Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder that affects genetically predisposed individuals. It manifests in susceptible individuals in response to exposure to Inhalant anesthetics, depolarizing muscle relaxants or extreme physical activity in hot environments. During exposure to these triggering agents, there is a rapid and sustained increase of myoplasmic calcium (Ca(2+)) concentration induced by hyperactivation of ryanodine receptor of skeletal muscle (RyR1), causing a profound change in Ca(2+) homeostasis, featuring a hypermetabolic state. RyR1, Ca(2+) release channels of sarcoplasmic reticulum, is the primary locus for MH susceptibility. Several mutations in the gene encoding the protein RyR1 have been identified; however, other genes may be involved. Actually, the standard method for diagnosing MH susceptibility is the muscle contracture test for exposure to halothane-caffeine (CHCT) and the only treatment is the use of dantrolene. However, with advances in molecular genetics, a full understanding of the disease etiology may be provided, favoring the development of an accurate diagnosis, less invasive, with DNA test, and also will provide the development of new therapeutic strategies for treatment of MH. Thus, this brief review aims to integrate molecular and clinical aspects of MH, gathering input for a better understanding of this channelopathy.
The purpose of this study was to evaluate the effects of Spirulina Platensis supplementation on selected blood markers of oxidative stress, muscle damage, inflammation, and performance in trained rats. Rats (250 g-300 g) were submitted to a strength training program (eight weeks), divided into four groups: control (GT) (trained without supplementation), trained with daily-supplementation of 50 mg/ kg (GT50), 150 mg/kg (GT150) and 500 mg/kg (GT500). Training consisted of a jump protocol in PVCcylinder containing water, with increasing load over experimental weeks. We evaluated the markers of oxidative stress (malondialdehyde-MDA and antioxidant capacity) and inflammation (C-reactive protein) at the end of the training. Among groups submitted to strength training, concentration of C-reactive protein decreased after 8 weeks of intervention in the trained group and GT500. Strength training enhanced plasma MDA concentration of malondialdehyde with supplementation of S. platensis in GT150 and GT500. In plasma analysis, strength training enhanced the percentage of oxidation inhibition, with spirulina supplementation in rates of 150 and 500 mg/kg. Spirulina supplementation for 8 weeks (in a dose-effect manner) improved antioxidant capacity as well as attenuated exercise-induced increases in ROS and inflammation. As a practical application, the use as high doses did not cause a reduction in positive physiological adaptations to exercise training. Additional studies are necessary to test the application of Spirulina Platensis in other contexts, as collective sports (basketball, football, soccer). Spirulina platensis is a microalga with biological activity as antioxidant, immunomodulatory, and anti-inflammatory and nowadays is used to produce nutritional supplements 1-3. S. platensis is composed of protein (55%-70%) 4 , carbohydrates (15%-20%) 5 , lipids (approximately 7%) 5 , fiber, ash, and water including various minerals, vitamins, γ-linolenic acid, chlorophyll, carotenoids, and phycocyanin 2,6. Recently, some researchers have reported that the latter played a crucial role in the antioxidative action of S. platensis 2 .
Obesity is a multifactorial disease related to metabolic disorders and associated with genetic determinants. Currently, ion channels activity has been linked to many of these disorders, in addition to the central regulation of food intake, energetic balance, hormone release and response, as well as the adipocyte cell proliferation. Therefore, the objective of this work is to review the current knowledge about the influence of ion channels in obesity development. This review used different sources of literature (Google Scholar, PubMed, Scopus, and Web of Science) to assess the role of ion channels in the pathophysiology of obesity. Ion channels present diverse key functions, such as the maintenance of physiological homeostasis and cell proliferation. Cell biology and pharmacological experimental evidences demonstrate that proliferating cells exhibit ion channel expression, conductance, and electrical properties different from the resting cells. Thereby, a large variety of ion channels has been identified in the pathogenesis of obesity such as potassium, sodium, calcium and chloride channels, nicotinic acetylcholine receptor and transient receptor potential channels. The fundamental involvement of these channels on the generation of obesity leads to the progress in the knowledge about the mechanisms responsible for the obesity pathophysiology, consequently emerging as new targets for pharmacological modulation.
