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Journal of Cachexia, Sarcopenia and... Aug 2018In recent years, electrical myostimulation (EMS) is becoming more and more popular to increase muscle function and muscle weight. Especially it is applied in healthy...
In recent years, electrical myostimulation (EMS) is becoming more and more popular to increase muscle function and muscle weight. Especially it is applied in healthy individual after injury to rebuild muscle mass and in severely atrophic patients who are not able or willing to perform conventional exercise training programs. Studies in experimental models as well as in human subjects confirmed that EMS can increase muscle mass by around 1% and improve muscle function by around 10-15% after 5-6 weeks of treatment. Despite a severe increase in circulating creatine kinase during the first session, EMS can be regarded as a safe therapeutic intervention. At the molecular level, EMS improves the anabolic/catabolic balance and stimulates the regenerative capacity of satellite cells. EMS intensity should be as high as individually tolerated, and a minimum of three sessions per week [large pulses (between 300-450 μs), high frequency (50-100 Hz in young and around 30 Hz in older individuals)] for at least 5-6 weeks should be performed. EMS improved functional performances more effectively than voluntary training and counteracted fast type muscle fibre atrophy, typically associated with sarcopenia. The effect of superimposing EMS on conventional exercise training to achieve more muscle mass and better function is still discussed controversially. Nevertheless, EMS should not be regarded as a replacement of exercise training per se, since the beneficial effect of exercise training is not just relying on building muscle mass but it also exerts positive effects on endothelial, myocardial, and cognitive function.
Topics: Animals; Clinical Studies as Topic; Disease Models, Animal; Electric Stimulation Therapy; Humans; Muscular Atrophy; Treatment Outcome
PubMed: 30028092
DOI: 10.1002/jcsm.12332 -
The British Journal of General Practice... Dec 2021
Topics: Atrophy; Humans; Urogenital System
PubMed: 34824066
DOI: 10.3399/bjgp21X717725 -
International Journal of Molecular... Dec 2020This review describes the role of bone resorption in muscle atrophy as well as in muscle protein anabolism. Both catabolic and anabolic pathways involve components of... (Review)
Review
This review describes the role of bone resorption in muscle atrophy as well as in muscle protein anabolism. Both catabolic and anabolic pathways involve components of the proinflammatory cytokine families and release of factors stored in bone during resorption. The juxtaposition of the catabolic and anabolic resorption-dependent pathways raises new questions about control of release of factors from bone, quantity of release in a variety of conditions, and relation of factors released from bone. The catabolic responses involve release of calcium from bone into the circulation resulting in increased inflammatory response in intensity and/or duration. The release of transforming growth factor beta (TGF-β) from bone suppresses phosphorylation of the AKT/mTOR pathway and stimulates ubiquitin-mediated breakdown of muscle protein. In contrast, muscle IL-6 production is stimulated by undercarboxylated osteocalcin, which signals osteoblasts to produce more RANK ligand, stimulating resorptive release of undercarboxylated osteocalcin, which in turn stimulates muscle fiber nutrient uptake and an increase in muscle mass.
Topics: Animals; Bone Resorption; Humans; Muscular Atrophy
PubMed: 33396572
DOI: 10.3390/ijms22010392 -
Translational Neurodegeneration Dec 2023TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal...
BACKGROUND
TDP-43 proteinopathies represent a spectrum of neurological disorders, anchored clinically on either end by amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The ALS-FTD spectrum exhibits a diverse range of clinical presentations with overlapping phenotypes, highlighting its heterogeneity. This study was aimed to use disease progression modeling to identify novel data-driven spatial and temporal subtypes of brain atrophy and its progression in the ALS-FTD spectrum.
METHODS
We used a data-driven procedure to identify 13 anatomic clusters of brain volume for 57 behavioral variant FTD (bvFTD; with either autopsy-confirmed TDP-43 or TDP-43 proteinopathy-associated genetic variants), 103 ALS, and 47 ALS-FTD patients with likely TDP-43. A Subtype and Stage Inference (SuStaIn) model was trained to identify subtypes of individuals along the ALS-FTD spectrum with distinct brain atrophy patterns, and we related subtypes and stages to clinical, genetic, and neuropathological features of disease.
RESULTS
SuStaIn identified three novel subtypes: two disease subtypes with predominant brain atrophy in either prefrontal/somatomotor regions or limbic-related regions, and a normal-appearing group without obvious brain atrophy. The limbic-predominant subtype tended to present with more impaired cognition, higher frequencies of pathogenic variants in TBK1 and TARDBP genes, and a higher proportion of TDP-43 types B, E and C. In contrast, the prefrontal/somatomotor-predominant subtype had higher frequencies of pathogenic variants in C9orf72 and GRN genes and higher proportion of TDP-43 type A. The normal-appearing brain group showed higher frequency of ALS relative to ALS-FTD and bvFTD patients, higher cognitive capacity, higher proportion of lower motor neuron onset, milder motor symptoms, and lower frequencies of genetic pathogenic variants. The overall SuStaIn stages also correlated with evidence for clinical progression including longer disease duration, higher King's stage, and cognitive decline. Additionally, SuStaIn stages differed across clinical phenotypes, genotypes and types of TDP-43 pathology.
CONCLUSIONS
Our findings suggest distinct neurodegenerative subtypes of disease along the ALS-FTD spectrum that can be identified in vivo, each with distinct brain atrophy, clinical, genetic and pathological patterns.
Topics: Humans; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia; Neurodegenerative Diseases; Brain; DNA-Binding Proteins; Atrophy
PubMed: 38062485
DOI: 10.1186/s40035-023-00389-3 -
Tidsskrift For Den Norske Laegeforening... Jun 2015Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal... (Review)
Review
BACKGROUND
Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition.
