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At least 1,027 records · Page 57Linked to original sources
PubMed2006

Dynamic responses of the glutathione system to acute oxidative stress in dystrophic mouse (mdx) muscles.

The precise mechanisms underlying skeletal muscle damage in Duchenne muscular dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation, with subsequent reperfusion during rest, has been documented. Therefore, one possibility is the presence of increased oxidative stress. We applied a model of acute hindlimb ischemia/reperfusion (I/R) in mdx mice (genetic homolog of DMD) to evaluate dynamic in vivo responses of dystrophic muscles to this form of oxidative stress. Before the application of I/R, mdx muscles showed: 1) decreased levels of total glutathione (GSH) with an increased oxidized (GSSG)-to-reduced (GSH) glutathione ratio; 2) greater activity of the GSH-metabolizing enzymes glutathione peroxidase (GPx) and glutathione reductase; and 3) lower activity levels of NADP-linked isocitrate dehydrogenase (ICDH) and aconitase, two metabolic enzymes that are sensitive to inactivation by oxidative stress and also implicated in GSH regeneration. Interestingly, nondystrophic muscles subjected to I/R exhibited similar changes in total glutathione, GSSG/GSH, GPx, ICDH, and aconitase. In contrast, all of the above remained stable in mdx muscles subjected to I/R. Taken together, these results suggest that mdx muscles are chronically subjected to increased oxidative stress, leading to adaptive changes that attempt to protect (although only in part) the dystrophic muscles from acute I/R-induced oxidative stress. In addition, mdx muscles show significant impairment of the redox-sensitive metabolic enzymes ICDH and aconitase, which may further contribute to contractile dysfunction in dystrophic muscles.

Aconitate Hydratase↗
PubMed2002

Cardiac abnormalities in patients with mitochondrial DNA mutation 3243A>G.

BACKGROUND: Tissues that depend on aerobic energy metabolism suffer most in diseases caused by mutations in mitochondrial DNA (mtDNA). Cardiac abnormalities have been described in many cases, but their frequency and clinical spectrum among patients with mtDNA mutations is unknown. METHODS: Thirty-nine patients with the 3243A>G mtDNA mutation were examined, methods used included clinical evaluation, electrocardiogram, Holter recording and echocardiography. Autopsy reports on 17 deceased subjects were also reviewed. The degree of 3243A>G mutation heteroplasmy was determined using an Apa I restriction fragment analysis. Better hearing level (BEHL0.5-4 kHz) was used as a measure of the clinical severity of disease. RESULTS: Left ventricular hypertrophy (LVH) was diagnosed in 19 patients (56%) by echocardiography and in six controls (15%) giving an odds ratio of 7.5 (95% confidence interval; 1.74-67). The dimensions of the left ventricle suggested a concentric hypertrophy. Left ventricular systolic or diastolic dysfunction was observed in 11 patients. Holter recording revealed frequent ventricular extrasystoles (>10/h) in five patients. Patients with LVH differed significantly from those without LVH in BEHL0.5-4 kHz, whereas the contribution of age or the degree of the mutant heteroplasmy in skeletal muscle to the risk of LVH was less remarkable. CONCLUSIONS: Structural and functional abnormalities of the heart were common in patients with 3243A>G. The risk of LVH was related to the clinical severity of the phenotype, and to a lesser degree to age, suggesting that patients presenting with any symptoms from the mutation should also be evaluated for cardiac abnormalities.

Arrhythmias, Cardiac↗
PubMed1989

Effect of denervation on loss of ions in chick skeletal muscle.

Leaching behaviour of chick gastrocnemius muscle has been studied with respect to the loss of Na+, K+ and Ca2+ ions in a donor-solvent (muscle-water) system under normal as well as denervated conditions. An attempt has been made to explain the alterations in the rate of electrolytic loss in terms of membrane dysfunctions induced as a result of loss of neural control.

Animals↗
PubMed2005

Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington's disease.

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the IT-15 gene; however, it remains unknown how the mutation leads to selective neurodegeneration. Several lines of evidence suggest impaired mitochondrial function as a component of the neurodegenerative process in HD. We assessed energy metabolism in the skeletal muscle of 15 HD patients and 12 asymptomatic mutation carriers in vivo using 31P magnetic resonance spectroscopy. Phosphocreatine recovery after exercise is a direct measure of ATP synthesis and was slowed significantly in HD patients and mutation carriers in comparison to age- and gender-matched healthy controls. We found that oxidative function is impaired to a similar extent in manifest HD patients and asymptomatic mutation carriers. Our findings suggest that mitochondrial dysfunction is an early and persistent component of the pathophysiology of HD.

Adenosine Triphosphate↗
PubMed1999

Fibre type characteristics and function of the human paraspinal muscles: normal values and changes in association with low back pain.

