RESUMO
Mutations in the nuclear structural protein lamin A produce rare, tissue-specific diseases called laminopathies. The introduction of a human Emery-Dreifuss muscular dystrophy (EDMD)-inducing mutation into the C. elegans lamin (LMN-Y59C), recapitulates many muscular dystrophy phenotypes, and correlates with hyper-sequestration of a heterochromatic array at the nuclear periphery in muscle cells. Using muscle-specific emerin Dam-ID in worms, we monitored the effects of the mutation on endogenous chromatin. An increased contact with the nuclear periphery along chromosome arms, and an enhanced release of chromosomal centers, coincided with the disease phenotypes of reduced locomotion and compromised sarcomere integrity. The coupling of the LMN-Y59C mutation with the ablation of CEC-4, a chromodomain protein that anchors H3K9-methylated chromatin at the nuclear envelope (NE), suppressed the muscle-associated disease phenotypes. Deletion of cec-4 also rescued LMN-Y59C-linked alterations in chromatin organization and some changes in transcription. Sequences that changed position in the LMN-Y59C mutant, are enriched for E2F (EFL-2)-binding sites, consistent with previous studies suggesting that altered Rb-E2F interaction with lamin A may contribute to muscle dysfunction. In summary, we were able to counteract the dominant muscle-specific defects provoked by LMNA mutation by the ablation of a lamin-associated H3K9me anchor, suggesting a novel therapeutic pathway for EDMD.
Assuntos
Proteínas de Caenorhabditis elegans/genética , Núcleo Celular/genética , Proteínas Cromossômicas não Histona/genética , Deleção de Genes , Distrofia Muscular de Emery-Dreifuss/genética , Animais , Sítios de Ligação/genética , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/patologia , Cromatina/genética , Modelos Animais de Doenças , Genoma Helmíntico/genética , Laminina/genética , Laminina/metabolismo , Músculos/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Mutação , Estrutura Terciária de Proteína/genética , Sarcômeros/química , Sarcômeros/genética , Transcrição Gênica/genéticaRESUMO
The purpose of this study was to investigate the effects of neck and shoulder pain (NSP) and the position of the head and neck on the intramuscular circulation of the cervical muscles such as the trapezius and levator scapulae muscles in young females. Ten NSP subjects (mean age: 20.9 ± 0.5 years) and ten non-NSP subjects (mean age: 20.6 ± 0.7 years) were recruited to this study. Near-infrared spectroscopy (NIRS) was used to non-invasively measure total haemoglobin (Total-Hb), oxygenated haemoglobin (Oxy-Hb), and deoxygenated haemoglobin (Deoxy-Hb) of the trapezius and levator scapulae muscles. The measurements of Total-Hb, Oxy-Hb, and Deoxy-Hb were taken in the neutral position, immediately after the maximally flexed (extended) position, and after 30 s in the maximally flexed (extended) position. In flexion, no significant main effect or interaction was observed with Total-Hb and Oxy-Hb. A significant interaction was observed with Deoxy-Hb (p < 0.01). There was no significant difference in the changes over time in the NSP group (p = 0.91). However, in the non-NSP group, a significant increase was noted at the neutral position to immediately after the maximally flexed position (p < 0.01) and at the end of maintaining the maximally flexed position (p < 0.01). In extension, no significant main effect or interaction was observed with Total-Hb and Oxy-Hb. A significant interaction was observed with Deoxy-Hb (p < 0.01). In the NSP group, no significant difference was observed in the changes over time (p = 0.91). In the non-NSP group, however, a significant decrease was observed from the neutral position to immediately after the maximally extended position (p < 0.01). The results of this study indicate that maintaining either maximal cervical flexion or extension may affect venous blood flow on non-NSP group. However, no effect on NSP group was observed due to existing diminished intramuscular circulation.
