Navegando por Palavras-chave "ryanodine"

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    Análise histomorfométrica da fibra muscular esquelética de pacientes suscetíveis à hipertermia maligna
    (Universidade Federal de São Paulo (UNIFESP), 2015-02-28) Santos, Joilson Moura dos [UNIFESP]; Silva, Helga Cristina Almeida da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Malignant Hyperthermia (MH) is a skeletal muscle disease characterized by hypermetabolism after administration of inhaled anesthetics and depolarizing muscle relaxants, which may progress to irreversible shock and death. Pathological examination of muscle fiber using histomorphometry can be an additional tool for the assessment of patients susceptible to MH, when analyzed in association with the different phenotypes that are part of the clinical presentation of susceptibility to MH. Objectives: Analyzing the histological aspect and histomorphometry of skeletal muscle fibers in patients susceptible to MH, and determining a potential correlation with clinical changes as atrophy or muscle hypertrophy. Casuistic and methods: 97 subjects, with a history suggestive of susceptibility to MH and tested for MH with muscle in vitro contracture test (IVCT) between 2004 and 2012 were analyzed for demographic characteristics, laboratory and clinical findings, histopathology with histochemistry and morphometry in their skeletal muscle biopsy. Results: The data analyzed were from patients in their forties with predominance of women (52), whites (72) and personal or family history of MH (73). Signs of motor unit syndrome were present in 17 patients and muscular hypertrophy in 24. The IVCT was positive for susceptibility to MH in 60% of the study sample. Those tested positive were mainly males and showed increased creatine kinase with three of them (5%) showing incidental cores. Among the six patients with family history of myopathy with cores, two had IVCT positive for susceptibility to MH. From the two patients with personal history of myopathy with cores, one had IVCT positive for susceptibility to MH. Qualitative histological analysis revealed that none of the changes found were significantly more frequent among those susceptible to MH, however, atrophic fibers were more frequent in individuals tested negative for MH susceptibility. Regarding quantitative analysis, although no significant difference was found between susceptible and non-susceptible individuals to MH concerning the percent of type I or II muscle fibers, the proportion of type I fibers were positively correlated with muscle hypertrophy determined in physical examination. The hypertrophy of muscle fibers was more frequent in women susceptible to MH than in those not susceptible. Furthermore, in the female group hypertrophy of muscle fibers correlated with the syndrome of motor unit (SMU), creatine kinase, coefficient of variability and centralization nuclear. In females, increased cross sectional area of both type-I and type-II muscle fibers correlated with increased CK. On the other hand, SMU and centralization nuclear correlated with increased cross sectional area of the fiber subtype II only, whereas the coefficient of variability correlated with increased cross sectional area of the fiber subtype I in females. Conclusions: Qualitative histological analysis did not identify any changes that were present more frequently in the group susceptible to MH, which did not allow for establishing a myopathy directly associated with MH. However, atrophic fibers were more frequent in individuals not susceptible to the HM, suggesting the existence of undiagnosed myopathies that could have led to atypical reactions during anesthesia. Concerning patients with a personal or family history of myopathy with cores, susceptibility to MH should necessarily be investigated using IVCT. Quantitative analysis of muscle fiber revealed relevant data for understanding the impact of MH, such as the correlation between clinical muscle hypertrophy and the proportion of type-I fibers in patients susceptible to MH, and the presence of hypertrophy of muscle fibers in women susceptible to MH, This increased cross-sectional area in women susceptible to MH correlated with serum CK levels, SMU, coefficient of variability and nuclear centralization.
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    Intracellular calcium mobilization by muscarinic receptors is regulated by micromolar concentrations of external Ca2+
    (Springer, 2001-06-01) Smaili, Soraya Soubhi [UNIFESP]; Carvalho, Solange Maria Torchia [UNIFESP]; Cavalcanti, Paulo MS [UNIFESP]; Jurkiewicz, Neide H. [UNIFESP]; Garcia, Antonio G.; Jurkiewicz, Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Autonoma Madrid
    Carbachol-induced contractions of rat stomach fundus strips, obtained in a nutrient solution containing 1.8 mM Ca2+, were resistant to Ca2+ withdrawal, even after 1 h of bathing the tissues in a nominal 0 Ca2+ solution. This was not observed when K+ was used to evoke contractions, which were rapidly inhibited after Ca2+ removal (t(1/)2=2 min). the effect of carbachol in 0 Ca2+ solution was reduced by using drugs that reduce intracellular pools of Ca2+, such as caffeine (1-3 mM), ryanodine (30 muM) or thapsigargin (1 muM), corroborating the involvement of intracellular Ca2+ stores. On the other hand, when the 0 Ca2+ solution contained EGTA, a complete decline of carbachol effects was observed within about 8 min, indicating the involvement of extracellular Ca2+. Atomic absorption spectrometry showed that our 0 Ca2+ solution still contained 45 muM Ca2+, which was drastically reduced to 5.9 nM in the presence of EGTA. Taken together, our results indicate that the effects of carbachol are due to the mobilization of caffeine-, ryanodine- and thapsigargin-sensitive intracellular Ca2+ stores, and that these stores are not inactivated or depleted if micromolar concentrations (45 muM), but not nanomolar concentrations (5.9 nM) of Ca2+ are maintained in the extracellular milieu.