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Scaini G.,University of the Extreme South of Santa Catarina
Molecular and cellular biochemistry | Year: 2012

The accumulation of octanoic (OA) and decanoic (DA) acids in tissue is the common finding in medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD), the most frequent defect of fatty acid oxidation. Affected patients present hypoketotic hypoglycemia, rhabdomyolysis, hepatomegaly, seizures and lethargy, which may progress to coma and death. At present, the pathophysiological mechanisms underlying hepatic and skeletal muscle alterations in affected patients are poorly known. Therefore, in the present work, we investigated the in vitro effects of OA and DA, the accumulating metabolites in MCADD, on various bioenergetics and oxidative stress parameters. It was verified that OA and DA decreased complexes I-III, II-III and IV activities in liver and also inhibit complex IV activity in skeletal muscle. In addition, DA decreased complexes II-III activity in skeletal muscle. We also verified that OA and DA increased TBA-RS levels and carbonyl content in both tissues. Finally, DA, but not OA, significantly decreased GSH levels in rat skeletal muscle. Our present data show that the medium-chain fatty acids that accumulate in MCADD impair electron transfer through respiratory chain and elicit oxidative damage in rat liver and skeletal muscle. It may be therefore presumed that these mechanisms are involved in the pathophysiology of the hepatopathy and rhabdomyolysis presented by MCADD-affected patients. Source

Pereira A.B.,University of the Extreme South of Santa Catarina
Arquivos brasileiros de cardiologia | Year: 2010

BACKGROUND: The myocardial bridge constitutes one of the main differential diagnoses of coronary artery disease. However, it remains an underdiagnosed condition and its physiopathological mechanisms and therapeutics are yet to be elucidated. OBJECTIVE: To analyze and describe the clinical and therapeutic evolution of patients with an angiographic diagnosis of myocardial bridge, comparing the data with that in the current literature, in order to clarify the patients' clinical profile and prognosis. METHODS: The results of coronary angiographies carried out from 2003 to 2007 in a Laboratory of Hemodynamics were reviewed; the analysis of patients' files was carried out and selected patients were interviewed. RESULTS: The frequency of myocardial bridge diagnosis was 3.6%. The mean age of patients was 56.8 years (SD = 11.83; CI = 0.73). The anterior descending artery was affected in isolation in 100% of the cases. After the selection, the analysis and interview of 31 patients were carried out. There was no correlation between symptoms and degree of angiographic narrowing observed in the studied patients. The drug treatment included the use of beta-blockers, calcium-channel antagonists, platelet antiaggregants and/or nitrates and resulted in clinical improvement in 30%, absence of alterations in the clinical picture in 60% and symptom worsening in 10% of the patients. One patient presented sudden death; two patients underwent angioplasty followed by significant clinical improvement and none of the patients underwent surgical procedures. CONCLUSION: Most of the patients with myocardial bridge have a good prognosis, but in the long term, there are not enough data, obtained from a large sample of symptomatic patients, to draw definitive conclusions. Source

Cholewa J.M.,Coastal Carolina University | Guimaraes-Ferreira L.,Federal University of Espirito Santo | Zanchi N.E.,University of the Extreme South of Santa Catarina
Amino Acids | Year: 2014

Betaine is a methyl derivative of glycine first isolated from sugar beets. Betaine consumed from food sources and through dietary supplements presents similar bioavailability and is metabolized to di-methylglycine and sarcosine in the liver. The ergogenic and clinical effects of betaine have been investigated with doses ranging from 500 to 9,000 mg/day. Some studies using animal models and human subjects suggest that betaine supplementation could promote adiposity reductions and/or lean mass gains. Moreover, previous investigations report positive effects of betaine on sports performance in both endurance- and resistance-type exercise, despite some conflicting results. The mechanisms underlying these effects are poorly understood, but could involve the stimulation of lipolysis and inhibition of lipogenesis via gene expression and subsequent activity of lipolytic-/lipogenic-related proteins, stimulation of autocrine/endocrine IGF-1 release and insulin receptor signaling pathways, stimulation of growth hormone secretion, increased creatine synthesis, increases in protein synthesis via intracellular hyper-hydration, as well as exerting psychological effects such as attenuating sensations of fatigue. However, the exact mechanisms behind betaine action and the long-term effects of supplementation on humans remain to be elucidated. This review aims to describe evidence for the use of betaine as an ergogenic and esthetic aid, and discuss the potential mechanisms underlying these effects. © 2014 Springer-Verlag. Source

Simon K.R.,University of the Extreme South of Santa Catarina
Biochemistry and cell biology = Biochimie et biologie cellulaire | Year: 2013

Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering that high levels of Phe are associated with neurological dysfunction and that the mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main objective of this study was to investigate the in vivo and in vitro effects of Phe on DNA damage, as determined by the alkaline comet assay. The results showed that, compared to control group, the levels of DNA migration were significantly greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an inhibitor of PAH), or a combination thereof in cerebral cortex and blood, indicating DNA damage. These treatments also provoked increase of carbonyl content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium, we observed an increase in the frequency and index of DNA damage in the cerebral cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex and blood of rats receiving Phe, suggesting that this mechanism could be, at least in part, responsible for the neurological dysfunction in PKU patients. Source

Avila P.R.,University of the Extreme South of Santa Catarina
The British journal of nutrition | Year: 2013

The exact mechanisms of the relationship between obesity and cardiovascular events are not yet fully understood; however, oxidative stress may be involved. Thus, the aim of the present study was to evaluate the effects of resveratrol and fish oil on catecholamine-induced mortality in obese rats. To begin with, rats were divided into five groups: (1) lean, (2) obese, (3) obese supplemented with resveratrol, (4) obese supplemented with fish oil and (5) obese supplemented with resveratrol and fish oil (n 18 rats per group), for 2 months. After supplementation, the groups were subdivided as with (n 10) and without (n 8) cardiovascular catecholaminergic stress after isoproterenol (60 mg/kg) injection. At 24 h later, the survival rate was analysed. The obese group showed lower survival rates (10 %) when compared with the lean group (70 %). On the other hand, resveratrol (50 %) and fish oil (40 %) increased the survival rate of obese rats (χ(2) test, P= 0·019). Biochemical analyses of the myocardium and aorta revealed that obese rats had higher levels of superoxide and oxidative damage to lipids and protein. This was associated with reduced superoxide dismutase and glutathione peroxidase activity in both the myocardium and aorta. The supplementation increased antioxidant enzyme activities and reduced oxidative damage. We also evaluated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 antioxidant pathway. Nrf2 protein levels that were reduced in obese rats were increased by the antioxidant treatment. Taken together, these results showed that resveratrol and fish oil reduce catecholamine-induced mortality in obese rats, partly through the reduction of oxidative stress. Source

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