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At least 1,279 records · Page 71Linked to original sources
PubMed2003

Lesions of rat skeletal muscle after local block of acetylcholinesterase and neuromuscular stimulation.

In skeletal muscle, a local increase of acetylcholine (ACh) in a few end plates has been hypothesized to cause the formation of contraction knots that can be found in myofascial trigger points. To test this hypothesis in rats, small amounts of an acetylcholinesterase inhibitor [diisopropylfluorophosphate (DFP)] were injected into the proximal half of the gastrocnemius muscle, and the muscle nerve was electrically stimulated for 30-60 min for induction of muscle twitches. The distal half of the muscle, which performed the same contractions, served as a control to assess the effects of the twitches without DFP. Sections of the muscle were evaluated for morphological changes in relation to the location of blocked end plates. Compared with the distal half of the muscle, the DFP-injected proximal half exhibited significantly higher numbers of abnormally contracted fibers (local contractures), torn fibers, and longitudinal stripes. DFP-injected animals in which the muscle nerve was not stimulated and that were allowed to survive for 24 h exhibited the same lesions but in smaller numbers. The data indicate that an increased concentration of ACh in a few end plates causes damage to muscle fibers. The results support the assumption that a dysfunctional end plate exhibiting increased release of ACh may be the starting point for regional abnormal contractions, which are thought to be essential for the formation of myofascial trigger points.

Acetylcholine↗
PubMed2004

Hypertrophic cardiomyopathy-related beta-myosin mutations cause highly variable calcium sensitivity with functional imbalances among individual muscle cells.

Disease-causing mutations in cardiac myosin heavy chain (beta-MHC) are identified in about one-third of families with hypertrophic cardiomyopathy (HCM). The effect of myosin mutations on calcium sensitivity of the myofilaments, however, is largely unknown. Because normal and mutant cardiac MHC are also expressed in slow-twitch skeletal muscle, which is more easily accessible and less subject to the adaptive responses seen in myocardium, we compared the calcium sensitivity (pCa(50)) and the steepness of force-pCa relations (cooperativity) of single soleus muscle fibers from healthy individuals and from HCM patients of three families with selected myosin mutations. Fibers with the Arg723Gly and Arg719Trp mutations showed a decrease in mean pCa(50), whereas those with the Ile736Thr mutation showed slightly increased mean pCa(50) with higher active forces at low calcium concentrations and residual active force even under relaxing conditions. In addition, there was a marked variability in pCa(50) between individual fibers carrying the same mutation ranging from an almost normal response to highly significant differences that were not observed in controls. While changes in mean pCa(50) may suggest specific pharmacological treatment (e.g., calcium antagonists), the observed large functional variability among individual muscle cells might negate such selective treatment. More importantly, the variability in pCa(50) from fiber to fiber is likely to cause imbalances in force generation and be the primary cause for contractile dysfunction and development of disarray in the myocardium.

Calcium↗
PubMed2006

Rate of force production and relaxation is impaired in patients with focal hand dystonia.

One factor, which may contribute to slowed movement in dystonia, is impairment in controlling the voluntary rate of motor output. This study examined the ability of patients with focal hand dystonia to rapidly turn force on and off at the wrist and elbow joints. Dystonic patients were slower than controls in rapidly turning on force from rest at both joints, passively relaxing force and rapidly reversing force output from a steady-state flexion contraction. Adding a preload did not improve the ability of dystonic subjects to rapidly turn on force. These results support the idea that dystonia is a disorder of impaired motor cortical activation, possibly due to basal ganglia dysfunction.

Adult↗
PubMed2004

Metabolic flexibility.

