Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Physical therapy protocols to attenuate skeletal muscle atrophy in critically ill patients: narrative review / Protocolos de terapia física para atenuar la atrofia del músculo esquelético en pacientes críticos: revisión narrativa

SUMMARY: To describe the physical therapy protocols used in critically ill patients to attenuate skeletal muscle atrophy. We conducted a search in PubMed and Embase from inception to November 2020. Observational or experimental studies published in English or Spanish that evaluated the effect of physical therapy protocols on the attenuation of skeletal muscle atrophy in critically ill patients through muscle strength or mass measurement were considered eligible. Studies were only included if they reported a detailed description of the dosing of the interventions. Seventeen studies met the eligibility criteria. We included randomised clinical trials (n = 16) and observational studies (n = 1). The total population of the included studies was 872 critically ill patients. The studies aimed to evaluate the reliability, safety or effectiveness of neuromuscular electrical stimulation (n = 10) protocols, early mobilisation (n = 3), ergometer training (n = 2), transfers in tilt table (n = 1), and blood flow restriction (n = 1). Physical therapy protocols are part of the critically ill patient's integral management. Strategies such as passive mobilisation, in-bed and out-of-bed transfers, gait training, ergometer training, and neuromuscular electrical stimulation substantially impact critically ill patients' prognoses and quality of life after hospital discharge.

RESUMEN: Describir los protocolos de terapia física usados en pacientes críticos para atenuar la atrofia muscular esquelética. Realizamos una búsqueda en PubMed y Embase desde el inicio hasta noviembre de 2020. Se consideraron los estudios observacionales o experimentales publicados en inglés o español que evaluaron el efecto de los protocolos de terapia física en la atenuación de la atrofia del músculo esquelético en pacientes críticos a través de la medición de la fuerza o la masa muscular. Los estudios solo se incluyeron si informaron una descripción detallada de la dosificación de las intervenciones. Diecisiete estudios cumplieron los criterios de elegibilidad. Se incluyeron ensayos clínicos aleatorizados (n = 16) y estudios observacionales (n = 1). La población total de los estudios incluidos fue de 872 pacientes en estado crítico. Los estudios tuvieron como objetivo evaluar la confiabilidad, seguridad o efectividad de los protocolos de estimulación eléctrica neuromuscular (n = 10), movilización temprana (n = 3), entrenamiento con ergómetro (n = 2), transferencias en mesa basculante (n = 1) y restricción del flujo sanguíneo (n = 1). Los protocolos de terapia física forman parte del manejo integral del paciente crítico. Es- trategias como la movilización pasiva, los traslados dentro y fuera de la cama, el entrenamiento de la marcha, el entrenamiento con ergómetro y la estimulación eléctrica neuromuscular tienen un impacto sustancial en el pronóstico y la calidad de vida de los pacientes críticos después del alta hospitalaria.

Role of autophagy in the maintenance of skeletal muscle mass / 中国骨伤

As an important exercise and energy metabolism organ of the human body, the normal maintenance of skeletal muscle mass is essential for the body to perform normal physiological functions. The autophagy-lysosome (AL) pathway is a physiological or pathological mechanism that is ubiquitous in normal and diseased cells. It plays a key role in the maintaining of protein balance, removing damaged organelles, and the stability of internal environment. The smooth progress of the autophagy process needs to go through multiple steps, which are completed under the coordinated action of multiple factors. Autophagy maintains the muscle homeostasis of a healthy body by removing cell components such as damaged myofibrils and isolated cytoplasmic proteins. Autophagy could also provide the initial energy required for cell proliferation, promote muscle regeneration and remodeling after injury. At the same time, autophagy disorder is also an important cause of age-related skeletal muscle atrophy. Autophagy could affect the response of skeletal muscle to exercise, and increasing the level of basic autophagy is beneficial to improve the adaptive response of skeletal muscle to exercise. This article summarizes the role and pathways of autophagy in the maintenance of skeletal muscle quality, in order to provide effective rehabilitation strategies for clinical prevention and treatment of muscle atrophy.

Effects of Rehmannia glutinosa polysaccharides on bone tissue structure and skeletal muscle atrophy in rats with disuse

ABSTRACT Purpose To study effects of Rehmannia glutinosa polysaccharides (RGP) on bone tissue structure and skeletal muscle atrophy in rats with disuse. Methods A rat model of disuse osteoporosis combined with muscle atrophy was established by removing the bilateral ovaries of rats and fixing their hind limbs for a long time. Forty SD rats were administered intragastrically for 12 weeks. The bone histomorphometry parameters and the level of oxidative stress were measured. In addition, the changes of muscle atrophy F-box (MAFbx), muscle RING-finger protein-1 (MuRF1), forkhead box O1 (FOXO1) mRNA expression in skeletal muscle of rats were observed. Results RGP significantly increased the percentage of fluorescence perimeter and bone mineralization deposition rate of the second lumbar vertebrae of rats. It also significantly increased the wet weight ratio and muscle fiber cross-sectional area of the gastrocnemius muscle of rats. At the same time, RGP significantly increased the levels of super oxide dismutase (SOD) and catalase (CAT) in the skeletal muscle of rats, and reduced the content of malondialdehyde (MDA). Rehmannia glutinosa polysaccharides also significantly reduced the expression levels of FOXO1, MAFbx and MuRF1 mRNA in rat skeletal muscle. Conclusions RGP could improve the bone structure of osteoporotic rats. It could also improve muscle that atrophy may be related to the inhibition of FOXO1-mediated ubiquitin-proteasome pathway.

