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1.
Nat Commun ; 12(1): 3450, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103504

RESUMO

The epigenetic mechanisms coordinating the maintenance of adult cellular lineages and the inhibition of alternative cell fates remain poorly understood. Here we show that targeted ablation of the histone chaperone HIRA in myogenic cells leads to extensive transcriptional modifications, consistent with a role in maintaining skeletal muscle cellular identity. We demonstrate that conditional ablation of HIRA in muscle stem cells of adult mice compromises their capacity to regenerate and self-renew, leading to tissue repair failure. Chromatin analysis of Hira-deficient cells show a significant reduction of histone variant H3.3 deposition and H3K27ac modification at regulatory regions of muscle genes. Additionally, we find that genes from alternative lineages are ectopically expressed in Hira-mutant cells via MLL1/MLL2-mediated increase of H3K4me3 mark at silent promoter regions. Therefore, we conclude that HIRA sustains the chromatin landscape governing muscle cell lineage identity via incorporation of H3.3 at muscle gene regulatory regions, while preventing the expression of alternative lineage genes.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Linhagem da Célula , Chaperonas de Histonas/metabolismo , Músculo Esquelético/patologia , Fatores de Transcrição/metabolismo , Acetilação , Animais , Proteínas de Ciclo Celular/deficiência , Linhagem Celular , Linhagem da Célula/genética , Loci Gênicos , Chaperonas de Histonas/deficiência , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Desenvolvimento Muscular/genética , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Regeneração , Sequências Reguladoras de Ácido Nucleico/genética , Células Satélites de Músculo Esquelético/metabolismo , Fatores de Transcrição/deficiência
2.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063460

RESUMO

The ubiquitously expressed adaptor protein Shc exists in three isoforms p46Shc, p52Shc, and p66Shc, which execute distinctly different actions in cells. The role of p46Shc is insufficiently studied, and the purpose of this study was to further investigate its functional significance. We developed unique rat mutants lacking p52Shc and p46Shc isoforms (p52Shc/46Shc-KO) and carried out histological analysis of skeletal and cardiac muscle of parental and genetically modified rats with impaired gait. p52Shc/46Shc-KO rats demonstrate severe functional abnormalities associated with impaired gait. Our analysis of p52Shc/46Shc-KO rat axons and myelin sheets in cross-sections of the sciatic nerve revealed the presence of significant anomalies. Based on the lack of skeletal muscle fiber atrophy and the presence of sciatic nerve abnormalities, we suggest that the impaired gait in p52Shc/46Shc-KO rats might be due to the sensory feedback from active muscle to the brain locomotor centers. The lack of dystrophin in some heart muscle fibers reflects damage due to dilated cardiomyopathy. Since rats with only p52Shc knockout do not display the phenotype of p52Shc/p46Shc-KO, abnormal locomotion is likely to be caused by p46Shc deletion. Our data suggest a previously unknown role of 46Shc actions and signaling in regulation of gait.


Assuntos
Cardiomiopatia Dilatada/genética , Marcha/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Animais , Cardiomiopatia Dilatada/patologia , Técnicas de Inativação de Genes , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Isoformas de Proteínas/genética , Ratos Transgênicos , Nervo Isquiático/patologia
3.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066978

RESUMO

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle-bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle-bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.


Assuntos
Osso e Ossos/patologia , Debilidade Muscular/patologia , Músculo Esquelético/patologia , Osteogênese Imperfeita/patologia , Animais , Fenômenos Biomecânicos , Osso e Ossos/fisiopatologia , Metabolismo Energético , Humanos , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Osteogênese Imperfeita/metabolismo , Osteogênese Imperfeita/fisiopatologia
4.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067082

RESUMO

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 µg/kg of animal weight) for 30 days. Water-soluble C60 fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C60 fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40-45%. Increasing the dose of C60 fullerene to 1 mg/kg increases the therapeutic effect by 55-65%, normalizing the studied biomechanical and biochemical parameters. Thus, C60 fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.