Human physiology needs to be well adapted to cope with major discontinuities in both the supply of and demand for energy. This adaptability requires 'a clear capacity to utilize lipid and carbohydrate fuels and to transition between them' (Kelley et al. 2002b). Such capacities characterize the healthy state and can be termed 'metabolic flexibility'. However, increasing evidence points to metabolic inflexibility as a key dysfunction of the cluster of disease states encompassed by the term 'metabolic syndrome'. In obese and diabetic individuals this inflexibility is manifest in a range of metabolic pathways and tissues including: (1) failure of cephalic-phase insulin secretion (impaired early-phase prandial insulin secretion concomitant with failure to suppress hepatic glucose production and NEFA efflux from adipose tissue); (2) failure of skeletal muscle to appropriately move between use of lipid in the fasting state and use of carbohydrate in the insulin-stimulated prandial state; (3) impaired transition from fatty acid efflux to storage in response to a meal. Finally, it is increasingly clear that reduced capacity for fuel usage in, for example, skeletal muscle, as indicated by reduced mitochondrial size and density, is characteristic of the metabolic syndrome state and a fundamental component of metabolic inflexibility. Key questions that remain are how metabolic flexibility is lost in obese and diabetic individuals and by what means it may be regained.

Adipose Tissue↗
PubMed2005

Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine.

OBJECTIVE: To determine if stavudine (alpha4T)-associated mitochondrial toxicity could be reversed by substitution with another nucleoside reverse transcriptase inhibitor. As apoptosis and dysfunction of electron transport chain (ETC) activities may underlie mitochondrial toxicity, these parameters were also evaluated. DESIGN: The 16 participants (on d4T for >3 years; with lipoatrophy and/or hyperlactatemia) substituted abacavir or zidovudine for stavudine in their antiretroviral regimen. Key parameters including dual-energy X-ray absorptiometry (DEXA) scans, fat apoptosis, mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells (PBMC), skeletal muscle and fat, as well as skeletal muscle mitochondrial ETC activities were evaluated at study entry and at 48 weeks after the substitution. METHODS: Quantitative PCR was used to evaluate mtDNA levels and the presence of deletions/rearrangements; CLIA-validated methods for ETC activities; terminal deoxynucleotidyl transferase dUTP-digoxigenin nick-end labeling assays to evaluate adipocyte apoptosis; and DEXA scans to measure changes in body fat. RESULTS: MtDNA was depleted at study entry in muscle, adipose tissue and PBMC but levels rebounded with respective mean increases of 141%, 146%, and 369% at week 48. Corresponding fat improvements were noted with DEXA increases of 21%, 11%, and 16% in arm, leg, and trunk, respectively. Quantitative adipocyte apoptosis were significantly increased at baseline (P < 0.01 versus HIV-negative controls), with a significant reduction at week 48 (P < 0.05 versus baseline). Mean values for seven mitochondrial enzyme activities assays at entry indicated substantial loss of function (48% to 85% of controls) with significant improvement of complex I activity by week 48. CONCLUSIONS: Substitution of stavudine with abacavir or zidovudine improves mitochondrial indices and fat apoptosis in the setting of lipoatrophy.

Adipocytes↗
PubMed2005

Manual treatment effects to the upper cervical apophysial joints before, during, and after endotracheal anesthesia: a placebo-controlled comparison.

OBJECTIVES: In this preliminary, placebo-controlled clinical trial, two different manual treatments were compared, spinal manipulation and postisometric relaxation, for dysfunctional motion segments of the upper cervical spinal column. The influence of the muscular portion on the joint-play restriction of a motion segment can be ignored in anesthesia, and the manual evaluation of this joint-play restriction must be focused on nonmuscular structures. By retesting in anesthesia, it is possible to examine whether mobilization and manipulation affect exclusively the muscular structures or also affect the other parts of the motion segment. Conclusions can be drawn about the superiority of one or both treatments and about the structural basis of the restricted joint play and its palpation. DESIGN: A total of 26 inpatients at the surgical or orthopedic department of the University of Rostock were examined manually at four testing times: before and after manual treatment, in anesthesia, and within 24 hrs of completing anesthesia. They were randomized into three groups: postisometric relaxation (mobilization), spinal manipulation (thrust technique), and placebo. RESULTS: A highly significant effect for both treatments was found posttherapeutically (P < 0.01) but not for placebo. In anesthesia, the treatment effect of spinal manipulation was further significant (P < 0.01) when compared with placebo. For postisometric relaxation, however, it was not (P = 0.160). A significant difference between spinal manipulation and postisometric relaxation was not found in anesthesia (P = 0.137). The treatment effect postnarcotically was further significant when compared with placebo only for spinal manipulation (P = 0.011). CONCLUSIONS: Both treatments are superior to placebo. Postisometric relaxation seems to affect mainly the muscular parts of the treated segments and less so the other parts, such as the joint capsule or the segmental affiliated ligaments and fascia. Spinal manipulation seems to influence all other segmental parts more effectively, and the treatment effect persists longer. A joint-play restriction cannot be an exclusively muscular tension phenomenon. Segmental motion dysfunctions show a high variability in their spontaneous course.