Assuntos
Músculos do Dorso , Músculos do Pescoço , Cervicalgia , Dor de Ombro , Adulto , Feminino , Humanos , Adulto Jovem , Hemodinâmica/fisiologia , Hemoglobinas/análise , Músculos/fisiopatologia , Oxiemoglobinas/análise , Dor de Ombro/fisiopatologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cervicalgia/fisiopatologia , Fluxo Sanguíneo Regional/fisiologia , Músculos do Pescoço/irrigação sanguínea , Músculos do Pescoço/fisiopatologia , Músculos do Dorso/irrigação sanguínea , Músculos do Dorso/fisiopatologiaRESUMO
Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting 1 in 3500-5000 newborn boys. It is due to mutations in the DMD gene with a consequent lack of dystrophin protein that leads to deterioration of myofibres and their replacement with fibro-adipogenic tissue. Out-of-frame mutations in the DMD gene can be modified by using antisense oligonucleotides (AONs) to promote skipping of specific exons such that the reading frame is restored and the resulting protein produced, though truncated, is functional. We have shown that AONs can also be used to knock down myostatin, a negative regulator of muscle growth and differentiation, through disruption of the transcript reading frame, and thereby enhance muscle strength. In young mdx mice, combined dystrophin and myostatin exon skipping therapy greatly improved DMD pathology, compared to the single dystrophin skipping approach. Here we show that in aged (>15-month-old) mdx mice, when the pathology is significantly more severe and more similar to the one observed in DMD patients, the effect of the combined therapy is slightly attenuated but still beneficial in improving the disease phenotype. These results confirm the beneficial outcome of the combination approach and support its translation into DMD clinical trials.
Assuntos
Distrofina/genética , Distrofina/metabolismo , Éxons , Regulação da Expressão Gênica , Músculos/metabolismo , Miostatina/genética , Miostatina/metabolismo , Splicing de RNA , Animais , Modelos Animais de Doenças , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos mdx , Músculos/patologia , Músculos/fisiopatologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Distrofia Muscular de Duchenne/fisiopatologia , RNA Mensageiro/genéticaRESUMO
BACKGROUND & AIMS: Studies exploring the relationship between muscle fat content and non-alcoholic fatty liver disease (NAFLD) are scarce. Herein, we aimed to evaluate the association of muscle mass and fatty infiltration with biopsy-assessed NAFLD in patients with obesity. METHODS: At inclusion (n = 184) and 12 months after a dietary intervention (n = 15) or bariatric surgery (n = 24), we evaluated NAFLD by liver biopsy, and skeletal muscle mass index (SMI) by CT (CT-SMI) or bioelectrical impedance analysis (BIA-SMI). We developed an index to evaluate absolute fat content in muscle (skeletal muscle fat index [SMFI]) from CT-based psoas muscle density (SMFIPsoas). RESULTS: Muscle mass was higher in patients with NAFLD than in those without (CT-SMI 56.8 ± 9.9 vs. 47.4 ± 6.5 cm2/m2, p <0.0001). There was no association between sarcopenia and non-alcoholic steatohepatitis (NASH). SMFIPsoas was higher in NASH ≥F2 and early NASH F0-1 than in NAFL (78.5 ± 23.6 and 73.1 ± 15.6 vs. 61.2 ± 12.6, p <0.001). A 1-point change in the score for any of the individual cardinal NASH features (i.e. steatosis, inflammation or ballooning) was associated with an increase in SMFIPsoas (all p <0.05). The association between SMFIPsoas and NASH was highly significant even after adjustment for multiple confounders (all p <0.025). After intervention (n = 39), NASH improvement, defined by NAFLD activity score <3 or a 2-point score reduction, was achieved in more than 75% of patients (n = 25 or n = 27, respectively) that had pre-established NASH at inclusion (n = 32) and was associated with a significant decrease in SMFIPsoas (p <0.001). Strikingly, all patients who had ≥11% reduction in SMFIPsoas achieved NASH improvement (14/14, p <0.05). CONCLUSIONS: Muscle fat content, but not muscle mass, is strongly and independently associated with NASH. All individuals who achieved a ≥11% decrease in SMFIPsoas after intervention improved their NASH. These data indicate that muscle fatty infiltration could be a potential marker for (and perhaps a pathophysiological contributor to) NASH. LAY SUMMARY: The fat content in skeletal muscles is highly reflective of the severity of non-alcoholic fatty liver disease (NAFLD) in patients with morbid obesity. In particular, muscle fat content is strongly associated with non-alcoholic steatohepatitis (NASH) and decreases upon NASH improvement. These data indicate that muscle fatty infiltration could be a marker and possible pathophysiological contributor to NASH.