Effects of ultrasound and stretching on skeletal muscle contusion in rats: immunohistochemistry analysis / Efectos de ultrasonido y estiramiento en la contusión muscular esqueletal en ratas: análisis inmunohistoquímico

SUMMARY: The aim of this study was to evaluate the effects of stretching and therapeutic ultrasound (TUS) on desmin and laminin contents of rat muscle after contusion. Male Wistar rats (n = 35, 8-9 weeks of age, 271 ± 14g body weight) were divided into five groups: Control group (CG) (n= 03); Injured group (IG) (n= 8); Injured + ultrasound group (IUSG) (n= 8); Injured+stretching group (ISG) (n= 8); Injured +ultrasound + stretching group (IUSSG) (n= 8). The application of ultrasound started 72 hours after the contusion, using the 50 % pulsed mode, 0.5 W/cm2, 5 min, once a day, for five consecutive days. Passive manual stretching was started on the tenth day after injury, with four repetitions of 30 s each and 30 s rest between repetitions, once a day, five times per week, for a total of ten applications. After 22 days, the rats were euthanazied and the gastrocnemius of both limbs removed for desmin and laminin immunohistochemistry morphometric measurement. Analysis was conducted using ANOVA one way post-hoc Tukey to parametric data and Kruskall-Wallis for non-parametric data. The IUSSG animals showed a larger area of desmin than ISG (p<0.05). It was found a decrease in laminin comparing IUSG to IG. However, laminin area was higher in ISG than all groups (p<0.05). UST isolated or in combination with stretching influenced gastrocnemius regeneration in different manners. While stretching applied isolated enhanced gastrocnemius regeneration noticed by the increase in laminin area, in combination with TUS strengthened the muscle healing rising desmin area.

RESUMEN: El objetivo de este estudio fue evaluar los efectos del estiramiento y la ecografía en los contenidos de desmina y laminina del músculo de rata después de la lesión. Ratas Wistar macho (n = 35, 8-9 semanas de edad, 271 ± 14 g de peso corporal) se dividieron en cinco grupos: grupo de control (CG) (n = 03); Grupo lesionado (GL) (n = 8); Lesionado + grupo de ultrasonido (LGU) (n= 8); Lesionado + grupo de estiramiento (LGE) (n = 8); Lesionado + ultrasonido + grupo de estiramiento (LUGE) (n = 8). La aplicación de ultrasonido comenzó 72 horas después de la lesión, usando el modo pulsado al 50 %, 0,5W / cm2, 5 min, una vez al día, durante cinco días consecutivos. El estiramiento manual pasivo se inició el décimo día después de la lesión, con cuatro repeticiones de 30 seg cada una y 30 seg de descanso entre repeticiones, una vez al día, cinco veces por semana, para un total de diez aplicaciones. Las ratas fueron sacrificadas después de 22 días, y se extrajo el músculo gastrocnemio de ambos miembros para la medición morfométrica de desmina y laminina a través de inmunohistoquímica. El análisis se realizó utilizando ANOVA unidireccional Tukey post-hoc para datos paramétricos y Kruskall-Wallis para datos no paramétricos. Los animales LUGE mostraron un área mayor de desmina que LGE (p <0,05). Se encontró una disminución en la laminina comparando LGU con GL. Sin embargo, el área de laminina fue mayor en LGE que en todos los grupos (p <0,05). El tratamiento con ultrasonido aislado o en combinación con estiramiento influyó en la regeneración del músculo gastrocnemio de diferentes maneras. Si bien el estiramiento aplicado, en combinación con tratamiento de ultrasonido, fortaleció el área de desmina, la regeneración del músculo gastrocnemio mejoró por el aumento en el área de laminina aumentando la curación muscular.

Hipofosfatasemia crónica persistente de causa no determinada y su repercusión músculo-esquelética / Persistent hypophosphatasemia and its musculoskeletal repercussion

La fosfatasa alcalina baja o hipofosfatasemia, ya sea debida a causas genéticas (hipofosfatasia) o secundarias, presenta correlato clínico. Nuestro objetivo es estimar la prevalencia de hipofosfatasemia crónica persistente y describir sus hallazgos osteometabólicos. Se realizó una búsqueda electrónica de afiliados adultos al Hospital Italiano de Buenos Aires, entre 2013 y 2017, con al menos 2 determinaciones de fosfatasa alcalina igual a 30 UI/l o menor y ninguna mayor de 30 UI/l (rango de referencia 30-100 UI/l). Se excluyeron aquellos con causas secundarias diagnosticadas y se analizaron los correlatos clínico y bioquímico. Se detectó hipofosfatasemia crónica persistente en 78 de 105.925, 0,07% (0,06-0,09) de los afiliados. Solo uno fue excluido por tener causa secundaria. Eran 61,1% mujeres de 44 (34-56) años, fosfatasa alcalina 24 (20-27) UI/L, fosfatemia 4,1 (3,8-4,6) mg/dl. Se observaron osteoartritis, calcificaciones vasculares y fracturas, menos frecuentemente litiasis renal, calcificación del ligamento longitudinal común anterior, pérdida dental y convulsiones. El 63,6% tenían al menos una de las características clínico-radiológicas evaluadas, pero en solo 5,2% fue mencionado el diagnóstico de hipofosfatasemia en la historia clínica. La densitometría evidenció algún grado de afección (osteopenia u osteoporosis) en 76,2%. Se constataron 19 fracturas, con predominio en radio. La prevalencia de hipofosfatasemia fue similar a lo previamente reportado. El reconocimiento fue bajo; sin embargo, se observaron variadas manifestaciones músculo-esqueléticas, similares a las descriptas en la hipofosfatasia del adulto, por lo cual ­ante una hipofosfatasemia sin causa secundaria­ se sugiere considerar este diagnóstico. (AU)