Adult↗
PubMed2004

Targeting the immune system to improve ventilatory function in muscular dystrophy.

Skeletal muscle is a unique tissue whose function is dependent in great part on its ultrastructure. Repeated intense muscular contractions, especially those resulting in muscle lengthening, can lead to alterations in muscle structure (i.e., muscle damage) and subsequent decline in contractile force. The damage-induced decline in contractile force can have a significant impact on exercise performance during an athletic performance. In some disease conditions such as Duchenne muscular dystrophy (DMD), the muscles are more vulnerable to contraction-induced damage than normal muscle. In the case of the respiratory muscles, for example, the diaphragm, the consequences of muscle weakness secondary to damage are profound in that respiratory failure leading to premature death often ensues. In normal skeletal muscle, damage is followed by an inflammatory response involving multiple cell types that subsides after several days. This transient inflammatory response is a normal homeostatic reaction to muscle damage. In contrast, a persistent inflammatory response is observed in dystrophic skeletal muscle that leads to an altered extracellular environment, including an increased presence of inflammatory cells (e.g., macrophages) and elevated levels of various inflammatory cytokines (e.g., TNF-alpha, TGF-beta). The signals that lead to successful muscle repair in healthy muscle may promote muscle wasting and fibrosis in dystrophic muscle. Preliminary data indicate that immunosuppression in dystrophic (mdx) mice has beneficial effects on some indices of muscle dysfunction, thereby indicating that targeted immunosuppression may offer some promise in delaying the pathological progression of this insidious muscular disease.

Animals↗
PubMedDate not supplied

Alterations in reactivity of small arterioles in rat skeletal muscle as a result of chronic ischaemia.

In a model of chronic hind limb ischaemia, we examined whether impaired muscle blood flow, particularly during exercise, is partly due to modification of the reactivity of skeletal muscle resistance vessels by prolonged low blood flow. Two or 5 weeks after unilateral iliac artery ligation, terminal (A4) and preterminal (A3) arterioles of extensor digitorum longus muscle were viewed by intravital microscopy using epi-illumination, and diameter changes to topical application of endothelium-dependent (bradykinin, acetylcholine) and endothelium-independent (adenosine, sodium nitroprusside and noradrenaline) agonists measured. Chronic ischaemia had no effect on resting diameters of A3 or A4 vessels. Two weeks after ligation, dilation to bradykinin was attenuated by 75% for A3 and 50% for A4 arterioles (p < 0.01 vs. control) and responses to acetylcholine were reversed from dilation to constriction (A3: control diameter change +29%, 2-week-ligated -17%; A4: control 18%, 2-week-ligated -13%). Five weeks after ligation, these effects were still apparent and, additionally, dilation to adenosine and sodium nitroprusside and constriction to noradrenaline were reduced. Thus, impaired dilation, most likely due to endothelial dysfunction, is an early manifestation of altered reactivity in the microcirculation of chronically ischaemic muscles, with functional impairment of vascular smooth muscle as a later consequence. These changes occurred despite modest improvements in muscle blood flow and perfusion pressure over the same time. These changes will act to the detriment of blood flow in contracting muscles and could limit the outcome of interventions to restore flow such as angioplasty or surgical bypass.

