Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myotonic muscular dystrophy is an inherited disorder affecting many organs, though the underlying biochemical defect is unknown. A recent publication [1] suggested that the metabolic lesion may be associated with defective phospholipid metabolism. These workers observed impaired calcium-stimulated phosphatidic acid accumulation in red cell ghosts from individuals with myotonic dystrophy compared with normal controls. The present study investigated some points of calcium-activated phosphatidylinositol metabolism in red cell ghosts from patients with myotonic dystrophy, those at risk of developing the disease and normal individuals. No differences between the three groups could be found in the incorporation of 32P into endogenous phosphatidylinositol nor in the distribution of label between the various phosphatidylinositols. Additionally, no differences were observed in either basal or calcium-activated phosphatidylinositol phosphate breakdown by phosphodiesterase. This would suggest that the observed decreased phosphatidate accumulation [1] may be due to impaired diacylglycerol kinase activity.
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PMID:In vitro studies on calcium activated phosphatidylinositol phosphodiesterase of erythrocyte ghosts from normal individuals and those with myotonic muscular dystrophy. 627 36

Platelets which have complex membranes and calcium shifts similar to those in muscles were investigated in 14 patients with muscular dystrophy and 20 suitable controls. In 4 Duchenne and one limb-girdle dystrophy aggregations were done and found to be depressed with adrenaline and ADP. Electron microscopic and chemical examinations revealed an increased number of dense bodies, changed permeability and/or binding of cations and elevated intracellular calcium in all the 9 cases of Duchenne dystrophy while the 2 limb-girdle and 3 myotonic dystrophies varied. A two phase polymer separation system applied to fixed platelets of all patients and controls showed no abnormality of surface negative charge.
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PMID:Platelet abnormalities in muscular dystrophy. 630 47

It is not surprising that calcium-channel blocking agents, which have numerous effects on various physiologic systems, have been employed for several "unapproved" uses. This manuscript reviews reports that have appeared within the last two years describing unapproved cardiovascular and noncardiovascular uses of the three available calcium-channel blocking agents. The cardiovascular uses discussed include hypertensive emergencies, pulmonary hypertension, congestive heart failure, aortic insufficiency, Raynaud's phenomenon, migraine headaches, antiplatelet effects and cardiac surgery. Areas of noncardiovascular use include muscular dystrophy, achalasia, esophageal spasm, dysmenorrhea, preterm labor, asthma, hyperuricemia, mania and depression and endocrinologic and oncologic conditions. While some of the data appear promising, other reports are conflicting and contradictory. Furthermore, because much of the information comes from poorly controlled trials or anecdotal reports, even the more promising uses must be studied further and compared with conventional therapy.
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PMID:Promising uses of calcium-channel blocking agents. 637 47

Serial consecutive frozen sections from 164 muscle biopsy specimens were studied cytochemically. We localized calcium and albumin as endogenous markers of extracellular fluid penetration and C3 and C9 complement components as markers of muscle fiber necrosis. In both Duchenne dystrophy and congenital muscular dystrophy, a significant percentage of fibers were overloaded with calcium and penetrated by albumin. Most of these fibers appeared opaque with trichrome stain. C3 and C9 complement components appeared only in necrotic fibers, which invariably were also penetrated by albumin. These observations support previous findings that muscle fiber necrosis is linked to massive inflow of extracellular fluid and complement activation. In addition, in both Duchenne and congenital dystrophies, numerous nonnecrotic fibers are penetrated by calcium-rich extracellular fluid.
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PMID:Muscle fiber degeneration and necrosis in muscular dystrophy and other muscle diseases: cytochemical and immunocytochemical data. 652 76

In two separate experiments, 72 crossbred ewes were fed hay, haylage (50% dry matter) and corn diets with ad libitum salt-mineral mixtures (SMM; Exp. 1) or salt (Exp. 2). Calcium phosphates (Ca X P) and(or) zinc (Zn) were added in a 2 X 2 factorial arrangement to salt + trace minerals for ewes 7 mo prepartum through lactation in Exp. 1 and to salt only for ewes 3 mo prepartum through lactation in Exp. 2. The diets fed were estimated to contain 23 and 28 mg Zn/kg dry diet (ppm), respectively, and .08 and .05 ppm Se. Large variations (up to fivefold) were found in SMM intake per month between replicates and from month-to-month within treatment; thus, monthly variations of up to sevenfold occurred in Zn and Se intakes of supplemented groups. There were no significant treatment effects on SMM intake. Small but significant Zn treatment effects were detected for plasma and wool Zn of ewes and lambs, but all values were in the normal range. There was no significant treatment effect on plasma alkaline phosphatase activity. In Exp. 2, erythrocyte glutathione peroxidase (GSH-Px) activity was significantly lower in all treatment groups compared with a Se-supplemented control group but only rare occurrences of subclinical muscular dystrophy were found. There was no significant treatment effect on GSH-Px activity, whole blood Se in ewes and lambs or plasma creatine phosphokinase activity in lambs. These results indicate large animal and seasonal variability in SMM intake and no significant treatment effects of Ca X P on SMM intake or on Zn and Se status. Zinc addition to SMM had no effect on Se status.
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PMID:Effect of calcium phosphates and zinc in salt-mineral mixtures on ad libitum salt-mix intake and on zinc and selenium status of sheep. 652 62

