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TEVA PHARMACEUTICAL INDUSTRIES LIMITED NOTES TO CONSOLIDATED FINANCIAL STATEMENTS-- Continued ; 3 ; In North America The North American subsidiaries mainly provide various defined contribution plans for the benefit of their employees. Under these plans, contributions are based on specified percentages of pay. Additionally, a multiemployer plan is maintained in accordance with various union agreements. 4 ; In Latin America The majority of the employees in Latin America are entitled to severance under local law. The severance payments are calculated based on service term and employee remuneration and accruals are maintained to reflect these amounts. c. Details relating to defined benefit plans: The Company has defined benefit plans primarily in Europe. 1 ; The main components of consolidated net periodic benefit costs are as follows. Retrieved september 19, 2007, from site drugs- for- herpes- treatment&id 265576 chicago style citation: bayarski, yury.
ASSOCIATION OF A MUTATION IN THE RYANODINE RECEPTOR 1 GENE WITH EQUINE MALIGNANT HYPERTHERMIA. Aleman, M., Riehl, J., Aldridge B.M., LeCouteur R.A., Stott, J.L. and Pessah, I.N. Veterinary Medical Teaching Hospital, University of California, Davis. Malignant hyperthermia MH ; is a potentially fatal pharmacogenetic disorder of skeletal muscle elicited by exposure to volatile anesthetics, depolarizing muscle relaxants and stress. Most cases of human and all cases of porcine and canine MH are associated with mutations in the skeletal muscle isoform of the ryanodine receptor RyR1 ; . Since the introduction of inhalation anesthesia in the horse in the 1970's, several horses with suspected MH episodes have been reported but never genetically confirmed. The purpose of our study is to determine if mutations in the candidate gene RyR1 are associated with MH in the horse. Two Quarter Horses that underwent halothane anesthesia with no pre-medication for other research purposes, exhibited a fatal MH episode clinically comparable to those observed in other species. Both cases developed hyperthermia, hypercapnia, lactic acidosis, and muscle rigidity. Multiple muscle biopsies were collected for histochemistry, genetic, functional and expression analysis. Mild non specific myopathic changes were observed on histochemistry. DNA sequencing revealed a common polymorphism that resulted in an amino acid change in these two horses MHRyR1 the polymorphism was not observed in 80 breed-matched controls WTRyR1 ; . Screening tests were developed for detection of heterozygous and homozygous individuals. There were no differences between MHRyR1 and WTRyR1 in activation by caffeine and calcium, and inhibition by calcium and magnesium under physiological buffer conditions. However, the affinity to [3H]-ryanodine of MHRyR1 was significantly higher than WTRyR1. Western blot analysis showed no difference in expression levels of MHRyR1 and WTRyR1. This is the first report of equine MH associated with a mutation in the RyR1 gene.
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