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Results for “Skeletal muscle dysfunction”

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At least 811 records · Page 45Linked to original sources

PubMed1996

H2O2 modulates twitch tension and increases Po of Ca2+ release channel in frog skeletal muscle.

The effect of H2O2 was examined to elucidate the basis of muscle injury after exercise. Exposure of single fibers to 1.5-6 mM H2O2 led to twitch potentiation followed by a marked decrease. Then, fibers contracted spontaneously. BAY K 8644 augmented twitch potentiation and slowed the decay of twitches. In 5 mM dithiothreitol (DTT), twitch potentiation and spontaneous contraction were not observed on H2O2 addition. Cytoplasmic application of 1.5-3 mM H2O2 to heavy sarcoplasmic reticulum (SR) vesicles incorporated into planar lipid bilayers increased the open probability of Ca2+ release channels, an effect reversed by DTT. We investigated oxidation of sulfhydryl groups on proteins in SR membrane by H2O2 with N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide. Pretreatment of light and heavy SR membranes with 1.5 mM H2O2 exponentially increased fluorescence intensity. The time constant of the intensity increase was increased markedly only in heavy SR in solution containing 50 microM cytoplasmic Ca2+, so Ca2+ release was associated with protein oxidation by H2O2. Thus extracellular H2O2 probably acts by oxidizing sulfhydryls of proteins at two distinct sites: the dihydropyridine receptors, oxidation of which elicits potentiation and subsequent inhibition of twitches, and Ca2+ release channels, whose oxidation elicits spontaneous contraction, resulting in muscle dysfunction.

Animals↗

PubMed2006

Metabolic therapy for patients with diabetes mellitus and coronary artery disease.

Patients with diabetes mellitus and ischemic heart disease more frequently develop heart failure and have a greater amount of myocardial ischemia, often silent, compared with patients without diabetes. Furthermore, patients with coronary artery disease (CAD) and diabetes or insulin resistance have altered myocardial metabolism and accelerated and diffuse atherogenesis with involvement of distal coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in patients with diabetes and CAD, the ischemic metabolic changes are heightened by the metabolic changes in patients with diabetes. An important metabolic alteration in patients with diabetes is the increase in free fatty acid (FFA) concentrations and the increased skeletal muscle and myocardial FFA uptake and oxidation. The increased uptake and utilization of FFA and the reduced utilization of glucose as a source of energy during stress and ischemia contribute to the increased susceptibility of diabetic hearts to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared with nondiabetic hearts. A therapeutic approach aimed at an improvement in cardiac metabolism through manipulations of the use of metabolic substrates should result in an improvement in myocardial ischemia and left ventricular (LV) function. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, increases cardiac resistance to ischemia, and therefore reduces the decrease of LV function caused by chronic hypoperfusion and repetitive episodes of myocardial ischemia in patients with and without diabetes. Thus, modulation of myocardial FFA metabolism should be the key target for metabolic interventions in patients with CAD with and without diabetes. In patients with diabetes, the effects of modulation of FFA metabolism should be even greater compared with those observed in patients without diabetes. Because of its effect on cardiac metabolism at rest and its effects on myocardial ischemia and LV function, trimetazidine should always be considered for the treatment of patients with diabetes with CAD with or without LV dysfunction.

Coronary Disease↗

PubMed1991

Linkage data suggesting allelic heterogeneity for paramyotonia congenita and hyperkalemic periodic paralysis on chromosome 17.

Paramyotonia congenita (PC), an autosomal dominant non-progressive muscle disorder, is characterised by cold-induced stiffness followed by muscle weakness. The weakness is caused by a dysfunction of the sodium channel in muscle fibre. Parts of the gene coding for the alpha-subunit of the sodium channel of the adult human skeletal muscle (SCN4A) have been localised on chromosome 17. To investigate the role of this gene in the etiology of PC, a linkage analysis in 17 well-defined families was carried out. The results (zeta = 20.61, theta = 0.001) show that the mutant gene responsible for the disorder is indeed tightly linked to the SCN4A gene. The mutation causing hyperkalemic periodic paralysis (HyperPP) with myotonia has previously been mapped to this gene locus by the same candidate gene approach. Thus, our data suggest that PC and HyperPP are caused by allelic mutations at a single locus on chromosome 17.

Alleles↗

PubMed2002

Plakins: a family of versatile cytolinker proteins.

