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At least 793 records · Page 44Linked to original sources
PubMed1993

The etiology and reversibility of muscle dysfunction in the aged.

Muscle weakness in the elderly is prevalent and morbid, closely linked to the frailty, functional decline, immobility, falls, and injuries in this population. The marked decrease in skeletal muscle strength and size with aging is a multifactorial syndrome which may be attributable in part to: (a) biological changes of aging itself; (b) the accumulation of acute and chronic diseases; (c) the assumption of a sedentary life style, and (d) selective or generalized nutritional inadequacies. Inactivity and undernutrition are potentially at least partially reversible with appropriate interventions, and therefore the delineation of the attributable risk of these two factors to the muscle weakness of aging is a critical research goal. Similarly, identification of appropriate modalities of physical activity and nutrition which have positive effects on muscle physiology in the aged is the focus of major investigations currently.

Aged↗
PubMed1999

Cysteine and glutathione in catabolic conditions and immunological dysfunction.

The conspicuous increase in the plasma cysteine disulphide/thiol ratio in elderly persons and cancer patients indicates a shift of the plasma redox state. The most important redox buffers in skeletal muscle tissue and blood plasma, i.e. glutathione and albumin, respectively, are significantly decreased in different models of cachexia. Treatment with N-acetyl cysteine, i.e. a thiol-containing antioxidant, was found to increase the plasma albumin level and to ameliorate the loss of body cell mass in cancer patients and healthy individuals. The treatment of HIV infection with N-acetyl cysteine, in contrast, serves mainly as a tool to ameliorate the physiological and immunological consequences of the virus-induced cysteine deficiency.

Acetylcysteine↗
PubMed1993

Assisted circulation using cardiomyoplasty together with aortomyoplasty.

Both dynamic cardiomyoplasty and counterpulsation by the synchronous paced contraction of skeletal muscles in aortomyoplasty can improve ventricular function. The goal of this study was to clarify the effect of cardiomyoplasty combined with aortomyoplasty on cardiac dysfunction in dogs. The percentage of increase in various hemodynamic parameters was calculated during assisted and unassisted cardiac cycles and was compared for three groups: cardiomyoplasty only (Group A), aortomyoplasty only (Group B), and both methods combined (Group C). In Group A, the left ventricular pressure (LVP), systolic aortic pressure (systolic AoP), and dp/dt of LVP (LV dp/dt) increased significantly; the diastolic aortic pressure (diastolic AoP) did not change; and the endocardial viability ration (EVR) decreased during assisted cardiac cycles. In Group B, the diastolic AoP and EVR were improved significantly, but the LVP, LV dp/dt, and systolic AoP were unchanged during assisted cardiac cycles. In contrast to Groups A and B, all parameters were improved in Group C during assisted cardiac cycles. Cardiac assistance using cardiomyoplasty together with aortomyoplasty was more effective than either procedure used alone.

Animals↗
PubMed1995

Rat skeletal muscle metabolism in experimental heart failure: effects of physical training.

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2006

Correlation of alpha-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in rats.

We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of alpha-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic pressure, ventricular weight and ventricular wall thickness. AC0.7 and AC0.4 rats also showed a larger amount of fibrosis and upregulation of alpha-skeletal actin expression associated with a higher vulnerability to ventricular arrhythmias (AC0.7 and AC0.4) and enhanced myocardial contractility (AC0.4). Our results illustrate the progressive changes in the extracellular matrix features accompanying early ventricular remodelling in response to different degrees of pressure overload that may be involved in the development of cardiac electrical instability. We also demonstrate for the first time a linear correlation between an increase in alpha-skeletal actin expression and the degree of compensated cardiac hypertrophy, possibly acting as an early compensatory mechanism to maintain normal mechanical performance.

Actins↗
PubMed1997

Frequency domain characteristics of muscle sympathetic nerve activity in heart failure and healthy humans.