Assuntos
Fulerenos/uso terapêutico , Glicina/análogos & derivados , Contração Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Animais , Antioxidantes/metabolismo , Biomarcadores/sangue , Fenômenos Biomecânicos/efeitos dos fármacos , Catalase/sangue , Glutationa/sangue , Glicina/toxicidade , Peróxido de Hidrogênio/sangue , Contração Muscular/efeitos dos fármacos , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
5.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071589

RESUMO

The complement system is a potent inflammatory trigger, activator, and chemoattractant for leukocytes, which play a crucial role in promoting angiogenesis. However, little information is available about the influence of the complement system on angiogenesis in ischemic muscle tissue. To address this topic and analyze the impact of the complement system on angiogenesis, we induced muscle ischemia in complement factor C3 deficient (C3-/-) and wildtype control mice by femoral artery ligation (FAL). At 24 h and 7 days after FAL, we isolated the ischemic gastrocnemius muscles and investigated them by means of (immuno-)histological analyses. C3-/- mice showed elevated ischemic damage 7 days after FAL, as evidenced by H&E staining. In addition, angiogenesis was increased in C3-/- mice, as demonstrated by increased capillary/muscle fiber ratio and increased proliferating endothelial cells (CD31+/BrdU+). Moreover, our results showed that the total number of leukocytes (CD45+) was increased in C3-/- mice, which was based on an increased number of neutrophils (MPO+), neutrophil extracellular trap formation (MPO+/CitH3+), and macrophages (CD68+) displaying a shift toward an anti-inflammatory and pro-angiogenic M2-like polarized phenotype (CD68+/MRC1+). In summary, we show that the deficiency of complement factor C3 increased neutrophil and M2-like polarized macrophage accumulation in ischemic muscle tissue, contributing to angiogenesis.


Assuntos
Capilares/fisiopatologia , Complemento C3/deficiência , Isquemia/fisiopatologia , Leucócitos/metabolismo , Músculo Esquelético/fisiopatologia , Animais , Capilares/metabolismo , Complemento C3/genética , Modelos Animais de Doenças , Imunofluorescência/métodos , Humanos , Isquemia/genética , Ativação de Macrófagos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Infiltração de Neutrófilos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
6.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064895

RESUMO

Skeletal muscles, being one of the most abundant tissues in the body, are involved in many vital processes, such as locomotion, posture maintenance, respiration, glucose homeostasis, etc. Hence, the maintenance of skeletal muscle mass is crucial for overall health, prevention of various diseases, and contributes to an individual's quality of life. Prolonged muscle inactivity/disuse (due to limb immobilization, mechanical ventilation, bedrest, spaceflight) represents one of the typical causes, leading to the loss of muscle mass and function. This disuse-induced muscle loss primarily results from repressed protein synthesis and increased proteolysis. Further, prolonged disuse results in slow-to-fast fiber-type transition, mitochondrial dysfunction and reduced oxidative capacity. Glycogen synthase kinase 3ß (GSK-3ß) is a key enzyme standing at the crossroads of various signaling pathways regulating a wide range of cellular processes. This review discusses various important roles of GSK-3ß in the regulation of protein turnover, myosin phenotype, and oxidative capacity in skeletal muscles under disuse/unloading conditions and subsequent recovery. According to its vital functions, GSK-3ß may represent a perspective therapeutic target in the treatment of muscle wasting induced by chronic disuse, aging, and a number of diseases.


Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Elevação dos Membros Posteriores , Músculo Esquelético/fisiopatologia , Atrofia Muscular/patologia , Miosinas/metabolismo , Estresse Oxidativo , Proteólise , Animais , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Fenótipo
7.
Phys Ther Sport ; 50: 166-172, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34038835

RESUMO

OBJECTIVES: To investigate the relationship between: (1) knee flexor strength, rate of torque development (RTD), and flexibility with pain level; (2) knee flexor strength and RTD with the performance in the single leg bridge test (SLBT) in women and men with patellofemoral pain (PFP). DESIGN: Cross-sectional. SETTING: Laboratory-based study. PARTICIPANTS: 39 women and 36 men with PFP. MAIN OUTCOME MEASURES: Knee flexor strength, RTD, and flexibility; performance in the SLBT, current, and worst pain level. RESULTS: Moderate to strong significant negative relationships were identified between the current pain level with knee flexor strength (r = -0.57 to -0.34) and flexibility (r = -0.44 to -0.35); and between knee flexor strength and RTD with the performance in the SLBT (r = 0.34 to 0.57) in women and men with PFP. Knee flexor RTD was not related to any pain level and no significant relationships were identified between the worst pain level with knee flexor strength and flexibility in women and men with PFP. CONCLUSIONS: Our results support the potential value of assessing knee flexor strength and flexibility in women and men with PFP. The SLBT may be a useful tool to assess knee flexor muscle capacity in individuals with PFP in a clinical setting.


