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Results for “Skeletal muscle dysfunction”

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At least 865 records · Page 48Linked to original sources

PubMed1998

[A primary study of transcranial magnetic stimulation (TMS)-induced muscle silent period(SP) in stroke patients with mild hemiparesis].

OBJECTIVE: To investigate the changes of muscle silent period (SP) induced by transcranial magnetic stimulation (TMS) and its value in the evaluation of motor function in patient with stroke. METHODS: 25 normals and 23 stroke patients with mild hemiparesis were involved in this study. A MES-10 magnetic stimulator and a 9 cm round coil were used to stimulate the brain at an intensity 50% above threshold for MEP with the subjects making sustained moderate contraction of the contralateral FDI. SP duration and interside ratio were measured and calculated and then compared between the two groups. RESULTS: Normal values of SP duration and interside ratio were 145 +/- 37 ms and 1.01 +/- 0.15 respectively. The SP duration on the paralytic side in stroke patients was 423 +/- 314 ms, significantly prolonged in comparison with that on the normal side (154 +/- 54 ms, P < 0.05) and that of normal value (P < 0.01). The interside SP ratio (paralytic/normal side) in stroke patients was 2.8 +/- 1.9, also significantly higher than the normal value (P < 0.01). CONCLUSION: SP might be a sensitive and valuable neurophysiological parameter in evaluation of the motor function of patients with central motor dysfunction.

Adult↗

PubMed2004

Skeletal muscle mitochondrial protein metabolism and function in ageing and type 2 diabetes.

PURPOSE OF REVIEW: Mitochondria are the site of oxidative substrate utilization to produce adenosine triphosphate for normal tissue function. Tissue substrate utilization is impaired in ageing and type 2 diabetes. Defects in mitochondrial gene expression, protein synthesis and function occur with ageing in various tissues including skeletal muscle, and are emerging in individuals with type 2 diabetes. The current review will discuss advances in the understanding of skeletal muscle mitochondrial alterations associated with age and type 2 diabetes. RECENT FINDINGS: Insulin acutely stimulates skeletal muscle mitochondrial protein synthesis and adenosine triphosphate production. These insulin effects are impaired in insulin-resistant patients with type 2 diabetes who also exhibit defective basal muscle mitochondrial function. The age-related reduction in mitochondrial adenosine triphosphate production has been confirmed in vivo in skeletal muscle in humans and rodents. SUMMARY: The emerging concept that insulin stimulates mitochondrial protein synthesis and function indicates potential novel molecular mechanisms of metabolic defects in type 2 diabetes, particularly in the post-prandial period characterized by acute increments of plasma insulin concentrations. The potential relationship between insulin resistance and basal post-absorptive muscle mitochondrial defects should be further investigated. As ageing is characterized by insulin resistance, the hypothesis that impaired insulin action could contribute to age-related muscle mitochondrial dysfunction, and metabolic alterations should be addressed.

Adenosine Triphosphate↗

PubMed1993

Cardiac involvement in Becker muscular dystrophy.

OBJECTIVES: The purpose of this study was to assess the incidence of myocardial involvement and the relation of cardiac disease to the molecular defect at the deoxyribonucleic acid (DNA) or protein level in Becker muscular dystrophy. BACKGROUND: Dystrophin gene mutations produce clinical manifestations of disease in the heart and skeletal muscle of patients with Becker muscular dystrophy. METHODS: Thirty-one patients underwent electrocardiographic and echocardiographic examination and 24-h Holter monitoring. The diagnosis was established by neurologic examination, dystrophin immunohistochemical assays or Western blot on muscle biopsy, or both, and DNA analysis. RESULTS: Electrocardiographic and echocardiographic findings were abnormal in 68% and 62% of the patients, respectively. Right ventricular involvement was detected in 52%. Left ventricular impairment was observed either as an isolated phenomenon (10%) or in association with right ventricular dysfunction (29%). Right ventricular disease was manifested in the teenagers, and an impairment of the left ventricle was observed in older patients. Right ventricular end-diastolic volumes were significantly increased compared with those in a control group. The left ventricular ejection fraction was significantly lower in older patients than in control subjects or younger patients. Life-threatening ventricular arrhythmias were detected in four patients. No correlations were found between skeletal muscle disease, cardiac involvement and dystrophin abnormalities. In our patients, exon 49 deletion was invariably associated with cardiac involvement. Exon 48 deletion was associated with cardiac disease in all but two patients. CONCLUSIONS: The cardiac manifestation of Becker muscular dystrophy is characterized by early right ventricular involvement associated or not with left ventricular impairment. Exon 49 deletion is associated with cardiac disease.