Low alkaline phosphatase (ALP) or hypophosphatasemia either due to genetic (hypophosphatasia) or secondary causes, presents a clinical correlate. Our objectives are to estimate the prevalence of persistent hypophosphatasemia and to describe the clinical findings. We performed a search using the electronic medical records of the members of the Hospital Italiano de Buenos Aires health care system, between 2013 and 2017. Adult members with ≥ 2 ALP ≤ 30 IU/l, no ALP >30 IU/l (normal range 30-100 UI/l) and without diagnosed secondary causes were analyzed. Persistent hypophosphatasemia was detected in 78 of 105.925, 0.07% (0.06-0.09) of members. Only one was excluded due to a secondary cause, 61.1% were women, 44 (34-56) year-old, ALP 24 (20-27) IU/l and phosphatemia 4.1 (3.8-4.6) mg/dl. Osteoarthritis, vascular calcifications and fractures were detected, and nephrolithiasis, DISH (Diffuse idiopathic skeletal hyperostosis), tooth loss, and seizures were less frequently observed. At least one of the mentioned characteristics were present in 63.6 %, but only 5.2% had hypophosphatasemia registered in their clinical record. Densitometry showed osteopenia or osteoporosis in 76.2%. There were 19 fractures, most of them in radius. The prevalence of hypophosphatasemia was similar to what has been previously reported. Hypophosphatasemia finding in medical records was low, but far from being asymptomatic, clinical manifestations were observed. In the presence of hypophosphatasemia without a secondary cause, adult hypophosphatasia should be uspected. (AU)

Quantification of DNA Damage in Different Tissues in Rats with Heart Failure / Quantificação de Dano em DNA em Diferentes Tecidos em Ratos com Insuficiência Cardíaca

Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.

Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.

Repercussions of adjuvant-induced arthritis on body composition, soleus muscle, and heart muscle of rats

This study investigated the repercussions of adjuvant-induced arthritis (AIA) on body composition and the structural organization of the soleus and cardiac muscles, including their vascularization, at different times of disease manifestation. Male rats were submitted to AIA induction by intradermal administration of 100 μL of Mycobacterium tuberculosis (50 mg/mL), in the right hind paw. Animals submitted to AIA were studied 4 (AIA4), 15 (AIA15), and 40 (AIA40) days after AIA induction as well as a control group of animals not submitted to AIA. Unlike the control animals, AIA animals did not gain body mass throughout the evolution of the disease. AIA reduced food consumption, but only on the 40th day after induction. In the soleus muscle, AIA reduced the wet mass in a time-dependent manner but increased the capillary density by the 15th day and the fiber density by both 15 and 40 days after induction. The diameter of the soleus fiber decreased from the 4th day after AIA induction as well as the capillary/fiber ratio, which was most evident on the 40th day. Moreover, AIA induced slight histopathological changes in the cardiac muscle that were more evident on the 15th day after induction. In conclusion, AIA-induced changes in body composition as well as in the soleus muscle fibers and vasculature have early onset but are more evident by the 15th day after induction. Moreover, the heart may be a target organ of AIA, although less sensitive than skeletal muscles.

Thumb adductor muscle thickness used in the nutritional assessment of chronic kidney disease patients under conservative treatment / Espessura do músculo adutor do polegar para avaliação nutricional de portadores de doença renal crônica em tratamento conservador

Abstract Introduction: Evaluate the association between the thumb adductor muscle thickness and the patient's nutritional status, and propose cutoff points for muscle mass depletion in elderly patients with chronic kidney disease (CKD) under conservative treatment. Epidemiological and cross-sectional study, including patients with CKD stages 3 to 5, older than 60 years. Socioeconomic, clinical, physical activity and anthropometric data was obtained. TAMT was described and compared according to CKD stage, socioeconomic data, physical activity, nutritional status and correlated with age, glomerular filtration rate and anthropometric variables. Receiver Operating Characteristic (ROC) curves were produced, considering the lean tissue index classification as reference. The cut-off point was defined by the Youden index. Results: We evaluated 137 individuals. The TAMT was lower in malnourished and/or depleted muscle mass individuals; among males it was higher among those who practiced physical activities (p <0.05). This measure was moderately correlated with BMI, calf and brachial circumferences, lean body tissue, lean tissue index and body cell mass (r <0.7); negatively with age (r = -0.34). The ROC curve analysis determined cut points of 15.33 mm for females and 20.33 mm for males, with 72.22% and 62.50% accuracy, respectively. Conclusion: TAMT is used to estimate muscle mass and we suggest the cutoff point is useful to rule out the likelihood of muscle mass depletion. It is recommended that it be used in a complementary way in nutritional assessment.