Summary: Correia ACC, Silva PCB, Silva BA -Malignant Hyperthermia: Clinical and Molecular Aspects. Content:Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder that affects genetically predisposed individuals. It manifests in susceptible individuals in response to exposure to Inhalant anesthetics, depolarizing muscle relaxants or extreme physical activity in hot environments. During exposure to these triggering agents, there is a rapid and sustained increase of myoplasmic calcium (Ca 2+ ) concentration induced by hyperactivation of ryanodine receptor of skeletal muscle (RyR1), causing a profound change in Ca 2+ homeostasis, featuring a hypermetabolic state. RyR1, Ca 2+ release channels of sarcoplasmic reticulum, is the primary locus for MH susceptibility. Several mutations in the gene encoding the protein RyR1 have been identified; however, other genes may be involved. Actually, the standard method for diagnosing MH susceptibility is the muscle contracture test for exposure to halothane-caffeine (CHCT) and the only treatment is the use of dantrolene. However, with advances in molecular genetics, a full understanding of the disease etiology may be provided, favoring the development of an accurate diagnosis, less invasive, with DNA test, and also will provide the development of new therapeutic strategies for treatment of MH. Thus, this brief review aims to integrate molecular and clinical aspects of MH, gathering input for a better understanding of this channelopathy.
RESUMO: "Estudo farmacológico do extrato etanólico de Maytenus rigida Mart (Celastraceae) em modelos animais". O extrato etanólico bruto (EEOH) da casca de Maytenus rigida Mart (Celastraceae) uma planta da medicina popular do Brasil, foi testado para a atividade antiinfl amatória, antiúlcera e antidiarréica em modelos animais. Não foi observado sinal de toxicidade aguda nos animais tratados com doses elevadas do EEOH (5000 mg/kg, v.o. ou 2000 mg/kg i.p.). O extrato nas doses de 250, 500 e 750 mg/kg mostrou um signifi cante efeito inibitório (P < 0,01) no edema de pata induzido por carragenina e exibiu propriedade protetora contra a ulceração induzida por etanol em ratos. Também uma atividade antidiarréica (P < 0,01) foi observada na diarréia induzida por óleo de rícino em camundongos. O trânsito intestinal foi reduzido signifi cativamente (P < 0.01), porém o pré-tratamento não reduziu o peso do conteúdo intestinal em ratos. Os resultados dão suporte à utilização de Maytenus rigida na medicina popular do Brasil para o tratamento da infl amação, da úlcera e da diarréia. Unitermos:Maytenus rigida, Celastraceae, antiinfl amatória, antiúlcera, antidiarréica. ABSTRACT: The crude ethanol extract (EEOH) of the bark of Maytenus rigidaMart (Celastraceae) a plant used in Brazil herbal traditional medicine, was tested for anti-infl ammatory, antiulcer and antidiarrhoeal activities in animal models. No acute toxicological sign was observed in animals treated with the highest dose (5000 mg/kg, p.o. or 2000 mg/kg i.p.) of EEOH. The extract doses of 250, 500 or 750 mg/kg revealed a signifi cant inhibitory effect (P < 0,01) in carrageenin-induced rat paw oedema and exhibited ulcer-protective properties against ethanolinduced ulceration in rats. An anti-diarrhoeal activity (P < 0.01) was also observed in castor-oilinduced diarrhoeal in mice. The intestinal transit was signifi cantly (P < 0.01) reduced, however the pretreatment did not reduce the weight of intestinal contents. These results support the popular applications of Maytenus rigida for the treatment of infl ammation, ulcer and diarrhoea in Brazil herbal traditional medicine.
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