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1.
Medicine (Baltimore) ; 98(40): e17361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577733

RESUMO

Limbs muscle wasting is a common disorder in patients with chronic obstructive pulmonary disease (COPD) that limits daily activities and exercise intolerance, especially in males. The present study aimed to estimate the prevalence of appendicular skeletal muscle mass (ASM) in male patients with stable COPD. In addition, factors associated with parameters of ASM were also investigated.We recruited 116 male patients with stable COPD from the outpatient clinic between September 2016 and December 2017. For each patient, we obtained demographic characteristics and measured post-bronchodilator forced expiratory volume in 1 second, symptoms, exacerbations history, and ASM. ASM was defined as the sum of the muscle masses of the 4 limbs.Appendicular skeletal muscle mass index (ASMI) in male patients with stable COPD was 8.2 ±â€Š0.9 kg/m, and the prevalence of low skeletal muscle mass was 7.8% (9 of 116 patients). Multiple linear-regression analysis showed that body mass index, occupation, fat-free mass index, and the modified medical research council scale were significantly correlated with ASMI. Compared with nonexercise group, lower limb muscle mass and ASM were significantly improved in physical exercise group.Underweight, retirement, fat-free mass depletion, and severe dyspnea are all risk factors for ASM in male patients with stable COPD. Our findings also justify the importance of exercise training in improving ASM.


Assuntos
Músculo Esquelético/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Pesos e Medidas Corporais , Estudos Transversais , Exercício , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Testes de Função Respiratória , Índice de Gravidade de Doença , Fatores Socioeconômicos
2.
Adv Exp Med Biol ; 1167: 191-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31520356

RESUMO

In humans, cancer-associated cachexia is a complex syndrome that reduces the overall quality of life and survival of cancer patients, particularly for those undergoing chemotherapy. The most easily observable sign of cachexia is organ wasting, the dramatic loss of skeletal muscle and adipose tissue mass. Estimates suggest that 80% of patients in advanced stages of cancer show signs of the syndrome and about 20% of cancer patients die directly of cachexia. Because there is no treatment or drug available to ameliorate organ wasting induced by cancer, cachexia is a relevant clinical problem. However, it is unclear how cachexia is mediated, what factors drive interactions between tumors and host tissues, and which markers of cachexia might be used to allow early detection before the observable signs of organ wasting. In this chapter, we review the current mammalian models of cachexia and the need to use new models of study. We also explain recent developments in Drosophila as a model for studying organ wasting induced by tumors and how fly studies can help unravel important mechanisms that drive cachexia. In particular, we discuss what lessons have been learned from tumor models recently reported to induce systemic organ wasting in Drosophila.


Assuntos
Caquexia/patologia , Drosophila , Neoplasias/patologia , Animais , Modelos Animais de Doenças , Humanos , Músculo Esquelético/patologia , Qualidade de Vida
3.
Life Sci ; 235: 116800, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472151

RESUMO

AIMS: It is well known that cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD) accompanied by skeletal muscle atrophy. Histone deacetylases (HDACs) that remove acetyl groups from target proteins are necessary for the muscle atrophy associated with skeletal muscle disuse. However, the role of HDACs and trichostatin A (TSA), a HDAC inhibitor, in skeletal muscle atrophy caused by CS exposure remains poorly understood. MAIN METHODS: Female mice were exposed to CS twice daily for 40 days and TSA injected intraperitoneally into CS-exposed mice on alternate days. Skeletal muscles were weighed and gastrocnemius (Gas) muscle histomorphology examined by hematoxylin and eosin staining. Histone deacetylases 1 and 2 (HDAC1/2), and markers of ubiquitin degradation, muscle differentiation, apoptosis, pyroptosis, and the cytoskeletal proteins were assessed by western blot and immunohistochemistry in Gas. KEYFINDINGS: CS exposure decreased body and skeletal muscle weights and triggered an increase in the percentage of fiber with centralized nuclei in Gas. HDAC1/2 proteins were upregulated in the Gas of mice exposed to CS, while TSA effectively inhibited HDAC1/2 protein levels and attenuated the loss of body weight and skeletal muscle wet weight induced by CS exposure. Markers for ubiquitin degradation, muscle differentiation, cytoskeletal proteins, apoptosis and pyroptosis were all upregulated following CS exposure and effectively restored by TSA. SIGNIFICANCE: TSA may inhibit skeletal muscle atrophy and histomorphological alterations induced by CS exposure by downregulating markers of ubiquitin degradation, muscle fiber differentiation, cytoskeletal proteins, apoptosis and pyroptosis via HDAC1/2 inhibition.