Assuntos
Tecido Adiposo/anormalidades , Hepatopatia Gordurosa não Alcoólica/etiologia , Tecido Adiposo/fisiopatologia , Adulto , Análise de Variância , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Músculos/anormalidades , Músculos/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Razão de ChancesRESUMO
OBJECTIVE: There was no study aimed at evaluating the effect of muscle function on SLE patients' quality of life using the Sarcopenia Quality of Life (SarQoL) questionnaire. METHODS: This cross-sectional study recruited 61 women with SLE consecutively, muscle function was measured with Jamar handheld-dynamometer and 6-meter walk test, HRQoL was measured with Sarcopenia Quality of Life (SarQoL) questionnaire. The cut-off point for low muscle strength (<18 kg) and low gait speed (<1.0 m/s) was according to the Asian Working Group on Sarcopenia 2019 criteria. Statistical analysis was conducted with a t-test for mean difference, and linear regression was used to adjust confounders (age, protein intake, physical exercise, and disease activity). RESULTS: The subjects' mean muscle strength was 19.54 kg (6.94), and 44.3% (n = 27) was found to have low muscle strength. The subjects' mean gait speed was 0.77 m/s (0.20), and 90.3% (n = 55) was found to have low gait speed. The difference of total SarQoL score in subjects with normal and low muscle strength was found to be significant; 74.86 (9.48) vs. 65.49 (15.51) (p = 0.009), and still statistically significant after adjustments with age, protein intake, physical exercise level, and disease activity [B 0.56; 95% CI 0.08-1.03; p = 0.022]. The difference of total SarQoL score in subjects with normal and low physical performance was found to be not significant, 70.67 (11.08) vs. 70.72 (13.56) (p = 0.993). CONCLUSION: There was a significant difference in SarQoL's total score in normal compared with low muscle strength groups of Indonesian women with SLE.
Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/psicologia , Força Muscular/fisiologia , Músculos/fisiopatologia , Adulto , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Humanos , Indonésia/epidemiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Força Muscular/imunologia , Proteínas/administração & dosagem , Proteínas/provisão & distribuição , Qualidade de Vida/psicologia , Sarcopenia/fisiopatologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Teste de Caminhada/métodos , Velocidade de Caminhada/fisiologiaRESUMO
Bone and muscle tissue are developed hand-in-hand during childhood and adolescence and interact through mechanical loads and biochemical pathways forming the musculoskeletal system. Chronic kidney disease (CKD) is widely considered as both a bone and muscle-weakening disease, eventually leading to frailty phenotype, with detrimental effects on overall morbidity. CKD also interferes in the biomechanical communication between two tissues. Pathogenetic mechanisms including systemic inflammation, anorexia, physical inactivity, vitamin D deficiency and secondary hyperparathyroidism, metabolic acidosis, impaired growth hormone/insulin growth factor 1 axis, insulin resistance, and activation of renin-angiotensin system are incriminated for longitudinal uncoordinated loss of bone mineral content, bone strength, muscle mass, and muscle strength, leading to mechanical impairment of the functional muscle-bone unit. At the same time, CKD may also interfere in the biochemical crosstalk between the two organs, through inhibiting or stimulating the expression of certain osteokines and myokines. This review focuses on presenting current knowledge, according to in vitro, in vivo, and clinical studies, concerning the pathogenetic pathways involved in the muscle-bone axis, and suggests approaches aimed at preventing bone loss and muscle wasting in the pediatric population. Novel therapeutic targets for preserving musculoskeletal health in the context of CKD are also discussed.
