RESUMO
Introdução: A obesidade se caracteriza como um processo oxidativo e inflamatório, que predispõe adolescentes, de modo precoce, a eventos até recentemente pouco frequentes nessa faixa etária. Assim, a ação da enzima Fosfolipase A associada às lipoproteínas (Lp-PLA ), que reduz fosfolipídios oxidados e gera lisofosfolipídios, bem como a disponibilidade de antioxidantes plasmáticos, representam um importante tema de pesquisa no contexto cardiovascular. Objetivo: Verificar se a atividade da LP-PLA 2 2 e a concentração de antioxidantes lipossolúveis se associam com os principais marcadores de risco cardiovascular em adolescentes. Métodos: Duzentos e quarenta e dois adolescentes (10 a 19 anos), de ambos os sexos foram distribuídos, segundo o índice de massa corporal (IMC), em três grupos: Eutróficos (n=77), Sobrepeso (n=82) e Obesos (n=83). A amostra foi caracterizada através de parâmetros sócio-econômicos, estado de saúde, uso de medicamentos, antedecentes familiares de doenças crônicas e prática de atividade física. Foram avaliados ainda os dados antropométricos (peso, altura e composição corporal - bioimpedância), e o consumo alimentar por meio de três recordatórios 24 h. A partir de uma amostra de sangue coletada após jejum (12h), realizaram-se as análises da atividade da Lp-PLA , LDL(-) e seus auto-anticorpos, perfil lipídico (colesterol total, LDL-C, HDL-C e triglicerídeos), tamanho da HDL, proteína transportadora de éster de colesterol (CETP), ácidos graxos não esterificados (NEFAs), adipocitocinas, assim como antioxidantes (retinol, licopeno, -tocoferol e -caroteno) no plasma. Resultados: Artigo 1: Lp-PLA maybe an important cardiovascular biomarker in obese adolescents. Verificou-se que o perfil lipídico, insulina, HOMA-IR (resistência à insulina) e LDL(-) evidenciaram um maior risco cardiovascular nos adolescentes obesos. A atividade da enzima Lp-PLA 2 mostrou uma variação proporcional ao IMC, circunferência da cintura e porcentagem de gordura.
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Fosfolipases A/fisiologia , Fosfolipases A/sangue , Lipoproteínas/fisiologia , Biomarcadores/sangue , Obesidade , Saúde do Adolescente , Antropometria , Índice de Massa Corporal , Proteção da Criança , Fatores de RiscoRESUMO
Amphibian skin secretions contain several bioactive compounds such as biogenic amines, alkaloids, steroids, proteins and peptides; being peptides a continuously growing field of interest. This work aims to describe the main physiopathological properties of the tree frog Phyllomedusa hypochondrialis skin secretion, obtained by manual stimulation of the dorsal skin surface. Intravenous skin secretion administration provoked lethal effect in mice after 5min. Low doses induced significant systemic and local effects like edema and nociception in mice and topic administration induced myonecrosis in the endothelium of cremaster mice. The presence of phospholipase A(2) activity, proteolytic activity and creatine kinase activity (in the plasma of treated mice) are reported and are very likely to be related to the physiopathological (edematic and myotoxic) activities observed. These data provide in vivo evidence of the complex toxic effects of the P. hypochondrialis skin secretion as well as possible mechanisms of action for these effects.