This review focuses on the role of the paraspinal muscles in relation to the development and existence of low back pain. It begins with a discussion of the deficits in paraspinal muscle strength and fatigue-resistance observed in low back pain patients and addresses the issue of 'cause or effect' with respect to muscle dysfunction and back pain. Our current knowledge regarding the 'normal' fibre type characteristics of the human erector spinae is then presented and the influence of these fibre type characteristics on the muscle's performance capacity is discussed. Alterations in the 'microanatomy' of the musculature in connection with low back pain, and the associated implications for the performance capacity of the patient, are then considered. Finally, a number of outstanding issues in relation to the clinical significance of back muscle dysfunction are identified, leading to the proposal of areas for future research.

Electromyography↗
PubMed2005

Soleus and EDL muscle contractility across the lifespan of female C57BL/6 mice.

All previous aging research on the contractility of rodent skeletal muscle has been conducted on male rodents. Because males and females age differently, we undertook this study to determine if and when age-related decrements in skeletal muscle contractility occur in female mice. Soleus and extensor digitorum longus (EDL) muscles from female C57BL/6 mice aged approximately 4, 8, 16, 24 and 28 mo were assessed in vitro for contractility and subsequently contractile protein content. EDL muscle was resistant to age-related changes in force generation but displayed characteristics of becoming more slow-twitch like. Maximal isometric tetanic force (Po) generated by soleus muscle declined with age. Soleus muscle size and contractile protein contents were not affected by age and thus could not explain the age-related force decrements. Soleus muscle specific Po declined with age being approximately 26% lower in muscles of 16-28 mo-old mice indicating that a deterioration in soleus muscle quality of female mice occurred beginning around the age of ovarian failure. Thus this study provides essential, comprehensive baseline data for future studies on age-related muscle dysfunction in the female mouse.

Aging↗
PubMed2002

Identifying the links between obesity, insulin resistance and beta-cell function: potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes.

A combination of insulin resistance and pancreatic beta-cell dysfunction underlies most cases of type 2 diabetes. While the interplay of these two impairments is believed to be important in the development and progression of type 2 diabetes, the mechanisms involved are unclear. A number of factors have been suggested as possibly linking insulin resistance and beta-cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) have deleterious effects on both glucose homeostasis and beta-cell function, and can disrupt insulin signalling pathways in both pancreatic beta cells and liver and adipose tissue. The anti-inflammatory activity of the thiazolidinedione anti-diabetic agents is potentially beneficial, given the possible role of pro-inflammatory cytokines in linking insulin resistance with beta-cell dysfunction.

Adipocytes↗
PubMed2004

The overtraining syndrome in athletes: a stress-related disorder.

Physical exercise is a type of allostatic load for several endocrine systems, notably the hypothalamic-pituitary-adrenal (HPA) axis. Athletes undergoing a strenuous training schedule can develop a significant decrease in performance associated with systemic symptoms or signs: the overtraining syndrome (OTS). This is a stress-related condition that consists of alteration of physiological functions and adaptation to performance, impairment of psychological processing, immunological dysfunction and biochemical abnormalities. Universally agreed diagnostic criteria for OTS are lacking. The pituitary-adrenal response to a standardized exercise test is usually reduced in overtrained athletes. This HPA dysfunction could reflect the exhaustion stage of Selye's general adaptation syndrome. The most attractive hypothesis that accounts for the observed neuro-endocrine-immune dysregulation is the Smith's cytokine hypothesis of OTS. It assumes that physical training can produce muscle and skeletal trauma, thus generating a local inflammatory reaction. With the excessive repetition of the training stimulus the local inflammation can generate a systemic inflammatory response. The main actors of these processes are the cytokines, polypeptides that modulate HPA function in and outside the brain at nearly every level of activity. It is hoped that future research will focus on endogenous risk factors for morbidities related to the neuro-endocrine-immune adaptation to exercise.

Adaptation, Physiological↗
PubMed2000

EMG and strength correlates of selected shoulder muscles during rotations of the glenohumeral joint.