Assuntos
Joelho/fisiopatologia , Força Muscular , Síndrome da Dor Patelofemoral/diagnóstico , Síndrome da Dor Patelofemoral/fisiopatologia , Adolescente , Adulto , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Masculino , Músculo Esquelético/fisiopatologia , Autorrelato , Torque , Adulto Jovem
8.
Clin Podiatr Med Surg ; 38(3): 291-302, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34053645

RESUMO

Pes cavus is a complicated, multiplanar deformity that requires a thorough understanding in order to provide the appropriate level of care. The foot and ankle surgeon should perform a comprehensive examination, including a neurologic evaluation, in the workup of this patient population. Understanding the cause of the patient's deformity is a critical step in predicting the disease course as well as the most acceptable form of treatment. The surgical correlation with the patient's pathologic anatomy requires an in-depth clinical evaluation, in addition to the radiographic findings, as the radiographic findings do not necessarily correlate with the patient's discomfort.


Assuntos
Pé Cavo/fisiopatologia , Pé Cavo/cirurgia , Articulação do Tornozelo/fisiopatologia , Contratura/fisiopatologia , Fáscia/fisiopatologia , Fasciíte Plantar/fisiopatologia , Ossos do Pé/fisiopatologia , Marcha/fisiologia , Humanos , Músculo Esquelético/fisiopatologia , Procedimentos Ortopédicos , Pé Cavo/etiologia , Dedos do Pé/fisiopatologia
9.
NeuroRehabilitation ; 48(4): 513-522, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967063

RESUMO

BACKGROUND: In hemiparetic patients, the skeletal muscle is mainly affected with a combination of abnormalities (denervation, remodeling, spasticity, and eventually muscular atrophy). OBJECTIVE: This study examined the role of eccentric exercise in strengthening muscles of the lower extremity and ultimately improving autonomy in patients with post-stroke hemiparesis during gait. METHODS: Thirty-seven patients hemiparetic adults were recruited, randomized into a control group (n = 19) and an intervention group receiving eccentric muscle strengthening (n = 18). The protocol consisted of three sets of five repetitions of eccentric contraction of the paretic limb after determining the maximum repetition (1 MRI). Evaluation of the 1RM, 10 meters and 6WMT was performed before and after the exercise for each group. Manova test was used to compare the differences between the control and intervention groups. RESULTS: The paretic limb showed significant increase in one-repetition maximum (1RM) between before and after rehabilitation (p≤0.00003). The two groups of Patients increased their walking speed (p≤0.0005), but we observed a significant difference between groups only for the 6MWT and not on the 10 meters Test. CONCLUSIONS: Eccentric training can be useful in strengthening the muscles of the lower limbs, and promoting gait performance. Eccentric training could complement other methods of managing patients with post-stroke hemiparesis.


Assuntos
Terapia por Exercício/métodos , Paresia/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Velocidade de Caminhada , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Paresia/etiologia , Acidente Vascular Cerebral/patologia
10.
NeuroRehabilitation ; 48(4): 523-532, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967064

RESUMO

BACKGROUND: Nearly half of individuals post-stroke are dependent in their daily activities. The ability to ascend and descend stairs is an important component of independence in the community. OBJECTIVE: To predict the future ability of post-stroke individuals at the beginning of the sub-acute rehabilitation phase to achieve ascending and descending staircase independence. METHODS: 36 participants were recruited for the study. OUTCOME MEASURES: independence in ascending and descending stairs up to the end of the sub-acute rehabilitation phase. Predictive measures included the knee extensors Muscles Strength (MS), the seated Modified Functional Reach (MFR) test, and Heart Rate Variability (HRV) measures. Logistic and Cox regression were used. RESULTS: Twenty-four participants (66.7%) completed the sub-acute rehabilitation phase being independent in ascending and descending stairs. MFR was the best predictor (R2 = 0.18), and with MS the best predictors for the time (days) to achieve this goal during the sub-acute rehabilitation. HRV measure was found to be the main predictor of the staircase ascent model (R2 = 0.32), and MFR the best predictor for the descent model (R2 = 0.24). CONCLUSIONS: Balance performance is the main predictor of independence in ascending and descending stairs. Improving this component during the sub-acute rehabilitation phase might be reflected in achieving staircase independence.


