Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A young, overweight dog presented with sudden onset lethargy and collapse following exercise in warm environmental conditions. Investigations revealed systolic hypotension, multiform ventricular premature complexes, irregular myocardial echogenicity with poor left ventricular systolic function and a markedly elevated troponin cTnI (180ng/mL, reference range <0.3ng/mL) consistent with severe myocyte damage. Infectious causes of myocarditis were ruled out on the basis of serological and polymerase chain reaction blood tests. Exercise-induced malignant hyperthermia was excluded from the history, an exercise tolerance test and genetic testing for the RYR1 V547A mutation. The diagnosis was myocardial damage secondary to suspected exertional heatstroke, from which the dog recovered uneventfully over a number of weeks and serum troponin normalised. This is the first case report in any species including man, documenting high troponin as a marker of severe myocardial damage following suspected heatstroke.
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PMID:High serum troponin I concentration as a marker of severe myocardial damage in a case of suspected exertional heatstroke in a dog. 1908 37

Muscle spindles from the hind limb muscles of adult Ryr1(I4895T/wt) (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies.
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PMID:Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1(I4895T/wt) mouse model of core myopathy. 2561 31

The heart is critically dependent on mitochondrial respiration for energy supply. Ischemia decreases oxygen availability, with catastrophic consequences for cellular energy systems. After a few minutes of ischemia, the mitochondrial respiratory chain halts, ATP levels drop and ion gradients across cell membranes collapse. Activation of cellular proteases and generation of reactive oxygen species by mitochondria during ischemia alter mitochondrial membrane permeability, causing mitochondrial swelling and fragmentation and eventually cell death. The mitochondria, therefore, are important targets of cardioprotection against ischemic injury. We have previously shown that ixazomib (IXA), a proteasome inhibitor used for treating multiple myeloma, effectively reduced the size of the infarct produced by global ischemia in isolated rat hearts and prevented degradation of the sarcoplasmic reticulum calcium release channel RyR2. The aim of this work was to further characterize the protective effect of IXA by determining its effect on mitochondrial morphology and function after ischemia. We also quantified the effect of IXA on levels of mitofusin-2, a protein involved in maintaining mitochondrial morphology and mitochondria-SR communication. We found that mitochondria were significantly preserved and functional parameters such as oxygen consumption, the ability to generate a membrane potential, and glutathione content were improved in mitochondria isolated from hearts perfused with IXA prior to ischemia. IXA also blocked the release of cytochrome c observed in ischemia and significantly preserved mitofusin-2 integrity. These beneficial effects resulted in a significant decrease in the left ventricular end diastolic pressure upon reperfusion and a smaller infarct in isolated hearts.
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PMID:Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia. 3245 73