Adolescent↗

PubMed2005

Muscular dystrophies related to the cytoskeleton/nuclear envelope.

Mutations in genes encoding proteins expressed in skeletal muscle cause a significant number of human diseases. Neuromuscular diseases are often severely debilitating for affected individuals, frequently leading to a shortened life span. Identifying the cause of these muscle diseases has provided insight not only into disease pathogenesis and muscle dysfunction, but also into the normal function of muscle. In 1987, dystrophin became the first disease-related human gene to be identified by positional cloning. Dystrophin is an integral component of the membrane-attached cytoskeleton of muscle fibres, with mutations in this gene causing Duchenne and Becker muscular dystrophy. One group of proteins known as the dystrophin-associated protein complex (DAPC), is believed to provide a molecular link between the actin cytoskeleton and the extracellular matrix in muscle cells, thereby sustaining sarcolemmal integrity during muscle contraction. Mutations in many members of the DAPC cause a variety of diseases, emphasising the importance of these genes. Another group of important proteins in skeletal muscle is the intermediate filament family, which provides mechanical strength and a supporting framework within the muscle cell. They anchor actin thin filaments through their expression at the Z-disk in sarcomeres, which in turn interact with myosin thick filaments to cause muscle contraction. This chapter will explore the protein components of the DAPC and the intermediate filament complex, highlighting a novel protein, which links the two, syncoilin. Human diseases and studies of existing animal models caused by mutations in these genes will also be described.

Animals↗

PubMedDate not supplied

Cardiac mitochondrial dysfunction in Leigh syndrome.

An infant with Leigh syndrome and associated cardiomyopathy is described. Abnormal activities of mitochondrial respiratory complexes III and V and a change in mtDNA at nt 8993 were detected in heart and skeletal muscle but not in liver.

Cardiomyopathies↗

PubMed2001

Minimal impairment of myocardial blood flow responses to exercise in the remodeled left ventricle early after myocardial infarction, despite significant hemodynamic and neurohumoral alterations.

OBJECTIVES: Previous studies have demonstrated a decreased flow reserve in the surviving hypertrophied left ventricle (LV) early after myocardial infarction. We hypothesized that exacerbation of hemodynamic abnormalities and neurohumoral activation during exercise could exhaust coronary flow reserve and thereby impair myocardial O(2) supply. Consequently, we studied hemodynamic, neurohumoral and regional myocardial perfusion and metabolic responses to exercise in pigs with LV hypertrophic remodeling 3 weeks after a myocardial infarction produced by permanent left circumflex coronary artery ligation. METHODS: Chronically instrumented pigs were exercised on a treadmill up to 85% of maximum heart rate. Pigs with a myocardial infarction (MI) had a lower cardiac output (21%), stroke volume (28%), LVdP/dt(max) (18%), systemic (22%) and pulmonary (20%) vascular conductance, and increased left atrial (225%) and pulmonary artery (75%) pressures, compared to normal pigs. In MI, the exercise-induced increases in cardiac pump function, and systemic and pulmonary vasodilation were blunted compared to normals. Consequently, perfusion of visceral organs became impaired during strenuous exercise, but cerebral and skeletal muscle blood flows were maintained. Exercise-induced increases in norepinephrine and endothelin levels were exacerbated and, while relative sympathetic drive was maintained, cardiac responsiveness to norepinephrine was blunted. Despite lower capillary densities in the hypertrophied non-infarcted LV and relative subendocardial hypoperfusion during strenuous exercise, which necessitated a slight increase in O(2) extraction, there was no metabolic evidence of overt myocardial ischemia during strenuous exercise as indicated by the arterio-coronary venous pH difference. CONCLUSIONS: LV dysfunction and neurohumoral activation were present in pigs with a 3-week-old infarction, particularly during exercise. However, although myocardial perfusion and O(2) supply were slightly impaired, myocardial ischemia did not occur even during exercise up to 85% of maximum heart rate, suggesting that perfusion abnormalities do not contribute to LV dysfunction early after infarction.

Animals↗

PubMed1996

The cardiopulmonary system and movement dysfunction.

Physical therapy primarily involves the identification and treatment of problems related to movement. Movement dysfunction usually is attributed to impairments of the neuromuscular and musculoskeletal systems. The cardiopulmonary system plays an important role in movement because of its function of transporting oxygen to skeletal muscle. Abnormalities of the cardiovascular and pulmonary systems can produce limitations in physical function. The purposes of this article are to describe the steps involved in the transfer of oxygen from atmospheric air to skeletal muscles and to provide examples of problems that can occur with each step of the process. Common signs and symptoms of potential problems involving the cardiovascular and pulmonary systems also will be discussed.