Assuntos
Osso e Ossos/fisiopatologia , Músculos/fisiopatologia , Insuficiência Renal Crônica , Doenças Ósseas Metabólicas , Criança , Humanos , Deficiência de Vitamina DRESUMO
Photobiomodulation therapy (PBMT) has been used to improve the physical performance of individuals with advanced age; however, there are no studies in the literature that support the application of light-emitting diode (LED) therapy for the muscular performance of individuals with diabetes mellitus who show a decline in functionality. The aim of the study was to analyze the acute effects of PBMT on strength and functional performance in type 2 diabetic individuals. Sixty-three volunteers were recruited and randomized into five groups: control (C), sham (S), red LED (R), infrared LED (IR), and red LED + infrared LED (R + IR). On the first day, the volunteers were evaluated using the time up and go (TUG), the 6-min walk test (6MWT), and isokinetic dynamometer of the ankle. In the following 3 days, groups R, IR, R + IR, and S returned for application of PBMT bilaterally, with 180 J of energy on each leg. On the fifth day, a reassessment was performed. There was no statistical difference between groups for the variables of the isokinetic dynamometer, TUG, and 6MWT. Analysis of the size of the clinical effect for the isokinetic variables showed that there was no pattern among the effects observed. There is a moderate effect in favor of R, IR, and R + IR in relation to C for the TUG and a moderate effect of R + IR in relation to C for the 6MWT. The PBMT applied for a short period does not bring important gains for the muscular performance and functionality of diabetic individuals.
Assuntos
Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/radioterapia , Terapia com Luz de Baixa Intensidade , Músculos/fisiopatologia , Feminino , Humanos , Masculino , Músculos/efeitos da radiação , Teste de CaminhadaRESUMO
Strenuous and unaccustomed exercise frequently lead to what has been coined "delayed onset muscle soreness" (DOMS). As implied by this term, it has been proposed that the associated pain and stiffness stem from micro-lesions, inflammation, or metabolite accumulation within the skeletal muscle. However, recent research points towards a strong involvement of the connective tissue. First, according to anatomical studies, the deep fascia displays an intimate structural relationship with the underlying skeletal muscle and may therefore be damaged during excessive loading. Second, histological and experimental studies suggest a rich supply of algogenic nociceptors whose stimulation evokes stronger pain responses than muscle irritation. Taken together, the findings support the hypothesis that DOMS originates in the muscle-associated connective tissue rather than in the muscle itself. Sports and fitness professionals designing exercise programs should hence consider fascia-oriented methods and techniques (e.g., foam rolling, collagen supplementation) when aiming to treat or prevent DOMS.
Assuntos
Tecido Conjuntivo/fisiologia , Fáscia/fisiologia , Mialgia/fisiopatologia , Exercício Físico/fisiologia , Humanos , Contração Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Músculos/fisiopatologia , Mialgia/metabolismo , Dor/metabolismo , Dor/fisiopatologia , Fatores de TempoRESUMO
Muscle wasting and cachexia are prominent comorbidities in cancer. Treatment with polyphenolic compounds may partly revert muscle wasting. We hypothesized that treatment with curcumin or resveratrol in cancer cachectic mice may improve muscle phenotype and total body weight through attenuation of several proteolytic and signaling mechanisms in limb muscles. In gastrocnemius and soleus muscles of cancer cachectic mice (LP07 adenocarcinoma cells, N = 10/group): (1) LC-induced cachexia, (2) LC-cachexia+curcumin, and (3) LC-cachexia + resveratrol, muscle structure and damage (including blood troponin I), sirtuin-1, proteolytic markers, and signaling pathways (NF-κB and FoxO3) were explored (immunohistochemistry and immunoblotting). Compared to nontreated cachectic mice, in LC-cachexia + curcumin and LC-cachexia + resveratrol groups, body and muscle weights (gastrocnemius), limb muscle strength, muscle damage, and myofiber cross-sectional area improved, and in both muscles, sirtuin-1 increased, while proteolysis (troponin I), proteolytic markers, and signaling pathways were attenuated. Curcumin and resveratrol elicited beneficial effects on fast- and slow-twitch limb muscle phenotypes in cachectic mice through sirtuin-1 activation, attenuation of atrophy signaling pathways, and proteolysis in cancer cachectic mice. These findings have future therapeutic implications as these natural compounds, separately or in combination, may be used in clinical settings of muscle mass loss and dysfunction including cancer cachexia.