Assuntos
Modelos Neurológicos , Subida de Escada , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Idoso , Marcha , Humanos , Joelho/fisiopatologia , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia
11.
FASEB J ; 35(6): e21644, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34033143

RESUMO

How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrß3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.


Assuntos
Tecido Adiposo Branco/fisiopatologia , Exercício Físico , Vesículas Extracelulares/fisiologia , Lipólise , MicroRNAs/genética , Músculo Esquelético/fisiopatologia , Estresse Mecânico , Fator de Transcrição AP-2/metabolismo , Adolescente , Adulto , Animais , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fator de Transcrição AP-2/genética , Adulto Jovem
12.
Eur J Endocrinol ; 185(1): 167-177, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33950861

RESUMO

Introduction: Patients with acromegaly show musculoskeletal symptoms which may persist despite disease control. Increased i.m. fat fraction is a known cause of muscle dysfunction in several disorders. Objective: To assess the degree of fat fraction in thigh muscles of controlled acromegaly patients and its relationship with muscle dysfunction. Methods: In a cross-sectional study, we included 36 patients with controlled acromegaly and 36 matched controls. We assessed the percentage of fat fraction in each thigh muscle, using MRI 2-point Dixon sequence, and muscle performance and strength using the gait speed, timed up and go, 30-s chair stand, and hand grip strength tests. We evaluated joint symptoms using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Results: Intramuscular fat fraction was greater in patients than controls (P < 0.05 for muscle compartments, rectus femoris (RF), vastus intermedius (VI), adductor magnus (AM) and semimembranosus). Patients had slower gait speed and poorer performance on the 30-s chair stand and timed up and go tests than controls (P < 0.05). The greater fat fraction in the combined anterior-posterior compartment and in each muscle was associated with worse performance on timed up and go (P < 0.05). The fat fraction in the anterior-posterior compartment predicted performance on timed up and go after adjusting for muscle area, IGF-I and WOMAC functional and pain scores (ß = 0.737 P < 0.001). Conclusions: Patients with controlled acromegaly have greater thigh i.m. fatty infiltration, which is associated with muscle dysfunction. Futures studies are needed to elucidate the mechanisms underlying this relationship.


Assuntos
Acromegalia , Tecido Adiposo/metabolismo , Músculos/fisiologia , Acromegalia/metabolismo , Acromegalia/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Exercício Físico/fisiologia , Feminino , Força da Mão/fisiologia , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Músculos/metabolismo
13.
Medicine (Baltimore) ; 100(21): e25947, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032704

RESUMO

ABSTRACT: To compare the speed of propagation of ultrasound (US) waves (SoS) of the lower leg with the clinical reference standard computed tomography (CT) at the level of lumbar vertebra 3 (L3) for muscle loss assessment. Both calf muscles of 50 patients scheduled for an abdominal CT were prospectively examined with ultrasound. A plexiglas-reflector located on the opposite side of the probe with the calf in between was used as a timing reference for SoS (m/s). CT measurements were performed at the level of L3 and included area (cm2) and attenuation (HU) of the psoas muscle, abdominal muscles, subcutaneous fat, visceral fat and abdominal area. Correlations between SoS, body mass index (BMI) and CT were determined using Pearson's correlation coefficient. Based on reported CT sarcopenia threshold values, receiver operating characteristic (ROC) analysis was performed for SoS. Inter-examiner agreement was assessed with the median difference, inter-quartile range (IQR) and intraclass correlation coefficients. SoS of the calf correlated moderately with abdominal muscle attenuation (r = 0.48; P < .001), psoas muscle attenuation (r = 0.40; P < .01), abdominal area (r = -0.44; P < .01) and weakly with subcutaneous fat area (r = -0.37; P < .01). BMI correlated weakly with psoas attenuation (r = -0.28; P < .05) and non-significantly with abdominal muscle attenuation. Normalization with abdominal area resulted in moderate correlations with abdominal muscle area for SoS (r = 0.43; P < .01) and BMI (r = -0.46; P < .001). Based on sarcopenia threshold values for skeletal muscle attenuation (SMRA), area under curve (AUC) for SoS was 0.724. Median difference between both examiners was -3.4 m/s with IQR = 15.1 m/s and intraclass correlation coefficient = 0.794. SoS measurements of the calf are moderately accurate based on CT sarcopenia threshold values, thus showing potential for muscle loss quantification.


