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1.
Brain Nerve ; 71(11): 1145-1151, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31722301

RESUMO

'Split hand' is dissociated hand muscle atrophy, characterized by preferential atrophies in the thenar and first dorsal interosseous muscles, with relative sparing of the hypothenar muscle. This symptom has been recognized as specific to amyotrophic lateral sclerosis (ALS), and distinct pathomechanisms are assumed to underlie this phenomenon. Recently, characteristic distributions of weakness and symptoms in ALS have been reported. Here, we describe characteristic symptoms of ALS, including split hand, split-hand plus sign, split elbow, split leg, relative preservation of finger flexion. Moreover, through these phenomena, potent mechanisms of motor neuron death in ALS are considered. Revealing the underlying pathophysiology of these symptoms may lead to the development of therapies for ALS.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Atrofia Muscular/fisiopatologia , Esclerose Amiotrófica Lateral/fisiopatologia , Mãos/fisiopatologia , Humanos , Neurônios Motores , Músculo Esquelético/fisiopatologia
2.
BMC Musculoskelet Disord ; 20(1): 454, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31630684

RESUMO

BACKGROUND: The paraspinal and psoas muscles have been considered to be essentially important for stabilizing the spinal column, and the muscle degeneration was found to exist in degenerative spinal kyphosis (DSK) patients. However, it is still not clear the relationship between muscle degeneration and spinal-pelvic alignment. The purpose of this study was to determine the correlations between the individual muscle degeneration at each lumbar spinal level and spinal-pelvic parameters in DSK patients. METHODS: The imaging data of 32 patients with DSK were retrospectively analyzed. The fat infiltration (FI) and relative cross-sectional area of muscle (RCSA) were quantitatively measured for multifidus (MF), erector spinae (ES) and psoas (PS) at each spinal level from L1/2 to L5/S1. The correlations were analyzed between RCSA and the sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT) and pelvic incidence (PI). RESULTS: The FI of MF and ES at L3/4, L4/5 and L5/S1 were higher than that at L1/2 and L2/3. The FI of PS at L4/5 and L5/S1 were lower than that of L1/2, L2/3 and L3/4. The RCSA of ES and PS from L1/2 to L5/S1 gradually increased, whereas the RCSA of ES from L1/2 to S5/S1 gradually decreased. The RCSA of MF at the L1/2 level was negatively correlated SVA (r = - 0.397,p = 0.024); the RCSA at L3/4, L4/5 and L5/S1 levels were negatively correlated with TK (r = - 0.364, p = 0.04; r = - 0.38, p = 0.032; r = - 0.432, p = 0.014); the RCSA at L4/5 level was positively correlated with LL (r = 0.528, p = 0.002). The RCSA of ES at L3/4 and L4/5 levels were positively correlated with PI (r = 0.377, p = 0.037) and SS (r = 0.420, p = 0.019). CONCLUSIONS: FI of MF and ES at lower lumbar level is higher than that at upper level, but FI of PS at upper lumbar level is higher than that at lower level. MF and ES have different roles for maintaining the sagittal spinal-pelvic balance.


Assuntos
Cifose/complicações , Atrofia Muscular/fisiopatologia , Músculos Paraespinais/patologia , Postura/fisiologia , Músculos Psoas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cifose/fisiopatologia , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/etiologia , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/fisiopatologia , Ossos Pélvicos/anatomia & histologia , Ossos Pélvicos/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Músculos Psoas/fisiopatologia , Estudos Retrospectivos
3.
BMC Complement Altern Med ; 19(1): 267, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615487

RESUMO

BACKGROUND: Cancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches. It is extremely urgent to explore effective anti-cachexia drugs to ameliorate muscle and fat loss in cachexia patients. METHODS: Lewis lung carcinoma bearing C57BL/6 mice were applied as the animal model to examine the therapeutic effect of Coix seed oil (CSO) on cancer cachexia. The food intake and body weight change were monitored every 3 days throughout the experiment. The IL-6 and TNF-α levels in serum were detected by ELISA assay. Several key proteins involved in muscle wasting and fat lipolysis were tested by Western blot to identify the potential mechanism of CSO. RESULTS: Administration of CSO through gavage significantly prevented body weight loss and ameliorated systemic inflammation without affecting food intake and tumor size. The weight and histological morphology of gastrocnemius muscle and epididymal adipose tissue in CSO-treated mice were also improved. In mechanism, we found that CSO decreased the expression of MuRF1 and the ratio of phospho-p65 (Ser536) to p65 in muscle tissue. Meanwhile, cancer-induced activation of HSL and AMPK was also inhibited by CSO administration. CONCLUSION: Coix seed oil exerts an anti-cachexia pharmaceutical effect by counteracting muscle and adipose tissue loss most likely through regulating NF-κB-MuRF1 and AMPK-HSL pathway.


