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

Malignant hyperthermia is an autosomal-dominant inherited disorder of the skeletal muscle cell characterized by a hypermetabolic response to all commonly used inhalational anaesthetics and depolarizing muscle relaxants. The clinical syndrome includes muscle rigidity, hypercapnia, tachycardia and myoglobinuria as result of increased carbon dioxide production, oxygen consumption and muscle membrane breakdown. In human beings and animals susceptible to malignant hyperthermia, it is generally accepted that an increase in the level of myoplasmic free calcium is the cause of the syndrome. Various hypotheses have been proposed to account for the increase of intracellular calcium levels, e.g. a defect in the calcium release channel of the sarcoplasmic reticulum (ryanodine receptor), an abnormality of the excitation-contraction coupling mechanisms, or alterations in second messenger systems of skeletal muscles. This review gives an overview of the main features of this disease and recent advances in research including pathophysiology, treatment, diagnosis and genetics as well as association with other disorders.
 ...
PMID:Malignant hyperthermia. 1155 40

As of yet, only a few strategies to prevent myocardial reperfusion injury have been tested clinically. In the first minutes of reperfusion, the myocardium can be damaged by contracture development, causing mechanical stiffness, tissue necrosis, and the "stone heart" phenomenon. Reperfusion-induced contracture can have two different causes, namely, Ca2+overload-induced contracture or rigor-type contracture. Ca2+ contracture results from rapid re-energization of contractile cells with a persistent Ca2+ overload. Strategies to prevent this type of injury are directed at cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity. Rigor-contracture occurs when re-energization proceeds very slowly. It does not depend on Ca2+ overload. It may be prevented by strategies improving early mitochondrial reactivation
 ...
PMID:Cellular mechanisms of ischemia-reperfusion injury. 1260 6

Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction to neuroleptic drugs, which is potentially fatal. It has been occasionally reported that NMS occurs subsequently after surgery. We report a case of a 53-year-old male patient who developed NMS following cardiac surgery due to the resumption of zotepine. The patient was attacked with hyperthermia, sweating, significant shivering, trembling of the fingers, disturbed consciousness and extreme muscle rigidity after the resumption of zotepine. Furthermore, laboratory measurements revealed increased levels of serum blood urea nitrogen, creatinine and creatine phosphokinase. In addition, elevation in white blood cell counts and myoglobinemia were also observed. After a diagnosis of NMS was established, administration of zotepine was stopped and treatments with administration of dantrolene and a large amount of fluid infusion intravenously were started. Following these treatments, the clinical symptoms subsided and the laboratory findings improved without need for hemodialysis. Dantrolene, which is able to effectively impede the abnormal flow of calcium from the sarcplasmic reticulum into the muscle cytoplasm, was beneficial to reduce the clinical symptoms of NMS. We hereby present a patient with NMS following cardiac surgery, and discuss its subsequent management.
 ...
PMID:Neuroleptic malignant syndrome following cardiac surgery: successful treatment with dantrolene. 1296 23

Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic predisposition associated with a susceptibility to volatile anesthetics and depolarizing muscle relaxants that lead to a fulminant anesthetic crisis with hyperthermia, skeletal muscle rigidity, respiratory and metabolic acidosis, and muscle rhabdomyolysis. Malignant hyperthermia crises are caused by an abnormal regulation of the calcium release mechanism, which reflects the consequences of disturbed skeletal muscle calcium homeostasis. We screened 64 individuals of 27 unrelated families for the most frequently described mutations associated with MH in the genes RYR1 and CACNL1A3. We identified only one family with the Arg614Cys mutation but with a discordant segregating pattern to the in vitro contracture test (IVCT). To elucidate which other mechanism could lead to susceptibility in the members of this family, we tested it for further MH susceptibility loci. The same haplotype was shown to segregate with the individuals carrying the Arg614Cys mutation in chromosome 19; however, the other susceptible and equivocal individuals do not share this haplotype. Markers for the susceptible locus in chromosome regions 17q, 7q, 3q, and 5p did not segregate with the IVCT phenotype in the susceptible individuals, suggesting that the positivity of the IVCT could be attributable to other ambient factors.
 ...
PMID:Screening for mutations in the RYR1 gene in families with malignant hyperthermia. 1450 Sep 92