Resumo Introdução: Avaliar a associação da espessura do músculo adutor do polegar (EMAP) com o estado nutricional e propor pontos de corte para depleção de massa muscular em idosos portadores da doença renal crônica (DRC) em tratamento conservador. Metodologia: Estudo epidemiológico, delineamento transversal, incluindo portadores de DRC estágios 3 a 5, acima de 60 anos. Obteve-se dados socioeconômicos, clínicos, prática de atividade física e antropométricos. A EMAP foi descrita e comparada de acordo com o estágio da DRC, dados socioeconômicos, atividade física e estado nutricional e correlacionada com idade, taxa de filtração glomerular e variáveis antropométricas. Foram produzidas curvas Receiver Operating Characteristic (ROC), considerando como padrão de referência a classificação do índice de tecido magro. O ponto de corte foi definido pelo índice Youden. Resultados: Avaliou-se 137 indivíduos. A EMAP foi inferior nos desnutridos e/ou com depleção de massa muscular; no sexo masculino foi superior nos praticantes de atividade física (p<0,05). A medida se correlacionou moderadamente com IMC, circunferência da panturrilha e braquial, tecido de massa magra, índice de tecido magro e massa celular corporal (r<0,7), e negativamente com a idade (r=-0,34). A análise da curva ROC determinou pontos de corte de 15,33 mm para o sexo feminino e 20,33 mm para o masculino, com acurácia de 72,22% e 62,50%, respectivamente. Conclusão: A EMAP serve para estimar a massa muscular, e o ponto de corte sugerido é útil para afastar a probabilidade de depleção de massa muscular. Recomenda-se que seja utilizada de forma complementar na avaliação nutricional.

Entrenamiento de fuerza y resistencia en hipoxia: efecto en la hipertrofia muscular / The training of strength-resistance in hypoxia: effect on muscle hypertrophy

Resumen El entrenamiento en altitud y el entrenamiento en hipoxia simulada producen adaptaciones fisiológicas y bioquímicas en el músculo esquelético como la capacidad oxidativa, así como modificaciones de la actividad mitocondrial, en el metabolismo aerobio y en el contenido demioglobina. El propósito de esta revisión fue analizar las adaptaciones del músculo esquelético en respuesta a la exposición temporal a la hipoxia combinada con ejercicios de fuerza y resistencia. Según los hallazgos de numerosos autores, las adaptaciones estructurales del músculo son similares en la hipoxia y en la 'normoxia', con excepción de un aumento en el volumen muscular y en el área de la sección transversal de la fibra muscular, que son mayores en la hipoxia. En conclusión, la sinergia del entrenamiento de fuerza y resistencia y la hipoxia normobárica produce mejores y mayores adaptaciones, ganancias y cambios fisiológicos beneficiosos en el tejido muscular, lo cual genera cambios fenotípicos favorables, como la hipertrofia del músculo esquelético.

Abstract Altitude and simulated-hypoxia training produces different physiological and/or biochemical adaptations in the skeletal muscle. These are: oxidative capacity, mitochondrial activity modifications, aerobic metabolism changes and myoglobin content. The purpose of this review was to analyze the adaptations of skeletal muscle in response to the combination of strength-resistance exercise and hypoxia. In general terms, the structural adaptations of the muscle are similar in hypoxia and normoxia except that hypoxia training produces an increase of the volume and cross-sectional area of the muscle fiber. In conclusion, the synergic effect of the combination of strength resistance training with normobaric hypoxia produces better and greater adaptations and beneficial physiological changes of the muscle tissue, which shows favorable phenotypic changes in skeletal muscle hypertrophy.

Miopatías inflamatorias idiopáticas: una mirada actualizada al diagnóstico y el manejo / Idiopathic inflammatory myopathies: a review

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of acquired immune-mediated diseases, which typically involve the striated muscle with a variable involvement of the skin and other organs. Clinically, they are characterized by proximal muscle weakness, elevation of muscle enzymes, myopathic changes on electromyography and an abnormal muscle biopsy. The different IIM have been classified according to their distinctive histopathologic features in dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). Several myositis-specific antibodies are associated with the different phenotypes, as well as with different risk of neoplastic disease and systemic complications. The basis for the treatment of DM, PM, and IMNM is immunosuppression. For IBM there are only symptomatic treatments. Steroids, associated or not with other immunosuppressant drugs, are the first line of treatment. Biologic drugs will allow future individualized therapies. The 10-year survival of DM, PM and IMNM is 62 to 90%. The leading causes of death are neoplastic, lung and cardiac complications. IBM does not impair survival, although it affects the quality of life.

Wound Age Estimation by Neutrophil Migration Distance / 法医学杂志

Objective To explore the application of neutrophil migration distance for wound age estimation of skeletal muscles in rats, and to provide methodological basis for follow-up study in future. Methods The skeletal muscle contusion model was established in rats, and the control group and the 2, 4, 6 h post-traumatic groups were set. The law of response of neutrophils that participated in the inflammation after injury was detected by immunohistochemical staining, and the relationship between neutrophil migration distance and injury time was detected by TissueFAXS PLUS software. Results The skeletal muscle was obviously infiltrated with neutrophils 2-6 h after injury. The positive rate of neutrophil was （28.75±0.94）% at 2 h post-traumatic, and reached the peak （45.50±3.63）% at 4 h post-traumatic, then decreased to （31.92±1.56）% at 6 h post-traumatic. The neutrophil migration distances increased with the progress of inflammation, and reached （124.80±12.32） μm, （229.03±21.45） μm and （335.04±16.75） μm at 2 h, 4 h and 6 h, respectively. Conclusion There is a relationship of neutrophil infiltrated number and migration distance and wound age within the 2-6 h after skeletal muscle injury, which could be used for the inference of skeletal muscle wound age.

