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)

1. For methods of vitamin E and selenium supplementation were evaluated using thirty-nine pregnant ewe-lambs fed on a ration containing 0.043 mg Se/kg and 25 mg vitamin E/kg. Treatments were control, fortified mineral mix (ESe salt) (300 mg vitamin E, 3 mg Se), ruminal Se pellets (505 mg Se), drench (300 mg vitamin E, 3 mg Se) and intramuscular injection (600 mg vitamin E, 3 mg Se). Only ewes supplemented, commencing approximately 50 d before parturition. 2. Birth weights were similar for all treatments and live-weight gains of lambs to 56 d of age were improved in all supplemented groups (P less than 0.05). There were no clinical cases of nutritional muscular dystrophy. 3. Se concentrations in whole blood were more than doubled in both lambs and ewes drenched or injected; responses to ESe salt and pellets were much smaller. 4. Plasma tocopherol levels were increased in injected dams and their lambs (P less than 0.001). 5. Haemoglobin concentration and erythrocyte counts were significantly higher (P less than 0.01) in control ewes and lambs than in treated lambs. 6. Lactate dehydrogenase (EC 1.1.1.27), creatine kinase (EC 2.7.3.2) and aspartate aminotransferase (EC 2.6.1.1) activities were increased in lambs from control, ESe salt and pellet groups (P less than 0.001). Glutathione peroxidase (EC 1.11.1.9) activity responded to Se supplementation in both ewes and their lambs (P less than 0.001) and the response was highest in the injected group, followed in order, by the drench, pellet, Ese salt and control groups. 7. These studies indicated that in terms of the haematological and blood chemistry changes investigated, the intramuscular injection was most effective, followed by the oral drench. Ruminal pellets and fortified salt were less satisfactory.
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PMID:Haematological and blood chemistry changes in ewes and lambs following supplementation with vitamin E and selenium. 69 59

Loxistatin is a possible therapeutic agent of muscular dystrophy. A single oral administration of loxistatin to male rats caused focal necrosis of the liver with inflammatory cell infiltration. The severity of the lesions was dose-dependent up to 200 mg/kg and also manifest by an increase in serum alanine aminotransferase and aspartate aminotransferase activities. Hepatic glutathione (GSH) levels decreased with a maximum 20% depletion within 5 hr after the oral administration of loxistatin. Pretreatment with diethyl maleate did not potentiate the loxistatin-induced hepatic injury. On the other hand, the hepatoprotective effect of cysteamine was observed when cysteamine was administered 24 hr before loxistatin dosing, but the effect was not observed when the antidote was administered concomitantly with loxistatin. Pretreatment of rats with phenobarbital or trans-stilbene oxide provided partial protection against the hepatotoxic effect of loxistatin. Pretreatment with SKF-525A resulted in increased hepatic injury, while pretreatment with piperonyl butoxide, cimetidine, or 3-methylcholanthrene had no effect on hepatic damage by loxistatin. Five hours after [14C]loxistatin administration to rats, the covalent binding of the radioactivity to proteins was greatest in the liver, followed by the kidney, then muscle and blood to a lesser extent. [14C]Loxistatin acid, the pharmacologically active form of loxistatin, irreversibly bound to rat liver microsomal proteins; more binding occurred when the NADPH-generating system was omitted and when the microsomes were boiled first. GSH did not alter the extent of irreversible binding, whereas N-ethylmaleimide decreased the binding of [14C]loxistatin acid to rat liver microsomal proteins by 75%. Unlike the rat, administration of loxistatin to hamsters caused neither hepatic injury nor hepatic GSH depletion even at a high dose (500 mg/kg). Both the distribution and covalent binding of radioactivity in the hamster liver were one-third of those in rats following [14C]loxistatin dosing. These results suggest that loxistatin causes species-specific hepatotoxicity and that, at least in part, some of the toxic effects of loxistatin are mediated by the nonenzymatic covalent binding of loxistatin acid to thiol residues on cellular macromolecules.
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PMID:An epoxysuccinic acid derivative(loxistatin)-induced hepatic injury in rats and hamsters. 239 99

Clinical and biochemical responses were studied after taking the measures to prevent nutrition muscular dystrophy in young cattle in the given ecological conditions. Analyzing the biological material (blood, hair, feed, soil), we found the sufficiently high saturation of heifer organisms with the microelement selenium and on the contrary, vitamin E deficiency. Sensitive indicators of the break-down of muscular tissue were the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and mainly creatinine kinase (CPK): the activities of these enzymes increased significantly after the heifers had been driven to pasture. The stay of animals in the run to get them used to the physical load before going to the pasture was not found to be a sufficient measure to prevent muscular nutrition myodystrophy if the animals had not been administered vitamin E and selenium supplements. Of the one hundred heifers we examined, seven animals began to show the signs of nutrition muscular dystrophy; none of these animals had been administered vitamin E and selenium supplements.
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PMID:[Clinical and biochemical response in the prevention of nutritional myodystrophy in heifers]. 310 11

