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At least 253 records · Page 14Linked to original sources

PubMed2002

Sodium channel gating: no margin for error.

Voltage-gated Na(+) channels are the workhorses of spike generation and propagation in excitable cells. Mutations in Na(+) channel genes have been identified in disorders causing episodic dysfunction of heart, skeletal muscle, and brain. Lossin and colleagues from Al George's lab report in this issue of Neuron that three missense mutations of SCN1A found in a dominant epilepsy syndrome disrupt inactivation, thereby producing small persistent inward Na(+) currents that may result in hyperexcitability and seizures.

Epilepsy↗

PubMed2000

Conditioned nutritional requirements and the pathogenesis and treatment of myocardial failure.

The majority of symptomatic patients with congestive heart failure have been shown to be significantly malnourished. Myocardial and skeletal muscle energy reserves are also diminished. Total daily energy expenditure in these patients is less than that in control individuals, and high protein-calorie feeds do not reverse the abnormalities; thus, the wasting that occurs in patients with congestive heart failure is metabolic rather than because of negative protein-calorie balance. Several specific deficiencies have been found in the failing myocardium: a reduction in the content of L-carnitine, coenzyme Q10, creatine and thiamine, nutrient cofactors that are important for myocardial energy production; a relative deficiency of taurine, an amino acid that is integral to the modulation of intracellular calcium levels; and an increase in myocardial oxidative stress, and a reduction of both endogenous and exogenous antioxidant defences. In addition, these processes may influence skeletal muscle metabolism and function. Cellular nutritional requirements conditioned by metabolic abnormalities in heart failure are important considerations in the pathogenesis of the skeletal and cardiac muscle dysfunction. A comprehensive restoration of adequate myocyte nutrition would seem to be essential to any therapeutic strategy designed to benefit patients suffering from this disease.

Calcium↗

PubMed1998

Alterations in heart failure of cyclic AMP-dependent inotropic and lusitropic properties of cardiac and skeletal muscle.

A central working hypothesis in our laboratory is that deficient cellular cyclic AMP concentrations may be responsible, at least in part, for striated muscle dysfunction, both cardiac and skeletal, in heart failure. These results suggest that therapy aimed at restoring cyclic AMP to normal levels may be effective with regard to improving systolic and diastolic function in the heart and may decrease the development of fatigue in skeletal muscle of patients with failure. The use of cyclic AMP-dependent drugs in clinical practice has been limited by side effects associated with raising total cellular content of this cyclic nucleotide. However, evidence suggesting that separate pools of cyclic AMP may exist within the cell raises the possibility that those pools associated with excitation/contraction coupling could serve as more specific therapeutic targets.

Animals↗

PubMed2005

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.

BACKGROUND: Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. METHODS: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). RESULTS: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). CONCLUSIONS: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

Administration, Oral↗

PubMed2005

Hyperleptinemia: protecting the heart from lipid overload.

In this review, we attempt to deduce teleologically the physiological mission of leptin. Because overnutrition and diet-induced obesity are the only known causes of hyperleptinemia, we contrast the differences in overnutrition in normally leptinized rodents, in which the added lipids are confined to adipocytes, with those of unleptinized rodents, in which the added lipids are distributed in liver, pancreatic islets, and heart and skeletal muscle, causing organ dysfunction and cell death with a disease cluster resembling metabolic syndrome. We focus here on lipid-induced cardiac dysfunction and the remarkable ability of hyperleptinemia to prevent it. We conclude that the hyperleptinemia of overnutrition prevents the ectopic lipid deposition by: (1) acting on hypothalamic appetite centers to limit the caloric surplus to fit the available adipocyte storage capacity and, (2) upregulating of fatty acid oxidation and downregulating lipogenesis in peripheral tissues to minimize ectopic lipid deposition. The causes of failure of this system and its clinical consequences are discussed.

Animals↗

PubMed1983

Tools of behavioral medicine: applications of biofeedback treatment for children and adolescents.

This article reviews the role of biofeedback as a tool in behavioral medicine with applications for children and adolescents. Biofeedback as a method for enhancing self-regulation and criteria for prescribing biofeedback interventions are detailed. Clinical and research investigations are reviewed to demonstrate the usefulness of biofeedback in a variety of clinical situations: headache, asthma, hyperactivity, skeletal and smooth muscle dysfunctions, anxiety states, and emotional disorders. Practical guidelines are presented for improving the effectiveness of biofeedback training procedures within a clinical setting and for improving generalization of training to the child's daily life.