Assuntos
Apoptose/efeitos dos fármacos , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Fumar/efeitos adversos , Animais , Proteínas do Citoesqueleto/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia
4.
Anticancer Res ; 39(9): 4603-4612, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519557

RESUMO

BACKGROUND/AIM: Sarcopenia describes the loss of skeletal muscle mass. While this condition is associated with a high mortality in cancer patients, its influence on survival is still underestimated. PATIENTS AND METHODS: A systematic review for articles was performed using the PubMed database, Cochrane Library, Biomed Central, Science Direct and by manual search. We used data of overall survival in sarcopenic patients for assessing the death risk. We extracted hazard ratio estimates from univariate and multivariate Cox proportional hazards models for meta-analysis. RESULTS: A total of 15 studies were eligible for meta-analysis including a total of 2,521 lung cancer patients. Univariate meta-analysis revealed a two-fold increased death risk in sarcopenic patients; multivariate meta-analysis yielded a significant, three-fold elevated risk of death. This higher mortality is independent of tumour stage. CONCLUSION: Muscle loss is an independent risk factor for increased death risk in lung cancer patients independent of cancer stage. This argues for implementing screening for sarcopenia into cancer care.


Assuntos
Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Sarcopenia/etiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Músculo Esquelético/patologia , Estadiamento de Neoplasias , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
5.
Cancer Imaging ; 19(1): 50, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315666

RESUMO

BACKGROUND: To investigate if iodine density overlay maps (IDO) and virtual monoenergetic images at 40 keV (VMI40keV) acquired from spectral detector computed tomography (SDCT) can improve detection of incidental skeletal muscle metastases in whole-body CT staging examinations compared to conventional images. METHODS: In total, 40 consecutive cancer patients who underwent clinically-indicated, contrast-enhanced, oncologic staging SDCT were included at this retrospective study: 16 patients with n = 108 skeletal muscle metastases confirmed by prior or follow-up CT, 18F-FDG-PET, MRI or histopathology, and a control group of 24 patients without metastases. Four independent readers performed blinded, randomized visual detection of skeletal muscle metastases in conventional images, IDO and VMI40keV, indicating diagnostic certainty for each lesion on a 5-point Likert scale. Quantitatively, ROI-based measurements of attenuation (HU) in conventional images and VMI40keV and iodine concentration in IDO were conducted. CNR was calculated and receiver operating characteristics (ROC) analysis of quantitative parameters was performed. RESULTS: Regarding subjective assessment, IDO (63.2 (58.5-67.8) %) and VMI40keV (54.4 (49.6-59.2) %) showed an increased sensitivity for skeletal muscle metastases compared to conventional images (39.8 (35.2-44.6) %). Specificity was comparable in VMI40keV (69.8 (63.2-75.8) %) and conventional images (69.2 (60.6-76.9) %), while in IDO, it was moderately increased to 74.2 (65.3-78.4) %. Quantitative image analysis revealed that CNR of skeletal muscle metastases to circumjacent muscle was more than doubled in VMI40keV (25.8 ± 11.1) compared to conventional images (10.0 ± 5.3, p ≤ 0.001). Iodine concentration obtained from IDO and HU acquired from VMI40kev (AUC = 0.98 each) were superior to HU attenuation in conventional images (AUC = 0.94) regarding differentiation between healthy and metastatic muscular tissue (p ≤ 0.05). CONCLUSIONS: IDO and VMI40keV provided by SDCT improve diagnostic accuracy in the assessment of incidental skeletal muscle metastases compared to conventional CT.