Assuntos
Tecido Adiposo/metabolismo , Caquexia/tratamento farmacológico , Coix/química , Lipólise/efeitos dos fármacos , Neoplasias Pulmonares/complicações , Atrofia Muscular/tratamento farmacológico , Óleos Vegetais/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Caquexia/etiologia , Caquexia/metabolismo , Caquexia/fisiopatologia , Feminino , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , NF-kappa B/genética , NF-kappa B/metabolismo , Sementes/química
4.
J Cardiovasc Surg (Torino) ; 60(6): 672-678, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31603293

RESUMO

BACKGROUND: Sarcopenia, commonly determined by measuring skeletal muscle mass index (SMI) at the third lumbar level, has been identified as a predictor of clinical outcome in a variety of diseases. For patients with peripheral arterial occlusive disease (PAOD), we hypothesized that lower extremity SMI (LESMI) might be a more precise predictor of outcome and the extent of chronic ischemia than the systemic muscle mass at the L3 level. We investigated the association between complete muscle volume and muscle area derived with single-slice 2-dimensional measurements in the legs to identify at which level cross-sectional single-slice measurements are most representative of the muscle volume and investigated whether LESMI is associated with systemic sarcopenia and PAOD severity. METHODS: Muscle volumes and areas were semiautomatically segmented from computed tomography (CT) scans of the affected and contralateral legs of 50 PAOD patients with Fontaine stage IIb and 50 PAOD patients with Fontaine stage IV. The muscle mass was determined for the complete volumes of the upper and lower legs and for cross-sectional slices at 40%, 50%, and 60% of the length of the femur and tibia. Patients were determined as sarcopenic based on sex-specific cut-off values at the L3 spinal segment. Two observers segmented 20 randomly selected patients to determine the interobserver reliability with the intraclass correlation coefficient. RESULTS: The correlation between the LESMI of the complete muscle volume and the three cross-sectional slices in all 200 upper and 200 lower legs was moderately strong to strong. Interobserver reliability of cross-sectional slice segmentation was excellent. The LESMI, both measured volumetrically and cross-sectionally, were significantly lower in patients with sarcopenia compared to patients without sarcopenia. The LESMI was lower in patients with Fontaine stage IV compared to patients with Fontaine stage IIb for both volumetric and cross-sectional measurements. CONCLUSIONS: Segmentation of skeletal muscle mass from cross-sectional single-slice CT in the upper and lower leg can accurately and precisely substitute complete volume segmentations. These findings warrant the use of measurements based on cross-sectional single-slice CT for assessing the LESMI. Patients with systemic sarcopenia are also at increased risk for muscle mass loss in the lower extremities. In the current study, LESMI was lower in patients with Fontaine class IV PAOD compared to patients with Fontaine class IIb PAOD. Future studies should assess the predictive value of the LESMI on clinical outcomes in PAOD patients.


Assuntos
Composição Corporal , Isquemia/diagnóstico por imagem , Extremidade Inferior/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Atrofia Muscular/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Sarcopenia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Variações Dependentes do Observador , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sarcopenia/fisiopatologia , Índice de Gravidade de Doença
5.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31559011

RESUMO

It is well established that mitochondria play a critical role in the metabolic and physiological adaptation of skeletal muscle to enhanced contractile activity. Several redox-sensitive signaling pathways such as PGC-1α, AMPK, IGF/Akt/mTOR, SIRT, NFκB, and FoxO are involved with extensive crosstalk to regulate vital cellular functions such as mitochondrial biogenesis, mitochondrial fusion and fission dynamics, autophagy/mitophagy, and apoptosis under altered demand and stress. However, when muscles cease contraction, such as during immobilization and denervation, mitochondria undergo a series of detrimental changes characterized by downregulation of PGC-1α and antioxidant defense, increased ROS generation, activated FoxO, NFκB, and inflammation, enhanced ubiquitination, and finally mitophagy and apoptotic cascades. The phenotypic outcome of the discord of mitochondrial homeostasis is elevated proteolysis and muscle atrophy. The demonstration that PGC-1α overexpression via transgene or in vivo DNA transfection can restore mitochondrial homeostasis and reverse myocyte atrophy supports the "mitostasis theory of muscle atrophy".


Assuntos
Atrofia Muscular , Transtornos Musculares Atróficos , Fatores de Transcrição , Humanos , Mitocôndrias , Atrofia Muscular/fisiopatologia
6.
Nutrients ; 11(9)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500089

RESUMO

Previously, we reported that polyphenol-rich fraction (named E80) promotes skeletal muscle hypertrophy induced by functional overload in mice. This study indicates that E80 has potential for affecting skeletal muscle mass. Then, we evaluate the effect of E80 on atrophic and recovery conditions of skeletal muscle in mice. Hindlimb suspension (unloading) and relanding (reloading) are used extensively to observe disuse muscle atrophy and subsequent muscle mass recovery from atrophy. Eight-week old C57BL/6 mice were fed either a normal diet or a diet containing 0.5% E80 for two weeks under conditions of hindlimb suspension and a subsequent 5 or 10 days of reloading. We found that E80 administration did not prevent atrophy during hindlimb suspension, but promoted recovery of slow-twitch (soleus) muscle mass from atrophy induced by hindlimb suspension. After five days of reloading, we discovered that phosphorylation of the Akt/mammalian target of rapamycin (mTOR) pathway proteins, such as Akt and P70 ribosomal protein S6 kinase (S6K), was activated in the muscle. Therefore, E80 administration accelerated mTOR signal and increased protein synthesis in the reloaded soleus muscle.


