Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The porcine stress syndrome is a genetic disorder of swine which, like neuroleptic malignant syndrome, is characterized by hyperthermia, muscle rigidity, and autonomic dysfunction. We investigated the porcine stress syndrome as a possible animal model for neuroleptic malignant syndrome in two ways. First, we administered haloperidol and lithium carbonate, alone and in combination, to susceptible and resistant swine. Second, we attempted to prevent the syndrome by pretreating animals with bromocriptine. Porcine stress syndrome was induced in 2 of 3 susceptible and 1 of 3 resistant swine by combined treatment with lithium and haloperidol, but was not triggered by treatment with lithium or haloperidol alone. Pretreatment with bromocriptine conferred no protection against the syndrome.
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PMID:Porcine stress syndrome: an animal model for the neuroleptic malignant syndrome? 211 11

The skeletal muscle ryanodine receptor (RYR1) is a calcium release channel that mediates efflux of calcium ions from the sarcoplasmic reticulum into the myoplasm during excitation-contraction coupling. Mutations in the RYR1 gene have been detected in about 50% of the patients suffering from malignant hyperthermia (MH), but evidence is accumulating that other genetic defects can also lead to MH in humans. MH is a life-threatening disorder induced by exposure to volatile anesthetics and/or the muscle relaxans succinylcholin during surgical procedures in affected patients. MH leads to skeletal muscle rigidity, hypermetabolism and rapid rise in body temperature. MH is also known in pigs where it is triggered by stress and therefore often referred to as porcine stress syndrome. The existence of an animal model has greatly faciliated the elucidation of the basis for the human disease. This review describes recent advances in the understanding of the physiological action of ryanodine receptors and new insights regarding the relation between different RYR1 mutations and distinct phenotypical appearances.
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PMID:Ryanodine receptors and their role in genetic diseases (review). 985 1

Malignant hyperthermia susceptibility (MHS), a skeletal muscle disorder, is mostly inherited as an autosomal dominant trait. Exposure of susceptible individuals to volatile halogenated anaesthetics can lead to a MH episode resulting in irreversible tissue damages or to the patient's death if not immediately reversed by dantrolene treatment. A MH episode is characterised by a combination of hyperthermia, skeletal muscle rigidity and hypermetabolism. Porcine stress syndrome has proved to be a valuable model for physiopathological studies of MHS. Malignant hyperthermia syndrome is associated with a failure of the calcium homeostasis in muscular fibres. Dysfunction of the calcium channels: the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR), which are involved in the release of the Ca2+ stored in sarcoplasmic reticulum has been clearly demonstrated. A biochemical test based on the analysis of the in vitro contracture response of muscular fibres to caffeine and halothane was developed to define the MHS status of patients. Although the genetic analysis of MHS has beneficiated from recent progresses, genetic testing is still far to answer to all testing situations. If in swine, hyperthermia syndrome was always associated with a unique mutation of the RyR1 gene, genetic analysis is far more complicated in human: i) more than 20 different MHS mutations in the RyR1 gene have been described; ii) a mutation of the gene encoding the dihydropyridine receptor has been identified; iii) 4 other potential MHS loci have been reported.
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PMID:[Biology of malignant hyperthermia: a disease of the calcium channels of the skeletal muscle]. 1076 Jul 1

Dantrolene-a nitrofurantoin derivative-was developed by Snyder et al. in 1967. After initial discovery of its muscle relaxation potential, investigations in a number of species demonstrated dose-dependent reductions in skeletal muscle tone that were long lasting, relatively nontoxic, and free of adverse effects such as respiratory impairment. Ellis et al. then published a number of papers investigating the means by which dantrolene produced these effects. Using a series of classic physiologic models, Ellis investigated potential sites of action for the new drug, eventually narrowing this down to the intracellular calcium-release mechanism. Ellis went on to play a pivotal role in the discovery of dantrolene's effectiveness for the treatment of malignant hyperthermia, after reading a scientific bulletin about muscle rigidity in pigs affected by porcine stress syndrome, contacting Gaisford Harrison and sending dantrolene to him for trial.
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PMID:Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D. 2827 43