Assuntos
Perna (Membro)/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Sarcopenia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/fisiopatologia , Perna (Membro)/fisiopatologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Curva ROC , Valores de Referência , Sarcopenia/fisiopatologia , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/fisiopatologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ultrassonografia
14.
J Orthop Traumatol ; 22(1): 18, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33959802

RESUMO

BACKGROUND: Due to the special anatomy of the lower leg, tibial diaphyseal fracture causes increased intracompartmental pressure (ICP). Not only is this increased ICP the manifestation of skeletal muscle injury, but it induces further deterioration of the injury. The aim of this study was to assess the association between short-term ICP elevation and long-term skeletal muscle recovery after severe limb trauma. METHODS: In this single-center ambispective cohort study, we retrospectively screened and recruited a cohort of tibial diaphyseal fracture patients with integrated ICP data during the early post-traumatic period, and performed a prospective observational study to evaluate their skeletal muscle recovery through long-term follow-up and MR imaging after the removal of the implants. We analyzed the association between ICP elevation and skeletal muscle recovery using statistical methods. RESULTS: A total of 46 patients with healed fractures underwent intramedullary nail removal and MR imaging. The absolute values of the Pearson product-moment correlation coefficients between various ICP parameters and the cross-sectional area ratio (CSAR) ranged from 0.588 to 0.793, and the correlation coefficients between the ICP parameters and the average T2-weighted signal intensity ratio (T2SIR) varied from 0.566 to 0.775. Statistically significant associations were observed between the ICP parameters and the MR imaging parameters when simple linear regression analysis was performed. Among the ICP parameters, the accumulated ΔP (ΔP = diastolic blood pressure minus ICP) had the highest determination coefficient and explained 62.1% and 59.1% of the variance in CSAR and T2SIR, respectively. CONCLUSIONS: Short-term ICP elevation was associated with long-term skeletal muscle recovery following tibial diaphyseal fracture, especially for ICP data that integrated time factors. LEVEL OF EVIDENCE: Level 3.


Assuntos
Síndrome do Compartimento Anterior/etiologia , Músculo Esquelético/fisiopatologia , Fraturas da Tíbia/complicações , Adulto , Idoso , Síndrome do Compartimento Anterior/fisiopatologia , Estudos de Coortes , Diáfises/lesões , Diáfises/fisiopatologia , Diáfises/cirurgia , Fixação Intramedular de Fraturas , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fraturas da Tíbia/fisiopatologia , Fraturas da Tíbia/cirurgia , Adulto Jovem
15.
Skelet Muscle ; 11(1): 10, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883014

RESUMO

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.


Assuntos
COVID-19/fisiopatologia , Creatina Quinase/sangue , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Quadriplegia/fisiopatologia , Síndrome do Desconforto Respiratório/fisiopatologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/terapia , Estado Terminal , Dexametasona/uso terapêutico , Eletromiografia , Glucocorticoides/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Imageamento por Ressonância Magnética , Masculino , Staphylococcus aureus Resistente à Meticilina , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Doenças Musculares/sangue , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Condução Nervosa , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Quadriplegia/etiologia , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2 , Índice de Gravidade de Doença , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Desmame do Respirador
16.
Skelet Muscle ; 11(1): 10, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: covidwho-1197351