Assuntos
Camellia sinensis/química , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Animais , Linhagem Celular , Modelos Animais de Doenças , Elevação dos Membros Posteriores , Masculino , Camundongos Endogâmicos C57BL , Peso Molecular , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/patologia , Fosforilação , Extratos Vegetais/isolamento & purificação , Polifenóis/isolamento & purificação , Biossíntese de Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Recuperação de Função Fisiológica , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
7.
Trials ; 20(1): 526, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443727

RESUMO

BACKGROUND: Persons with spinal cord injury (SCI) are at heightened risks of developing unfavorable cardiometabolic consequences due to physical inactivity. Functional electrical stimulation (FES) and surface neuromuscular electrical stimulation (NMES)-resistance training (RT) have emerged as effective rehabilitation methods that can exercise muscles below the level of injury and attenuate cardio-metabolic risk factors. Our aims are to determine the impact of 12 weeks of NMES + 12 weeks of FES-lower extremity cycling (LEC) compared to 12 weeks of passive movement + 12 weeks of FES-LEC on: (1) oxygen uptake (VO2), insulin sensitivity, and glucose disposal in adults with SCI; (2) skeletal muscle size, intramuscular fat (IMF), and visceral adipose tissue (VAT); and (3) protein expression of energy metabolism, protein molecules involved in insulin signaling, muscle hypertrophy, and oxygen uptake and electron transport chain (ETC) activities. METHODS/DESIGN: Forty-eight persons aged 18-65 years with chronic (> 1 year) SCI/D (AIS A-C) at the C5-L2 levels, equally sub-grouped by cervical or sub-cervical injury levels and time since injury, will be randomized into either the NMES + FES group or Passive + FES (control group). The NMES + FES group will undergo 12 weeks of evoked RT using twice-weekly NMES and ankle weights followed by twice-weekly progressive FES-LEC for an additional 12 weeks. The control group will undergo 12 weeks of passive movement followed by 12 weeks of progressive FES-LEC. Measurements will be performed at baseline (B; week 0), post-intervention 1 (P1; week 13), and post-intervention 2 (P2; week 25), and will include: VO2 measurements, insulin sensitivity, and glucose effectiveness using intravenous glucose tolerance test; magnetic resonance imaging to measure muscle, IMF, and VAT areas; muscle biopsy to measure protein expression and intracellular signaling; and mitochondrial ETC function. DISCUSSION: Training through NMES + RT may evoke muscle hypertrophy and positively impact oxygen uptake, insulin sensitivity, and glucose effectiveness. This may result in beneficial outcomes on metabolic activity, body composition profile, mitochondrial ETC, and intracellular signaling related to insulin action and muscle hypertrophy. In the future, NMES-RT may be added to FES-LEC to improve the workloads achieved in the rehabilitation of persons with SCI and further decrease muscle wasting and cardio-metabolic risks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02660073 . Registered on 21 Jan 2016.


Assuntos
Ciclismo , Terapia por Estimulação Elétrica/métodos , Metabolismo Energético , Músculo Esquelético/inervação , Atrofia Muscular/terapia , Treinamento de Resistência/métodos , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Insulina/sangue , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/sangue , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Treinamento de Resistência/efeitos adversos , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Virginia , Adulto Jovem
8.
Acta Med Port ; 32(7-8): 520-528, 2019 Aug 01.
Artigo em Português | MEDLINE | ID: mdl-31445532