METHOD
The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group.
RESULTS
Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful.
INTERPRETATION
Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.
Topics: Aged; Atrophy; Cerebral Cortex; Disease Progression; Humans; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Vision Disorders
PubMed: 26037756
DOI: 10.4045/tidsskr.14.1127 -
Transplantation Jan 2024This review outlines the molecular disease states in kidney transplant biopsies as documented in the development of the Molecular Microscope Diagnostic System (MMDx).... (Review)
Review
This review outlines the molecular disease states in kidney transplant biopsies as documented in the development of the Molecular Microscope Diagnostic System (MMDx). These states include T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), recent parenchymal injury, and irreversible atrophy-fibrosis. The MMDx project, initiated through a Genome Canada grant, is a collaboration involving many centers. MMDx uses genome-wide microarrays to measure transcript expression, interprets the results using ensembles of machine learning algorithms, and generates a report. Experimental studies in mouse models and cell lines were extensively used to annotate molecular features and interpret the biopsy results. Over time, MMDx revealed unexpected aspects of the disease states: for example, AMR is usually C4d-negative and often DSA-negative, and subtle "Minor" AMR-like states are frequent. Parenchymal injury correlates with both reduced glomerular filtration rate and increased risk of graft loss. In kidneys with rejection, injury features, not rejection activity, are the strongest predictors of graft survival. Both TCMR and AMR produce injury, but TCMR induces immediate nephron injury and accelerates atrophy-fibrosis, whereas AMR induces microcirculation and glomerular damage that slowly leads to nephron failure and atrophy-fibrosis. Plasma donor-derived cell-free DNA levels correlate strongly with AMR activity, acute kidney injury, and in a complex way with TCMR activity. Thus, the MMDx project has documented the molecular processes that underlie the clinical and histologic states in kidney transplants, and provides a diagnostic tool that can be used to calibrate biomarkers, optimize histology interpretation, and guide clinical trials.
Topics: Animals; Mice; Kidney Transplantation; Kidney; Antibodies; Phenotype; Fibrosis; Atrophy; Graft Rejection; Biopsy
PubMed: 37310258
DOI: 10.1097/TP.0000000000004624 -
Cells Dec 2023The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent... (Review)
Review
The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of human- and animal-based studies over the past 100 years and has resulted in the commonly used term of 'disuse atrophy'. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.
Topics: Animals; Humans; Quality of Life; Muscle, Skeletal; Muscular Disorders, Atrophic; Muscle Fibers, Skeletal; Atrophy
PubMed: 38132132
DOI: 10.3390/cells12242811 -
EMBO Molecular Medicine Feb 2023Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of...
Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.
Topics: Humans; Iron Chelating Agents; Retinal Diseases; Cell Death; Atrophy
PubMed: 36645044
DOI: 10.15252/emmm.202216525 -
International Journal of Molecular... Aug 2021The weight of skeletal muscle accounts for approximately 40% of the whole weight in a healthy individual, and the normal metabolism and motor function of the muscle are... (Review)
Review
The weight of skeletal muscle accounts for approximately 40% of the whole weight in a healthy individual, and the normal metabolism and motor function of the muscle are indispensable for healthy life. In addition, the skeletal muscle of the maxillofacial region plays an important role not only in eating and swallowing, but also in communication, such as facial expressions and conversations. In recent years, skeletal muscle atrophy has received worldwide attention as a serious health problem. However, the mechanism of skeletal muscle atrophy that has been clarified at present is insufficient, and a therapeutic method against skeletal muscle atrophy has not been established. This review provides views on the importance of skeletal muscle in the maxillofacial region and explains the differences between skeletal muscles in the maxillofacial region and other regions. We summarize the findings to change in gene expression in muscle remodeling and emphasize the advantages and disadvantages of denervation-induced skeletal muscle atrophy model. Finally, we discuss the newly discovered beneficial effects of natural compounds on skeletal muscle atrophy.
Topics: Animals; Biological Products; Denervation; Humans; Muscle, Skeletal; Muscular Atrophy
PubMed: 34361076
DOI: 10.3390/ijms22158310 -
American Journal of Physiology.... Jul 2022Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving... (Review)
Review
Skeletal muscle is an integral tissue system that plays a crucial role in the physical function of all vertebrates and is a key target for maintaining or improving health and performance across the lifespan. Based largely on cellular and animal models, there is some evidence that various forms of heat stress with or without resistance exercise may enhance skeletal muscle growth or reduce its loss. It is not clear whether these stimuli are similarly effective in humans or meaningful compared with exercise alone across various heating methodologies. Furthermore, the magnitude by which heat stress may influence whole body thermoregulatory responses and the connection to skeletal muscle adaptation remains ambiguous. Finally, the underlying mechanisms, which may include interaction between relevant heat shock proteins and intracellular hypertrophy and atrophy related factors, remain unclear. In this narrative review, we examine the relevant literature regarding heat stress alone or in combination with resistance exercise emphasizing skeletal muscle hypertrophy and atrophy across cellular and animal models, as well as human investigations. In addition, we present working mechanistic theories for heat shock protein-mediated signaling effects regarding hypertrophy and atrophy-related signaling processes. Importantly, continued research is necessary to determine the practical effects and mechanisms of heat stress with and without resistance exercise on skeletal muscle function via growth and maintenance.
Topics: Animals; Atrophy; Exercise; Heat-Shock Proteins; Heat-Shock Response; Hypertrophy; Muscle, Skeletal; Muscular Atrophy
PubMed: 35536704
DOI: 10.1152/ajpregu.00048.2022