Relationship between Expression Changes of CB2R and Wound Age of Brain Contusion in Mice / 法医学杂志

Objective To investigate the expression of cannabinoid type 2 receptor （CB2R） at different time points after brain contusion and its relationship with wound age of mice. Methods A mouse brain contusion model was established with PCI3000 Precision Cortical Impactor. Expression changes of CB2R around the injured area were detected with immunohistochemical staining, immunofluorescent staining and Western blotting at different time points. Results Immunohistochemical staining results showed that only a few cells in the cerebral cortex of the sham operated group had CB2R positive expression. The ratio of CB2R positive cells gradually increased after injury and reached the peak twice at 12 h and 7 d post-injury, followed by a decrease to the normal level 28 d post-injury. The results of Western blotting were consistent with the immunohistochemical staining results. Immunofluorescent staining demonstrated that the changes of the ratio of CB2R positive cells in neurons, CB2R positive cells in monocytes and CB2R positive cells in astrocytes to the total cell number showed a single peak pattern, which peaked at 12 h, 1 d and 7 d post-injury, respectively. Conclusion The expression of CB2R after brain contusion in neurons, monocytes and astrocytes in mice suggests that it is likely to be involved in the regulation of the biological functions of those cells. The changes in CB2R are time-dependent, which suggests its potential applicability as a biological indicator for wound age estimation of brain contusion in forensic practice.

Adductor Pollicis Muscle Thickness for nutritional assessment: a systematic review / Espesura del Músculo Aductor del Pulgar para evaluación nutricional: una revisión sistemática / Espessura do Músculo Adutor do Polegar para avaliação nutricional: uma revisão sistemática

ABSTRACT Objective: The aim of this study is to systematically review the scientific findings about the efficacy of the measure of the Adductor Pollicis Muscle Thickness for nutritional assessment of individuals in various clinical conditions. Method: Systematic review study performed according to the methodology Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: 13 original articles published between 2004 and 2016 were included. The measure was associated/correlated to parameters of nutritional status (such as weight, body mass index and Global Subjective Assessment) and muscle mass markers (such as circumference brachial muscle circumference, brachial muscle area, calf circumference, and muscle mass). All these correlations were weak or moderate. Conclusion: The measurement can be used in different populations, being able to estimate nutritional status and muscle mass. However, it is suggested that it be used in a complementary way to the nutritional evaluation, not constituting a single diagnostic/monitoring parameter.

RESUMEN Objetivo: Revisar de forma sistemática las constataciones científicas acerca de la eficacia de la medida de la Espesura del Músculo Aductor del Pulgar para evaluación nutricional de los individuos bajo diversas condiciones clínicas. Método: Estudio de revisión sistemática, realizado conforme la metodología Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Resultados: Se incluyeron 13 artículos originales publicados entre 2004 y 2016. La medida se presentó asociada/correlacionada a los parámetros de evaluación del estado nutricional (peso, índice de masa corporal y Evaluación Subjetiva Global) y a los marcadores de masa muscular (como circunferencia braquial, circunferencia muscular braquial, área muscular braquial, circunferencia de la pantorrilla y masa muscular). Todas estas correlaciones fueron débiles o moderadas. Conclusión: La medida puede ser utilizada en diferentes poblaciones, siendo capaz de estimar el estado nutricional y la masa muscular. Sin embargo, se sugiere que se emplee de forma complementaria la evaluación nutricional, no constituyendo un parámetro único de diagnóstico/monitoreo.

RESUMO Objetivo: Revisar de forma sistemática as constatações científicas acerca da eficácia da medida da Espessura do Músculo Adutor do Polegar para avaliação nutricional de indivíduos em diversas condições clínicas. Método: Estudo de revisão sistemática, realizado conforme a metodologia PreferredReportingItems for SystematicReviewsand Meta-Analyses (PRISMA). Resultados: Foram incluídos 13 artigos originais publicados entre 2004 e 2016. A medida apresentou-se associada/correlacionada aos parâmetros de avaliação do estado nutricional (como peso, índice de massa corporal e Avaliação Subjetiva Global) e aos marcadores da massa muscular (como circunferência braquial, circunferência muscular braquial, área muscular braquial, circunferência da panturrilha e massa muscular). Todas essas correlações foram fracas ou moderadas. Conclusão: A medida pode ser utilizada em diferentes populações, sendo capaz de estimar o estado nutricional e a massa muscular. No entanto, sugere-se que seja empregada de modo complementar à avaliação nutricional, não constituindo um parâmetro único de diagnóstico/monitoramento.