Assuntos
Neoplasias Musculares/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/secundário , Músculo Esquelético/patologia , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X/normas
6.
J Photochem Photobiol B ; 197: 111530, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279287

RESUMO

A novel nano-formulations of biocompatible, biodegradable and thermo-responsive graphene quantum dots (GQDs) loaded dextran/poly(N-isopropylacrylamide) (Dex/PNIPAM) copolymeric matrix was synthesized and analyzed the materials characterization, sustained drug delivery system, tissue feasibility in the tissue implantation site. This research report was aimed to grafting and functionalizing thermo-responsive (Dex/PNIPAM) copolymeric composite with presence of graphene quantum dots to achieve thermal responsive drug delivery (TrDD) with no harm effect in the implantation site. The synthesized GQD by using ionic liquid were evaluated by spectroscopic (DLS, PL, XRD and Raman spectroscopy) and Transmission electron microscopic analysis (TEM). The ultra-small GQDs loaded Dex/PNIPAM and was appeared to be asymmetric and open uniform porous structure, which can be significantly favorable for cell uptake and greatly influenced to be an effective drug carrier into the cellular compartment with good fluid flow. The PNIPAM polymeric composite were exhibited sustained and enhanced drug release percentages with increasing temperature at above low critical solution temperature (LCST) is 39 °C comparable to the cumulative drug release profile of below LCST (32 °C), which demonstrated that thermo-responsive polymer was played a significant role in the delivery system. The treated group of GQDs-Dex/PNIPAM was observed that no inflammation and shows noteworthy stromal cell infiltration, demonstrating that the synthesized drug carriers did not harm to the nerves and tissues and only was responsible for the pain management.


Assuntos
Buprenorfina/química , Portadores de Fármacos/química , Grafite/química , Hidrogéis/química , Manejo da Dor , Pontos Quânticos/química , Resinas Acrílicas/química , Animais , Buprenorfina/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dextranos/química , Portadores de Fármacos/farmacologia , Feminino , Corantes Fluorescentes/química , Glicóis/química , Hidrogéis/farmacologia , Camundongos , Músculo Esquelético/patologia , Dor/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
7.
Medicine (Baltimore) ; 98(26): e16172, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261548

RESUMO

INTRODUCTION: A progressive decline in lean body mass and increase in fat mass occur with aging, and result in progressive weakness and impaired mobility; these features are altogether landmarks of the ageing frailty syndrome. High-fat mass and low muscle mass are both associated with an increased risk of cardiovascular events and are supposed to be risk factors for arterial stiffness. Little data analyzing the relationship between body composition and cardio-ankle vascular index (CAVI) are currently available. The main objective of this study was to verify whether low muscle mass and/or high fat mass could be associated with arterial stiffness measured by CAVI. METHODS: Data are from the cross-sectional assessment of the "Al passo con la tua salute", a clinical study aimed to promote physical function among free-living elderly subjects.After a screening interview and a clinical visit aimed to exclude ineligible persons, 52 volunteers were enrolled in the study. All underwent: clinical examination, physical performance assessment, an interview on lifestyle and dietary habits, and lastly, a blood sample collection after at least 8 hours of fasting. RESULTS: CAVI was statistically significantly higher in those participants in the highest tertile of distribution for fat mass compared to all other subjects (P = .03). In those participants in the lowest tertile of distribution of muscle mass, compared to all other, CAVI was also statistically significant higher (P = .01) independently of age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and systolic blood pressure. CONCLUSIONS: Low muscle mass and high fat mass were landmarks in the frailty model of aging; therefore, it is not inconsistent that both clinical conditions might share with the "aging vessel" a common pathway, probably mediated through signaling network deregulation and/or through alteration of the balance between energy availability and energy demand.


Assuntos
Tecido Adiposo , Composição Corporal , Músculo Esquelético , Rigidez Vascular , Tecido Adiposo/patologia , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Colesterol/sangue , Estudos Transversais , Dieta , Feminino , Fragilidade/epidemiologia , Fragilidade/patologia , Fragilidade/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Fatores de Risco
9.
Rev Med Chil ; 147(3): 342-355, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344172

RESUMO

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


Assuntos
Miosite/patologia , Anticorpos , Dermatomiosite/patologia , Eletromiografia , Humanos , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Músculo Esquelético/patologia , Miosite/tratamento farmacológico , Polimiosite/patologia
11.
Arkh Patol ; 81(3): 45-50, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31317930