Animals↗
PubMed1998

Magnetic resonance imaging of muscle in amyotrophic lateral sclerosis.

OBJECTIVE: To characterize leg muscle abnormalities in patients with ALS using MRI, and to correlate MRI with standard neurologic measures of motor neuron dysfunction. METHODS: Eleven ALS patients were studied twice (once at baseline and again after 4 months) and compared with eight normal control subjects. MRI data of the lower extremities were compared with tibialis anterior compound muscle action potential amplitude (CMAPa) and foot dorsiflexion maximal voluntary isometric contraction (MVIC). RESULTS: Muscle MRI was abnormal by visual inspection in six of 11 patients. The mean muscle T1 time and muscle volume were not different in patients compared with normal control subjects (p > 0.1). However, the mean T2 times were increased in the patients compared with normal control subjects (p = 0.009). T1 times did not correlate with CMAPa or MVIC. Muscle volume correlated with MVIC (r = 0.73 to 0.78, p < 0.02) but not with CMAPa (p > 0.05). There was a strong negative correlation (r < -0.8, p < or = 0.01) between muscle T2 time and MVIC and CMAPa. Also, the change in T2 relaxation time correlated with the change in CMAPa as the disease progressed (r = -0.63, p = 0.037). CONCLUSION: Of the MRI characteristics studied, T2 relaxation time was the best indicator of motor neuron dysfunction and may have a role in objective evaluation of motor neuron dysfunction.

Action Potentials↗
PubMed2001

[Tubular aggregate congenital myopathy associated with neuromuscular block].

Various myopathies are described associated with tubular aggregates. However, in several cases tubular aggregates constitute the main structural feature allowing to consider myopathy with tubular aggregates as a distinct entity. A 50-year-old woman whose parents were consanguinous, presented frequent falls. She walked only after 18 months of age and did poorly in gymnastics. The weakness, which has myasthenic feature, involved predominantly the pelvis girdle. The serum creatine kinase was 206 UI/L (normal < 110 UI/L). Electromyogram showed a myogenic pattern in proximal muscles. Repetitive stimulation on the trapezius revealed 50 p. cent decrementing response. Muscle biopsy showed numerous tubular aggregates in type II fibers. Anti-acetylcholine receptor (AChR) antibodies were absent. There was no thymoma. The neostigmine test was negative. Clinical and electrical myasthenic features characterize one of the numerous forms of myopathy with tubular aggregates. In our case, the lack of AChR antibodies and the negative response to neostigmine argue in favor of a dysfunction of the AChR. This unusual observation highlights the therapeutic difficulties in this myopathy with neuromuscular block.

Biopsy↗
PubMed2004

Effects of carnitine supplementation on muscle metabolism by the use of magnetic resonance spectroscopy and near-infrared spectroscopy in end-stage renal disease.

BACKGROUND/AIM: A defect in skeletal muscle mitochondrial metabolism develops in patients with chronic renal failure on haemodialysis. Treatment with carnitine, a compound essential for normal mitochondrial function, has been suggested to have significant benefits in such patients, so we carried out a study to see if carnitine acts by improving muscle bioenergetics and function. METHODS: In a phase II randomised double-blind trial, patients with end-stage renal disease received placebo or intravenous L-carnitine (20 mg/kg dry body weight three times weekly after haemodialysis) for 16 weeks (n = 13 in each group). 31P magnetic resonance spectroscopy, 1H magnetic resonance imaging and near-infrared spectroscopy were used to measure muscle bioenergetics and function at baseline and at 16 weeks. RESULTS: There were no significant differences between groups at baseline. Mean plasma carnitine rose 10-fold in the carnitine group but was unchanged in the placebo group. L-carnitine had no statistically significant effect on any of the parameters measured. The rate of proton efflux from muscle, as a measure of tissue perfusion, was low in both groups and was not affected by treatment. CONCLUSIONS: The study failed to show any significant effect of 16 weeks' L-carnitine supplementation on these objective measures of muscle metabolism and function. Slow proton efflux from muscle provides evidence supporting low blood flow and, therefore, decreased oxygen availability, as an underlying mechanism for muscle mitochondrial dysfunction in this disorder.