An evaluation of an animal model of cerebral palsy: the effects on the morphology of the extensor digitorum longus muscle / Evaluación de un modelo animal de parálisis cerebral: los efectos sobre la morfología del músculo extensor largo de los dedos

Cerebral Palsy (CP) refers to chronic childhood encephalopathy. The objective of this study was to verify effects of CP model that combines prenatal exposure to LPS, perinatal anoxia and sensorimotor restriction on EDL muscle. Male Wistar rat pups were separated: a) Control - pups of mothers injected with saline during pregnancy and b) Cerebral Palsy - pups of mothers injected with LPS during pregnancy, and submitted to perinatal anoxia and sensorimotor restriction. The CP group presented hypertrophy in the type IIB fibers and increase of nuclei/fiber and capillary/fiber ratios. The intrafusal fibers of CP group presented 26 % atrophy in the crosssectional area and intramuscular collagen volume increase 34 %. CP group showed myofibrillar disruption and Z-line disorganization and the NMJs presented increases of 22 % in area.This animal model of CP produces motor deficits and macro and microscopic alterations and in the ultrastructure of the EDL muscle.

La parálisis cerebral (PC) se refiere a la encefalopatía crónica infantil. El objetivo de este estudio fue verificar los efectos del modelo PC que combina la exposición prenatal a LPS, la anoxia perinatal y la restricción sensitivo-motora en el músculo extensor largo de los dedos (MELD). Se separaron las crías de ratas Wistar machos: a) Control: crías de madres inyectadas con solución salina durante la preñez y b) Parálisis cerebral: crías de madres inyectadas con LPS durante la preñez y sometidas a anoxia perinatal y restricción sensitivo-motora. El grupo PC presentó hipertrofia en las fibras tipo IIB y aumento de la relación núcleo / fibra y capilar / fibra. Las fibras intrafusales del grupo PC presentaron un 26 % de atrofia en el área de la sección transversal y el volumen de colágeno intramuscular aumentó un 34 %. El grupo PC mostró disrupción miofibrilar y desorganización de la línea Z y los NMJ presentaron aumentos de 22 % en el área. Este modelo animal de PC produce déficit motores y alteraciones macro y microscópicas y cambios en la ultraestructura del MELD.

Low intensity training provokes adaptations on muscle fibrosis of a muscular dystrophy model / El entrenamiento de baja intensidad provoca adaptaciones en la fibrosis muscular de un modelo de distrofia muscular

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder with progressive clinical signs until death, around the second decade of life. Mdx is the most used animal model to pre-clinical studies of DMD. Parameters of exercise on this muscular disease are still unknown. This research aimed to investigate if the low intensity treadmill training would exacerbate the markers of muscle injury, fibrosis, and the composition of the extracellular matrix by type I and III collagens of the mdx model. Dystrophic 11-week-old male mice were separated in exercised (mdxE, n=8) and sedentary (mdxC, n=8) groups. Wild-type mice were used as control (WT, n=8). Exercised group underwent a LIT protocol (9 m/min, 30min, 3days/week, 60 days) on a horizontal treadmill. Gastrocnemius muscle was collected at day 60 and processed to morphological and morphometric analyzes. Sedentary mdx animals presented inflammatory infiltrate and necrotic fibers. Histochemical analysis revealed that the perimysium of the mdxC group is organized into thick and clustered collagen fibers, which generates a larger area of intramuscular collagen fibers for these animals. Histomorphometry attested that fraction area of collagen fibers of mdxC group was higher than mdxE group (p=0.04) and mdxE group values similar to WT group (p=1.00). Centrally located nuclei fibers and the variance coefficient (VC) of minimal Feret's diameter was similar in mdxE and mdxC groups (p=1.00) and both groups presented higher mean values than WT group (p<0.00). Immunohistochemistry revealed the presence of type I collagen mainly in the mdxC group. LIT protocol had not exacerbated muscle injuries resulting from the dystrophindeficiency membrane fragility at the same time that had reduced the intramuscular collagen deposition. LIT had positively influenced these markers of dystrophic muscle injury on gastrocnemius muscle of mdx model.

La distrofia muscular de Duchenne (DMD) es un trastorno neuromuscular genético con signos clínicos progresivos hasta la muerte, alrededor de la segunda década de la vida. Mdx es el modelo animal más utilizado para estudios preclínicos de DMD. Los parámetros del ejercicio en esta enfermedad muscular aún se desconocen. Esta investigación tuvo como objetivo investigar si el entrenamiento de cinta de baja intensidad exacerbaría los marcadores de lesión muscular, fibrosis y la composición de la matriz extracelular por colágenos tipo I y III del modelo mdx. Ratones machos de 11 semanas de edad con distrofia se separaron en grupos ejercitados (mdxE, n = 8) y sedentarios (mdxC, n = 8). Se usaron ratones de tipo salvaje como control (WT, n = 8). El grupo sometido a ejercicio se sometió a un protocolo LIT (9 m / min, 30 min, 3 días / semana, 60 días) en una cinta de trotar horizontal. El músculo gastrocnemio se retiró el día 60 y se procesó para realizar análisis morfológicos y morfométricos. Los animales sedentarios mdx presentaron infiltrado inflamatorio y fibras necróticas. El análisis histoquímico reveló que el perimisio del grupo mdxC está organizado en fibras de colágeno gruesas y agrupadas, lo que genera una mayor área de fibras de colágeno intramusculares para estos animales. La histomorfometría indicó que el área de fracción de las fibras de colágeno del grupo mdxC era más alta que el grupo mdxE (p = 0,04) y los valores del grupo mdxE eran similares al grupo WT (p = 1,00). Las fibras de los núcleos ubicados centralmente y el coeficiente de varianza (VC) del diámetro mínimo de Feret fueron similares en los grupos mdxE y mdxC (p = 1,00) y ambos grupos presentaron valores medios más altos que el grupo WT (p <0,00). La inmunohistoquímica reveló la presencia de colágeno tipo I principalmente en el grupo mdxC. El protocolo LIT no había agravado las lesiones musculares resultantes de la fragilidad de la membrana con deficiencia de distrofina al mismo tiempo que había reducido la deposición intramuscular de colágeno. LIT ha influido positivamente en estos marcadores de lesión muscular distrófica en el músculo gastrocnemio del modelo mdx.