Adolescent↗

PubMed1996

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Analysis of Variance↗

PubMed1990

Alcohol and skeletal muscle disease.

Skeletal muscle myopathy is caused by prolonged ethanol misuse and affects between half and two-thirds of chronic alcohol misusers. This chronic myopathy is characterized by a selective reduction in Type II (fast twitch) fibre area; Type I (slow twitch) fibres are relatively unaffected. The myopathy is not mediated by the patients' corticosteroid and nutritional status, liver dysfunction or neurological changes, and there is little correlation between alcoholic myopathy and alcohol intake. However, plasma alpha-tocopherol and selenium levels in myopathic alcoholics are reduced. The myopathy may in some way be related to the reduced fractional rates of skeletal muscle protein synthesis that occur in alcohol misusers and implicates free radical reactions in the pathogenesis of the myopathy. We have established a rat model of chronic alcoholic myopathy. In this model anatomically distinct skeletal muscles were taken to represent Type I (i.e. soleus) or Type II (i.e. plantaris) fibres. There were selective losses of Type II muscle protein at the end of 6 weeks of ethanol feeding. These changes were also not apparently mediated by nutritional limitations, neurological changes or liver dysfunction. Skeletal muscle protein synthesis was also reduced, as was plasma alpha tocopherol and selenium levels. Thus the rat model is amendable for further work to elucidate the molecular mechanisms responsible for alcohol-induced muscle loss.

Alcoholism↗

PubMed2004

NOS upregulation attenuates vascular endothelial dysfunction in the late phase of ischemic preconditioning in skeletal muscle.

Previously, we have demonstrated a late phase protection of ischemic preconditioning in the microcirculation of cremaster muscle. This microvascular protection was blocked by a non-specific NOS inhibitor. The purpose of present study was to evaluate endothelial function in the terminal arteriole of cremaster muscle after 24-h of ischemic preconditioning followed by 4-h warm ischemia and to evaluate eNOS and iNOS gene and protein expression at 24 h after ischemic preconditioning in the cremaster muscle. A vascular pedicle isolated cremaster muscle in male SD rats underwent 45-min of ischemic preconditioning and 24 h later, 4-h of warm ischemia followed by reperfusion. Endothelial-dependent and -independent vasodilatation was evaluated on day 2 after 4-h ischemia and 60-min of reperfusion. Cremaster muscles were harvested at 24 h after ischemic preconditioning for measuring of eNOS and iNOS gene expression by reverse transcriptase polymerase chain reaction (RT-PCR) and protein expression by western blotting analysis. We found that IPC significantly attenuated endothelial dysfunction induced by 4-h warm ischemia and reperfusion. The expression of eNOS and iNOS mRNA shown a 229% and 135% increase respectively in IPC treated cremaster muscles as compared to normal cremaster muscles (P<0.05). The expression of eNOS and iNOS protein exhibited a 133% and 148% increase respectively in IPC treated cremaster muscles as compared to normal cremaster muscles (P<0.05). There was no statistically significant difference between normal cremaster muscle and sham IPC treated cremaster muscle. The results suggest that IPC preventing vascular endothelial dysfunction from ischemia/reperfusion injury may be due to the enhanced NOS expression. These results combined with the results from our previous studies suggest that IPC-induced microvascular protection in the skeletal muscle may act through a NOS-dependent mechanism.

Acetylcholine↗

PubMed2000

Influence of vibration to the neck, trunk and lower extremity muscles on equilibrium in normal subjects and patients with unilateral labyrinthine dysfunction.

To investigate the role of proprioceptors of different skeletal muscles in postural control, in normal subjects and patients with unilateral labyrinthine dysfunction (ULD), the effect of vibration on these muscles was studied by postulography. The subjects comprised 59 normal subjects and 12 patients with ULD due to resection of acoustic tumours. Sagittal body sway was observed during vibration to the triceps surae, tibialis anterior and upper dorsal neck muscles. No significant change in sway was observed in the frontal plane in normal subjects. Significant differences between normal subjects and patients were found on stimulation of the muscle groups of triceps surae and biceps femoris during vibration. In patients with ULD, vibration to the dorsal neck muscles caused a deviation towards the diseased side. It can be speculated that the upper dorsal neck muscle plays an important role in maintaining the body balance in the frontal plane in patients with ULD. On the other hand, the lower extremity muscles, especially the muscles on the dorsal side of the body, play a significant role in adjusting the standing posture in the sagittal plane.