Blood Chemical Analysis↗
PubMed1999

Skeletal muscle mitochondrial defects in nonspecific neurologic disorders.

A group of 25 children (5 months to 20 years of age) presenting with intractable seizures, developmental delay, and severe hypotonia, who did not fall into the known categories of mitochondrial encephalomyopathies, underwent muscle biopsy for evaluation of mitochondrial function and were compared with age-matched control subjects. Biopsied skeletal muscle was analyzed for six mitochondrial enzyme-specific activities, mitochondrial DNA point mutations and deletions, and mitochondrial DNA levels. The data reveal a high incidence of specific mitochondrial enzyme activity defects. Reduced activity levels were evident in complex I (11 patients), III (24 patients), IV (nine patients), and V (10 patients). Two patients also exhibited pronounced reduction in mitochondrial DNA levels (80% reduction compared with control subjects). Two patients manifested increased levels of 5-kb and 7.4-kb mitochondrial DNA deletions. Pathogenic mutations previously described in association with mitochondrial encephalomyopathies were not evident. The data suggest that mitochondrial dysfunction, including extensive defects in specific enzyme activities, may be frequently present in children with seizures, developmental delay, and hypotonia that do not fall within the known mitochondrial encephalomyopathies. These mitochondrial deficiencies can be primarily ascertained by biochemical analysis and are rarely accompanied by mitochondrial ultrastructural changes. The molecular basis of these defects, their role in these disorders, and potential treatment warrant further study.

Adult↗
PubMed1978

Modern urodynamic evaluations in the urologist's office.

Patients with voiding disturbances comprise 20 per cent of the yearly outpatient visits to urologists. Of this number 25 per cent have significant neurogenic bladder dysfunction. The theoretical basis and experimental demonstration of urodynamics have been established and reported by multiple investigators during the last 15 years. Recent advances in clinical applications of fast-flow gas cystometry have led to the development of complete, portable urodynamic units that can be used conveniently in the urologist's office and are capable of simultaneously recording parameters of detrusor, urethral and skeletal muscle phincter function. This equipment is simple, efficient, economical and can be operated by well trained paramedical personnel, with minimal immediate direction required by a physician. With recent recognition by many third party carriers this equipment may amortize itself rapidly but, more importantly, it may serve to identify neurological diseases of the bladder that are undetected by other conventional methods of investigation. During the last 9 months 213 patients have undergone urodynamic evaluation at our outpatient urology clinic. These patients were categorized according to type and incidence of voiding disturbance and the number of neurogenic bladders diagnosed within each group was compiled and discussed. Several of the more interesting and unusual clinical examples are presented to familiarize the urologist with the interpretative aspects of this study.

Ambulatory Care↗
PubMed2005

Hemorrhagic shock resuscitation affects early and selective mesenteric artery endothelial function through a free radical-dependent mechanism.

