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)

Corticosteroid administration on alternate days to five boys with Duchenne's muscular dystrophy (DMD) lowered the high serum creatine kinase and lactate dehydrogenase activities in three, caused no change in one, and increased these activities in one. These observations indicate that, as given, this therapy can partially normalize a major biochemical abnormality of this disease in some but not all patients with DMD.
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PMID:Variable effects of corticosteroid treatment of serum enzyme activities in Duchenne's muscular dystrophy. 7 Aug 32

The effects of diethylstilbestrol (DES) and prednisolone (Pr), administered alone or in combination, on the serum enzyme activities in Duchenne's muscular dystrophy (DMD) have been evaluated. When DES and Pr were given simultaneously to four boys with DMD, the mean creatine phosphokinase and lactate dehydrogenase levels fell to about one half those achieved with either agent alone. No untoward or unexpected side effects were encountered. These observations, and our previous demonstration that both agents reduce enzyme efflux from skeletal muscle, give promise that a safe combination therapy may be found to approximately normalize the serum in DMD. This will permit us to test the hypothesis that lowering the serum enzymes, by reducing their loss from skeletal muscle, will slow or arrest the muscle deterioration characteristic of this disease.
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PMID:Effects of the simultaneous administration of diethylstilbestrol and prednisolone on serum enzymes in Duchenne's muscular dystrophy. 26 98

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

We have previously shown that pretreatment of mice with diethylstilbestrol (DES) or prednisolone (Pr) lowered enzyme efflux from isolated mouse skeletal muscle. These same agents also lowered the high serum enzyme activities in boys with Duchenne's muscular dystrophy (DMD). In a continuing search for other agents with similar effects, the influence of penicillamine (Pe) on enzyme efflux from isolated muscle was assessed, because it lowered the high plasma creatine phosphokinase (CPK) and produce beneficial effects in avian muscular dystrophy. Three groups of mice received 0, 1, or 10 mg Pe daily for 14 days. All mice were given supplementary pyridoxine. The egress of CPK and lactate dehydrogenase from the isolated left gastrocnemius and heart was determined over a 5 hour period. Pe produced more modest effects than did DES or Pr. The 10 mg dose reduced enzyme efflux from the gastrocnemius by 10%. In contrast, heart enzyme efflux was augmented by 20%. Similar dose-related disparate effects on enzyme efflux from skeletal muscle and heart have been previously noted for DES and Pr. Pe is the third agent found to lower the high serum enzyme activities in muscular dystrophy and reduce gastrocnemius enzyme efflux from isolated mouse skeletal muscle. This further establishes the usefulness of the mouse assay for identifying agents that lower the high serum enzyme activities in muscular dystrophy.
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PMID:Penicillamine effects on enzyme efflux from skeletal and heart muscle. 87 14

Allosterism allows individual assay of both isoenzymes, one abundant in muscle, of pyruvate kinase (PK), recently reported superior to serum creatine phosphokinase (CPK) in detecting patients with and female carriers of X-linked recessive (Duchenne) muscular dystrophy (DMD). Extensive comparative studies did not support these findings and confirmed the marked superiority of CPK over rariants of PK or other enzymes in sensitivity, stability and convenience. Deducting the adenylate kinase increment (AKI) further refined the CPK assay, eliminating the effect of haemolysis in diagnosis and enabling studies of blood cell content. Both leucocytes and erythrocytes liberated PK and lactate dehydrogenase (LDH) after brief chilling or disruption. Only erythrocytes showed a CPK content, however, constantly adjusted to match that of serum as if by free cell membrane passage, but less accomodating to a sudden large influx of CPK than of LDH, where an apparent buffering effect could account for differences in clinical response.
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PMID:Carrier detection in X-linked recessive (Duchenne) muscular dystrophy: pyruvate kinase isoenzymes and creatine phosphokinase in serum and blood cells. 88 69

Diethyistibestrol was administered orally to 11 boys with Duchene muscular dystrophy (DMD). Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, characteristically high in DMD, and presumably of muscle origin, were reduced significantly (P LESS THAN .05). On ther other hand, the activity of alkaline phosphatase, an enzyme not of muscle origin, increased. These enzyme changes were reversible when diethyistibestrol was discontinued. Despite appreciable alterations in totoal serum enzyme activity, no important change was found in the isozyme patterns. Piperazine estrone sulfate was administered to another patient with DMD. The effects of this physiologic hormone were, in part, similar to those of diethyistibestrol. Experimentally, diethylstilbestrol reduced the efflux of CPK and LDH from mouse skeletal muscle. This may be the manner by which diethylstilbesterol reduced the serum enzyme levels in DMD, but this has not been proved directly. These studies are the first step in an effort to identify various agents that in combinations may normalize serum enzyme levels.
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PMID:Diethylstilbestrol effects on serum enzymes and isozymes in muscular dystrophy. 93 73