By connecting cytoskeletal elements to each other and to junctional complexes, the plakin family of cytolinkers plays a crucial role in orchestrating cellular development and maintaining tissue integrity. Plakins are built from combinations of interacting domains that bind to microfilaments, microtubules, intermediate filaments, cell-adhesion molecules and members of the armadillo family. Plakins are involved in both inherited and autoimmune diseases that affect the skin, neuronal tissue, and cardiac and skeletal muscle. Here, we describe the members of the plakin family and their interaction partners, and give examples of the cellular defects that result from their dysfunction.

Amino Acid Sequence↗

PubMed1995

Shoulder problems in high level swimmers--impingement, anterior instability, muscular imbalance?

The objective was to study prevalence and underlying pathology of "swimmer's shoulder". Twenty-two competitive swimmers of national "D-Kader" (elite development swimmers) were evaluated by means of questionnaire, clinical examination and isokinetic testing of external rotation and internal rotation. At the examination current interfering pain necessitating a cessation or reduction of practice was found in 5 (23%) athletes. At isokinetic testing 8 (36%) athletes complained of shoulder pain. Any history of pain was seen in 14 (64%) swimmers. A positive impingement sign was noted in 11 (50%) athletes. Apprehension sign which is indicative of anterior instability was found in 11 (50%) swimmers. Clinical equivalents of dysfunction of scapulothoracic muscles such as scapular winging (5 athletes) and shoulder protraction (12 athletes) were noted. For comparison of results of isokinetic testing a control group of non-swimmers was selected matching the group of swimmers exactly in terms of age, sex and dominant side. External rotation/internal rotation ratio of peak torque and total work at 60 deg/sec and 180 deg/sec was significantly lower in swimmers than in controls. The ratio was independent of sex, dominant side, history of pain and pain at examination. During internal rotation competitive swimmers produced significantly higher peak torques and total work than controls. There was no significant difference in external rotation. In conclusion there are several different abnormalities of function contributing to the pathology of "swimmer's shoulder":--Laxity of anterior-inferior capsuloligamentous structures with atruamatic anterior instability due to repetitive overload.--Impingement with rotator cuff tendinitis.--Muscular imbalance of the rotator cuff muscles and scapulothoracic dysfunction.

Adolescent↗

PubMed2003

Review of integrated neuromusculoskeletal release and the novel application of a segmental anterior/posterior approach in the thoracic, lumbar, and sacral regions.

Integrated neuromusculoskeletal release (INR) using a segmental anterior/posterior approach is an osteopathic manipulative treatment technique that is easily learned and applied. The segmental anterior/posterior approach to INR was developed as a practical osteopathic manipulative treatment procedure for the inpatient setting, but also has equal efficacy in the outpatient setting. It builds on the principles of INR and myofascial release techniques, as well as other techniques. This approach focuses on both the anterior and posterior connectivity of the body through the neuromusculoskeletal system and uses this connectivity to effectively treat somatic dysfunctions. The principles of INR are discussed, as well as the role of INR in the diagnosis and treatment of somatic dysfunctions in the thoracic, lumbar, and sacral regions.

Fascia↗

PubMed2002

Investigation of muscle recruitment patterns in scoliosis using a biomechanical finite element model.

The objective of this project is to study the characteristics of trunk muscle recruitment strategies experimentally observed for scoliotic subjects using a finite element model of the trunk. The personalized biomechanical model includes elements representing the osseo-ligamentous structures of the spine, rib cage and pelvis. It also integrates the principal agonistic muscles necessary for trunk movement and a neural control model based on the Equilibrium Point hypothesis (lambda model of Feldman). Muscle recruitment patterns of normal and scoliotic subjects obtained from the simulation of lateral bending movements were qualitatively compared. The generation process of motor control variables was studied by analysing the relationships between central commands and spine segment mobility. Differences in recruitment patterns between normal and scoliotic subjects were observed, especially for paraspinal fascicles crossing the thoracic curve segment. The generation of central commands for normal subjects was strongly correlated with the amplitude of bending, but this relation was weaker for scoliotic subjects and this difference was worst at the apex vertebra. These results show that neuromuscular disorders could occur at a local level. The proposed approach should provide a simulation tool to study the multifactorial origin of scoliosis, and to investigate the implication of muscles and central commands in spinal dysfunctions.

Humans↗

PubMed2001

Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity: a potential model to investigate environmental contributions to neurodegenerative diseases.