Adult↗

PubMed2004

Adult skeletal muscle stem cells differentiate into endothelial lineage and ameliorate renal dysfunction after acute ischemia.

We previously demonstrated that endothelial cells are severely damaged during renal ischemia-reperfusion and that transplantation of adult human endothelial cells into athymic nude rats subjected to renal ischemia resulted in a dramatic protection of the kidney against injury and dysfunction. Morphological studies demonstrated the engraftment of transplanted cells into renal microvasculature. The goal of the present study was to determine the potential efficacy of in vitro expanded skeletal muscle-derived stem cells (MDSC) differentiated along the endothelial lineage in ameliorating acute renal injury. MDSC obtained from the Tie-2-green fluorescent protein (GFP) mice were used as donors of differentiated and nondifferentiated stem cells. FVB mice, used as recipients, were subjected to renal ischemia and transplanted with the above MDSC. The differentiation of MDSC along the endothelial lineage was monitored by the appearance of Tie-2 promotor-driven expression of GFP. These mouse endothelial cell antigen-, endothelial nitric oxide synthase (eNOS)-, Flk-1-, Flt-1-, and CD31-positive cells engrafted into renal microvasculature and significantly protected short-term renal function after ischemia. Transplantation of nondifferentiated MDSC characterized by the expression of Sca-1 (low levels of CD34, Flk-1, and cKit, and negative for GFP, eNOS, and CD31) did not improve short-term renal dysfunction. In conclusion, the data 1) provide a rich source of MDSC, 2) delineate protocols for their in vitro expansion and differentiation along the endothelial lineage, and 3) demonstrate their efficacy in preserving renal function immediately after ischemic insult.

Acute Disease↗

PubMed2005

Regeneration of dystrophin-expressing myocytes in the mdx heart by skeletal muscle stem cells.

Cell transplantation holds promise as a potential treatment for cardiac dysfunction. Our group has isolated populations of murine skeletal muscle-derived stem cells (MDSCs) that exhibit stem cell-like properties. Here, we investigated the fate of MDSCs after transplantation into the hearts of dystrophin-deficient mdx mice, which model Duchenne muscular dystrophy (DMD). Transplanted MDSCs generated large grafts consisting primarily of numerous dystrophin-positive myocytes and, to a lesser degree, dystrophin-negative non-myocytes that expressed an endothelial phenotype. Most of the dystrophin-positive myocytes expressed a skeletal muscle phenotype and did not express a cardiac phenotype. However, some donor myocytes, located at the graft-host myocardium border, were observed to express cardiac-specific markers. More than half of these donor cells that exhibited a cardiac phenotype still maintained a skeletal muscle phenotype, demonstrating a hybrid state. Sex-mismatched donors and hosts revealed that many donor-derived cells that acquired a cardiac phenotype did so through fusion with host cardiomyocytes. Connexin43 gap junctions were not expressed by donor-derived myocytes in the graft. Scar tissue formation in the border region may inhibit the fusion and gap junction connections between donor and host cells. This study demonstrates that MDSC transplantation warrants further investigation as a potential therapy for cardiac dysfunction in DMD.

Animals↗

PubMed2003

Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans.

The hypothesis that the aging process is associated with mitochondrial dysfunction and oxidative stress has been investigated in human skeletal muscle. Muscle biopsy samples were taken from seven old male subjects [OS; 75 (range 61-86) years] and eight young male subjects [YS; 25 (22-31) years]. Oxidative function was measured both in permeabilised muscle fibres and isolated mitochondria. Despite matching the degree of physical activity, OS had a lower training status than YS as judged from pulmonary maximal O(2) consumption ( Vdot;O(2)max, -36%) and handgrip strength (-20%). Both maximal respiration and creatine-stimulated respiration were reduced in muscle fibres from OS (-32 and -34%, respectively). In contrast, respiration in isolated mitochondria was similar in OS and YS. The discrepancy might be explained by a biased harvest of "healthy" mitochondria and/or disruption of structural components during the process of isolation. Cytochrome C oxidase was reduced (-40%, P<0.01), whereas UCP3 protein tended to be elevated in OS ( P=0.09). Generation of reactive oxygen species by isolated mitochondria and measures of antioxidative defence (muscle content of glutathione, glutathione redox status, antioxidative enzymes activity) were not significantly different between OS and YS. It is concluded that aging is associated with mitochondrial dysfunction, which appears to be unrelated to reduced physical activity. The hypothesis of increased oxidative stress in aged muscle could not be confirmed in this study.