The purpose of this study was to characterize oscillations in muscle sympathetic nerve activity (MSNA) in the frequency domain in healthy subjects and patients with congestive heart failure (CHF) and to relate these to blood pressure (BP), heart rate (HR), and breathing frequency. MSNA burst frequency was significantly greater in CHF [52 +/- 21 (n = 12) vs. 35 +/- 11 (n = 19) bursts/min, P < 0.05], whereas breathing frequency and HR were similar. There was no significant difference between CHF and healthy subjects in total power, harmonic power, and nonharmonic power in the MSNA spectrum from 0 to 0.5 Hz, but low frequency power (LF, 0.05-0.15 Hz, P < 0.05) was reduced in heart failure patients. There was less coherence between BP and MSNA in the LF range, but similar spectral power in both groups in the very LF (VLF, 0-0.05 Hz) and high frequency (0.15-0.5 Hz) ranges. The transfer of MSNA oscillations into BP in the VLF (P < 0.05) and LF (P < 0.02) ranges was significantly lower in CHF, but gains in the transfer function and in the coherence between BP and MSNA and in the coherence between respiration and MSNA were similar in the two groups. These observations indicate that modulation of MSNA by the arterial baroreflex and respiration is preserved in CHF. The loss of LF power in the MSNA signal may be due to impaired neuroeffector transduction. The higher sympathetic nerve firing rate in CHF would therefore appear to be caused by factors other than the loss of regulation by these two inhibitory influences.

Adult↗
PubMed2001

Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis.

Recent studies have indicated that sepsis is associated with enhanced generation of several free-radical species (nitric oxide [NO], superoxide, hydrogen peroxide) in skeletal muscle. It is also known that this enhanced free-radical generation results in reductions in skeletal muscle force-generating capacity, but the precise mechanism(s) by which free radicals exert this effect in sepsis has not been determined. We postulated that free radicals might react directly with the contractile proteins in this condition, altering contractile protein force-generating capacity. To test this theory, we compared the force generation of single Triton-skinned diaphragmatic fibers (Triton skinning exposes the contractile apparatus, permitting direct assessment of contractile protein function) from the following groups of rats: (1) control animals; (2) endotoxin-treated animal; (3) animals given endotoxin plus polyethylene glycol- superoxide dismutase (PEG-SOD), a superoxide scavenger; (4) animals given endotoxin plus N(omega)-nitro-L-arginine methylester (L-NAME), a NO synthase inhibitor; (5 ) animals given only PEG-SOD or L-NAME; and (6 ) animals given endotoxin plus denatured PEG-SOD. We found that endotoxin administration produced both a reduction in the maximum force-generating capacity (Fmax) (i.e., a decrease in Fmax) of muscle fibers and a reduction in fiber calcium sensitivity (i.e., an increase in the Ca2+ concentration required to produce half-maximal activation [Ca50]). L-NAME and PEG-SOD administration preserved Fmax and Ca50 in endotoxin-treated animals; neither drug affected these parameters in non-endotoxin treated animals. Denatured PEG-SOD failed to inhibit endotoxin-related alterations in contractile protein function. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of skinned fibers from endotoxin-treated animals revealed a selective depletion of several proteins; administration of L-NAME or PEG-SOD to endotoxin-treated animals prevented this protein depletion, paralleling the effect of these two agents to prevent a reduction in contractile protein force-generating capacity. These data indicate that free radicals (superoxide, NO, or daughter species of these radicals) play a central role in altering skeletal muscle contractile protein force-generating capacity in endotoxin-induced sepsis.

Animals↗
PubMed2005

Histomorphometry of penile smooth muscle fiber in severe erectile dysfunction.

CONTEXT AND OBJECTIVE: Smooth muscle fiber has fundamental importance in erection. Alterations in its function or quantity may be associated with erectile dysfunction. The study objective was to assess the proportion of penile smooth muscle fiber in patients with severe erectile dysfunction. DESIGN AND SETTING: Clinical study, in the Sexual Dysfunction Group, Universidade Federal de São Paulo (Unifesp), and in the Anatomy Laboratory, Universidade Estadual do Rio de Janeiro (UERJ). METHODS: Twenty patients with severe erectile dysfunction were selected to form two groups of ten patients: one with normal arterial flow (age range: 44 to 78 years) and the other with altered arterial flow (age range: 38 to 67 years). These groups were compared with a group formed by ten cadavers aged 18 to 25 years that were presumed to have been potent. Quantification of the smooth muscle fibers was done by means of an immunohistochemical study. RESULTS: The proportion of smooth muscle fiber found was 41.15% for the control group. The patients with erectile dysfunction and normal arterial flow presented 27.24% and those with altered arterial flow presented 25.74%; 19 patients presented at least one chronic disease or risk factor for erectile dysfunction, with prominence for diabetes mellitus, systemic arterial hypertension and smoking. CONCLUSION: Among patients with severe erectile dysfunction, the arterial flow on its own does not present interference in the proportion of smooth muscle fiber. The diminution of the proportion of smooth muscle fiber may result from chronic diseases and vascular risk factors.