RESUMO

OBJECTIVE: To identify the morphological features of paraspinal muscles in patients with spinal pathology caused by progressive muscular dystrophy. SUBJECT AND METHODS: The Traumatologic-and-Orthopedic Department of Axial Skeleton Pathology examined patients with scoliotic spinal deformity due to muscular dystrophy: 1) severe Duchenne X-linked muscular dystrophy (n=7); 2) Erb-Roth's autosomal recessive muscular dystrophy (n=2); 3) Landouzy-Dejerine facioscapulohumeral muscular dystrophy (n=2). For histopathological analysis of paraspinal muscles, an excisional biopsy was performed in the region of the apex of the strain angle (the convex side), and the specimens were fixed with 10% neutral formalin. Paraffin sections were stained with hematoxylin and eosin according to the Van Gieson and Masson trichrome staining methods. The preparations were examined using an AxioScope.A1 stereo microscope and an AxioCam digital camera ('Carl Zeiss MicroImaging GmbH', Germany). RESULTS: Sluggish moderate paraparesis and grade IV progressive neurogenic thoracolumbar scoliosis were predominant in the clinical picture of the disease. The muscle biopsy specimens were established to have muscle fiber profiles with lost polygonality, increased diameter variability, and centrally positioned or numerous internal nuclei (myophagy) and to be characterized by fiber contractures, fatty degeneration fields, interstitial fibrosis, and signs of axonopathy of intramuscular nerve conductors. The arterial blood vessels were spastic with fibrotic t. media and t. adventicia; the venous bed vessels were dilated, thin-walled, full-blooded, which causes blood corpuscle transudation and numerous hemorrhages. CONCLUSION: The identified morphopathological characteristics of muscle tissue in patients with progressive muscular dystrophy are very similar. However, Duchenne muscular dystrophy is the most severe pathology, in which fatty degeneration and sclerotization of muscle tissue and perimysial vessels are most pronounced. To solve this problem, there is a need for the integration of geneticists, biochemists, molecular biologists, pharmacologists, and histologists.


Assuntos
Músculo Esquelético , Distrofia Muscular Facioescapuloumeral , Escoliose , Biópsia , Fibrose , Humanos , Músculo Esquelético/patologia , Distrofia Muscular Facioescapuloumeral/complicações , Distrofia Muscular Facioescapuloumeral/patologia , Escoliose/complicações
12.
Clin Interv Aging ; 14: 987-996, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213785

RESUMO

Background: Sarcopenia is typically defined as the loss of muscle mass, strength and low physical performance with aging. Ultrasound is a safe and easy method for evaluating muscle mass and quality by muscle thickness (MT) and pennation angle (PA), respectively. Although the positive correlations between MT and muscle mass and handgrip strength were observed, the relationship between MT, PA and physical performance remains unclear. Purpose: This study aimed to investigate the correlation of aforementioned ultrasound parameters with muscle mass, muscle strength and physical performance and explore the utility of ultrasound in predicting sarcopenia. Patients and methods: A total of 265 elderly Chinese community dwellers were included. MT of both forearm and lower leg as well as PA of gastrocnemius was assessed by ultrasound. Muscle mass was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by a Jamar hand dynamometer. Physical performance was assessed by the Short Physical Performance Battery (SPPB). Results: Anterior radial MT in men and regional MTs except posterior fibula in women were negatively correlated with the age. No significant correlation was observed between PA and the age in both genders. Posterior tibial MT and posterior fibula MT were positively correlated with the relative appendicular skeletal muscle mass in men and women, respectively. Anterior ulnar MT was positively correlated with grip strength in both genders. Moreover, gastrocnemius medialis PA showed a positive association with gait speed and SPPB in women but not in men. Conclusion: A combination of posterior fibula MT, anterior ulnar MT and gastrocnemius medialis PA measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly women. In addition, a combination of posterior tibial MT and anterior ulnar MT measured by muscle ultrasound is helpful for the assessment of sarcopenia in Chinese elderly men.


Assuntos
Força da Mão , Força Muscular , Músculo Esquelético , Sarcopenia , Absorciometria de Fóton/métodos , Idoso , China/epidemiologia , Feminino , Humanos , Vida Independente/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Ultrassonografia/métodos
13.
Harefuah ; 158(6): 372-377, 2019 Jun.
Artigo em Hebraico | MEDLINE | ID: mdl-31215189