RESUMO

INTRODUCTION: Invasive mechanical ventilation contributes to ventilator-induced diaphragmatic dysfunction, delaying extubation and increasing mortality in adults. Despite the possibility of having a higher impact in paediatrics, this dysfunction is not routinely monitored. Diaphragm ultrasound has been proposed as a safe and non-invasive technique for this purpose. The aim of this study was to describe the evolution of diaphragmatic morphology and functional measurements by ultrasound in ventilated children. MATERIAL AND METHODS: Prospective exploratory study. Children admitted to Paediatric Intensive Care Unit requiring mechanical ventilation > 48 hours were included. The diaphragmatic thickness, excursion and the thickening fraction were assessed by ultrasound. RESULTS: Seventeen cases were included, with a median age of 42 months. Ten were male, seven had comorbidities and three in seventeen had malnutrition at admission. The median time under mechanical ventilation was seven days. The median of the initial and minimum diaphragmatic thickness was 2.3 mm and 1.9 mm, respectively, with a median decrease in thickness of 13% under pressure-regulated volume control. Diaphragmatic atrophy was observed in 14/17 cases. Differences in the median thickness variation were found between patients with sepsis and without (0.70 vs 0.25 mm; p = 0.019). During pressure support ventilation there was a tendency to increase diaphragmatic thickness and excursion. Extubation failure occurred for diaphragmatic thickening fraction ≤ 35%. DISCUSSION: Under pressure-regulated volume control there was a tendency for a decrease in diaphragmatic thickness. In the pre-extubation stage under pressure support, there was a tendency for it to increase. These results suggest that, by titrating ventilation using physiological levels of inspiratory effort, we can reduce the diaphragmatic morphological changes associated with ventilation. CONCLUSION: The early recognition of diaphragmatic changes may encourage a targeted approach, namely titration of ventilation, in order to reduce ventilator-induced diaphragmatic dysfunction and its clinical repercussions.


Assuntos
Diafragma/diagnóstico por imagem , Atrofia Muscular/diagnóstico por imagem , Respiração Artificial/efeitos adversos , Adolescente , Criança , Pré-Escolar , Diafragma/patologia , Diafragma/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Atrofia Muscular/prevenção & controle , Estudos Prospectivos , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Ultrassonografia/métodos , Desmame do Respirador
9.
Anesthesiology ; 131(3): 605-618, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31408447

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Diaphragm dysfunction and atrophy develop during controlled mechanical ventilation. Although oxidative stress injures muscle during controlled mechanical ventilation, it is unclear whether it causes autophagy or fiber atrophy. WHAT THIS ARTICLE TELLS US THAT IS NEW: Pretreatment of rats undergoing 24 h of mechanical ventilation with N-acetylcysteine prevents decreases in diaphragm contractility, inhibits the autophagy and proteasome pathways, but has no influence on the development of diaphragm fiber atrophy. BACKGROUND: Diaphragm dysfunction and atrophy develop during prolonged controlled mechanical ventilation. Fiber atrophy has been attributed to activation of the proteasome and autophagy proteolytic pathways. Oxidative stress activates the proteasome during controlled mechanical ventilation, but it is unclear whether it also activates autophagy. This study investigated whether pretreatment with the antioxidant N-acetylcysteine affects controlled mechanical ventilation-induced diaphragm contractile dysfunction, fiber atrophy, and proteasomal and autophagic pathway activation. The study also explored whether proteolytic pathway activity during controlled mechanical ventilation is mediated by microRNAs that negatively regulate ubiquitin E3 ligases and autophagy-related genes. METHODS: Three groups of adult male rats were studied (n = 10 per group). The animals in the first group were anesthetized and allowed to spontaneously breathe. Animals in the second group were pretreated with saline before undergoing controlled mechanical ventilation for 24 h. The animals in the third group were pretreated with N-acetylcysteine (150 mg/kg) before undergoing controlled mechanical ventilation for 24 h. Diaphragm contractility and activation of the proteasome and autophagy pathways were measured. Expressions of microRNAs that negatively regulate ubiquitin E3 ligases and autophagy-related genes were measured with quantitative polymerase chain reaction. RESULTS: Controlled mechanical ventilation decreased diaphragm twitch force from 428 ± 104 g/cm (mean ± SD) to 313 ± 50 g/cm and tetanic force from 2,491 ± 411 g/cm to 1,618 ± 177 g/cm. Controlled mechanical ventilation also decreased diaphragm fiber size, increased expression of several autophagy genes, and augmented Atrogin-1, MuRF1, and Nedd4 expressions by 36-, 41-, and 8-fold, respectively. Controlled mechanical ventilation decreased the expressions of six microRNAs (miR-20a, miR-106b, miR-376, miR-101a, miR-204, and miR-93) that regulate autophagy genes. Pretreatment with N-acetylcysteine prevented diaphragm contractile dysfunction, attenuated protein ubiquitination, and downregulated E3 ligase and autophagy gene expression. It also reversed controlled mechanical ventilation-induced microRNA expression decreases. N-Acetylcysteine pretreatment had no affect on fiber atrophy. CONCLUSIONS: Prolonged controlled mechanical ventilation activates the proteasome and autophagy pathways in the diaphragm through oxidative stress. Pathway activation is accomplished, in part, through inhibition of microRNAs that negatively regulate autophagy-related genes.


Assuntos
Acetilcisteína/farmacologia , Diafragma/efeitos dos fármacos , Diafragma/fisiopatologia , Oxidantes/farmacologia , Proteólise/efeitos dos fármacos , Respiração Artificial/efeitos adversos , Animais , Autofagia/efeitos dos fármacos , Modelos Animais de Doenças , Depuradores de Radicais Livres/farmacologia , Masculino , Atrofia Muscular/fisiopatologia , Ratos , Ratos Wistar
10.
Trials ; 20(1): 456, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340849

RESUMO

BACKGROUND: Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. METHODS: This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. DISCUSSION: If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN44340629. Registered on 26 October 2017.