Adolescent↗
PubMed2001

Cancer anorexia and cachexia.

Patients with cancer cachexia experience a profound wasting of adipose tissue and lean body mass. Anorexia, although often present, is insufficient to account for tissue wasting because 1) cachexia involves massive depletion of skeletal muscle that does not occur during anorexia, 2) nutritional supplementation cannot replenish the loss of lean body mass, 3) cachexia can occur without anorexia, and 4) food intake might be normal for the lower weight of the cancer patient. Anorexia can arise from 1) decreased taste and smell of food, 2) early satiety, 3) dysfunctional hypothalamic membrane adenylate cyclase, 4) increased brain tryptophan, and 5) cytokine production. Appetite stimulants such as cyproheptadine, medroxyprogesterone acetate, and megestrol acetate do not significantly improve lean body mass. Tumor products might be more important in the development of cachexia. Cachectic patients excrete in their urine a lipid-mobilizing factor that directly stimulates lipolysis in a cyclic AMP-dependent manner and increases energy expenditure. Loss of skeletal muscle in cachexia is caused by upregulation of the ubiquitin-proteasome catabolic pathway. Cachexia-inducing tumors elaborate a sulfated glycoprotein, which directly initiates protein catabolism in skeletal muscle. The action of this proteolysis-inducing factor is attenuated by the polyunsaturated fatty acid eicosapentaenoic acid, which is also effective in preventing loss of skeletal muscle in cancer patients. Antagonists of tumor catabolic factors will provide important new agents in the treatment of cancer cachexia.

Anorexia↗
PubMed1994

'Oil globules' in Duchenne muscular dystrophy--history, demonstration, and metabolic significance.

Duchenne, Meryon, Wernich, Clarke, Down and other dystrophy pioneers recognized, illustrated and/or described Duchenne muscular dystrophy skeletal muscle's 'oil globules'. Rarely mentioned or acknowledged since the introduction in 1869 by Klebs of paraffin embedding and modern histological technique (in which tissue lipids are eliminated) this microscopical marker of metabolic dysfunction is utilized to find its metabolic site of origin in the living cell, to identify the disease's major dysfunctioning metabolic pathway, and finally to determine its dystrophin connection which accounts for the primary metabolic malfunction and the clinical manifestations of disease. This paper presents a working hypothesis developed through a long-term empirical study and suggests a practical method of therapy.

Dystrophin↗
PubMed1997

[Physiology of erection].

The peripheral pharmacology of local mechanisms of penile erection is known today thanks to recent advance in the study of the regulation of erectile tissue smooth muscle tone. Smooth muscle fibers present in the corpus cavernosum and arteries destined to the penis relax in response to the release of non adrenergic non cholinergic neuromediators synthetized by postganglionic parasympathetic nerve fibers present in the cavernous nerves. Nitric oxide is the main proerectile neuromediator. Noradrenaline, released by sympathetic fibers, contracts penile smooth muscle fibers and is antierectile. Recent progress in the peripheral pharmacology of penile erection allows new perspectives in the treatment of erectile dysfunction. The spinal cord represents a major site for the neural regulation of penile erection. The latter occurs in response to stimuli from peripheral or supraspinal origin. Different neural structures in the brainstem (nucleus paragigantocellularis), pons and hypothalamus (nucleus paraventricularis) send projections to the thoracolumbar sympathetic and lumbosacral parasympathetic nuclei at the origin of proerectile peripheral pathways. Serotonin and oxytocin are candidates as neuromediators involved in the supraspinal control of penile erection. Studying the central command of penile erection allows an approach to the pathophysiology of psychogenic erectile dysfunction.

Animals↗
PubMed1999

The role of muscle weakness in the pathogenesis of osteoarthritis.