Malignant hyperthermia (MH) is an uncommon, life-threatening, acute pharmacogenetic disorder of the skeletal muscle cell. It manifests in susceptible individuals as a hypermetabolic response on exposure to halogenated volatile anaesthetics and depolarizing muscle relaxants. There may also be a relationship between susceptibility to MH, heat stroke and exercise-induced rhabdomyolysis. The pathophysiology of the crisis involves an uncontrolled release of cytoplasmic free calcium from the sarcoplasmic reticulum leading to activation of energy-producing biochemical pathways. Organ system failure and rhabdomyolysis may occur as a result of high fever, hyperkalaemia and acidosis. The ryanodine receptor, the calcium-release channel of the sarcoplasmic reticulum, is the primary locus for malignant hypothermia susceptibility. Multiple mutations in the gene for the ryanodine receptor protein are causative. Other genes may also be involved. A classical fulminant crisis presents with a rising end-tidal carbon dioxide, skeletal muscle rigidity, tachycardia, hyperthermia and acidosis. Mortality may be as high as 70% if the syndrome is not recognized and treated. Immediate discontinuation of triggering agents, oxygenation, and correction of acidosis and electrolyte abnormalities, cooling and dantrolene are essential for treatment of the syndrome. Thanks to clinical and research investigations, widespread education and the introduction of dantrolene sodium, the mortality from MH is less than 5%. This chapter provides an overview and an update of MH.
 ...
PMID:Malignant hyperthermia. 1466 55

Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating bronchospasm and alleviating the symptoms of chronic obstructive pulmonary disease (COPD) in the horse. In other species (rats, mice, sheep, and cattle), chronic high doses of clenbuterol (typically in the milligram per kilogram body weight range) has been shown to cause a muscle directed protein anabolic response. Clenbuterol can also modify muscle fibre composition and therefore potentially affect muscle function. This has implications for the performance of exercising horses being treated with therapeutic doses of clenbuterol (typically in the microgram per kilogram body weight range) for bronchospasm or COPD. It is not known whether clenbuterol treatment affects muscle fibre function in horses. The purpose of this study was to examine the effects of a therapeutic dose of clenbuterol, with and without exercise, on the contractile activation characteristics of single membrane permeabilized fibres prepared from muscle biopsies. We tested the hypothesis that therapeutic treatment with clenbuterol would not affect muscle fibre function. Unfit Standardbred mares were treated for 8 weeks with; clenbuterol (2.4 microg/kg twice/day, 5 days/week) plus exercise (20 min at 50% VO2(max) 3 d/wk; CLENEX), clenbuterol only (CLEN), or exercise only (EX). Muscle biopsies were taken from the gluteus medius muscle before and after treatment and stored in a glycerol-based solution to prepare permeabilized muscle fibres. The force-pCa relationship for fibres from CLEN horses was steeper (P < 0.05) indicative of greater cooperative interactions within the thin filament, however, fibre sensitivity to Ca2+ was unchanged. In contrast, the steepness of the force-pCa relationship was not changed in fibres from EX and CLENEX horses and Ca2+ sensitivity was also unaffected. Rigor force, activation in the absence of ATP, was not affected by any treatment indicating an approximately equivalent number of participating cross-bridges during activation. The results indicate that a therapeutic dose of clenbuterol to Standardbred horses does not affect the Ca(2+)-activated contractile characteristics of isolated muscle fibres.
 ...
PMID:Therapeutic clenbuterol treatment does not alter Ca2+ sensitivity of permeabilized fast muscle fibres from exercise trained or untrained horses. 1467 50

