RESUMO
Biophysical skin parameters are indicators of age-related structural and functional changes in skin tissues. This randomized, double-blind, placebo-controlled study in healthy adults tested the effect of Efamol evening primrose oil [EPO, a gamma-linolenic acid (GLA) containing vegetable oil] on skin moisture, transepidermal water loss (TEWL), redness, firmness, elasticity, fatigue resistance and roughness. Efamol EPO was administered orally in soft gel capsules, 3 x 500 mg b.i.d. for 12 weeks. Measurements were taken at baseline and at weeks 4 and 12. The two treatment groups did not differ at baseline and at week 4. At week 12, however, all measured variables, with the exception of skin redness, were significantly different in the EPO group compared with placebo. Skin moisture, TEWL, elasticity, firmness, fatigue resistance and roughness had significantly improved by 12.9, 7.7, 4.7, 16.7, 14.2 and 21.7%, respectively. The two-sided levels of significance in favor of the EPO treatment ranged between 0.034 and 0.001. These findings lend further support to the notion that GLA is a conditionally essential fatty acid for the skin, i.e. it is unable to synthesize GLA, and therefore depends on preformed GLA for optimal structure and function.
RESUMO
The ability of beta-carotene (BC) to reduce lipid peroxidation in humans was investigated. In this randomized double-blind controlled trial, 42 nonsmokers and 28 smokers received either 20 mg BC or placebo daily for 4 wk. Twenty-five smokers and 38 nonsmokers completed the trial. Changes in plasma BC concentrations increased significantly (P < 0.0005) and to the same extent in both groups supplemented with BC. There were no significant changes among the placebo groups. At baseline, lipid peroxidation measured by breath-pentane output (BPO) was significantly higher in the two smoking groups (BC: 8.8 +/- 1.1, placebo: 9.4 +/- 1.4 pmol.kg-1.min-1) than in the two nonsmoking groups (BC: 5.7 +/- 0.5, placebo: 5.9 +/- 0.6 pmol.kg-1.min-1) (P < 0.005). BPO decreased significantly only in smokers receiving BC (6.5 +/- 0.7 pmol.kg-1.min-1) (P < 0.04). Changes in breath-ethane output were not significant. Therefore, lipid peroxidation measured by BPO is significantly higher in smokers than in nonsmokers and is reduced by BC supplementation in smokers. There was no significant change (95% CI - 1.26, 1.12) in BPO when nonsmokers received BC.
Assuntos
Carotenoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fumar/metabolismo , Adulto , Idoso , Antioxidantes/farmacologia , Análise Química do Sangue , Testes Respiratórios , Carotenoides/administração & dosagem , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , beta CarotenoRESUMO
The influence of diets containing gamma-linolenic acid (GLA; 18:3n-6) on sciatic nerve conduction velocity (NCV) was determined in diabetic rats. NCV was lower in diabetic rats fed diets supplemented with olive oil or sunflower seed oil than in nondiabetic rats; rats supplemented with GLA during a 5-wk diabetic period, however, did not exhibit significantly lower NCV. The mean proportion of the phospholipid fatty acid linoleic acid (18:2n-6) was higher in the sciatic nerves of diabetic rats than in the nondiabetic groups irrespective of dietary lipid treatment. Additionally, the proportion of linoleic acid was higher in the diabetic rats fed sunflower oil than in all other groups. Dietary GLA supplementation did not significantly influence the fatty acid composition of nerve membrane phospholipids and there was no obvious correlation between the fatty acid composition of nerve membrane phospholipids and NCV. The content of fructose and glucose in sciatic nerves was higher, whereas that of myo-inositol was lower, in diabetic rats than in nondiabetic rats; however, this was not significantly influenced by dietary GLA. GLA administration did not significantly influence Na(+)-K(+)-exchanging ATPase or ouabain binding activity in sciatic nerve preparations, both of which remained nonsignificantly different in the diabetic and nondiabetic groups. The results suggest that dietary GLA can prevent the deficit in NCV induced by diabetes and that this effect is independent of the nerve phospholipid fatty acid profile, sugar and polyol content, Na(+)-K(+)-exchanging ATPase activity, and ouabain binding. GLA may prevent the deficit in NCV indirectly, possibly by its role as a precursor of vasodilatory prostaglandins. These results confirm that GLA is the active component of evening primrose oil.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/prevenção & controle , Ácidos Graxos Insaturados/uso terapêutico , Condução Nervosa/efeitos dos fármacos , Ácido gama-Linolênico/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Centrifugação com Gradiente de Concentração , Neuropatias Diabéticas/dietoterapia , Eletrofisiologia , Ácidos Graxos Essenciais/uso terapêutico , Glucose/análise , Ácidos Linoleicos , Masculino , Condução Nervosa/fisiologia , Oenothera biennis , Ouabaína/química , Fosfolipídeos/análise , Óleos de Plantas , Ratos , Ratos Wistar , Nervo Isquiático/fisiopatologia , ATPase Trocadora de Sódio-Potássio/análise , EstreptozocinaRESUMO