In two families with severe sex-linked muscular dystrophy, high levels of alpha-hydroxybutyrate dehydrogenase (HBD), lactate dehydrogenase (LD), aspartate transaminase (AspT), aldolase, and creatine phosphokinase (CPK) were found in the sera of three young affected males. In both families the mother had a raised level of HBD activity. Four sisters of the three affected boys had raised serum enzyme levels, and they are regarded as presumptive carriers of the disease. Biopsy specimens of dystrophic muscle had LD and HBD contents which were significantly lower than those of control specimens, while the HBD/LD ratios were markedly greater. Muscle from two unaffected members of the same family also exhibited high ratios, indicating the presence of the electrophoretically fast LD isoenzymes, and this was confirmed by acrylamide-gel electrophoresis.
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PMID:Alpha-hydroxybutyrate dehydrogenase activity in sex-linked muscular dystrophy. 593 10

The activities of cytoplasmic and mitochondrial aspartate aminotransferase isoforms in serum in 20 outpatients with Duchenne's progressive muscular dystrophy and seven carriers of the gene of that disease were determined. The control group consisted of 19 patients with other neuromuscular disorders. Twenty, age-matched healthy persons comprised the normal control group. The activity of the cytoplasmic isoform was increased in 85% of Duchenne's dystrophy cases. In these cases the reaction of the cytoplasmic isoenzyme in the presence of pyridoxal 5'-phosphate was abnormal. In the remaining Duchenne's dystrophy cases normal activity of this isoform and normal stimulation to pyridoxal 5'-phosphate was found. The mitochondrial isoform was significantly increased in 30% of Duchenne's dystrophy cases. In all Duchenne's dystrophy patients the reaction of the mitochondrial isoenzyme to supplementation with pyridoxal 5'-phosphate was normal. We conclude that the evaluation of aspartate aminotransferase isoforms in serum in Duchenne's dystrophy can be of clinical importance, especially in evaluating the degree of muscle cell damage.
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PMID:Serum cytoplasmic and mitochondrial aspartate aminotransferase in Duchenne's progressive muscular dystrophy. 760 78

Because of the very low concentrations of selenium in the dry matter of grass, grass silage, hay and maize silage Slovenian dairy herds need to be supplemented with selenium. Selenium in the form of mineral and feed mixtures maintained adequate mean (sd) blood serum selenium concentrations of 43.9 (27.6) to 65.3 (18.5) micrograms/litre in lactating cows, but in late lactation and in the dry period when only mineral mixtures were used, about 60 per cent of the cows had marginal serum selenium concentrations, mainly because of the low intake of the mineral supplement. In 18 herds which were either unsupplemented or irregularly supplemented with selenium, the mean (sd) concentrations in blood serum were 13.7 (5.5) micrograms/litre and 17.4 (9.2) micrograms/litre, respectively, for selenium and 2.98 (2.72) mg/litre and 1.62 (1.73) mg/litre for vitamin E, indicating that under extensive farming conditions in Slovenia the lack of both micronutrients may be responsible for nutritional muscular dystrophy in calves. Among 37 clinical cases, cardiorespiratory signs predominated in 25 of the calves and skeletal myopathy was dominant in 12. A very low mean serum selenium concentration [9.7 (7.2) micrograms/litre] and typically high activities of aspartate aminotransferase (AST) [1125 (373) U/litre] and creatine kinase (CK) [9169 (3681) U/litre) were observed for the myocardial form of the disease, and 2797 (550) U/litre and 22,650 (13,500) U/litre were observed for the skeletal form of the disease. A highly significant (P < 0.0001) difference in the selenium concentration of liver dry matter between the regularly supplemented [402 (207) micrograms/kg] and irregularly supplemented [173 (69) micrograms/kg] herds was observed. If a minimum value of 300 micrograms/kg of liver dry matter is accepted as the criterion for the determination of adequate selenium status, 93 per cent of the samples from the irregularly supplemented herds were selenium deficient. A similar proportion was estimated to be selenium deficient when the criterion was taken to be 30 micrograms selenium/litre of blood serum.
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PMID:Assessment of selenium and vitamin E deficiencies in dairy herds and clinical disease in calves. 891 12