Deficits in oxidative phosphorylation have been implicated in many neurodegenerative diseases. In this study, cytochrome oxidase activity was inhibited following a 28-d systemic administration of nonlethal sodium azide via subcutaneous osmotic pumps. Quantitative enzyme histochemistry was performed on tissue sections from brain, skeletal muscle, and heart to localize cytochrome oxidase activity both globally and in regions within each tissue. Significant decreases of cytochrome oxidase activity were found in the brain and skeletal muscle but not heart. In addition, regions within each tissue were also analyzed, such as cortex and striatum in the brain and red and white fibers in skeletal muscle. The tissue specific inhibition of cytochrome oxidase by sodium azide could serve as a positive control for studies of other mitochondrial toxins in aerobically compromised cells. Therefore, chronic nonlethal sodium azide administration may provide a potential rat model for the study of mitochondrial dysfunction and the role of environmental pollutants in brain and muscle tissues affected in certain neurodegenerative diseases.

Analysis of Variance↗

PubMed2006

Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms.

Endothelial dysfunction contributes to cardiovascular diseases, including hypertension, atherosclerosis, and coronary artery disease, which are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders, including type 2 diabetes mellitus and obesity, which are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Therapeutic interventions in animal models and human studies have demonstrated that improving endothelial function ameliorates insulin resistance, whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In the present review, we discuss pathophysiological mechanisms, including inflammatory processes, that couple endothelial dysfunction with insulin resistance and emphasize important therapeutic implications.

Animals↗

PubMed2001

Cytokines and oxidative signalling in skeletal muscle.

A growing body of literature indicates that cytokines regulate skeletal muscle function, including gene expression and adaptive responses. Tumour necrosis factor-alpha (TNF-alpha) is the cytokine most prominently linked to muscle pathophysiology and, therefore, has been studied most extensively in muscle-based systems. TNF-alpha is associated with muscle catabolism and loss of muscle function in human diseases that range from cancer to heart failure, from arthritis to AIDS. Recent advances have established that TNF-alpha causes muscle weakness via at least two mechanisms, accelerated protein loss and contractile dysfunction. Protein loss is a chronic response that occurs over days to weeks. Changes in gene expression required for TNF-alpha induced catabolism are regulated by the transcription factor nuclear factor-kappaB which is essential for the net loss of muscle protein caused by chronic TNF-alpha exposure. Contractile dysfunction is an acute response to TNF-alpha stimulation, developing over hours and resulting in decreased force production. Both actions of TNF-alpha involve a rapid rise in endogenous oxidants as an essential step in post-receptor signal transduction. These oxidants appear to include reactive oxygen species derived from mitochondrial electron transport. Such information provides insight into the cellular and molecular mechanisms of TNF-alpha action in skeletal muscle and establishes a scientific basis for continued research into cytokine signalling.

Animals↗

PubMed2002

Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family.

Acyl-CoA dehydrogenases (ACADs) are a family of mitochondrial enzymes catalyzing the initial rate-limiting step in the beta-oxidation of fatty acyl-CoA. The reaction provides main source of energy for human heart and skeletal muscle. Eight human ACADs have been described. Deficiency of these enzymes, especially very long-chain acyl-CoA dehydrogenase (VLCAD), usually leads to severe human organic diseases, such as sudden death in infancy, infantile cardiomyopathy (CM), hypoketotic hypoglycemia, or hepatic dysfunction. By large-scale random sequencing, we identified a novel homolog of ACADs from human dendritic cell (DC) cDNA library. It contains an open reading frame (ORF) of 1866bp, which encodes a 621 amino acid protein. It shares approximately 47% amino acid identity and 65% similarity with human VLCAD. So, the novel molecule is named as acyl-CoA dehydrogenase-9 (ACAD-9), the ninth member of ACADs. The new gene consists of 18 exons and 17 introns, and is mapped to chromosome 3q26. It contains the two signatures shared by all members of the ACADs. ACAD-9 mRNA is ubiquitously expressed in most normal human tissues and cancer cell lines with high level of expression in heart, skeletal muscles, brain, kidney, and liver. Enzymatic assay proved that the recombinant ACAD-9 protein has the dehydrogenase activity on palmitoyl-coenzyme A (C16:0) and stearoyl-coenzyme A (C18:0). Our results indicate that ACAD-9 is a novel member of ACADs.

Acyl-CoA Dehydrogenase↗

PubMed2002

Nitric oxide is not involved in the endotoxemia-induced alterations in Ca2+ and ryanodine responses in mouse diaphragms.