Cardiovascular System↗

PubMed2004

Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig.

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.

Adipose Tissue↗

PubMed2026

COVID-19 multi-omics reveal organ-specific responses and biomarkers.

OBJECTIVE: Post-COVID-19 syndrome is characterised by persistent immune dysfunction and multi-organ sequelae. This study aimed to characterise the systemic blood molecular landscape induced by SARS-CoV-2 infection and identify prognostic markers linked to skeletal muscle mass loss, a key driver of poor outcomes. METHODS: We enrolled 30 healthy controls and 307 COVID-19 patients, collecting 422 plasma samples for integrated proteomic and metabolomic profiling to investigate organ-specific molecular alterations in COVID-19. RESULTS: We comprehensively mapped the molecular landscape of COVID-19, encompassing immune, tissue-specific, and metabolic perturbations, and delineated their interactions. Focusing on organ-damage-related molecular patterns associated with disease progression and mortality, we found that skeletal muscle mass loss contributed to poor clinical outcomes of COVID-19 (p < 0.0001). Dysregulated arginine metabolism emerged as a key metabolic signature in fatal COVID-19 cases, with GLUL, GOT1, and citrulline showing significant correlation with skeletal muscle mass loss. Longitudinal analyses further revealed that reduced citrulline levels underlie the poor outcome of COVID-19 patients with muscle mass loss. These findings were robustly supported through multiple approaches: Mendelian randomization confirmed causal relationships between citrulline depletion, sarcopenia/fat-free mass loss, and COVID-19 mortality (p < 0.05), transcriptomic analyses of SARS-CoV-2-infected golden hamsters (GSE231910) provided additional support in enrichment of arginine biosynthesis (FDR < 0.05), and in vitro experiments further demonstrated that citrulline depletion promotes pro-inflammatory M1 macrophage polarisation — a key immunological feature of critical COVID-19. Leveraging these insights, we developed a skeletal muscle loss-specific prognostic prediction model for COVID-19 using GLUL, GOT1, and citrulline. This model effectively stratified patients into high- and low-risk groups (p = 0.035). CONCLUSION: Our study advances the understanding of COVID-19-induced organ pathophysiology and provides a foundation for developing targeted therapeutic strategies for post-COVID sequelae.

COVID-19↗

PubMed2006

Duchenne's cardiomyopathy: two case reports.

We describe two cases of Duchenne's cardiomyopathy with severe cardiac dysfunction, sporadic episodes of myoglobinuria induced by effort and increased levels of serum creatine kinase. Very mild signs of skeletal myopathy were clinically evident. Left ventriculography showed diffuse severe hypokinesia. Skeletal muscle biopsy demonstrated a dystrophic process. The patients had no familial background of the disease. These 2 patients might have a sporadic inheritance pattern with severe cardiac involvement.

Adolescent↗

PubMed2000

Cadmium modulates diabetes-induced alterations in murine neuromuscular junction.

Skeletal muscle function is compromised in diabetes mellitus and exposure to heavy metals may further complicate neuromuscular impairments. The present study investigated the effects of cadmium on diabetes induced dorsiflexor muscle dysfunction in C57 BL adult male mice. Forty mice were divided randomly into 2 groups (n=20 each). One group served as control and the other was injected once with i.p. streptozotocin (STZ) solution (60 mg/kg) to induce experimental diabetes. Each group was then divided into two sub-groups (n=10) of which one received 5 mM cadmium. Utilizing intracellular recording method, resting membrane potential (RMP) and miniature endplate potentials (MEPPs) were measured in dorsiflexor muscle obtained from urethane-anaesthetized (2 mg/g, i.p.) four weeks diabetic and matched control mice. Comparative analyses of isometric contractile characteristics of in situ dorsiflexor muscle were also conducted in both groups. In control mice, flexor muscle exposure to 5 mM cadmium for 10 min resulted in significant reduction in MEPPs frequencies and isometric twitch tensions without affecting RMP. In STZ-diabetic mice, the same exposure did not modify resting membrane potential and further decreased MEPPs frequencies and isometric twitch tensions. Current results indicated that cadmium probably via a Ca2+ antagonist and chelating activity at nerve terminals exacerbates diabetes complications.

Animals↗

PubMed2006

Absence of peroxisome proliferators-activated receptors (PPAR)alpha enhanced the multiple organ failure induced by zymosan.

