foi p<0,05. A equação de Lee superestimou em 30% quando comparada com a ASMI da DXA. Quando estratificada por estado nutricional, a equação de Lee superestimou o ASMI em 30% em pacientes com sobrepeso e em 50% em pacientes obesos em comparação com DXA (p<0,05). Esses valores estimados de equações ajustadas para ASMI foram mais próximos daqueles obtidos por DXA do que aqueles estimados pela equação de Lee original (p<0,05). Essa maior concordância foi confirmada pelos coeficientes de correlação interclasses observados e pelos gráficos de dispersão de Bland-Altman. Em conclusão, a predição da massa muscular em pacientes com AR pode ser realizada com equações que consideram o estado nutricional dos pacientes.
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OBJETIVOS: Avaliar o estado nutricional de crianças e de adolescentes por meio de indicadores antropométricos e avaliar a associação desses resultados com a pressão arterial. MÉTODOS: Foram incluídos neste estudo crianças e adolescentes entre quatro e 19 anos de idade, oriundos de escolas rurais e urbanas de um município do Rio Grande do Sul. Foram excluídos aqueles que recusaram (ou cujos pais recusaram) participar ou não assinaram o termo de consentimento livre e esclarecido, ou nos quais não foi possível realizar as medidas antropométricas ou da pressão arterial. Foram mensurados peso, estatura, circunferência da cintura, pregas cutâneas e pressão arterial, e foi calculado o índice de massa corporal. Os dados foram descritos por média, desvio padrão, amplitude de variação, frequências absolutas e relativas. Foi realizada estratificação por sexo, índice de massa corporal e obesidade central, para analisar a influência destas variáveis sobre as demais. O Qui-quadrado de Pearson foi utilizado para avaliar as associações. O nível de significância foi de p<0,05. RESULTADOS: No período da coleta de dados estavam matriculados nas escolas do município 7.082 crianças e adolescentes dentro da faixa etária determinada, os quais foram convidados a participar. Após aplicação dos critérios de exclusão, 5.936 crianças/adolescentes foram incluídos no estudo. A amostra apresentou prevalência de excesso de peso de 30,3%, obesidade central 31,1% e excesso de gordura corporal 8,7%. O excesso de peso foi maior em crianças de escolas particulares (44,1%) quando comparadas com escolas estaduais (29,5%) e municipais (29,9%) (p<0,001). Foram encontradas associações estatisticamente significativas de hipertensão arterial com sobrepeso, obesidade e obesidade central (p<0,001). CONCLUSÕES: A prevalência de excesso de peso foi elevada e a hipertensão arterial associou-se com sobrepeso, obesidade e obesidade central nas crianças e adolescentes da população estudada.
AIMS: To evaluate the nutritional status of children and adolescents by anthropometric indicators and to evaluate the association of these results with blood pressure. METHODS: Children and adolescents between four and 19 years of age from rural and urban schools of a municipality of Rio Grande do Sul were included in this study. Those who refused (or whose parents refused) to participate or did not sign the consent form, or in whom it was not possible to carry out the anthropometric or blood pressure measurements, were excluded. Weight, height, waist circumference, skin folds and blood pressure were measured, and the body mass index was calculated. Data were described by mean, standard deviation, amplitude of variation, absolute and relative frequencies. Stratification by gender, body mass index and central obesity was performed to analyze the influence of these on the other variables. Pearson's Chi-square was used to evaluate the associations. The level of significance was p<0.05. RESULTS: At the time of data collection, 7,082 children and adolescents within the age group were enrolled in the municipal schools, and they were invited to participate. After applying the exclusion criteria, 5,936 children/adolescents were included in the study. The sample presented prevalence of overweight of 30.3%, central obesity 31.1% and excess body fat 8.7%. Overweight was higher in children from private schools (44.1%) than in state schools (29.5%) and municipal schools (29.9%) (p<0.001). There were statistically significant associations of high blood pressure with overweight, obesity, and central obesity (p<0.001). CONCLUSIONS: Prevalence of overweight was high and hypertension was associated with overweight, obesity and central obesity in children and adolescents of the studied population.