Lipopolysaccharide (LPS, endotoxin)-induced diaphragmatic contractile dysfunction and sarcolemmal injury in animals has been identified. However, the precise nature of sepsis-related alterations in diaphragm myofiber function and the activity of Ca(2+) release from sarcoplasmic reticulum of skeletal muscle remain unclear. The present study investigated the in vivo effects of LPS on the Ca(2+)-dependent mechanical activity and ryanodine response in mouse diaphragm and Ca(2+) release from isolated sarcoplasmic reticulum membrane vesicles, and aimed to examine the role of nitric oxide (NO) in these responses. When diaphragms were bathed in a solution that was Cl(-)-free, Na(+)-free, but contained high K(+), a Ca(2+)-induced contracture was elicited. Increases in external Ca(2+) concentration produced increases in peak tension of Ca(2+)-induced contracture in control diaphragm, while a decrease was seen in endotoxemic diaphragm. Ryanodine induced a marked contracture in control diaphragms, which was diminished after endotoxemia. This finding is correlated with the decrease of ryanodine-induced Ca(2+) release and the suppression of [(3)H]ryanodine binding on the isolated SR of the skeletal muscle from LPS-treated rats. In mice treated with LPS significantly increased levels of plasma nitrite and serum TNF-alpha were observed, changes inhibited by aminoguanidine [an inhibitor of inducible NO synthase (iNOS)] and pentoxifylline (an inhibitor of tumor necrosis factor-alpha formation), respectively. Moreover, LPS treatment resulted in a significant expression of mRNA for iNOS in mouse diaphragms. The inhibitory effects on Ca(2+)- and ryanodine responses by LPS could be prevented by treatment with polymyxin B (LPS neutralizer) and pentoxifylline, but not by treatment with dexamethasone, N(G)-nitro- L-arginine or aminoguanidine (NOS inhibitors). These results imply that the NO-related pathway may not be involved in the dysfunction of the Ca(2+) release mechanism in the sarcoplasmic reticulum of mouse diaphragm during endotoxemia.

Animals↗

PubMed2006

Reciprocal relationships between insulin resistance and endothelial dysfunction: insights from therapeutic interventions.

Endothelial dysfunction contributes to cardiovascular diseases that are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders including Type 2 diabetes, obesity, and the metabolic syndrome that are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. PI 3-kinase-dependent insulin signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct non-metabolic branches of insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 (ET-1) in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in PI 3-kinase-dependent signaling that in endothelium may cause imbalance between production of NO and secretion of ET-1 leading to decreased blood flow that worsens insulin resistance. Therapeutic interventions in both animal models and human studies demonstrate that improving endothelial function ameliorates insulin resistance while improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In this review, pathophysiological mechanisms that couple endothelial dysfunction with insulin resistance will be discussed with an emphasis on important therapeutic implications for the metabolic syndrome.

Animals↗

PubMed2004

Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin.

Vascular calcification often occurs with advancing age, atherosclerosis, various metabolic disorders such as diabetes mellitus and end-stage renal disease, or in rare genetic diseases, leading to serious clinical consequences. Such mineralization can occur at various sites (cardiac valves, arterial intima or media, capillaries), involve localized or diffuse widespread calcification, and result from numerous causes that provoke active inflammatory and osteogenic processes or disordered mineral homeostasis. Although valuable research has defined many key factors and cell types involved, surprising new insights continue to arise that deepen our understanding and suggest novel research directions or strategies for clinical intervention in calcific vasculopathies. One emerging area in vascular biology involves the RANKL/RANK/OPG system, molecules of the tumor necrosis factor-related family recently discovered to be critical regulators of immune and skeletal biology. Evidence is accumulating that such signals may be expressed, regulated, and function in vascular physiology and pathology in unique ways to promote endothelial cell survival, angiogenesis, monocyte or endothelial cell recruitment, and smooth muscle cell osteogenesis and calcification. Concerted research efforts are greatly needed to understand these potential roles, clarify whether RANKL (receptor activator of nuclear factor kappaB ligand) promotes and osteoprotegerin (OPG) protects against vascular calcification, define how OPG genetic polymorphisms relate to cardiovascular disease, and learn whether elevated serum OPG levels reflect endothelial dysfunction in patients. Overall, the RANKL/RANK/OPG system may mediate important and complex links between the vascular, skeletal, and immune systems. Thus, these molecules may play a central role in regulating the development of vascular calcification coincident with declines in skeletal mineralization with age, osteoporosis, or disease.