RESUMO

INTRODUCTION: Muscle biopsy is an important diagnostic procedure for the evaluation of neuromuscular disorders, commonly employed when patients present with muscle weakness, high creatine-kinase or electromyography which suggest myopathy. The diagnostic value of this procedure when these are normal is unclear. AIMS: To characterize the pathology in muscle biopsies of patients without clinical, laboratory or electromyographic suggestion for myopathy. METHODS: Retrospective chart and pathology review of consecutive patients who were evaluated by muscle biopsy at Sheba Medical Center. RESULTS: Of 109 patients, 12 (11%) had no indication for myopathy prior to biopsy. Pathology was identified in 2/3 of cases. Inflammation was detected in 5 cases (42%), with a perivascular infiltrate in four, and endomysial in one. A mild myopathy was present in 3/5 of these cases. Type-2 muscle fiber atrophy as the primary or only pathology was seen in 2 cases (17%) and mild neurogenic changes in one (8%). A history of systemic disease, additional laboratory tests or imaging suggestive for inflammation were predictive for inflammatory pathology in 4/5 of cases (P = 0.006). CONCLUSIONS: Perivascular inflammation without significant muscle fiber damage is common and meaningful in patients with inflammatory conditions in spite of normal evaluation for myopathy. DISCUSSION: Muscle disease is characterized by damage to muscle fibers, connective tissue or vessels. In the absence of fiber damage, muscle strength, creatine-kinase and electromyography may remain normal. These tests therefore do not rule-out perivascular inflammation and mild myopathy. Muscle biopsy is effective for the detection of inflammation in patients with inflammatory conditions in spite of normal strength creatine-kinase and electromyography.


Assuntos
Biópsia , Doenças Musculares , Creatina Quinase , Eletromiografia , Humanos , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , Estudos Retrospectivos
14.
Nat Commun ; 10(1): 2788, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243277

RESUMO

Many potentially therapeutic molecules have been identified for treating Duchenne muscular dystrophy. However, targeting those molecules only to sites of active pathology is an obstacle to their clinical use. Because dystrophic muscles become extensively inflamed, we tested whether expressing a therapeutic transgene in leukocyte progenitors that invade muscle would provide selective, timely delivery to diseased muscle. We designed a transgene in which leukemia inhibitory factor (LIF) is under control of a leukocyte-specific promoter and transplanted transgenic cells into dystrophic mice. Transplantation diminishes pathology, reduces Th2 cytokines in muscle and biases macrophages away from a CD163+/CD206+ phenotype that promotes fibrosis. Transgenic cells also abrogate TGFß signaling, reduce fibro/adipogenic progenitor cells and reduce fibrogenesis of muscle cells. These findings indicate that leukocytes expressing a LIF transgene reduce fibrosis by suppressing type 2 immunity and highlight a novel application by which immune cells can be genetically modified as potential therapeutics to treat muscle disease.


Assuntos
Terapia Genética , Fator Inibidor de Leucemia/metabolismo , Distrofia Muscular Animal/terapia , Animais , Células da Medula Óssea/metabolismo , Regulação da Expressão Gênica , Fator Inibidor de Leucemia/genética , Masculino , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/patologia , Distribuição Aleatória , Organismos Livres de Patógenos Específicos , Transgenes
15.
BMC Neurol ; 19(1): 135, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31216995

RESUMO

BACKGROUND: Myotonic Dystrophy 1 (DM1) causes progressive myopathy of extremity muscles. DM1 may also affect muscles of the trunk. The aim of this study was to investigate fat infiltration and muscle size in trunk muscles in DM1 patients, and in an age and gender matched control group. Further, explore how fat infiltration and degree of atrophy in these muscles are associated with motor and respiratory function in DM1 patients. METHOD: We measured fat infiltration and trunk muscle size by MRI in 20 patients with genetically confirmed classic form of DM1, and compared these cases with 20 healthy, age and gender matched controls. In the DM1 group, we investigated correlations between MRI findings and clinical measures of muscle strength, mobility and respiration. We used sum scores for fat infiltration and muscle size in trunk flexors and trunk extensors in the analysis of group differences and correlations. RESULTS: Significant differences between cases and controls were present for fat infiltration in trunk flexors (p = 0.001) and trunk extensors (p = < 0.001), and for muscle size in trunk flexors (p = 0.002) and trunk extensors (p = 0.030). Fat infiltration in trunk flexors were significant correlated to back extension strength (rho = - 0.523 p = 0.018), while muscle size in trunk flexors was significantly correlated to trunk flexion strength (rho = 0.506 p = 0.023). Fat infiltration in trunk flexors was significantly correlated with lower general mobility (rho = - 0.628, p = 0.003), reduced balance (rho = 0.630, p < 0.003) and forced vital capacity (rho - 0.487 p = 0.040). CONCLUSIONS: Trunk muscles in DM1 patients had significant higher levels of fat infiltration and reduced muscle size compared to age and gender matched controls. In DM1 patients, fat infiltration was associated with reduced muscle strength, mobility, balance and lung function, while muscle size was associated with reduced muscle strength and lung function. These findings are of importance for clinical management of the disease and could be useful additional outcome measures in future intervention studies.