Malignant hyperthermia is an autosomal dominant disorder which results in a severe reaction to anesthetic agents in approximately 0.0005 to 0.5% of patients exposed to general anesthesia. Malignant hyperthermia is characterized by severe muscle rigidity, myoglobunuria, high fever, tachycardia, and arrhythmia precipitated by depolarizing muscle relaxants (succinylcholine) and inhalational anesthetic agents (halothane). When MH occurs, the anesthetic agents must be discontinued immediately and dantrolene should be administered.
Clin Calcium 2001 Nov
PMID:[Current diagnosis and therapy of malignant hyperthermia]. 1577 67

Malignant hyperthermia (MH) is a pharmacogenetic clinical syndrome that manifests as a hypermetabolic crisis when a susceptible individual is exposed to an anesthetic triggering agent. Clinical signs include unexplained elevation of end-tidal carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea, hyperthermia, and evidence of rhabdomyolysis. This process is a result of an abnormally increased release of calcium from the sarcoplasmic reticulum, which is often caused by an inherited mutation in the gene for the ryanodine receptor (RYR1) that resides in the membrane of the sarcoplasmic reticulum. The gold standard for determination of MH susceptibility is the caffeine-halothane contracture test. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13.1) responsible for conferring MH susceptibility. Ryanodine receptor mutations are found in at least 25% of known MH susceptible individuals in North America. Mutation analysis has recently become available in the United States and is expected to play an integral role in the diagnosis of MH susceptibility in the future.
 ...
PMID:Malignant hyperthermia: update on susceptibility testing. 1595 37

Malignant hyperthermia (MH) is a life-threatening disorder characterized by skeletal muscle rigidity and elevated body temperature in response to halogenated anesthetics such as isoflurane or halothane. Mutation of tyrosine 522 of RyR1 (the predominant skeletal muscle calcium release channel) to serine has been associated with human malignant hyperthermia. In the present study, mice created harboring this mutation were found to represent the first murine model of human malignant hyperthermia. Mice homozygous for the Y522S mutation exhibit skeletal defects and die during embryonic development or soon after birth. Heterozygous mice, which correspond to the human occurrence of this mutation, are MH susceptible, experiencing whole body contractions and elevated core temperatures in response to isoflurane exposure or heat stress. Skeletal muscles from heterozygous mice exhibit increased susceptibility to caffeine- and heat-induced contractures in vitro. In addition, the heterozygous expression of the mutation results in enhanced RyR1 sensitivity to activation by temperature, caffeine, and voltage but not uncompensated sarcoplasmic reticulum calcium leak or store depletion. We conclude that the heterozygous expression of the Y522S mutation confers susceptibility to both heat- and anesthetic-induced MH responses.
 ...
PMID:Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse. 1628 4

Fyn-mediated tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) receptor subunits has been implicated in various brain functions, including ethanol tolerance, learning, and seizure susceptibility. In this study, we explored the role of Fyn in haloperidol-induced catalepsy, an animal model of the extrapyramidal side effects of antipsychotics. Haloperidol induced catalepsy and muscle rigidity in the control mice, but these responses were significantly reduced in Fyn-deficient mice. Expression of the striatal dopamine D(2) receptor, the main site of haloperidol action, did not differ between the two genotypes. Fyn activation and enhanced tyrosine phosphorylation of the NMDA receptor NR2B subunit, as measured by Western blotting, were induced after haloperidol injection of the control mice, but both responses were significantly reduced in Fyn-deficient mice. Dopamine D(2) receptor blockade was shown to increase both NR2B phosphorylation and the NMDA-induced calcium responses in control cultured striatal neurons but not in Fyn-deficient neurons. Based on these findings, we proposed a new molecular mechanism underlying haloperidol-induced catalepsy, in which the dopamine D(2) receptor antagonist induces striatal Fyn activation and the subsequent tyrosine phosphorylation of NR2B alters striatal neuronal activity, thereby inducing the behavioral changes that are manifested as a cataleptic response.
 ...
PMID:Fyn is required for haloperidol-induced catalepsy in mice. 1640 46


<< Previous 1 2 3 4 5 6 7 Next >>