A single direct injection of a local anesthetic, 0.5% bupivacaine hydrochloride (BPVC) (Marcaine), into rat soleus and extensor digitorum longus (EDL) muscles produced massive fiber necrosis with extensive phagocytosis followed by rapid regeneration, predominantly in the soleus. Since the sarcoplasmic reticulum (SR) was functionally disturbed by BPVC administration as confirmed by an in vitro study, the sarcolemmal lysis seen in the early phase of degeneration was not assumed to simply result from direct damage to the plasma membrane caused by BPVC. The extracellular fluid containing a high concentration of calcium (Ca) ions then permeated into the sarcoplasm through the defective membrane resulting in hyper-contracted myofibrils. Selective damage to the Z-line, an early sign of muscle degeneration, was shown by electron microscopy and SDS gel electrophoresis (preferential loss of alpha-actinin). Administration of leupeptin, a thiol protease inhibitor, proved to be ineffective in inhibiting the necrotic process, because the BPVC induced muscle fiber breakdown was probably too acute and fulminant to demonstrate the inhibitory effect upon the degenerative process. Well preserved satellite cells, peripheral nerves, and acetylcholinesterase activity, and the absence of fibrous tissue proliferation in this system may be responsible for the extremely rapid regeneration with complete muscle fiber type differentiation. Since the sequence of fiber breakdown induced by BPVC administration was similar to that of progressive muscular dystrophy, this chemical will be one of the most useful tools for studying the pathophysiology of fiber necrosis and regeneration in diseased muscle.
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PMID:Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine). 661 29

Rat diaphragms were treated with calcium ionophore, A23187, for 60 min at 37 degrees C, and twitch, tetanus and their derivatives were studied on the basis of the active state concept. Results were than compared with those of human dystrophic muscle. Like dystrophic muscle, maximum tetanic force and maximum velocity of tetanus development were markedly reduced. Changes in twitch parameters, which tend to appear in an early stage of muscular dystrophy, were not noted after the treatment with this ionophore, except alterations relating to prolongation of the active state. Twitch/tetanus ratio was thus increased, while it was decreased in dystrophic muscle. Isoproterenol-induced change of twitch was normally seen in the A23187-treated muscle, while dystrophic muscle responded to catecholamine in a manner different from control. Therefore, the muscle treated with calcium ionophore is not wholly similar to dystrophic muscle.
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PMID:Contractile and chemosensitive properties of muscle treated with calcium ionophore A23187. Comparison with dystrophic muscle. 679 24

A number of recent reports suggest that intracellular calcium concentration is increased in skeletal muscle in duchenne muscular dystrophy (DMD). Leucocyte chemiluminescent responses are dependent on calcium ions and can be induced by the calcium ionophore A23187. Chemiluminescence may therefore reflect intracellular calcium levels. In order to determine whether non-muscle cells in DMD share the calcium abnormality, we have examined A23187-induced chemiluminescence in DMD leucocytes. Peak calcium dependent chemiluminescence occurred at 0.25-0.75 mM added calcium chloride. Peak chemiluminescent responses in the 13-paired samples were reduced in DMD leucocytes (P less than 0.01) using a paired t-test. These result suggest that there is an abnormality of calcium dependent A23187-induced chemiluminescence in DMD leucocytes and that there may be a generalised abnormality of calcium metabolism in DMD.
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PMID:Decreased A23187-induced chemiluminescence in Duchenne muscular dystrophy granulocytes. 681 7

Chickens with inherited muscular dystrophy (Line 413) were treated in two separate trials with daily intraperitoneal injections of 10% DMSO-water solutions containing the proteinase inhibitors, Ep475 and E64. Drug therapy in each case significantly prolonged the functional ability of the treated chickens. Diluent control chickens around day 35 ex ovo characteristically reached a maximum ability to right from the supine position in a standardized functional test for muscle weakness. Subsequently, the control chickens were found to decline progressively in their ability to right. Treatment with the proteinase inhibitors had no effect on the typically elevated levels of plasma creatine kinase activity. In a histological analysis of the affected pectoralis major muscle, drug treatment had no effect on the relative distribution of degenerating, and vacuolated fibers, inflammatory cells, and abnormal fiber diameters. An exception was seen in decreased necrotic fibers of chickens treated with high doses of Ep475. Moreover, both inhibitors had positive effects on two biochemical abnormalities common to the dystrophic pectoralis muscle: increase in noncollagen protein, and reduction in total calcium.
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PMID:Limited benefit to genetically dystrophic chickens from a synthetic proteinase inhibitor: Ep475. 687 13

Calcium (Ca) and magnesium (Mg) content were determined in muscle of 27 patients with Duchenne muscular dystrophy, 36 with other neuromuscular diseases, and 22 whose muscle biopsy specimens were histochemically normal. Muscle Ca was significantly elevated in all diseases studied but was about 50% higher in Duchenne dystrophy patients (p less than 0.0001). Mg was decreased by 44% in Duchenne dystrophy, compared with less striking deficits in other diseases (p less than 0.005). In older, nonambulatory Duchenne dystrophy patients, Mg was significantly lower than in younger, ambulatory patients (p less than 0.001); muscle Ca was the same in both groups. On the basis of noncollagen nitrogen concentration, muscle MG depletion could not be attributed solely to reduced muscle mass. These findings strengthen arguments for a role of Ca in the pathogenesis of muscular dystrophy and may implicate Mg depletion as another pathogenetic factor.
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PMID:Muscle calcium and magnesium content in Duchenne muscular dystrophy. 688 95


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