Assuntos
Caquexia/etiologia , Caquexia/fisiopatologia , Curcumina/farmacologia , Músculos/patologia , Músculos/fisiopatologia , Neoplasias/complicações , Proteólise , Resveratrol/farmacologia , Animais , Biomarcadores/metabolismo , Linhagem Celular , Feminino , Camundongos Endogâmicos BALB C , Proteínas Musculares/metabolismo , Músculos/efeitos dos fármacos , Atrofia Muscular/metabolismo , Fenótipo , Proteólise/efeitos dos fármacos , Transdução de Sinais , Sirtuína 1/metabolismoRESUMO
PURPOSE OF REVIEW: To examine recent developments relating to cardiac involvement in the adult idiopathic inflammatory myopathies (IIM) and those inherited muscle diseases which may present in adulthood and mimic IIM. RECENT FINDINGS: Cardiac involvement is a common feature of IIM and inherited muscle diseases. Frequency according to disease subtype varies, with serotype having particular influence in IIM, and genotype in the inherited muscle diseases. Innovative techniques for examining cardiac function have been investigated further, including speckle-tracking echocardiography and cardiac magnetic resonance tomography. The present work has highlighted a likely underestimate of the burden of cardiac disease to date. The complex relationship between IIM, atherosclerosis, and traditional cardiovascular risk factors has been further elucidated. Consensus recommendations for managing patients with inherited muscle diseases and prominent cardiac involvement have been recently published. In addition to supportive care, disease modifying treatments are increasingly becoming available for inherited muscle diseases which may also improve cardiac outcomes. SUMMARY: Cardiac involvement is associated with significant morbidity and mortality. We suggest having a low threshold for considering the possibility of cardiac involvement in all patients with muscle disease.
Assuntos
Cardiopatias/fisiopatologia , Coração/fisiopatologia , Músculos/fisiopatologia , Miosite/fisiopatologia , Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Músculos/diagnóstico por imagem , Miosite/diagnóstico por imagemRESUMO
This study aims to assess whether older adults with low muscle mass or strength, in the presence of obesity, have an increased risk of knee (TKR) and hip replacement (THR) over 13 years. 1082 community-dwelling older adults (51% women; mean age 62.9 ± 7.5 years) were studied at baseline and multiple time points over 13 years. The incidence of TKR and THR was determined by data linkage to National Joint Replacement Registry. Appendicular lean and fat mass were measured using DXA. Lower-limb muscle strength (LMS) was assessed by dynamometer. Low muscle mass and strength were defined as the lowest sex-specific tertiles for appendicular lean mass (adjusted for height and total body fat mass) and lower-limb strength, respectively. Obesity was defined as the highest sex-specific tertile for total body fat mass. Competing risk regression models were used to estimate the sub-distribution hazard ratio (SHR) for TKR and THR. Over 13 years of follow-up, 6.8% (n = 74/1082) of the participants had a TKR and 4.7% (n = 50/1066) had THR. Participants with the combination of obesity and low muscle strength (SHR 3.36, 95% CI 1.50, 7.53) but low muscle mass (SHR 1.11, 95% CI 0.52, 2.40) had a significantly increased risk of TKR, compared to individuals with neither obesity nor low muscle mass/strength. However, obesity with low muscle strength did not lead to a significantly greater risk of TKR compared to having low muscle strength or obesity alone. There was no evidence for an association between obesity with low muscle mass or strength and THR (all p > 0.05). This finding suggests that combining muscle and fat assessments to predict the future risk of TKR is no better than each condition on its own.
Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Força Muscular , Músculos/fisiopatologia , Obesidade/complicações , Sarcopenia/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
microRNAs are short, (18-22 nt) non-coding RNAs involved in important cellular processes due to their ability to regulate gene expression at the post-transcriptional level. Exosomes are small (50-200 nm) extracellular vesicles, naturally secreted from a variety of living cells and are believed to mediate cell-cell communication through multiple mechanisms, including uptake in destination cells. Circulating microRNAs and exosome-derived microRNAs can have key roles in regulating muscle cell development and differentiation. Several microRNAs are highly expressed in muscle and their regulation is important for myocyte homeostasis. Changes in muscle associated microRNA expression are associated with muscular diseases including muscular dystrophies, inflammatory myopathies, and congenital myopathies. In this review, we aim to highlight the biology of microRNAs and exosomes as well as their roles in muscle health and diseases. We also discuss the potential crosstalk between skeletal and cardiac muscle through exosomes and their contents.
Assuntos
Exossomos/metabolismo , MicroRNAs/genética , Músculos/fisiopatologia , HumanosRESUMO
The loss of muscle mass and function with age, termed sarcopenia, is an inevitable process, which has a significant impact on quality of life. During ageing we observe a progressive loss of total muscle fibres and a reduction in cross-sectional area of the remaining fibres, resulting in a significant reduction in force output. The mechanisms which underpin sarcopenia are complex and poorly understood, ranging from inflammation, dysregulation of protein metabolism and denervation. However, there is significant evidence to demonstrate that modified ROS generation, redox dis-homeostasis and mitochondrial dysfunction may have an important role to play. Based on this, significant interest and research has interrogated potential ROS-targeted therapies, ranging from nutritional-based interventions such as vitamin E/C, polyphenols (resveratrol) and targeted pharmacological compounds, using molecules such as SS-31 and MitoQ. In this review we evaluate these approaches to target aberrant age-related ROS generation and the impact on muscle mass and function.
Assuntos
Envelhecimento , Músculos/fisiopatologia , Qualidade de Vida , Espécies Reativas de Oxigênio/metabolismo , Sarcopenia , Humanos , Estresse Oxidativo , Sarcopenia/prevenção & controleRESUMO
BACKGROUND: Muscle weakness following critical illness is the consequence of loss of muscle mass and alteration of muscle quality. It is associated with long-term disability. Ultrasonography is a reliable tool to quantify muscle mass, but studies that evaluate muscle quality at the critically ill bedside are lacking. Shear wave ultrasound elastography (SWE) provides spatial representation of soft tissue stiffness and measures of muscle quality. The reliability and reproducibility of SWE in critically ill patients has never been evaluated. METHODS: Two operators tested in healthy controls and in critically ill patients the intra- and inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. Reliability was calculated using the intra-class correlation coefficient and a bootstrap sampling method assessed their consistency. RESULTS: We collected 560 images. Longitudinal views of the diaphragm (ICC 0.83 [0.50-0.94]), the biceps brachii (ICC 0.88 [0.67-0.96]) and the rectus femoris (ICC 0.76 [0.34-0.91]) were the most reliable views in a training set of healthy controls. Intra-class correlation coefficient for inter-operator reproducibility and intra-operator reliability was above 0.9 for all muscles in a validation set of healthy controls. In critically ill patients, inter-operator reproducibility and intra-operator 1 and 2 reliability ICCs were respectively 0.92 [0.71-0.98], 0.93 [0.82-0.98] and 0.92 [0.81-0.98] for the diaphragm; 0.96 [0.86-0.99], 0.98 [0.94-0.99] and 0.99 [0.96-1] for the biceps brachii and 0.91 [0.51-0.98], 0.97 [0.93-0.99] and 0.99 [0.97-1] for the rectus femoris. The probability to reach intra-class correlation coefficient greater than 0.8 in a 10,000 bootstrap sampling for inter-operator reproducibility was respectively 81%, 84% and 78% for the diaphragm, the biceps brachii and the rectus femoris respectively. CONCLUSIONS: SWE is a reliable technique to evaluate limb muscles and the diaphragm in both healthy controls and in critically ill patients. TRIAL REGISTRATION: The study was registered (ClinicalTrial NCT03550222).