Assuntos
Venenos de Anfíbios/toxicidade , Anuros/metabolismo , Venenos de Anfíbios/química , Venenos de Anfíbios/metabolismo , Animais , Permeabilidade Capilar/efeitos dos fármacos , Creatina Quinase/sangue , Edema/induzido quimicamente , Ativação Enzimática/efeitos dos fármacos , Camundongos , Músculos/efeitos dos fármacos , Músculos/patologia , Medição da Dor , Peptídeo Hidrolases/metabolismo , Fosfolipases A/sangue , Pele/metabolismoRESUMO
INTRODUCTION AND OBJECTIVE: Parkinson's disease (PD) is characterized by a progressive, slow loss of dopaminergic neurones in the substance nigra. Although the cause of this neurone loss is unknown, at the present time many papers suggest oxidative stress (OS), secondary to dopaminergic metabolism, as an aetiopathogenic factor of PD. Therefore study of the part played by OS in this would permit the use of antioxidants (AO) as another possibility for treatment of the disease. It would also be a major step forward in the search for possible biological markers. MATERIAL AND METHODS: A study using spectrophotometric techniques was made of the serum levels of four biochemical indicators: catalase (CAT), malonyl aldehyde (MDA), phospholipase A2 (PLA2) and Vitamin C (VITC) in controls and in patients with PD. We found the average value for each of the variables studied in controls and in patients, taking AO treatment into account. RESULTS: The effect of clinical variables on serum levels of CAT, MDA, PLA2 and VITC was analyzed. It was seen that only the clinical state of Hoen and Yahr was related to the biochemical indicators. The CAT activity and VITC concentration showed statistically significant differences between patients (independently of their AO treatment) and controls. The CAT activity was significantly less in those treated with AO. The patients with PD did not all have the same degree of OS. The effect of AO treatment on plasma markers showed changes only in one subgroup of Parkinson patients. CONCLUSIONS: Our study suggests that AO treatment in this condition should be tailored to the individual patient according to the degree of OS present.
Assuntos
Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Ácido Ascórbico/sangue , Biomarcadores , Catalase/sangue , Progressão da Doença , Humanos , Malondialdeído/sangue , Doença de Parkinson/enzimologia , Fosfolipases A/sangue , Fosfolipases A/metabolismo , Fosfolipases A2 , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria/métodosRESUMO
A protein that neutralizes the biological activities of basic phospholipase A2 (PLA2) myotoxin isoforms from the venom of the snake Bothrops asper was isolated from its blood by affinity chromatography with Sepharose-immobilized myotoxins. Biochemical characterization of this B. asper myotoxin inhibitor protein (BaMIP) indicated a subunit molecular mass of 23-25 kDa, an isoelectric point of 4, and glycosylation. Gel-filtration studies revealed a molecular mass of 120 kDa, suggesting that BaMIP possesses an oligomeric structure composed of five 23-25 kDa subunits. Functional studies indicated that BaMIP inhibits the PLA2 activity of B. asper basic myotoxins I and III, as well as the myotoxicity and edema-forming activity in vivo and cytolytic activity in vitro towards cultured endothelial cells, of all four myotoxin isoforms (I-IV) tested. Sequence analysis of the first 63 amino acid residues from the N-terminus of BaMIP indicated more than 65% sequence similarity to the PLA2 inhibitors isolated from the blood of the crotalid snakes Trimeresurus flavoviridis and Agkistrodon blomhoffii siniticus. These inhibitors also share sequences similar to the carbohydrate-recognition domains of human and rabbit cellular PLA2 receptors, suggesting a common domain evolution among snake plasma PLA2 inhibitors and mammalian PLA2 receptors. Despite this similarity, this is the first description of a natural anti-myotoxic factor from snake blood.
Assuntos
Bothrops/sangue , Fosfolipases A/sangue , Sequência de Aminoácidos , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Venenos de Crotalídeos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fosfolipases A/farmacologia , Fosfolipases A2 , CoelhosRESUMO
1. Preheparin plasma from mice, but not rats or man, contains high levels of phospholipase A and lysophospholipase activities which are distinct from lecithin:cholesterol acyltransferase (LCAT). 2. Neither the phospholipase A nor the lysophospholipase activities in preheparin plasma are inhibited by incubation in the presence of protamine sulphate or high salt concentrations. 3. When mouse plasma is incubated in the presence of an antiserum specific for rat hepatic triacylglycerol lipase (HTGL), the phospholipase activities are abolished. 4. These observations suggest that the phospholipase activities are attributable to the action of HTGL, which, in the mouse appears to be a freely circulating enzyme, whereas for other species this enzyme only appears in the blood following administration of heparin.