To date, very few studies have investigated the role of muscle dysfunction in the pathogenesis of osteoarthritis (OA). Using largely indirect evidence, this article hypothesizes that motor and sensory dysfunction of muscle may be important factors in the pathogenesis of articular damage and are not simply a consequence of joint damage. A new paradigm is constructed to better describe the complex interrelationship between muscle sensorimotor dysfunction, joint damage, and disability in OA. If the hypothesis is correct, because muscle is a relatively plastic tissue, maintaining well-conditioned muscles may delay or prevent the onset of OA, and rehabilitation exercise therapy that reverses muscle sensorimotor dysfunction may ameliorate the effects of OA.

Humans↗
PubMed2006

Primary myocardial dysfunction in autosomal dominant EDMD. A tissue doppler and cardiovascular magnetic resonance study.

BACKGROUND: Emery-Dreifuss muscular dystrophy is a genetically heterogeneous form of muscular dystrophy. One form is inherited in an X-linked fashion and is secondary to mutations in the gene encoding the nuclear protein emerin. A more common variant is inherited in an autosomal dominant way (EDMD2) due to mutations affecting the nuclear lamina protein lamin A/C. Typical features of both conditions are relatively mild skeletal muscle weakness, but cardiac involvement develops almost invariably by adult age, including conduction defects, arrhythmias and cardiomyopathy. Thus, early detection of cardiac abnormalities may be important for planning early therapeutic intervention. AIM: In this study, we hypothesized that early myocardial dysfunction can be detected by tissue Doppler echocardiography and CMR in unselected patients with the autosomal dominant form of Emery-Dreifuss muscular dystrophy. This would suggest that fibrosis could be implicated in the pathogenesis of cardiac dysfunction in EDMD2. METHODS: Eight consecutive patients with genetically proven EDMD2 without pacemakers were enrolled in the study and compared to eight age-matched controls. All patients and controls first underwent a comprehensive echocardiographic-Doppler examination, followed by measurement of mitral annular velocities using pulsed tissue Doppler. Color M-mode tissue images were recorded from the parasternal long axis projections to derive Myocardial Velocity Gradients (MVG). Subsequently, all subjects underwent cardiovascular magnetic resonance (CMR) imaging for function, intrinsic myocardial tissue contrast using T1 and T2 weighted spin echo (TSE) for fat deposition and extrinsic contrast (Gadolinium-DTPA late fibrosis imaging). Strain measurements, using harmonic phase imaging (HARP) tagging were also derived. RESULTS: Cavity dimensions LV mass and fractional shortening were similar between patients and controls. The overall body mass index was less in patients than in controls (14.5 +/- 1.4 vs. 18.1 +/- 2.4 g/m2, p < 0.002). While systolic MVG were similar between groups, the early diastolic MVG was lower in patients than in controls (4 +/- 1.2 s-1 vs. 7.1 +/- 2.7, p < 0.02). On CMR, LA and LV, RV volumes were similar between patients and controls. CMR strain patterns, however, showed a significant reduction in inferior wall contractility in patients compared to controls (-0.06 +/- 0.02 vs -0.09 +/- 0.03, p < 0.05). No patient showed late gadolinium enhancement. CONCLUSION: Patients with EDMD2 have abnormal left ventricular function prior to developing any cardiac symptoms. The absence of myocardial fibrosis, however, by CMR suggests that this functional abnormality may not be secondary to scarring but could precede it. Tissue Doppler echocardiography and CMR are sensitive methods of assessing the presence of myocardial dysfunction prior to the development of any cardiovascular symptoms.

Adolescent↗
PubMed2026

PIEZO1 Mediates Myoblast Proliferation Under Simulated Microgravity.