Calf circumference: clinical validation for evaluation of muscle mass in the elderly / Circunferencia de la pantorrilla: validación clínica para evaluación de masa muscular en mayores / Circunferência da panturrilha: validação clínica para avaliação de massa muscular em idosos

ABSTRACT Objective: To validate calf circumference as a technology for assessing muscle mass in the elderly. Method: Cross-sectional study with 132 elderly people from Goiânia, Goiás, Brazil. Decreased muscle mass was determined by the skeletal muscle mass index (IME) using Dual Energy X-Ray Absortometry (DEXA). The cutoff circumferences (CC) cutoff points to indicate muscle mass decrease were estimated by ROC curve, sensitivity, specificity and accuracy. Results: The most accurate cut-off points for detecting decreased muscle mass in the elderly were 34 cm for men (sensitivity: 71.5%, specificity: 77.4%) and 33 cm for women (sensitivity: 80.0%; specificity: 84.6%). Conclusion: CC can be used as a measure for early identification of muscle mass decrease in routine evaluations of the elderly in primary care.

RESUMEN Objetivo: Validar la circunferencia de la pantorrilla como tecnología de evaluación de masa muscular en mayores. Método: Estudio transversal con 132 mayores de Goiânia, Goiás, Brasil. La disminución de masa muscular fue determinada por el índice de masa muscular esquelética (IME) por medio de la Absorciometría por Rayos-X de Dupla Energía (DEXA). Los puntos de corte de la medida de circunferencia de la pantorrilla (CP) para indicar disminución de masa muscular fueron estimados por medio de curva ROC, sensibilidad, especificidad y precisión. Resultados: Los puntos de corte con mejor precisión para detección de masa muscular disminuida en mayores fue 34 cm para hombres (sensibilidad: 71,5%; especificidad: 77,4%) y 33 cm en mujeres (sensibilidad: 80,0%; especificidad: 84,6%). Conclusión: La CP puede ser utilizada como medida para identificación precoz de disminución de masa muscular en evaluaciones de rutina de mayores en la atención primaria.

RESUMO Objetivo: Validar a circunferência da panturrilha como tecnologia de avaliação de massa muscular em idosos. Método: Estudo transversal com 132 idosos de Goiânia, Goiás, Brasil. A diminuição de massa muscular foi determinada pelo índice de massa muscular esquelética (IME) por meio da Absorciometria por Raios-X de Dupla Energia (DEXA). Os pontos de corte da medida de circunferência da panturrilha (CP) para indicar diminuição de massa muscular foram estimados por meio de curva ROC, sensibilidade, especificidade e acurácia. Resultados: Os pontos de corte com melhor acurácia para detecção de massa muscular diminuída em idosos foi 34 cm para homens (sensibilidade: 71,5%; especificidade: 77,4%) e 33 cm em mulheres (sensibilidade: 80,0%; especificidade: 84,6%). Conclusão: A CP pode ser utilizada como medida para identificação precoce de diminuição de massa muscular em avaliações de rotina de idosos na atenção primária.

¿Podemos mejorar la cicatrización de un desgarro muscular masivo? / Can we improve the healing of a massive muscle tear?

OBJETIVOS: Evaluar macroscópica e histológicamente la cicatrización muscular utilizando Dexametasona (DEX) o Traumeel (TRM), en un modelo experimental animal. MATERIAL Y MÉTODOS: Estudio experimental en 45 ratones BKS. Se seccionó transversal y completamente el cuádriceps derecho en todos los animales. Se definieron 3 grupos de estudio de 15 ratones cada uno, un grupo control, un grupo tratado con Dexametasona y uno con Traumeel. Los animales fueron sacrificados a las 1,2 y 4 semanas después del procedimiento y se les extrajo ambos cuádriceps (derecho como intervención e izquierdo como control) y luego fueron analizados macroscópica e histológicamente por un patólogo calificado, de manera ciega. Los datos se analizaron estadísticamente con el test de Kruskal - Wallis (p < 0,05), utilizando el programa Stata V12.1. RESULTADOS: Macroscopía: A la semana, en todos los grupos se evidenció ausencia de cicatrización con gap persistente. A la segunda semana, se evidencia cicatrización inicial sin gap en todos los grupos. A las 4 semanas todas las muestras estaban cicatrizadas. HISTOLOGÍA: La administración de Dexametasona disminuye el infiltrado inflamatorio y aumenta las fibras regenerativas, pero induce mayor fibrosis y pérdida de masa muscular. La adición de Traumeel aumenta la cantidad de fibras regenerativas, pero incrementa el infiltrado inflamatorio. CONCLUSIONES: A las 4 semanas ninguno de los grupos de estudio presentó regeneración muscular completa, con resultados macroscópicos e histológicos variables.