A 4-year-old girl was referred for evaluation for a mild but persistent serum aspartate aminotransferase (AST) elevation detected incidentally during routine blood screening for a skin infection. Serum creatine kinase activity was found to be increased. Immunohistochemical study for dystrophin in her muscle biopsy showed results consistent with a carrier state for muscular dystrophy. Molecular work-up showed the proposita to be a carrier of a deletion mutation of exon 48 of the dystrophin gene. Four male relatives also had the deletion mutation, yet showed no clinical symptoms of muscular dystrophy (age range 8-58 yrs). Linkage analysis of the dystrophin gene in the family showed a spontaneous change of an STR45 allele, which could be due to either an intragenic double recombination event, or CA repeat length mutation leading to identical size alleles. To our knowledge, this is the first documentation of an asymptomatic dystrophinopathy in multiple males of advanced age. Based on molecular findings, this family would be given a diagnosis of Becker muscular dystrophy. This diagnosis implies the development of clinical symptoms, even though this family is clearly asymptomatic. This report underscores the caution which must be exercized when giving presymptomatic diagnoses based on molecular studies.
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PMID:Asymptomatic dystrophinopathy. 909 54

Five male children are reported in whom incidental recognition of elevated serum alanine aminotransferase (ALT) activity initiated investigation to identity the cause of suspected hepatocellular injury. All five were later diagnosed with X chromosome-linked muscular dystrophy. The serum level of ALT, generally considered to be specific for hepatocellular injury, was increased two to 25 times above normal in all the reported cases. Paradoxically, the increase in ALT activity was greater than that of serum aspartate aminotransferase (three to 16 times normal), an enzyme whose elevation is generally recognized as being less specific and indicative of muscle, cardiac, kidney, pancreatic, red blood cell or hepatic injury. At presentation to the gastrointestinal service, one case, age 2.5 months, had no symptoms or signs of neuromuscular dysfunction, while the other four had previously unrecognized hypertrophy of the calves, proximal limb weakness, positive Gower's sign or delayed gross motor skills. All five patients had marked elevation of serum creatine kinase activity and histopathologically confirmed muscular dystrophy. The practical clinical implication of this report is that children with elevated serum ALT, in the absence of other signs and symptoms of hepatic injury, may have occult muscular disease--most frequently muscular dystrophy. Although the clinical signs of muscular dystrophy may be subtle or absent, early determination of creatine kinase will suggest the correct diagnosis and minimize extensive and invasive investigation focusing on hepatic injury.
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PMID:Elevated aminotransferase activity as an indication of muscular dystrophy: case reports and review of the literature. 919 75

Three cats affected with dystrophin deficiency and hypertrophic muscular dystrophy developed peracute rhabdomyolysis with a fatal outcome. Two cats were anesthetized with isoflurane for routine procedures and did not recover properly from the anesthetic procedure. One cat was manually restrained for an echographic examination and started staggering after a short struggle; its condition worsened, and it died. Blood chemistry findings included severe hyperkalemia, hyperphosphatemia, hypocalcemia, massive increases in creatine kinase, aspartate aminotransferase, and alanine aminotransferase concentrations, and high ion gap metabolic acidosis. Light microscopic evaluation of skeletal muscle revealed severe acute rhabdomyolysis with marked extensive necrosis of large groups of fibers and endomysial edema. These lesions were observed in many skeletal muscles but particularly in the masseter and supraspinatus muscles and in the diaphragm. Typical changes associated with dystrophin deficiency in cats were also noted. Histochemical analysis revealed that the dystrophin deficiency was associated with a decrease in the percentage of type 1 myofibers in all three cats. This change was marked in the 20-month-old cat and milder in the younger cats (6.5 and 8.5 months of age). Percentages of type 2A fibers were markedly decreased and percentages of type 2X fibers were markedly increased in the younger cats. Rhabdomyolysis has been reported in dystrophinopathic humans but not in other animal models of dystrophin deficiency. An increased sensitivity of the dystrophin-deficient sarcolemmal membrane to volatile anesthetic agents, stress, or intense muscular activity is suspected.
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PMID:Lethal peracute rhabdomyolysis associated with stress and general anesthesia in three dystrophin-deficient cats. 953 65

Prolonged elevation of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) is often attributed to hepatic diseases. However, these enzymes are also present in a variety of extrahepatic tissues, including skeletal muscle. Five children (all boys) were referred to the pediatric department of the National Taiwan University Hospital because of persistent elevation of serum aminotransferase activities. The ages of these children were between 4 months and 5.5 years. The neurological findings were all not remarkable. The initial ALT and AST values were 114-581 U/L and 183-700 U/L, respectively. Serum creatine kinase was checked first after 0 to 30 months follow-up and found to be markedly elevated (range, 10,557 U/L to 62,508 U/L). Muscle biopsies in the five cases all showed degenerating and regenerating myofibers with interstitial fibrosis. In Cases 3, 4 and 5, complete absence of dystrophin immunoreactivity was found. Genetic studies showed deletions in the DMD gene (exons 45-48 in case 2 and 49-50 in case 4). This experience indicates that occult muscle diseases should be taken into account in patients with unexplained long-lasting hypertransaminasemia and therefore measurement of serum creatine kinase activity and muscle biopsy should be done early for the correct diagnosis of muscular dystrophy.
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PMID:Persistent hypertransaminasemia as the presenting findings of muscular dystrophy in childhood. 1092 57


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