Assuntos
Debilidade Muscular/prevenção & controle , Músculo Esquelético/irrigação sanguínea , Atrofia Muscular/prevenção & controle , Oclusão Terapêutica/métodos , Estado Terminal , Inglaterra , Estudos de Viabilidade , Humanos , Estudos Multicêntricos como Assunto , Debilidade Muscular/diagnóstico , Debilidade Muscular/fisiopatologia , Atrofia Muscular/diagnóstico , Atrofia Muscular/fisiopatologia , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluxo Sanguíneo Regional , Oclusão Terapêutica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
11.
Nutrients ; 11(8)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344809

RESUMO

Military personnel may be exposed to circumstances (e.g., large energy deficits, sleep deprivation, cognitive demands, and environmental extremes) of external stressors during training and combat operations (i.e., operational stressors) that combine to degrade muscle protein. The loss of muscle protein is further exacerbated by frequent periods of severe energy deficit. Exposure to these factors results in a hypogonadal state that may contribute to observed decrements in muscle mass. In this review, lessons learned from studying severe clinical stressed states and the interventions designed to mitigate the loss of muscle protein are discussed in the context of military operational stress. For example, restoration of the anabolic hormonal status (e.g., testosterone, insulin, and growth hormone) in stressed physiological states may be necessary to restore the anabolic influence derived from dietary protein on muscle. Based on our clinical experiences, restoration of the normal testosterone status during sustained periods of operational stress may be advantageous. We demonstrated that in severe burn patients, pharmacologic normalization of the anabolic hormonal status restores the anabolic stimulatory effect of nutrition on muscle by improving the protein synthetic efficiency and limiting amino acid loss from skeletal muscle. Furthermore, an optimal protein intake, and in particular essential amino acid delivery, may be an integral ingredient in a restored anabolic response during the stress state. Interventions which improve the muscle net protein balance may positively impact soldier performance in trying conditions.


Assuntos
Proteínas na Dieta/administração & dosagem , Medicina Militar , Militares , Contração Muscular , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/prevenção & controle , Doenças Profissionais/prevenção & controle , Estresse Fisiológico , Animais , Proteínas na Dieta/metabolismo , Metabolismo Energético , Hormônios/metabolismo , Humanos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Estado Nutricional , Doenças Profissionais/metabolismo , Doenças Profissionais/patologia , Doenças Profissionais/fisiopatologia , Saúde do Trabalhador , Fatores de Proteção , Fatores de Risco
12.
Life Sci ; 233: 116699, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31356902

RESUMO

AIMS: Skeletal muscle wasting is associated with many chronic diseases. Effective prevention and treatment of muscle wasting remain as a challenging task due to incomplete understanding of mechanisms by which muscle mass is maintained and regulated. This study investigated the functional role of Ubiquitin C-terminal hydrolase L1 (UCHL1) in skeletal muscle. MAIN METHODS: Mice with skeletal muscle specific gene knockout of UCHL1 and C2C12 myoblast cells with UCHL1 knockdown were used. Muscle fiber types and size were measured using tissue or cell staining. The mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 activities were assessed with the phosphorylation of their downstream targets. KEY FINDINGS: In mouse skeletal muscle, UCHL1 was primarily expressed in slow twitch muscle fibers. Mice with skeletal muscle specific knockout (skmKO) of UCHL1 exhibited enlarged muscle fiber sizes in slow twitch soleus but not fast twitch extensor digitorum longus (EDL) muscle. Meanwhile, UCHL1 skmKO enhanced mTORC1 activity and reduced mTORC2 activity in soleus but not in EDL. Consistently, in C2C12 cells, UCHL1 knockdown increased the myotube size, enhanced mTORC1 activity, and reduced mTORC2 activities as compared with control cells. UCHL1 knockdown did not change the major proteins of mTOR complex but decreased the protein turnover of PRAS40, an inhibitory factor of mTORC1. SIGNIFICANCE: These data revealed a novel function of UCHL1 in regulation of mTORC1 activity and skeletal muscle growth in slow twitch skeletal muscle. Given the upregulation of UCHL1 in denervation and spinal muscle atrophy, our finding advances understanding of regulators that are involved in muscle wasting.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fibras Musculares de Contração Lenta/fisiologia , Músculo Esquelético/fisiologia , Atrofia Muscular/fisiopatologia , Mioblastos/fisiologia , Ubiquitina Tiolesterase/fisiologia , Animais , Células Cultivadas , Feminino , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Camundongos Knockout , Fibras Musculares de Contração Lenta/citologia , Músculo Esquelético/citologia , Atrofia Muscular/metabolismo , Mioblastos/citologia , Fosforilação , Ubiquitina Tiolesterase/antagonistas & inibidores
13.
Biomed Res Int ; 2019: 7132494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179332