Mesenteric ischemia/reperfusion occurring during hemorrhagic shock and resuscitation (H/R) induces a systemic inflammatory response and damages endothelial cells. Our aim was to investigate whether H/R affects selectively mesenteric vascular reactivity and the roles of free radicals and inducible nitric oxide (NO) synthase (iNOS) in these changes. Rats subjected to H (30 min)/R (60 min) in the presence or absence of the free radical scavenger N-2 mercaptopropionyl glycine (MPG), or the specific inhibitor of iNOS [(3) N-(3-aminomethyl)benzyl) acetaminide; 1400W] were studied. Saline requirements to maintain systemic blood pressure during R (53.4 +/- 5.2 mL/kg/h) were reduced by MPG (26.2 +/- 3.1) and 1400W (37.5 +/- 4.1). H/R reduced maximal mesenteric arteries relaxation to acetylcholine (sham: 70% +/- 5%, H/R: 21% +/- 3%) and this impairment was prevented by MPG (66% +/- 10%) and reduced by 1400W (49% +/- 9%). H/R did not affect the endothelium-independent relaxations. Maximal responses to phenylephrine were reduced in mesenteric arteries by H/R (3.6 +/- 0.5 mN/mm vs. sham 6.5 +/- 0.5), this impairment was prevented by 1400W and MPG. No impaired response to acetylcholine was detected in skeletal muscle arteries. H/R was associated with an increased production of TNF-alpha (169 +/- 8.5 ng/mL vs. sham 38 +/- 5 ng/mL), and this was reduced to 75 +/- 8 ng/mL in MPG-treated rats. Total intestinal content of iNOS mRNA was also increased by H/R and this increase was partly reduced by treatment with MPG. H/R induces an early and selective mesenteric endothelial cell dysfunction through a mechanism that involves oxygen-derived free radicals and NO produced by iNOS. H/R is associated with a mesenteric hyporeactivity through an induction of NOS and may be prevented by scavenging free radicals. This early impairment in endothelial function is associated with a local inflammatory response.

Acetylcholine↗
PubMed1991

Effect of estrogen replacement on liver function in ovariectomized rats.

The effect of estrogen (17 beta-estradiol; E2) replacement on the liver function was examined in ovariectomized rats. Ovariectomy decreased serum transaminase activity and physiological dosage levels of E2 replacement returned the activity up to or above non-ovariectomized levels. Under the conditions of this experiment the elevated serum transaminase levels in the E2 replacement were not coincident with histological changes suggestive of liver dysfunction. The elevations of both serum glutamic oxaloacetic transaminase (GOT) and serum mitochondrial GOT were accompanied by increased hepatic tissue activity, suggesting that the elevated serum levels can be attributed to the accelerated synthesis of the enzymes. On the other hand, the elevation of serum glutamic pyruvic transaminase was not accompanied by increased tissue activity in the original organs, namely liver, kidney, heart and skeletal muscle. Ovariectomy decreased serum albumin and inhibited development of rough endoplasmic reticulum in the liver, and E2 replacement returned them up to or above the non-ovariectomized levels.

Alanine Transaminase↗
PubMed2001

Beta-amyloid peptide expression is sufficient for myotube death: implications for human inclusion body myopathy.

Inclusion body myositis (sIBM) is the most common disorder of skeletal muscle in aged humans. It shares biochemical features with Alzheimer's disease, including congophilic deposits, which are immunoreactive for beta-amyloid peptide (Abeta) and C'-terminal betaAPP epitopes. However, the etiology of myofiber loss and the role of intracellular Abeta in IBM is unknown. Here we report correlative evidence for apoptotic cell death in myofibers of IBM patients that exhibit pronounced Abeta deposition. HSV-1-mediated gene transfer of Abeta(42) into cultured C2C12 myotubes resulted in a 12.6-fold increase in dUTP-labeled and condensed nuclei over nonexpressing myotubes (P < 0.05). The C'-terminal betaAPP domain C99 also induced myotube apoptosis, but to a significantly lesser extent than Abeta. Apoptosis specific to Abeta-expressing myotubes was also demonstrated through DNA fragmentation, decreased mitochondrial function and the loss of membrane phospholipid polarity. Myotubes laden with Abeta(42), but not other transgene products, developed cytoplasmic inclusions consisting of fibrillar material. Furthermore, injection of normal mouse gastrocnemius muscle with HSV-encoding Abeta cDNA resulted in TUNEL-positive myofibers with pyknotic nuclei. We conclude that Abeta is sufficient to induce apoptosis in myofibers both in vivo and in vitro and suggest it may contribute to myofiber loss and muscle dysfunction in patients with IBM.

Amyloid beta-Peptides↗