OBJECTIVE: To identify activation patterns of several muscles acting on the shoulder joint during isokinetic internal and external rotation. DESIGN: Combined EMG and isokinetic strength analysis in healthy subjects. BACKGROUND: EMG studies of the shoulder region revealed intricate muscular activation patterns during elevation of the arm but no parallel studies regarding pure rotations of the joint could be located. METHODS: Fifteen (n=30 shoulders) young, asymptomatic male subjects participated in the study. Strength production during isokinetic concentric and eccentric internal and external rotations at 60 and 180 degrees /s was correlated with the EMG activity of the rotator cuff, biceps, deltoid and pectoralis major. Analysis of the smoothed EMG related to the timing of onset of the signal and to the normalized activity at the angle of the peak moment. Determination of the association between the EMG and the moment was based on strength ratios. RESULTS: Findings indicated that for both types of rotations, the rotator cuff and biceps were active 0.092+/-0.038-0.215+/-0.045 s prior to the initiation of the actual movement and 0.112-0.034 s prior to onset of deltoid and pectoralis major activity. These differences were significant in all of the eight conditions (P<0.05). In terms of the strength ratios, strong association was found between electrical activity and moment production in the subscapularis and infraspinatus (r(2)=0.95 and 0. 72, respectively) at the low and high angular velocities. CONCLUSIONS: Prior to actual rotation of the shoulder joint, normal recruitment of the rotator cuff and biceps is characterized by a non-specific presetting phase which is mainly directed at enhancing the joint 'stiffness' and hence its stability. Once movement is in progress, the EMG patterns of these muscles become movement specific and are correlated with the resultant moment. RELEVANCE: Muscular dysfunction relating to delayed onset activity or altered activation patterns, due to pain, perturbed mechanics or disturbed neural activation have been implicated as concomitant factors in other joint associated pathologies. Through highlighting the role of the rotator cuff in shoulder joint rotations, this study lends further support to the argument that a parallel situation may prevail with respect to shoulder joint dysfunction. This could lead to the development of rehabilitation protocols aimed specifically at redressing such dysfunction.

Adolescent↗
PubMed1998

Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog.

The aim of the present study was to determine whether cardiac nitric oxide (NO) production changes during the progression of pacing-induced heart failure and whether this occurs in association with alterations in myocardial metabolism. Dogs (n=8) were instrumented and the heart paced until left ventricular end-diastolic pressure reached 25 mm Hg and clinical signs of severe failure were evident. Every week, hemodynamic measurements were recorded and blood samples were withdrawn from the aorta and the coronary sinus for measurement of NO metabolites, O2 content, free fatty acids (FFAs), and lactate and glucose concentrations. Cardiac production of NO metabolites or consumption of O2 or utilization of substrates was calculated as coronary sinus-arterial difference times coronary flow. In end-stage failure, occurring at 29+/-1.6 days, left ventricular end-diastolic pressure was 25+/-1 mm Hg, left ventricular systolic pressure was 92+/-3 mm Hg, mean arterial pressure was 75+/-2.5 mm Hg, and dP/dtmax was 1219+/-73 mm Hg/s (all P<0.05). These changes in hemodynamics were associated with a fall of cardiac NO metabolite production from 0.37+/-0.16 to -0.28+/-0.13 nmol/beat (P<0.05). O2 consumption and lactate uptake did not change significantly from control, while FFA uptake decreased from 0.16+/-0.03 to 0.05+/-0.01 microEq/beat and glucose uptake increased from -2.3+/-7.0 to 41+/-10 microgram/beat (P<0.05). The cardiac respiratory quotient also increased significantly by 28%. In 14 normal dogs the same measurements were performed at control and 1 hour after we injected 30 mg/kg of nitro-L-arginine, a competitive inhibitor of NO synthase .O2 consumption increased from 0.05+/-0.002 mL/beat at control to 0.071+/-0.003 mL/beat after nitro-L-arginine, while FFA uptake decreased from 0.1+/-0.01 to 0.06+/-0.01 microEq/beat, lactate uptake increased from 0.15+/-0.04 to 0.31+/-0.03 micromol/beat, glucose uptake increased from 8.2+/-5.0 to 35.4+/-9.5 microgram/beat, and RQ increased by 23% (all P<0.05). Our results indicate that basal cardiac production of NO falls below normal levels during cardiac decompensation and that there are shifts in substrate utilization. This switch in myocardial substrate utilization also occurs after acute pharmacological blockade of NO production in normal dogs.

Animals↗
PubMedDate not supplied

Masticatory myofascial pain: an explanatory model integrating clinical, epidemiological and basic science research.

Masticatory myofascial pain (MMP) is a regional muscle pain disorder characterized by localized muscle tenderness in taut bands of skeletal muscles and pain and is one of the most common causes of persistent regional pain. The affected muscles may also display an increased fatigability, stiffness, subjective weakness, pain in movement, and slight restricted ROM that is unrelated to joint restriction. Although the exact etiology of MMP is unclear, recent research has improved our understanding of factors that contribute to the development and progression of MMP. Understanding these factors can help to validate an explanatory model for etiology and treatment of MMP. This model includes peripheral mechanisms from local biomechanical strain leading to the onset of early cases of MMP while central mechanisms associated with psychosocial factors lead to increased chronicity of MMP. As MP persists, chronic pain characteristics often precede or follow it's development. Management of the syndrome naturally follows from this model with therapy to rehabilitate the trigger points (TrPs) while focusing effort on reducing all contributing factors.