Adult↗

PubMed1994

Peripheral factors in the management of congestive heart failure.

Maladaptive changes in the periphery largely account for the symptomatology of patients with congestive heart failure (CHF). A decline in the systolic function of the left ventricle precipitates activation of neural and humoral systems to provide circulatory support. These include sympathetic release of norepinephrine, increases in angiotensin II, elevated levels of circulating arginine vasopressin, and impairment of the counterregulatory function of atrial natriuretic peptide. The resultant circulatory changes are ultimately responsible for the declining function of the peripheral vasculature and skeletal muscles of patients with CHF. In the peripheral vasculature, impaired vasodilatory capacity results from excess vessel wall stiffness, endothelial dysfunction, and structural abnormalities. The skeletal muscles develop poor aerobic capacity as a result of a change in predominant fiber type and excess reliance on glycolytic metabolic pathways. Physical deconditioning induced by symptoms tends to further promote these peripheral changes. Therapeutic interventions with symptomatic and prognostic benefits have essentially been targeted at the periphery. Angiotensin converting enzyme inhibitors may act by normalizing electrolyte and water balance, improving vascular endothelial function, and reversing structural changes in peripheral vessels. Exercise training appears to exert its benefit at the level of the vascular endothelium. Advances in the therapy of CHF depend on a greater understanding of changes in the periphery.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1986

Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential.

Lethal infections are associated with cellular dysfunction as evidenced by a decrease in the resting transmembrane potential difference (Em) of skeletal muscle fibers. Endotoxin stimulation of macrophages evokes production of cachectin, a protein that has been implicated as a mediator of the lethal effects of endotoxemia. In the present study, rat skeletal muscle fiber Em decreased when incubated with recombinant human cachectin. The reduction of Em induced by cachectin occurred in a dose-related fashion and was inhibited by mAb against the monokine. Infusion of cachectin induced a decline of skeletal muscle Em in vivo, and suggests that cachectin may acutely mediate alterations of skeletal muscle membrane function after infection.

Animals↗

PubMed2002

Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors.

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.

Animals↗

PubMedDate not supplied

A case of neuroleptic malignant syndrome with acute renal failure after the discontinuation of sulpiride and maprotiline.

A 46-year-old man developed neuroleptic malignant syndrome with acute myoglobinuric renal failure after the discontinuation of sulpiride and maprotiline treatment. He showed the characteristic features of hyperpyrexia, altered consciousness, muscle rigidity, and autonomic dysfunction. Laboratory data showed lysis of skeletal muscle cells and renal impairment. Muscle biopsy revealed necrosis and regenerative changes in muscle fibers. Renal biopsy showed focal tubulitis and interstitial infiltration of small inflammatory cells. The combination of sulpiride and maprotiline has not previously been reported to be the cause of neuroleptic malignant syndrome and acute myoglobinuric renal failure.

Acute Kidney Injury↗

PubMed1996

Mechanisms of postischemic injury in skeletal muscle: intervention strategies.

Reperfusion of ischemic skeletal muscle leads to adverse local and systemic effects. These detrimental effects may be attenuated by interfering with or modulating the pathophysiological processes that are set in motion during ischemia and/or reperfusion. The purpose of this paper is to review the different intervention strategies that have been employed in an attempt to elucidate the mechanisms involved in the pathogenesis of skeletal muscle ischemia-reperfusion injury. The results of these studies indicate that the postischemic injury processes that lead to cell dysfunction and death are multifactorial in nature and include oxidant generation, elaboration of proinflammatory mediators, infiltration of leukocytes, Ca2+ overload, phospholipid peroxidation and depletion, impaired nitric oxide metabolism, and reduced ATP production. Although the etiopathogenesis of skeletal muscle ischemia-reperfusion is complex, careful delineation of the mechanisms that contribute to postischemic microvascular dysfunction and muscle necrosis has progressed to the point where rational intervention strategies may be proposed and implemented as potential treatments for skeletal muscle dysfunction associated with ischemia-reperfusion.

Animals↗