The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study is to evaluate the role of PPAR-alpha receptor on the development of multiple-organ dysfunction syndrome (MODS) induced by zymosan. MODS was induced by peritoneal injection of zymosan (dose, 500 mg/kg i.p. as a suspension in saline) in PPAR-alpha wild-type (PPAR-alphaWT) and PPAR-alpha knockout (PPAR-alphaKO) mice, was assessed 18 h after the administration of zymosan, and was monitored for 12 days (for loss of body weight and mortality). A severe inflammatory process, induced by zymosan administration in wild-type mice, coincided with the damage of liver, kidney, pancreas, and small intestine. Myeloperoxidase activity, indicative of neutrophil infiltration, and lipid peroxidation were significantly increased in zymosan-treated wild-type mice. Zymosan in the wild-type mice also induced a significant increase in the plasma levels of nitrite/nitrate. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine and Fas ligand in the intestine of zymosan-treated wild-type mice. In contrast, the degree of (1) peritoneal inflammation and tissue injury, (2) nitrotyrosine formation and Fas ligand expression, and (3) neutrophil infiltration were markedly enhanced in intestinal tissue obtained from zymosan-treated PPAR-alphaKO mice. Zymosan-treated PPAR-alphaKO mice also showed a significantly increased mortality. Taken together, the present study clearly demonstrates that PPAR-alpha pathway modulates the degree of MODS associated with zymosan-induced nonseptic shock.

Animals↗

PubMed2005

The adenine nucleotide translocase type 1 (ANT1): a new factor in mitochondrial disease.

Mitochondrial disorders of oxidative phosphorylation (OXPHOS) comprise a growing list of potentially lethal diseases caused by mutations in either mitochondrial (mtDNA) or nuclear DNA (nDNA). Two such conditions, autosomal dominant progressive external ophthalmoplegia (adPEO) and Senger's Syndrome, are associated with dysfunction of the heart and muscle-specific isoform of the adenine nucleotide translocase (ANT1), a nDNA gene product that facilitates transport of ATP and ADP across the inner mitochondrial membrane. AdPEO is a mtDNA deletion disorder broadly characterized by pathology involving the eyes, skeletal muscle, and central nervous system. In addition to ANT1, mutations in at least two other nuclear genes, twinkle and POLG, have been shown to cause mtDNA destabilization associated with adPEO. Senger's syndrome is an autosomal recessive condition characterized by congenital heart defects, abnormalities of skeletal muscle mitochondria, cataracts, and elevated circulatory levels of lactic acid. This syndrome is associated with severe depletion of ANT1, which may be the result of an as yet unidentified ANT1-specific transcriptional or translational processing error. ANT1 has also been associated with a third condition, autosomal dominant facioscapulohumeral muscular dystrophy (FSHD), an adult onset disorder characterized by variable muscle weakness in the face, feet, shoulders, and hips. FSHD patients possess specific DNA deletions on chromosome 4, which appear to cause derepression of several nearby genes, including ANT1. Early development of FSHD may involve mitochondrial dysfunction and increased oxidative stress, possibly associated with overexpression of ANT1.

Adenine Nucleotide Translocator 1↗

PubMed1992

Effect of angiotensin-converting enzyme inhibitors on the peripheral circulation in heart failure.

In patients with chronic heart failure, the increase in blood flow to working muscle is attenuated and oxygen consumption is lower for any given workload of exercise, compared with normal subjects. This impaired metabolic vasodilation during exercise cannot be restored with short-term administration of angiotensin-converting enzyme (ACE) inhibitors. However, long-term ACE inhibition increases blood flow to skeletal muscle, and this increase is closely correlated with improvement in systemic oxygen consumption. The delayed effect of ACE inhibitors may be related to an interference with the vascular tissue renin-angiotensin system and remodeling of the vascular wall. In addition, endothelial-dependent dilation in response to acetylcholine is blunted in the forearm of patients with chronic heart failure, indicating an impaired endothelial function in this setting. There is experimental evidence that long-term ACE inhibition improves endothelial dysfunction; thus, one might speculate that the beneficial long-term effect of ACE inhibitors on peripheral flow may be, in part, related to its ability to restore normal endothelial function. Vasodilators such as hydralazine that improve blood flow to working muscle after acute administration do not increase skeletal muscle oxygen consumption, indicating that oxygen utilization is not improved. Ultrastructural analysis of skeletal muscle revealed that intrinsic alterations of skeletal muscle exist in patients with chronic heart failure; that is, the oxidative capacity of skeletal muscle is impaired in severe heart failure and contributes to the reduced exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Statement on cardiopulmonary exercise testing in chronic heart failure due to left ventricular dysfunction: recommendations for performance and interpretation. Part I: definition of cardiopulmonary exercise testing parameters for appropriate use in chronic heart failure.