Adaptation, Psychological↗
PubMed1988

Kinetics of drug action in disease states. XXVII. Effect of experimental renal failure on the pharmacodynamics of zoxazolamine and chlorzoxazone.

The purpose of this investigation was to determine whether the pharmacodynamics of the centrally acting skeletal muscle relaxants zoxazolamine (ZOX) and chlorzoxazone (CZX) are altered in renal failure. Male Lewis rats with renal failure due to bilateral ligation of ureters and sham-operated controls (ZOX and CZX), as well as rats with uranyl nitrate-induced renal dysfunction and saline-injected controls (ZOX only), received an infusion of ZOX or CZX until onset of loss of righting reflex. Drug concentrations in serum, brain and cerebrospinal fluid at that time were substantially lower in animals with renal failure or dysfunction than in normal controls. The ZOX concentrations in the cerebrospinal fluid correlated negatively with indices of renal function (serum creatinine and urea concentrations). Administration of a concentrated dialyzate of serum from rats with uranyl nitrate-induced renal dysfunction to normal animals also decreased the concentrations of ZOX at onset of loss of righting reflex. Thus, the sensitivity of the central nervous system of rats to the depressant action of ZOX and CZX is significantly increased by renal failure. This effect appears to be mediated, at least in part, by an endogenous, dialyzable substance that accumulates in the blood of rats with impaired renal function.

Acute Kidney Injury↗
PubMed1995

The childhood muscular dystrophies: diseases sharing a common pathogenesis of membrane instability.

New observations demonstrate that several childhood forms of muscular dystrophy share a common pathogenesis. In muscle, dystrophin occurs as part of a membrane complex (dystrophin-glycoprotein) linking the cytoskeleton to the basal lamina. In Duchenne muscular dystrophy, dystrophin deficiency disrupts the linkage of the integral glycoproteins of the sarcolemma and leads to muscle fiber necrosis. In severe childhood autosomal recessive muscular dystrophy, a selective deficiency of adhalin (50-kd glycoprotein) also causes dysfunction of the dystrophin-glycoprotein complex. Most recently, a form of congenital muscular dystrophy demonstrates deficiency of laminin M (merosin) further demonstrating that sarcolemmal instability results from defects in structural proteins of the basal lamina. Animal models have been identified also demonstrating defects in specific proteins linking the subsarcolemmal cytoskeleton to the extracellular matrix. The mdx mouse has a defect in the gene encoding dystrophin. The cardiomyopathic hamster shows a specific deficiency of adhalin in skeletal muscle. The dy/dy mouse has been found deficient in merosin. These animal models will help researchers to understand their human counterparts and provide a system for testing therapeutic strategies.

Animals↗
PubMed1993

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Heart failure-related myopathy. Clinical and pathophysiological insights.

AIMS: To evaluate the relationship of skeletal and respiratory muscular dysfunction with the degree of clinical severity, cardiac impairment and exercise intolerance in patients with chronic heart failure. METHODS AND RESULTS: Ninety-one patients (age 52.7+/-8 years) on standard therapy and in a stable clinical condition with normal nutritional status underwent evaluation of (1) clinical severity and metabolic status (NYHA class, weight, albuminaemia, natraemia, cortisol, insulin, neurohormones), (2) cardiac function (Echo, right heart catheterization), (3) exercise tolerance (peak VO(2)), (4) dynamic isokinetic forces of the quadriceps and hamstring (Cybex method), and respiratory muscle strength (maximal inspiratory and expiratory pressures). Fifty patients had a peak VO(2)<14 ml x kg(-1) x min(-1)(10.6+/-2) and 41 had values >/=14 (18.3+/-4). In the former group, leg and respiratory strength were significantly lower (extensors: 80+/-24 vs 100.9+/-22 Nm; flexors: 48.5+/-24 vs 75.3+/-22, both P<0.001; maximal expiratory pressure: 85.5+/-30 vs 104.8+/-31, P<0.01). Muscular strength was not related to indices of clinical severity, metabolic status, neurohormones or to the degree of systolic/diastolic cardiac function, but it was related to weight and age. Multivariate analysis of the peak VO(2)with clinical, haemodynamic and peripheral indicators showed weight (beta= 0.32, P = 0.007), muscular strength (beta= 0.32, P = 0.01) and NYHA class (beta= 0.31, P = 0.001) as the only independent predictors. The joint adjusted R(2)value was 0.48 (P<0.001). CONCLUSION: Muscular dysfunction is part of the syndrome of heart failure. Together with symptom perception, it predicts nearly half of the variation in exercise tolerance.

Female↗