RESUMO

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth (CMT) disease and over 80 different mutations have been identified so far. This study analyzed the clinical and genetic characteristics of a Vietnamese CMT family that was affected by a novel GDAP1 mutation. Methods: We present three children of a family with progressive weakness, mild sensory loss, and absent tendon reflexes. Electrodiagnostic analyses displayed an axonal type of neuropathy in affected patients. Sequencing of GDAP1 gene was requested for all members of the family. Results: All affected individuals manifested identical clinical symptoms of motor and sensory impairments within the first three years of life, and nerve conduction study indicated the axonal degeneration. A homozygous GDAP1 variant (c.667_671dup) was found in the three affected children as recessive inheritance pattern. The mutation leads to a premature termination codon that shortens GDAP1 protein (p.Gln224Hisfs∗37). Further testing showed heterozygous c.667_671dup variant in the parents. Discussion: Our study expands the mutational spectrum of GDAP1-related CMT disease with the new and unreported GDAP1 variant. Alterations in GDAP1 gene should be evaluated as CMT causing variants in the Vietnamese population, predominantly axonal form of neuropathy in CMT disease.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Mutação , Proteínas do Tecido Nervoso/genética , Adolescente , Grupo com Ancestrais do Continente Asiático , Doença de Charcot-Marie-Tooth/fisiopatologia , Criança , Pré-Escolar , Éxons , Família , Feminino , Genes Recessivos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/genética , Atrofia Muscular/fisiopatologia , Linhagem , Fenótipo , Análise de Sequência de DNA
14.
BMC Musculoskelet Disord ; 20(1): 290, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31208400

RESUMO

BACKGROUND: Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP). METHODS: Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test. RESULTS: No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength. CONCLUSION: While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.


Assuntos
Terapia por Exercício/métodos , Dor Lombar/terapia , Atrofia Muscular/terapia , Músculos Paraespinais/fisiopatologia , Treinamento de Resistência , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Dor Lombar/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia Muscular/complicações , Atrofia Muscular/fisiopatologia , Músculos Paraespinais/diagnóstico por imagem , Padrão de Cuidado , Resultado do Tratamento
15.
Phys Ther ; 99(9): 1167-1176, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31197369

RESUMO

BACKGROUND: Neuromuscular electrical stimulation (NMES) is a viable intervention for improving impaired muscle function in individuals with rheumatoid arthritis (RA). However, there is limited evidence about the dose-response relationship between NMES and muscle function in these individuals. OBJECTIVE: The objectives of this study were to investigate the dose-response relationship between NMES and muscle function in individuals with RA and to establish the minimal NMES training intensity for promoting improvements. DESIGN: This study was a secondary analysis of data obtained before and after an NMES intervention in a randomized study. METHODS: The study took place at a research clinic. Only adults diagnosed with RA were included. The intervention consisted of 36 NMES treatment sessions for the quadriceps muscles over 16 weeks. Muscle function was measured before and after the intervention; quadriceps cross-sectional area and muscle quality were assessed using computed tomography, and strength was measured with an isokinetic dynamometer. NMES training intensity was calculated as a percentage by dividing NMES-elicited quadriceps muscle torque by the maximum voluntary isometric contraction. Improvements in muscle function were calculated using paired-sample t tests. The dose-response relationship was determined using curve estimation regression statistics. The minimum NMES training intensity was defined as that sufficient to significantly improve all muscle function measures. RESULTS: Twenty-four people (48 legs) participated (75% women; mean [SD] age = 58 [8] years; mean body mass index = 32 [7] kg/m2). Quadriceps cross-sectional area, muscle quality, and strength improved after the intervention. Associations between NMES training intensity and muscle quality (r2 = 0.20) and strength (r2 = 0.23) were statistically significant, but that between NMES training intensity and muscle cross-sectional area was not (r2 = 0.02). The minimum NMES training intensity necessary to improve all measures of muscle function ranged from 11% to 20% of the maximum voluntary isometric contraction. LIMITATIONS: The relatively small sample size was a limitation. CONCLUSIONS: The minimum NMES training intensity for significant gains in muscle function was ∼15%. Higher NMES intensities may promote better muscle quality and strength in individuals with RA.


