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)

The protease inhibitor leupeptin decreases protein degradation in rat skeletal and cardiac muscle incubated in vitro, while protein synthesis remains unaltered. Leupeptin also lowers protein breakdown in denervated rat muscles and affected muscles from mice with hereditary muscular dystrophy. Leupeptin may thus be useful in retarding tissue atrophy. Since homogenates of leupeptin-treated muscles had decreased cathepsin B activity, this lysosomal protease may play a role in protein turnover in normal and diseased muscles.
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PMID:Leupeptin, a protease inhibitor, decreases protein degradation in normal and diseased muscles. 62 52

In murine muscular dystrophy, hindlimb muscle contains a functionally defective thiol protease inhibitor (TPI) which has been implicated in the onset and progression of the disease in mice. More recently, this protease inhibitor has been identified as parvalbumin, a calcium binding protein. In this study, a polyclonal antibody against mouse muscle parvalbumin was used to study the concentration and distribution of this protein in normal and dystrophic male mice at various ages. Immunodetection assays were used to screen extracts of hindlimb, forelimb, brain, heart, lung, liver, and kidney in 60-day-old normal and dystrophic male mice for parvalbumin content. Parvalbumin was detected in relatively high amounts in both hindlimb and forelimb muscle extracts, while much lower concentrations were detected in brains of normal and dystrophic animals. No parvalbumin was detected in the lung, liver, heart, or kidney extracts using the immunoassay. With aging, the parvalbumin concentration in hindlimb muscle of normal mice remained fairly constant for 90 days, whereupon the level increased at 120 days. In contrast, the parvalbumin concentration in hindlimb muscle of dystrophic mice decreased steadily with age to about 22%% of normal animals at 120 days. The parvalbumin content was also reduced in dystrophic brain.
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PMID:Age-related changes and tissue distribution of parvalbumin in normal and dystrophic mice of strain 129 ReJ. 185 61

Continued administration of the dipeptide protease inhibitor Bestatin to 34 mice with genetic muscular dystrophy from the onset of clinical deficit, cured about half of the animals within 3 months. Cessation of treatment in the recovered mice at age 4 months was not followed by relapse. Examinations of these mice revealed recovery of (1) weight gain and life span, (2) muscle strength, and (3) marker enzyme activities in skeletal muscle and serum, as well as (4) disappearance of myopathological features characteristic of the disease such as necrosis of muscle fibers, centralization or a chain like arrangement of nuclei, or a marked infiltration of collagenous fibers. Finally, (5) the genetic confirmation of the animals which attained remission was confirmed to be dy/dy.
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PMID:Successful treatment of murine muscular dystrophy with the protease inhibitor bestatin. 371 32

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