Assuntos
Diafragma/fisiopatologia , Técnicas de Imagem por Elasticidade/instrumentação , Extremidades/fisiopatologia , Músculos/anormalidades , Ultrassonografia/instrumentação , Ultrassonografia/normas , Adulto , Estado Terminal , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/tendências , Feminino , França , Hospitais Universitários/organização & administração , Hospitais Universitários/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/fisiopatologia , Escores de Disfunção Orgânica , Estudos Prospectivos , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Ultrassonografia/métodosRESUMO
This cross-sectional study compares the muscle mass, core strength and physical fragility of patients recently diagnosed with colorectal cancer (pRD-CRC) with those of healthy subjects and identifies variables to be considered when designing pre-treatment physical interventions for such patients. Body composition, anthropometric variables, the muscle architecture of the lumbopelvic region, physical fitness and frailty were assessed in 32 pRD-CRC and 29 healthy control subjects. The patients showed a reduction in muscle mass (F = 10.059; P = 0.003), in the width of the lumbar multifidus (F = 21.869; P < 0.001), in the transverse abdominal muscle (U = 323.00; P = 0.042) and in the abdominal strength resistance (F = 12.264; P = 0.001). They were also frailer (P = 0.002) than the controls. These results suggest that pRD-CRC are affected by reduced strength and myopenia, leading to frailty. The early incorporation of these patients into strength-enhancing programs may be advisable.
Assuntos
Neoplasias Colorretais/fisiopatologia , Músculos/fisiopatologia , Composição Corporal , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Estudos Transversais , Feminino , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculos/patologia , Aptidão Física/fisiologiaRESUMO
BACKGROUND: Only a few small studies have previously reported episodes of hypoglycemia in children with neuromuscular diseases; however, there has been no broader investigation into the occurrence of hypoglycemia in children with congenital muscle disease (CMD). METHODS: Pediatric patients enrolled in the CMD International Registry (CMDIR) with a history of hypoglycemia were included in this retrospective review. Hypoglycemic episodes and associated clinical and biochemical characteristics were characterized. RESULTS: Ten patients with CMD (5 with LAMA2-related muscular dystrophy) reported at least one episode of hypoglycemia beginning at an average age of 3.5 years. Predominant symptoms included altered mental status and nausea/vomiting, and laboratory studies demonstrated metabolic acidosis and ketonuria, consistent with ketotic hypoglycemia. CONCLUSION: Patients with CMD may have an increased risk of hypoglycemia during fasting, illness, or stress due to their relatively low muscle mass and hence, paucity of gluconeogenic substrate. Clinicians should therefore maintain a high index of suspicion for hypoglycemia in this high-risk patient population and caregivers should routinely be trained to recognize and treat hypoglycemia.