Assuntos
Artrite Reumatoide/terapia , Terapia por Estimulação Elétrica/métodos , Contração Isométrica/fisiologia , Músculo Quadríceps/fisiopatologia , Artrite Reumatoide/fisiopatologia , Índice de Massa Corporal , Terapia por Estimulação Elétrica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Debilidade Muscular/terapia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Atrofia Muscular/terapia , Músculo Quadríceps/diagnóstico por imagem , Análise de Regressão , Tamanho da Amostra , Torque
16.
Metabolism ; 97: 57-67, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31153978

RESUMO

BACKGROUND: Muscle atrophy is defined as decreased muscle mass, associated with aging as well as with various chronic diseases and is a fundamental cause of frailty, functional decline and disability. Frailty represents a huge potential public health issue worldwide with high impact on healthcare costs. A major clinical issue is therefore to devise new strategies preventing muscle atrophy. In this study, we tested the efficacy of Vital01, a novel oral nutritional supplement (ONS), on body weight and muscle mass using a caloric restriction-induced mouse model for muscle atrophy. METHODS: Mice were calorically restricted for 2 weeks to induce muscle atrophy: one control group received 60% kcal of the normal chow diet and one intervention group received 30% kcal chow and 30 kcal% Vital01. The effects on body weight, lean body mass, muscle histology and transcriptome were assessed. In addition, the effects of Vital01, in mice with established muscle atrophy, were assessed and compared to a standard ONS. To this end, mice were first calorically restricted on a 60% kcal chow diet and then refed with either 100 kcal% chow, a mix of Vital01 (receiving 60% kcal chow and 40 kcal% Vital01) or with a mix of standard, widely prescribed ONS (receiving 60 kcal% chow and 40 kcal% Fortisip Compact). RESULTS: Vital01 attenuated weight loss (-15% weight loss for Vital01 vs. -25% for control group, p < 0.01) and loss of muscle mass (Vital01 with -13%, -12% and -18%, respectively, for gastrocnemius, quadriceps and tibialis vs. 25%, -23% and -28%, respectively, for control group, all p < 0.05) and also restored body weight, fat and muscle mass more efficiently when compared to Fortisip Compact. As assessed by transcriptome analysis and Western blotting of key proteins (e.g. phospoAKT, mTOR and S6K), Vital01 attenuated the catabolic and anabolic signaling pathways induced by caloric restriction and modulated inflammatory and mitochondrial pathways. In addition, Vital01 affected pathways related to matrix proteins/collagens homeostasis and tended to reduce caloric restriction-induced collagen fiber density in the quadriceps (with -27%, p = 0.051). CONCLUSIONS: We demonstrate that Vital01 preserves muscle mass in a calorically restricted mouse model for muscle atrophy. Vital01 had preventive effects when administered during development of muscle atrophy. Furthermore, when administered in a therapeutic setting to mice with established muscle atrophy, Vital01 rapidly restored body weight and accelerated the recurrence of fat and lean body mass more efficiently than Fortisip Compact. Bioinformatics analysis of gene expression data identified regulatory pathways that were specifically influenced by Vital01 in muscle.


Assuntos
Peso Corporal/fisiologia , Músculo Esquelético/fisiologia , Atrofia Muscular/fisiopatologia , Animais , Composição Corporal/fisiologia , Índice de Massa Corporal , Restrição Calórica/métodos , Suplementos Nutricionais , Modelos Animais de Doenças , Ingestão de Energia/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Perda de Peso/fisiologia
17.
Physiology (Bethesda) ; 34(4): 232-239, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165685

RESUMO

Skeletal muscle atrophy proceeds through a complex molecular signaling network that is just beginning to be understood. Here, we discuss examples of recently identified molecular mechanisms of muscle atrophy and how they highlight an immense need and opportunity for focused biochemical investigations and further unbiased discovery work.


Assuntos
Músculo Esquelético/fisiologia , Atrofia Muscular/fisiopatologia , Animais , Humanos , Transdução de Sinais/fisiologia
18.
Nat Rev Nephrol ; 15(7): 393-411, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31036905

RESUMO

Intracellular proteins continuously turn over by degradation and synthesis in all organ tissues. Owing to its irreversible nature, protein degradation is a highly selective process to avoid irreparable breakdown of cellular constituents, thereby disrupting cellular stability, integrity and signalling. The majority of intracellular proteins are degraded by the ubiquitin-proteasome system (UPS), a multi-enzyme process that involves the covalent conjugation of ubiquitin to a substrate protein and its recognition and degradation by the core multicomponent proteolytic complex of the UPS, the proteasome. In addition to labelling misfolded, damaged, aggregation-prone and intact but unneeded proteins for proteasomal degradation, ubiquitylation regulates a multitude of cellular processes, such as transcription, translation, endocytosis, and receptor activity and subcellular localization. In addition, the proteasome generates peptides for antigen presentation in the immune system and for further degradation by peptidases to provide amino acids for protein biosynthesis and gluconeogenesis. Alterations of the UPS or of protein substrates that render them more or less susceptible to degradation are responsible for disorders associated with renal cell dysfunction. In this Review, we provide insight into the elegant and complex nature of UPS-mediated proteostasis and focus on its established and potential roles in renal cell physiology and pathophysiology.