Assuntos
Atrofia/patologia , Músculo Esquelético/patologia , Distrofia Miotônica/patologia , Distrofia Miotônica/fisiopatologia , Respiração , Tronco/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Adulto Jovem
16.
Life Sci ; 231: 116533, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173783

RESUMO

AIM: The aim of this study was to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against skeletal muscle ischemia-reperfusion (IR) injury and to determine the underlying mechanism. MAIN METHODS: C57BL/6 mice were randomly divided into 3 groups: skeletal muscle IR injury group (IR), CIHH pretreatment following IR group (IR + CIHH), and sham operation group (Sham). The skeletal muscle IR injury model was induced by the unilateral application of a tourniquet on a hind limb for 3 h and then releasing it for 24 h. CIHH pretreatment simulating a 5000-m altitude was applied 6 h per day for 28 days. The functional and morphological performance of IR-injured gastrocnemius muscle was evaluated using contraction force, H&E staining, and transmission electron microscopy. IR injury-induced CD68+ macrophage infiltration was assessed by immunofluorescence. TNFα levels in serum and muscle were measured by ELISA and western blotting, respectively. Apoptosis was examined by TUNEL staining and Cleaved Caspase-3 protein expression. KEY FINDINGS: Acute IR injury resulted in reduced contraction tension, morphological destruction, macrophage infiltration, increased TNFα levels, and apoptosis in gastrocnemius muscle. CIHH pretreatment significantly ameliorated contraction function and morphological performance in IR-injured skeletal muscle. In addition, CIHH pretreatment resulted in marked decreases in CD68+ macrophage infiltration, TNFα levels, and apoptosis. SIGNIFICANCE: These data demonstrated that CIHH has a protective effect against acute IR injury in skeletal muscle via inhibition of inflammation and apoptosis.


Assuntos
Hipóxia/patologia , Músculo Esquelético/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Hipóxia/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Fator de Necrose Tumoral alfa/metabolismo
17.
Histochem Cell Biol ; 152(3): 227-237, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183542

RESUMO

Type I spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by the loss or mutation of the survival motor neuron 1 (SMN1) gene. The reduction in SMN protein levels in SMA leads to the degeneration of motor neurons and muscular atrophy. In this study, we analyzed the nuclear reorganization in human skeletal myofibers from a type I SMA patient carrying a deletion of exons 7 and 8 in the SMN1 gene and two SMN2 gene copies and showing reduced SMN protein levels in the muscle compared with those in control samples. The morphometric analysis of myofiber size revealed the coexistence of atrophic and hypertrophic myofibers in SMA samples. Compared with controls, both nuclear size and the nuclear shape factor were significantly reduced in SMA myonuclei. Nuclear reorganization in SMA myonuclei was characterized by extensive heterochromatinization, the aggregation of splicing factors in large interchromatin granule clusters, and nucleolar alterations with the accumulation of the granular component and a loss of fibrillar center/dense fibrillar component units. These nuclear alterations reflect a severe perturbation of global pre-mRNA transcription and splicing, as well as nucleolar dysfunction, in SMA myofibers. Moreover, the finding of similar nuclear reorganization in both atrophic and hypetrophic myofibers provides additional support that the SMN deficiency in SMA patients may primarily affect the skeletal myofibers.


Assuntos
Núcleo Celular/genética , Músculo Esquelético/patologia , RNA/genética , RNA/metabolismo , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/patologia , Núcleo Celular/metabolismo , Humanos , Recém-Nascido , Masculino , Músculo Esquelético/metabolismo
18.
Nat Commun ; 10(1): 2430, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31160583

RESUMO

Muscle loss due to fibrotic or adipogenic replacement of myofibers is common in muscle diseases and muscle-resident fibro/adipogenic precursors (FAPs) are implicated in this process. While FAP-mediated muscle fibrosis is widely studied in muscle diseases, the role of FAPs in adipogenic muscle loss is not well understood. Adipogenic muscle loss is a feature of limb girdle muscular dystrophy 2B (LGMD2B) - a disease caused by mutations in dysferlin. Here we show that FAPs cause the adipogenic loss of dysferlin deficient muscle. Progressive accumulation of Annexin A2 (AnxA2) in the myofiber matrix causes FAP differentiation into adipocytes. Lack of AnxA2 prevents FAP adipogenesis, protecting against adipogenic loss of dysferlinopathic muscle while exogenous AnxA2 enhances muscle loss. Pharmacological inhibition of FAP adipogenesis arrests adipogenic replacement and degeneration of dysferlin-deficient muscle. These results demonstrate the pathogenic role of FAPs in LGMD2B and establish these cells as therapeutic targets to ameliorate muscle loss in patients.