Skeletal muscle atrophy is a major health risk of prolonged spaceflight, yet how microgravity reshapes muscle cells through mechanotransduction remains poorly understood. Here, we examined the mechanosensitive cation channel PIEZO1 in myoblast proliferation under simulated microgravity. Using a two-dimensional clinostat combined with Hi-C-based 3D genomics, transcriptomics, and functional assays, we found that simulated microgravity promotes C2C12 myoblast proliferation and upregulates Piezo1. Piezo1 mRNA knockdown reduced both proliferation and depolarization-induced Ca2 + influx, each partially restored under simulated microgravity, consistent with PIEZO1 being a central mediator of the response. Simulated microgravity also drove extensive 3D genome reorganization alongside changes in proliferation-related gene expression. Integrating chromatin architecture with transcriptomics, we found that PIEZO1 inhibition increased Elavl2 mRNA expression, PIEZO1 activation suppressed Elavl2 mRNA expression, and Elavl2 mRNA knockdown enhanced cell proliferation. These findings define a PIEZO1-ELAVL2 mechanotransduction axis, coupled to 3D chromatin remodeling, that regulates myoblast proliferation under simulated microgravity, and thus may be a target for countering spaceflight-associated muscle dysfunction.

Cell Proliferation↗
PubMed2003

Lipotoxicity: when tissues overeat.

PURPOSE OF REVIEW: This review will provide the reader with an update on our understanding of the adverse effects of fatty acid accumulation in non-adipose tissues, a phenomenon known as lipotoxicity. Recent studies will be reviewed. Cellular mechanisms involved in the lipotoxic response will be discussed. Physiologic responses to lipid overload and therapeutic approaches to decreasing lipid accumulation will be discussed, as they add to our understanding of important pathophysiologic mechanisms. RECENT FINDINGS: Excess lipid accumulation in non-adipose tissues may arise in the setting of high plasma free fatty acids or triglycerides. Alternatively, lipid overload results from mismatch between free fatty acid import and utilization. Evidence from human studies and animal models suggests that lipid accumulation in the heart, skeletal muscle, pancreas, liver, and kidney play an important role in the pathogenesis of heart failure, obesity and diabetes. Excess free fatty acids may impair normal cell signaling, causing cellular dysfunction. In some circumstances, excess free fatty acids induce apoptotic cell death. SUMMARY: Recent studies provide clues regarding the cellular mechanisms that determine whether excess lipid accumulation is well tolerated or cytotoxic. Critical in this process are physiologic mechanisms for directing excess free fatty acids to specific tissues as well as cellular mechanisms for channeling excess fatty acid to particular metabolic fates. Insight into these mechanisms may contribute to the development of more effective therapies for common human disorders in which lipotoxicity contributes to pathogenesis.

Animals↗
PubMed2000

Age-related changes in activities of mitochondrial electron transport complexes in various tissues of the mouse.

The purpose of the present study was to examine the role of mitochondria in the aging process by determining whether the activities of various electron transport chain oxidoreductases are deleteriously affected during aging and whether the hypothesized age-related alterations in different tissues follow a common pattern. Activities of respiratory complexes I, II, III, and IV were measured in mitochondria isolated from brain, heart, skeletal muscle, liver, and kidney of young (3.5 months), adult (12-14 months), and old (28-30 months) C57BL/6 mice. Activities of some individual complexes were decreased in old animals, but no common pattern can be discerned among various tissues. In general, activities of the complexes were more adversely affected in tissues such as brain, heart, and skeletal muscle, whose parenchyma is composed of postmitotic cells, than those in the liver and kidney, which are composed of slowly dividing cells. The main feature of age-related potentially dysfunctional alterations in tissues was the development of a shift in activity ratios among different complexes, such that it would tend to hinder the ability of mitochondria to effectively transfer electrons down the respiratory chain and thus adversely affect oxidative phosphorylation and/or autooxidizability of the respiratory components.

Aging↗
PubMed1983

Neurourologic findings in Parkinson's disease.

A total of 30 patients with an established diagnosis of Parkinson's disease and symptomatic voiding dysfunction underwent neurourologic evaluation. Detrusor hyperreflexia associated with appropriate sphincter relaxation was found to be the most common urodynamic pattern, occurring in 75 per cent of the cases. Two types of increased electromyogram activity at the time of detrusor contraction were identified: 1) pseudo-dyssynergia (7 per cent)--a voluntary contraction of the perineal floor in an attempt to prevent leakage and 2) sphincter bradykinesia (11 per cent)--a manifestation of skeletal muscle hypertonicity characteristic of parkinsonism. On the basis of these observations it is assumed that the effect of the basal ganglia on micturition is inhibitory in nature. The diagnostic and therapeutic approach to the parkinsonian patient with voiding dysfunction is discussed.

Aged↗