Animals↗

PubMed2002

Origin of symptoms in patients with cachexia with special reference to weakness and shortness of breath.

Cachexia is a complication of many disorders. It is associated with an extremely poor prognosis and many symptoms. The wasting process affects particularly skeletal muscle causing extreme fatigue and weakness. In many underlying conditions associated with cachexia, the patient also suffers an often unexplained severe dyspnoea along with weakness, asthenia and exhaustion. There appears to be marked similarities in the cause of dyspnoea and fatigue between different cachectic conditions. Using the example of cardiac cachexia, this article reviews the evidence linking skeletal muscle reflex inputs to ventilatory control and exaggerated chemoreflex responses as candidates for the heightened perception of dyspnoea which cannot be explained by heart or lung dysfunction in many patients. Evidence is reviewed that similar processes may occur in other cachexias, especially those complicating cancer, AIDS, chronic liver disease, and chronic lung disease. Potential novel therapeutic strategies to combat these cachexia symptoms are reviewed.

Cachexia↗

PubMed2002

Decreased erythrocyte insulin binding in hypertensive subjects with hyperinsulinemia.

BACKGROUND: This study investigates erythrocyte insulin receptor binding and affinity in subjects with hypertension and hyperinsulinemia. Insulin receptor-binding function has not been extensively studied in hypertensive subjects. METHODS: Insulin receptor density, binding affinity, and protein tyrosine kinase activity were measured in erythrocytes from 18 hypertensive and 16 normotensive subjects. Insulin sensitivity was measured by the fasting plasma insulin/glucose ratio and the homeostatic assessment model algorithm (HOMA) index. Erythrocyte insulin binding was determined by a competitive binding assay and protein tyrosine kinase activity was measured by an enzyme-linked immunoabsorbent assay technique. RESULTS: Fasting plasma insulin/glucose ratio and the insulin resistance index (HOMA) were significantly higher in the hypertensive versus normotensive subjects. Receptor saturation of the high affinity binding sites (Bmax) was reduced in the hypertensive versus control subjects. The Kd values were lower in the erythrocytes from hypertensive than control subjects. Insulin-induced protein tyrosine kinase activity was decreased in erythrocytes from hypertensive versus control subjects. CONCLUSIONS: A reduced erythrocyte insulin receptor density and tyrosine protein kinase activity may reflect insulin receptor dysfunction in hypertensive individuals who have insulin resistance and hyperinsulinemia. More information is needed examining insulin receptor function in other target tissues such as fat or skeletal muscle cells before defects in the insulin receptor can be firmly proposed as a cause of the metabolic syndrome.

Adult↗

PubMed1996

The assessment of trapezius muscle symptoms of patients with temporomandibular disorders by the use of liquid crystal thermography.

OBJECTIVE: To test the hypothesis that neuromuscular symptoms of patients with temporomandibular disorders that occur in the upper back and neck can be evaluated by recording the temperature patterns in the skin overlying the muscles. STUDY DESIGN: Liquid crystal contact thermography was evaluated on patients with temporomandibular disorders to demonstrate temperature changes in the muscles of the neck and upper back. The study consisted of 22 patients with temporomandibular disorders and 22 normal controls. RESULTS: The mean right-versus-left-side temperature difference of the control group was 0.13 degree C whereas the patient group showed a difference of 0.78 degree C. Of the 22 patients with temporomandibular disorders, 21 (95.5%) showed an increased temperature over the trapezius muscle on the symptomatic side. CONCLUSIONS: These findings indicate that thermography may be useful in the diagnosis of myofascial symptoms that may be associated with temporomandibular disorders.

Adult↗

PubMed2003

Different expressions of X-linked cardiomyopathy in monozygotic triplets with Becker's dystrophy.

Cardiac involvement is common in skeletal muscles disorders associated with dystrophin defect. It has been suggested however, that X-linked dilated cardiomyopathies with minimal or absent skeletal disease are distinct entities, resulting from mutations in cardiac-specific regions of dystrophin gene. This study presents a unique observation of phenotypic variability in monozygotic triplets with Becker's muscular dystrophy. The expressions of the disease range from severe peripheral myopathy to severe congestive heart failure. No deletion in dystrophin gene was observed and the mechanisms responsible for selective impairment of morphologically and functionally different muscles in three monozygotic siblings remain unclear.

Adult↗