We have previously shown that diethylstilbestrol (DES) almost always, and prednisolone (Pr) less frequently, lowered the high serum enzyme activities in Duchenne's muscular dystrophy (DMD). In experimental studies, it was shown that pretreatment of mice with each of these agents lowered enzyme efflux from isolated skeletal muscle incubated in vitro, but efflux was augmented by higher doses of Pr. This suggested that these agents may influence skeletal muscle enzyme efflux in man also, producing the effects noted in DMD. The present studies were undertaken to assess the effect on enzyme efflux from skeletal muscle and heart that these two agents would exert when given in combination. Four groups of mice (14/group) were injected with saline, 250 mug DES, 35 mug Pr, or 250 mug DES plus 35 mug Pr in saline every other day for 22 days. The left gastroecnemius and heart were isolated from animals of each group, and placed in separate tubes containing incubation medium at 25 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which issued from each organ was determined over a 5 hour period. In the doses tested, it was found that: 1) DES selectively reduced enzyme efflux from skeletal muscle, but had no effect on enzyme efflux from heart; 2) a Pr dose which decreased enzyme efflux from the heart, augmented efflux from the gastrocnemius; and 3) DES prevented the enhanced enzyme efflux produced by Pr. These studies indicate that these hormones, in pharmacological doses, influence enzyme efflux from muscle. This suggests, but it is not established, that these hormones also exert a similar physiological role. Finally, this experimental model appears to be useful in assessing the effects of single agents, and agents in combination, on enzyme efflux, and should be of aid in selecting appropriate agents which may be therapeutically useful in Duchenne's muscular dystrophy.
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PMID:Disparate effects of diethylstillbestrol and prednisolone on enzyme efflux from heart and skeletal muscle. 96 73

In 200 patients with neuromuscular diseases the author studied malonic dehydrogenase and lactic dehydrogenase activity comparing it with the activity of serum creatine kinase and aldolase. A significant rise in the values of all these enzymes was found only in the Duchenne type of muscular dystrophy, in polymyositis, and less frequently in the limb-girdle type of muscular dystrophy. Raised activity of creatine kinase and sidolase was observed in mothers and sisters of patients with Duchenne type of dystrophy, in patients with non-progressive myopathy, periodic paralysis, amyotrophic lateral sclerosis and polyneuropathy. With progression of dystrophy the activity of these enzymes decreases.
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PMID:[Serum enzymatic activity in neuromuscular diseases]. 112 44

We have previously shown that oral diethylstilbestrol (DES) lowers the high serum enzyme levels characteristic of Duchenne's muscular dystrophy (DMD). The present studies were undertaken to assess the effect of DES on the efflux of enzymes from isolated mouse skeletal muscle. Thirty-four male mice were used. Half received daily subcutaneous injections of 10 mug diethylstilbestrol-diphosphate (DES-DP) in saline for up to 3 wk and half daily saline injections. Left gastrocnemii were isolated from control and treated mice, and placed in separate incubation media at 37 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) from each was compared over a 4- to 5-hr period. In 15 of 18 there was a reduction in efflux of both enzymes from muscles isolated from DES-DP-treated mice. The greatest effect was noted during the second hour, when the mean efflux of each enzyme was reduced about 30%. Minor differences in muscle weight, water content, and enzyme activities did not explain the reduced efflux. These results suggest that DES has either reduced the permeability of the sarcolemma or enhanced the intracytoplasmic stability of these enzymes. This is the first drug reported to reduce the spontaneous enzyme efflux from isolated skeletal muscle. It remains to be established that a similar effect accounts for the reduction in serum enzyme levels when DES is administered to persons with DMD.
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PMID:Reduction of enzyme efflux from skeletal muscle by diethylstilbestrol. 114 55

In a previous study, the efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which takes place from isolated mouse skeletal muscle was shown to be significantly reduced by pretreatment of the intact animal with diethylstilbestrol (DES). This compound is known to reduce the high serum enzymes present in patients with Duchenne's muscular dystrophy (DMD). Glucocorticoids also reduce the serum enzymes in DMD. The purpose of this study was to determine if pretreatment with the glucocorticoid, prednisolone, also lowered the efflux from isolated mouse skeletal and cardiac muscle. The results of these studies show that prednisolone pretreatment lowers the enzyme efflux from isolated skeletal muscle, but not from heart. There is an optimal dose which produces this reduction, which if exceeded, augments the efflux. Thus two agents are now known which lower the efflux of CPK and LDH from isolated skeletal muscle. These same two agents lower the high serum enzymes in DMD. This suggests, but does not prove, that the mechanism by which these agents lower the serum enzymes in DMD is by reducing enzyme efflux from skeletal muscle.
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PMID:Effect of pretreatment with prednisolone on enzyme efflux from isolated skeletal and heart muscle. 119 19


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