Assuntos
Heparina/farmacologia , Soros Imunes , Lipase/imunologia , Fígado/enzimologia , Lisofosfolipase/antagonistas & inibidores , Fosfolipases A/antagonistas & inibidores , Animais , Humanos , Lisofosfolipase/sangue , Camundongos , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Fosfolipases A/sangue , Protaminas/farmacologia , Ratos , Cloreto de Sódio/farmacologiaRESUMO
Se estudió la influencia del tiempo de tratamiento con prajmalina sobre las concentraciones plasmáticas de la fosfolipasa A2, y se correlacionaron estos resultados con los niveles de las enzimas creatin fosfoquinasa (CPK) y transaminasa glutamicooxalacética (GOT). Los parámetros enzimáticos exhibieron tendencias semejantes, las cuales disminuían con respecto al tiempo de tratamiento con el antiarrítmico. Cuando se evaluaron las relaciones CPK/fosfolipasa A2 y GOT/fosfolipasa A2 se encontró que estas relaciones eran representativas del momento a partir del cual se producía la lesión orgánica
Assuntos
Coelhos , Animais , Fosfolipases A/sangue , Prajmalina/uso terapêuticoRESUMO
Because previous investigations have suggested that platelet activating factor and tumor necrosis factor-alpha (TNF-alpha) are important mediators of experimental necrotizing enterocolitis in the rat, we measured platelet activating factor, acetylhydrolase (the platelet activating factor breakdown enzyme), and TNF-alpha in the plasma of 12 human neonates with necrotizing enterocolitis and eight age-matched control subjects with similar gestational ages, postnatal ages, and weights. Almost all patients with necrotizing enterocolitis had elevated plasma platelet activating factor values (18.1 +/- 3.6 ng/ml vs. 3.1 +/- 0.9 ng/ml in control subjects, p less than 0.01). Plasma acetylhydrolase activity was lower in patients than in control subjects (10.6 +/- 0.7 nmol/ml/min vs 23.0 +/- 1.4 nmol/ml/min, p less than 0.01). Plasma TNF-alpha concentration was significantly elevated in patients with necrotizing enterocolitis (136 +/- 75 U/ml vs 1.5 +/- 0.8 U/ml, p less than 0.05), although the individual variation was high. There was no correlation between individual TNF-alpha and platelet activating factor levels. We conclude that platelet activating factor and TNF-alpha are elevated in patients with necrotizing enterocolitis and that suppressed platelet activating factor degradation contributes to the increased platelet activating factor levels; platelet activating factor and TNF-alpha may contribute to the pathophysiology of necrotizing enterocolitis.
Assuntos
Enterocolite Pseudomembranosa/fisiopatologia , Fator de Ativação de Plaquetas/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , 1-Alquil-2-acetilglicerofosfocolina Esterase , Enterocolite Pseudomembranosa/sangue , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Fosfolipases A/sangue , Fosfolipases A/fisiologia , Fator de Ativação de Plaquetas/análise , Contagem de Plaquetas , Fator de Necrose Tumoral alfa/análiseRESUMO
We measured phospholipase A2 (PLA2; EC 3.1.1.4) activity in normal and uremic plasma, using [1-14C]oleate-labeled autoclaved Escherichia coli as substrate. Hydrolysis of bacterial phospholipid by crude plasma from both groups was optimal at pH 5.5, was specific for the 2-acyl position of phospholipids, and had an absolute requirement for calcium. Activity was greatest in the presence of added Ca2+, 5 mmol/L, but this increase was inhibited by several divalent cations (Mg2+, Zn2+, Cu2+, Ba2+, Co2+, Pb2+, Fe2+) and by Fe3+. PLA2 activity was also inhibited by heparin at acid and alkaline pH, normal plasma being more sensitive than uremic plasma to this inhibition. Enzyme activity in undiluted plasma was eightfold greater in uremic than in normal plasma. Dilution of plasma by two to fourfold increased the total activity of both normal and uremic plasma. However, the relative differences in total activity between the groups remained constant (eight- to 11-fold). The cause and consequences of the increased PLA2 activity in uremia remain to be established.