Assuntos
Nefropatias/fisiopatologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Ubiquitinadas/metabolismo , Ubiquitinação/fisiologia , Autofagia/fisiologia , Transporte Biológico/fisiologia , Eritropoetina/metabolismo , Glucose/metabolismo , Homeostase/fisiologia , Humanos , Rim/fisiologia , Nefropatias/metabolismo , Lisossomos/metabolismo , Atrofia Muscular/fisiopatologia , Podócitos/metabolismo , Inibidores de Proteassoma/farmacologia , Sódio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Doença de von Hippel-Lindau/metabolismo , Doença de von Hippel-Lindau/fisiopatologia
19.
Aerosp Med Hum Perform ; 90(5): 440-446, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31023403

RESUMO

INTRODUCTION: Microgravity leads to a progressive loss in muscular strength, endurance, and aerobic capacity (Vo2peak). Blood flow restricted (BFR) exercise has been shown to elicit rapid gains in muscular strength and Vo2peak. Rowing exercise combined with BFR could be a supplemental countermeasure to maintain preflight muscle function and Vo2peak, especially within future space vehicles with restricted physical volume.METHODS: There were 20 men who completed 19 min of rowing exercise during CON or BFR in a randomized order. Exercise intensity for all sets was 30% of peak work load achieved during a separate incremental maximal exercise test. Kaatsu training cuffs were inflated around each leg during BFR. Muscle oxygen saturation (Smo2) and heart rate (HR) were measured throughout exercise and rest. Rate of perceived exertion (RPE) and muscle activation, using surface electromyography (sEMG), were measured during the last 30 s of each exercise set. Blood pressure (BP) and whole blood lactate ([La-]b) were measured at rest and postexercise.RESULTS: Smo2 declined significantly in BFR during exercise and rest by 13% and 14%, respectively. HR and RPE showed significant increases during BFR (120.5 ± 5.53 vs. 128.9 ± 9.86 bts · min-1) (9.8 ± 1.85 vs. 11.8 ± 1.88 arbitrary units). No differences were observed for BP, [La-]b, and sEMG.DISCUSSION: Findings indicate exercise intensity and cuff pressure elicited acute muscular, cardiovascular, and perceptual responses. BFR rowing exercise could be advantageous as an adjunct for future exercise countermeasures where aerobic and anaerobic exercise may be performed on one device or in limited physical space.Mahoney SJ, Dicks ND, Lyman KJ, Christensen BK, Hackney KJ. Acute cardiovascular, metabolic, and muscular responses to blood flow restricted rowing exercise. Aerosp Med Hum Perform. 2019; 90(5):440-446.


Assuntos
Músculo Esquelético/fisiologia , Atrofia Muscular/prevenção & controle , Treinamento de Resistência/métodos , Voo Espacial , Ausência de Peso/efeitos adversos , Adulto , Eletromiografia , Voluntários Saudáveis , Humanos , Masculino , Força Muscular/fisiologia , Músculo Esquelético/irrigação sanguínea , Atrofia Muscular/diagnóstico , Atrofia Muscular/etiologia , Atrofia Muscular/fisiopatologia , Resistência Física/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Fatores de Tempo , Esportes Aquáticos/fisiologia , Adulto Jovem
20.
PLoS One ; 14(4): e0215489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30998788

RESUMO

Hibernating mammals experience prolonged periods of torpor and starvation during winter for up to 5-7 months. Though physical inactivity and malnutrition generally lead to profound loss of muscle mass and metabolic dysfunction in humans, hibernating bears show limited muscle atrophy and can successfully maintain locomotive function. These physiological features in bears allow us to hypothesize that hibernating bears uniquely alter the regulation of protein and energy metabolism in skeletal muscle which then contributes to "muscle atrophy resistance" against continued physical inactivity. In this study, alteration of signaling pathways governing protein and energy metabolisms was examined in skeletal muscle of the Japanese black bear (Ursus thibetanus japonicus). Sartorius muscle samples were collected from bear legs during late November (pre-hibernation) and early April (post-hibernation). Protein degradation pathways, through a ubiquitin-proteasome system (as assessed by increased expression of murf1 mRNA) and an autophagy-dependent system (as assessed by increased expression of atg7, beclin1, and map1lc3 mRNAs), were significantly activated in skeletal muscle following hibernation. In contrast, as indicated by a significant increase in S6K1 phosphorylation, an activation state of mTOR (mammalian/mechanistic target of rapamycin), which functions as a central regulator of protein synthesis, increased in post-hibernation samples. Gene expression of myostatin, a negative regulator of skeletal muscle mass, was significantly decreased post-hibernation. We also confirmed that the phenotype shifted toward slow-oxidative muscle and mitochondrial biogenesis. These observations suggest that protein and energy metabolism may be altered in skeletal muscle of hibernating bears, which then may contribute to limited loss of muscle mass and efficient energy utilization.


Assuntos
Hibernação , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Inanição/fisiopatologia , Ursidae , Animais , Estações do Ano
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