OBJETIVES: To macroscopically and histologically evaluate a muscle strain healing model, using Dexamethasone and Traumeel. MATERIALS AND METHODS: Experimental study in 45 BKS mice. 3 groups of 15 mice were defined: control group, Dexamethasone treated group and Traumeel treated group. The animals were sacrificed at the 1st, 2nd and 4th week, both quadriceps were resected (right as intervention and left as control) and then analyzed macroscopically and histologically by a qualified and blinded pathologist. Results were analyzed statistically using Kruskal - Wallis test (p<0.05). RESULTS: Macroscopy: the first week, all groups showed absence of healing with persistent gap. At the 2nd week, evidence of initial healing without gap in all groups. By week 4, all samples were healed. HISTOLOGY: Dexamethasone decreased the inflammatory infiltration and increased the regenerative fibers, but induced a higher fibrosis and loss of muscle mass. Traumeel increased the amount of regenerative fibers and the inflammatory infiltration. DISCUSSION: The results of our study fail to define a definitive posture. We observed that Traumeel actually increases the amount of regenerative fibers and contrary to the literature, it increases the inflammatory infiltrate. On the other hand, Dexamethasone showed similar results in both regenerative fibers, fatty infiltration and muscle mass, but with increased necrosis. CONCLUSIONS By the 4th week none of the groups showed complete muscle regeneration with macroscopic and histological variable results.

Sericin and swimming on histomorphometric parameters of denervated plantar muscle in Wistar rats / Sericina e natação sobre parâmetros histomorfométricos de músculo plantar desnervado de ratos Wistar

Abstract Objective To analyze the combined effects of the silk protein sericin and swimming exercise on histomorphometry of the plantar muscle in Wistar rats. Methods Forty adult rats were randomly allocated into 5 groups comprising 8 animals each, as follows: Control, Injury, Sericin, Swim, and Swim plus Sericin. Three days after crushing of the sciatic nerve the rats in the Swim and Swim plus Sericin Groups were submitted to swimming exercise for 21 days. Rats were then euthanized and the plantar muscle harvested and processed. Results Cross-sectional area, peripheral nuclei and muscle fiber counts, nucleus/fiber ratio and smallest muscle fiber width did not differ significantly between groups. Morphological analysis revealed hypertrophic fibers in the Swim Group and evident muscle damage in the Swim plus Sericin and Injury Groups. The percentage of intramuscular collagen was apparently maintained in the Swim Group compared to remaining groups. Conclusion Combined treatment with sericin and swimming exercise did not improve muscle properties. However, physical exercise alone was effective in maintaining intramuscular connective tissue and preventing progression of deleterious effects of peripheral nerve injury.

RESUMO Objetivo Analisar o efeito da proteína sericina associada ao exercício físico de natação na histomorfometria do músculo plantar de ratos Wistar. Métodos Foram utilizados 40 ratos adultos divididos aleatoriamente em 5 grupos, com 8 animais cada: Controle, Lesão, Sericina, Natação, Natação e Sericina. Três dias após a compressão do nervo isquiático, os Grupos Natação e Exercício e Sericina foram submetidos ao exercício físico de natação durante 21 dias. Após, os animais foram sacrificados, e o músculo plantar foi processado. Resultados Não houve diferença da área da secção transversa entre os grupos, quantidade de núcleos periféricos, quantidade de fibra, relação núcleo/fibra e diâmetro menor. A análise morfológica revelou que no Grupo Natação ocorreu hipertrofia das fibras, assim como nos Grupos Exercício e Sericina e Lesão, o dano muscular foi evidente. O percentual de conjuntivo intramuscular parece ter sido mantido no Grupo Exercício em relação aos demais grupos. Conclusão A associação da proteína sericina e exercício físico de natação não foi eficiente na melhora das propriedades musculares, embora a aplicação do exercício físico tenha sido eficiente na manutenção do conjuntivo intramuscular, e no não agravamento dos efeitos deletérios consequentes da lesão nervosa periférica.

Cutoff values for appendicular skeletal muscle mass and strength in relation to fear of falling among Brazilian older adults: cross-sectional study

ABSTRACT CONTEXT AND OBJECTIVE: Sarcopenia is an emerging public health issue in Brazil. Because of its high prevalence and the lack of national data, the objective here was to identify cutoff points for appendicular skeletal muscle (ASM) and handgrip strength in relation to fear of falling among Brazilian older adults. DESIGN AND SETTING: Cross-sectional study; in the community. METHODS: Participants underwent morphological and functional evaluations; and were asked about previous falls and fear of falling. Different adjustments to ASM and handgrip strength were used. Slow walking speed was defined as < 0.8 m/s or 1.0 m/s. Gender and age groups were compared using t tests, analysis of variance (ANOVA), chi-square test or Fisher's exact test. Receiver operating characteristic curves were used to identify cutoffs for ASM and handgrip strength in relation to fear of falling. RESULTS: 578 older adults participated in this study. Function levels decreased with increasing age, and body composition differed between the sexes. In relation to fear of falling, the cutoffs for ASM adjusted for body mass index (BMI) were < 0.85 for men and < 0.53 for women; the cutoffs for absolute handgrip strength and relative handgrip strength (adjusted for BMI) were 30.0 kgf and 21.7 kgf, and 1.07 and 0.66, for men and women, respectively. CONCLUSION: The values presented can be used as references in clinical practice and research. We recommend use of ASM adjusted for BMI and choosing between absolute and relative handgrip strength for men and women, according to study needs.