Assuntos
Tecido Adiposo/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Células-Tronco/citologia , Adipócitos/patologia , Adipogenia/efeitos dos fármacos , Tecido Adiposo/patologia , Adolescente , Idade de Início , Animais , Anexina A2/metabolismo , Estudos de Casos e Controles , Disferlina/genética , Venenos Elapídicos/toxicidade , Feminino , Fibrose , Humanos , Técnicas In Vitro , Masculino , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Fenilalanina/análogos & derivados , Fenilalanina/farmacologia , Inibidores de Proteases/farmacologia , Índice de Gravidade de Doença , Células-Tronco/efeitos dos fármacos , Tiofenos/farmacologia , Adulto Jovem
19.
BMC Neurol ; 19(1): 125, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189464

RESUMO

BACKGROUND: Non-dystrophic myotonias (NDMs) are skeletal muscle disorders involving myotonia distinct from myotonic dystrophy. It has been reported that the muscle pathology is usually normal or comprises mild myopathic changes in NDMs. We describe various pathological findings mimicking those of myotonic dystrophy (DM) in biopsied muscle specimens from a patient with NDMs with a long disease duration. CASE PRESENTATION: A 66-year-old Japanease man presented eye closure myotonia, percussion myotonia and grip myotonia together with the warm-up phenomenon and cold aggravation from early childhood. On genetic analysis, a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.L689F), with no mutation of the CLCN1, DMPK, or ZNF9/CNBP gene, was detected. He was diagnosed as having NDMs. A biopsy of the biceps brachii muscle showed increasing fiber size variation, internal nuclei, chained nuclei, necrotic fibers, fiber splitting, endomysial fibrosis, pyknotic nuclear clumps and disorganized intermyofibrillar networks. Sarcoplasmic masses, tubular aggregates and ragged-red fibers were absent. CONCLUSION: It is noteworthy that the present study revealed various pathological findings resembling those seen in DM, although the pathology is usually normal or mild in NDMs. The pathological similarities may be due to muscular modification with long-standing myotonia or excessive muscle contraction based on abnormal channel activity.


Assuntos
Músculo Esquelético/patologia , Miotonia/genética , Miotonia/patologia , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Idoso , Heterozigoto , Humanos , Masculino , Mutação
20.
Anim Sci J ; 90(8): 1060-1069, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218792

RESUMO

The objective of this study was to determine the effect of two different freezing rate then thaw-aging regimens on the quality attributes of lamb loins. The loins were randomly allocated to one of five different freezing/thawing/aging regimes: fast-(FF1A0) and slow-(SF1A0) frozen only; fast-(FF1A2) and slow-(SF1A2) frozen then thaw-aged for 14 days; aged for 14 days never frozen (A2). FF1A2 samples had a significantly higher water-holding capacity compared to the slow frozen regardless of further aging periods. FF1A2 samples had lower (p < 0.05) shear force values than A2 and higher (p < 0.05) water-holding capacity compared to the SF1A2. Fast freezing resulted in more intracellular cryo-damage, whereas slow freezing resulted in extracellular cryo-damage. FF1A0 and SF1A0 samples had lower (p < 0.05) myofibrillar proteins degradation. This study demonstrated that fast freezing then thaw-aging can result in an improved water-holding capacity and tenderness through the minimization of extracellular ice crystal formation, reduction in purge and drip losses, and improved proteolysis in thawed lamb.


Assuntos
Conservação de Alimentos/métodos , Qualidade dos Alimentos , Congelamento , Carne , Animais , Congelamento/efeitos adversos , Carne/análise , Proteínas Musculares/metabolismo , Músculo Esquelético/química , Músculo Esquelético/patologia , Proteólise , Resistência ao Cisalhamento , Ovinos , Fatores de Tempo , Água/análise
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