Assuntos
Hipoglicemia , Distrofias Musculares , Criança , Pré-Escolar , Jejum , Humanos , Hipoglicemia/complicações , Hipoglicemia/diagnóstico , Músculos/fisiopatologia , Distrofias Musculares/complicações , Estudos RetrospectivosRESUMO
Although the prevalence of muscle weakness in the general population is uncertain, it occurs in about 5% of U.S. adults 60 years and older. Determining the cause of muscle weakness can be challenging. True muscle weakness must first be differentiated from subjective fatigue or pain-related motor impairment with normal motor strength. Muscle weakness should then be graded objectively using a formal tool such as the Medical Research Council Manual Muscle Testing scale. The differential diagnosis of true muscle weakness is extensive, including neurologic, rheumatologic, endocrine, genetic, medication- or toxin-related, and infectious etiologies. A stepwise approach to narrowing this differential diagnosis relies on the history and physical examination combined with knowledge of the potential etiologies. Frailty and sarcopenia are clinical syndromes occurring in older people that can present with generalized weakness. Asymmetric weakness is more common in neurologic conditions, whereas pain is more common in neuropathies or radiculopathies. Identifying abnormal findings, such as Chvostek sign, Babinski reflex, hoarse voice, and muscle atrophy, will narrow the possible diagnoses. Laboratory testing, including electrolyte, thyroid-stimulating hormone, and creatine kinase measurements, may also be helpful. Magnetic resonance imaging is indicated if there is concern for acute neurologic conditions, such as stroke or cauda equina syndrome, and may also guide muscle biopsy. Electromyography is indicated when certain diagnoses are being considered, such as amyotrophic lateral sclerosis, myasthenia gravis, neuropathy, and radiculopathy, and may also guide biopsy. If the etiology remains unclear, specialist consultation or muscle biopsy may be necessary to reach a diagnosis.
Assuntos
Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Exame Neurológico/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Músculos/fisiopatologia , Doenças Musculares/diagnóstico , Exame Neurológico/métodos , Neurologia/normasRESUMO
Rigidity is one of the cardinal symptoms of Parkinson´s disease (PD). Present in up 89% of cases, it is typically assessed with clinical scales. However, these instruments show limitations due to their subjectivity and poor intra- and inter-rater reliability. To compile all of the objective quantitative methods used to assess rigidity in PD and to study their validity and reliability, a systematic review was conducted using the Web of Science, PubMed, and Scopus databases. Studies from January 1975 to June 2019 were included, all of which were written in English. The Strengthening the Reporting of observational studies in Epidemiology Statement (STROBE) checklist for observational studies was used to assess the methodological rigor of the included studies. Thirty-six studies were included. Rigidity was quantitatively assessed in three ways, using servomotors, inertial sensors, and biomechanical and neurophysiological study of muscles. All methods showed good validity and reliability, good correlation with clinical scales, and were useful for detecting rigidity and studying its evolution. People with PD exhibit higher values in terms of objective muscle stiffness than healthy controls. Rigidity depends on the angular velocity and articular amplitude of the mobilization applied. There are objective, valid, and reliable methods that can be used to quantitatively assess rigidity in people with PD.
Assuntos
Rigidez Muscular/complicações , Doença de Parkinson/complicações , Eletromiografia , Humanos , Articulações/fisiopatologia , Movimento , Rigidez Muscular/fisiopatologia , Músculos/fisiopatologia , Estudos Observacionais como Assunto , Doença de Parkinson/fisiopatologiaRESUMO
Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota's composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.
Assuntos
Caquexia/etiologia , Músculos/efeitos dos fármacos , Inibidores da Bomba de Prótons/efeitos adversos , Sarcopenia/etiologia , Animais , Caquexia/fisiopatologia , Doença Crônica , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Magnésio/metabolismo , Músculos/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Sarcopenia/fisiopatologiaRESUMO
Striated muscle contraction occurs when myosin thick filaments bind to thin filaments in the sarcomere and generate pulling forces. This process is regulated by calcium, and it can be perturbed by pathological conditions (e.g., myopathies), physiological adaptations (e.g., ß-adrenergic stimulation), and pharmacological interventions. Therefore, it is important to have a methodology to robustly determine the impact of these perturbations and statistically evaluate their effects. Here, we present an approach to measure the equilibrium constants that govern muscle activation, estimate uncertainty in these parameters, and statistically test the effects of perturbations. We provide a MATLAB-based computational tool for these analyses, along with easy-to-follow tutorials that make this approach accessible. The hypothesis testing and error estimation approaches described here are broadly applicable, and the provided tools work with other types of data, including cellular measurements. To demonstrate the utility of the approach, we apply it to elucidate the biophysical mechanism of a mutation that causes familial hypertrophic cardiomyopathy. This approach is generally useful for studying muscle diseases and therapeutic interventions that target muscle contraction.