RESUMO

BACKGROUND: SARS-CoV2 virus could be potentially myopathic. Serum creatinine phosphokinase (CPK) is frequently found elevated in severe SARS-CoV2 infection, which indicates skeletal muscle damage precipitating limb weakness or even ventilatory failure. CASE PRESENTATION: We addressed such a patient in his forties presented with features of severe SARS-CoV2 pneumonia and high serum CPK. He developed severe sepsis and acute respiratory distress syndrome (ARDS) and received intravenous high dose corticosteroid and tocilizumab to counter SARS-CoV2 associated cytokine surge. After 10 days of mechanical ventilation (MV), weaning was unsuccessful albeit apparently clear lung fields, having additionally severe and symmetric limb muscle weakness. Ancillary investigations in addition with serum CPK, including electromyogram, muscle biopsy, and muscle magnetic resonance imaging (MRI) suggested acute myopathy possibly due to skeletal myositis. CONCLUSION: We wish to stress that myopathogenic medication in SARS-CoV2 pneumonia should be used with caution. Additionally, serum CPK could be a potential marker to predict respiratory failure in SARS-CoV2 pneumonia as skeletal myopathy affecting chest muscles may contribute ventilatory failure on top of oxygenation failure due to SARS-CoV2 pneumonia.


Assuntos
COVID-19/fisiopatologia , Creatina Quinase/sangue , Músculo Esquelético/fisiopatologia , Doenças Musculares/fisiopatologia , Quadriplegia/fisiopatologia , Síndrome do Desconforto Respiratório/fisiopatologia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/terapia , Estado Terminal , Dexametasona/uso terapêutico , Eletromiografia , Glucocorticoides/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Unidades de Terapia Intensiva , Imageamento por Ressonância Magnética , Masculino , Staphylococcus aureus Resistente à Meticilina , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Doenças Musculares/sangue , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Condução Nervosa , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Embolia Pulmonar/fisiopatologia , Quadriplegia/etiologia , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2 , Índice de Gravidade de Doença , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Desmame do Respirador
17.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33925872

RESUMO

Cancer cachexia is a common condition in many cancer patients, particularly those with advanced disease. Cancer cachexia patients are generally less tolerant to chemotherapies and radiotherapies, largely limiting their treatment options. While the search for treatments of this condition are ongoing, standards for the efficacy of treatments have yet to be developed. Current diagnostic criteria for cancer cachexia are primarily based on loss of body mass and muscle function. However, these criteria are rather limiting, and in time, when weight loss is noticeable, it may be too late for treatment. Consequently, biomarkers for cancer cachexia would be valuable adjuncts to current diagnostic criteria, and for assessing potential treatments. Using high throughput methods such as "omics approaches", a plethora of potential biomarkers have been identified. This article reviews and summarizes current studies of biomarkers for cancer cachexia.


Assuntos
Biomarcadores Tumorais , Caquexia , Neoplasias/complicações , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Caquexia/diagnóstico , Caquexia/fisiopatologia , Humanos , Músculo Esquelético/fisiopatologia , Fatores de Risco , Perda de Peso
18.
Clin Interv Aging ; 16: 611-619, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883888

RESUMO

Purpose: Many studies have demonstrated that Sarcopenia causes a serious impact on health, including death in older adults. The objective of this study was to determine the association of sarcopenia and pre-sarcopenia with all-cause mortality in older Chileans. Subjects and Methods: Follow-up of 2311 community-dwelling people ≥ 60y from the Alexandros cohort. Anthropometric measurements, handgrip strength, mobility, and physical performance tests were performed. Sarcopenia, pre-sarcopenia, and severe sarcopenia were defined using the 2010 European Working Group on Sarcopenia in Older People (EWGSOP1) algorithm. Muscle mass was estimated using a prediction model with cut-off points validated for the Chilean population. Physical performance was determined by 3 m walking speed or five chair-stands or time up go test (TUG). Mortality data were obtained from death certificates of the National Civil Registry. Life tables for survival data, Kaplan Meier estimations, and Cox regression were calculated. Results: The prevalence of sarcopenia was 20.2% (95% CI:18.6% to 21.9%) and similar in both sexes; pre-sarcopenia was identified in 20.4% (95% CI:18.8% to 22.1%) of the sample. Kaplan Meier survival estimates demonstrated lower survival rates for the people with sarcopenia and pre-sarcopenia (Log rank test for equality of survivor functions: p<0.0001). A dose-response was observed in the survival rates according to the stages of sarcopenia, showing the lowest survival rates for the people with severe sarcopenia, followed by older adults with sarcopenia, pre-sarcopenia, and without sarcopenia (Log rank test for equality of survivor functions: p<0.0001). After adjusting for age, sex, nutritional status, and number of chronic diseases, hazard ratios for death showed higher risk for subjects with sarcopenia (HR=1.47, 95% CI:1.17-1.83) and pre-sarcopenia (HR=1.35, 95% CI:1.03-1.78) in comparison with people without sarcopenia. Conclusion: The results confirm a dose-response increase in the risk of all-cause death in older adults with sarcopenia and pre-sarcopenia compared to non-sarcopenic individuals.