Cardiopulmonary exercise testing (CPET) provides a global assessment of the integrated response to exercise involving the pulmonary, cardiovascular, haematopoietic, neuropsychological, and skeletal muscle systems. This information cannot be obtained through investigation of the individual organ systems in isolation. The non-invasive, dynamic physiological overview permits the evaluation of both submaximal and peak exercise responses, providing the physician with relevant information for clinical decision making. The use of CPET in management of the chronic heart failure patient is increasing with the understanding that resting pulmonary and cardiac function testing cannot reliably predict exercise performance and functional capacity and that, furthermore, overall health status and prognosis are predicted better by indices of exercise tolerance than by resting measurements. Our aim is to produce a statement which provides recommendations on the interpretation and clinical application of CPET in heart failure, based on contemporary scientific knowledge and technical advances: the focus is on clinical indications, issues of standardization, and interpretative strategies for CPET.

Cardiac Output↗

PubMed1999

The use of gait analysis for surgical recommendations in traumatic brain injury.

Traumatic brain injury causes unpredictable errors in the patient's gait by introducing varying mixtures of spasticity, contractures, primitive flexion and extension synergies, and impaired selective control. Surgical release or transfer of the offending muscles can improve the patient's ability to walk if functional errors have been accurately identified. While clinical testing is inadequate, instrumented motion analysis and dynamic electromyography can supply an accurate definition of the abnormalities in muscle action and provide guidelines for distinguishing local from referred motion errors. Examples of the diagnostic differences related to the equinovarus foot and the common types of knee dysfunction are presented.

Brain Injuries↗

PubMed1996

Insulin and the vasculature--old actors, new roles.

I have presented data to support an interaction of insulin with the vascular endothelium to cause the release of NO and vasodilation. In effect, insulin-mediated vasodilation can be viewed as a novel test of endothelial function. The physiologic significance of insulin-mediated, endothelium-dependent vasodilation is not fully understood, but some insight has been gained. Insulin-mediated vasodilation in skeletal muscle appears to be an important mechanism to amplify insulin's overall action to stimulate skeletal muscle glucose uptake in insulin-sensitive man. Insulin-resistant states of obesity, hypertension, and NIDDM exhibit blunted insulin-mediated vasodilation and impaired endothelium-dependent vasodilation. Together, the data suggest that endothelial dysfunction is an integral aspect of the syndrome of insulin resistance, independent of hyperglycemia, and as such may contribute to worsen insulin resistance, increase vascular reactivity, 32 and predispose to macrovascular disease. Thus, the insulin/EDNO interaction provides a potential mechanism (but certainly not the only one) linking insulin resistance, hypertension, thrombosis, and atherosclerosis-key features of the insulin resistance syndrome (Figure 7). Future research into the signal transduction steps leading to insulin-mediated, endothelium-derived NO production and its dysregulation in insulin-resistant states will be extremely useful to elucidate the mechanisms underlying the increased macrovascular risk in insulin-resistant man.

Blood Vessels↗

PubMed2003

Mitochondrial Dysfunction in Sepsis.

Sepsis is an increasingly common problem, particularly among critically ill patients. Mechanisms by which sepsis induces organ dysfunction have not been elucidated. The coexisting findings (unique to sepsis) of metabolic acidosis yet increased tissue oxygen tensions suggest cellular availability but decreased use of oxygen (tissue dysoxia). Because mitochondria use more than 90% of total body oxygen consumption for adenosine triphosphate (ATP) generation, a bioenergetic abnormality is implied. Cell and animal data have shown that nitric oxide (and its metabolites), produced in considerable excess in patients with sepsis, can affect oxidative phosphorylation by inhibiting several of its component respiratory enzymes. Human data are scarce. However, in skeletal muscle biopsies taken from patients with sepsis, we have recently demonstrated a relationship between increased nitric oxide production, antioxidant depletion, reduced respiratory chain complex I activity, and low ATP levels. These findings correlated with severity of disease and outcome and support the notion that mitochondrial dysfunction resulting in bioenergetic failure may be an important factor in the pathophysiology of sepsis-associated multiorgan failure. However, a reasonable argument can be made that the reduction in energy supply could represent a last-ditch adaptive response to ongoing inflammation, resulting in a cellular shutdown analogous to hibernation that allows eventual restoration of organ function and long-term survival in patients fit enough to survive the acute phase.

Journal Article↗