Assuntos
Causas de Morte , Mortalidade/tendências , Sarcopenia/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Estudos de Coortes , Feminino , Avaliação Geriátrica/métodos , Força da Mão , Humanos , Vida Independente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Desempenho Físico Funcional , Prevalência , Modelos de Riscos Proporcionais
19.
Nutrients ; 13(4)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805065

RESUMO

Iron deficiency (ID), with or without anemia, is responsible for physical fatigue. This effect may be linked to an alteration of mitochondrial metabolism. Our aim was to assess the impact of ID on skeletal striated muscle mitochondrial metabolism. Iron-deficient non-anemic mice, obtained using a bloodletting followed by a low-iron diet for three weeks, were compared to control mice. Endurance was assessed using a one-hour submaximal exercise on a Rotarod device and activities of mitochondrial complexes I and IV were measured by spectrophotometry on two types of skeletal striated muscles, the soleus and the quadriceps. As expected, ID mice displayed hematologic markers of ID and reduced iron stores, although none of them were anemic. In ID mice, endurance was significantly reduced and activity of the respiratory chain complex I, normalized to citrate synthase activity, was significantly reduced in the soleus muscle but not in the quadriceps. Complex IV activities were not significantly different, neither in the soleus nor in the quadriceps. We conclude that ID without anemia is responsible for impaired mitochondrial complex I activity in skeletal muscles with predominant oxidative metabolism. These results bring pathophysiological support to explain the improved physical activity observed when correcting ID in human. Further studies are needed to explore the mechanisms underlying this decrease in complex I activity and to assess the role of iron therapy on muscle mitochondrial metabolism.


Assuntos
Ferro/deficiência , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Estresse Oxidativo/fisiologia , Resistência Física/fisiologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal
20.
Biomed Res Int ; 2021: 6671390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855078

RESUMO

Whole-body vibration (WBV) training may improve the strength of lower extremity muscles in patients with knee osteoarthritis (KOA), but the inconsistency in vibration parameters leads to differences in findings. This cross-sectional study is aimed at observing the effects of different vibration frequencies and knee flexion angles on the activation of lower extremity muscles in patients with KOA. Enrolled participants received WBV training at 0, 30, and 60° knee flexion angles with vibration frequencies of 0, 5, 10, and 20 Hz. Activation rates for vastus medialis, vastus lateralis, rectus femoris, biceps femoris, and semitendinosus in different combinations were collected through surface electromyography. The effects of frequency and angle on muscle activation rate were quantified by repeated measures ANOVA. Individual and synergistic effects of frequency and angle were also analysed. Twenty-six participants with KOA were included. Muscle activation increased with the vibration frequency in 0-20 Hz range and with knee flexion angle in 0-60° range. WBV training at 20 Hz was the most effective for knee muscle activation, and static squatting at 60° was the most suitable for WBV training. Therefore, WBV training can increase the activation rate of knee flexor and extensor muscles in patients with KOA, and the most efficient combination was 20 Hz vibration frequency and 60° knee flexion. When applying WBV to patients with KOA, individual differences and rehabilitation purposes should be considered in selecting vibration parameters and knee angle to effectively increase neuromuscular activity.


Assuntos
Músculo Esquelético/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Vibração , Eletromiografia , Feminino , Humanos , Pessoa de Meia-Idade , Postura/fisiologia
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