The differential quantitation of platelet deposition in perfusion studies is a major problem. We report on methods to prepare semithin sections of platelet deposits on collagen coated on glass and plastic cover slips, to study growth and stability of thrombi in three dimensions, and the development of a computer-assisted differential quantitation of platelet-collagen interactions. The interactions were quantified as percentage of the surface covered with platelets (platelet adhesion), thrombus height, thrombus density and thrombus area per unit sectional length, respectively. Cover slips coated with fibrillar equine collagen in parallel-plate perfusion chambers were exposed to flowing citrated blood at shear rates ranging from 200 to 2,600 s-1. Thrombi, partially enmeshed in the collagen meshwork, prevailed on the surface at all shear rates. Maximal platelet adhesion and thrombus density were seen at greater than 5 micrograms/cm2 collagen, while thrombus area and height were maximal at greater than 10 micrograms/cm2. The volume of the thrombi appeared correlated to the number of deposited platelets (r = 0.92). En face preparations showed deposits of platelet islands which grew in diameter with time, particularly in the direction of the blood flow, becoming progressively confluent. Sections cut parallel to the direction of the blood stream indicated that this growth pattern was at least partially caused by thrombi bent in the direction of the blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Adesividade Plaquetária , Trombose/sangue , Citratos/farmacologia , Colágeno/metabolismo , Computadores , Vidro , Humanos , Microscopia Eletrônica , Plásticos , Trombose/patologia , Gravação em VídeoRESUMO
Platelet adhesion to natural and artificial surfaces and adhesion-induced aggregation were investigated in vitro using an annular perfusion chamber. The surfaces were exposed to anticoagulated blood under identical flow conditions (approximately arterial shear rates). The initial attachment of platelets (contact) appeared less surface specific than spreading and release. Fibrillar collagen was the most powerful inducer of platelet degranulation whereas elastin, microfibrils and epon were virtually inactive. Fibrillar collagen caused release also in the absence of spreading. Surface coverage with platelets did not exceed 25% unless spreading occurred. Perfusion with platelet-free plasma or platelet-poor blood did not remove adhering platelets. However, platelets were translocated from mural thrombi to the surface by such perfusion. In addition, platelets which detached from mural thrombi adhered more readily to elastin or microfibrils than platelets from the circulating blood. The initial attachment of platelets to subendothelium was inhibited in von Willebrand's disease, the Bernard-Soulier syndrome and at high concentrations of dipyridamole; spreading was inhibited in storage pool disease of rats, at low temperature (20 degrees C), with EDTA (3 MM) and Prostaglandin E1 (1 muM); and adhesion-induced aggregation was inhibited in thrombasthenia, storage pool disease and after ingestion of sulfinpyrazone or Aspirin. It is concluded that the initial attachment (contact) of platelets, spreading and surface-induced release of platelet constituents are at least partially indendent phenomena, the latter two being highly surface specific. At flow conditions which cause the disappearance of platelet adhesion appears as an irreversible process.
Assuntos
Adesividade Plaquetária , Animais , Membrana Basal , Plaquetas/metabolismo , Vasos Sanguíneos , Colágeno , Elastina , Resinas Epóxi , Transtornos Hemorrágicos/sangue , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária , Coelhos , Reologia , Serotonina/metabolismo , Propriedades de SuperfícieRESUMO
Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.
Assuntos
Arritmias Cardíacas/prevenção & controle , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Hipertensão/prevenção & controle , Animais , Dieta , Gorduras Insaturadas na Dieta/administração & dosagem , Masculino , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Proteinúria/etiologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Especificidade da EspécieRESUMO
Calcium accumulating vesicles were prepared from washed human platelets. Ca2+ uptake could be stimulated with calmodulin. The stimulation of Ca2+ uptake was not abolished by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, thus excluding enhanced cAMP formation as a possible cause for the calmodulin effect. Our findings suggest that, in addition to cAMP, calmodulin is also involved in the regulation of platelet free Ca2+ concentrations, i.e. Ca2+ homeostasis in platelets is under dual control.
Assuntos
Plaquetas/metabolismo , Cálcio/sangue , Calmodulina/farmacologia , Didesoxiadenosina/análogos & derivados , Microssomos/metabolismo , Adenilil Ciclases/sangue , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Encéfalo , Calmodulina/antagonistas & inibidores , Bovinos , AMP Cíclico/farmacologia , Desoxiadenosinas/análogos & derivados , Desoxiadenosinas/farmacologia , Homeostase , Humanos , Imidazóis/farmacologia , Cinética , Microssomos/efeitos dos fármacos , Oxalatos/farmacologiaRESUMO
Young adult male Hooded Wistar rats were rendered diabetic by administration of streptozotocin and maintained for 5 weeks on a diet containing either 6% olive oil as the total source of fat (OO diet), or purified gamma-linolenic acid (GLA) at a concentration of 0.5% with the remaining 5.5% provided by olive oil (GLA diet). Rats were treated with the angiotensin converting inhibitor, cilazapril, administered in the drinking water at a dose of 20 mg kg-1 body weight day-1. For the OO diet groups, sciatic nerve conduction velocity (NCV) in diabetic rats was reduced by 32% (p < 0.01) in comparison with nondiabetic (vehicle-treated) rats and 27.5% (p < 0.05) in comparison with diabetic rats treated with cilazapril. Diabetic, cilazapril-treated rats showed no reduction in NCV. For the nondiabetic, diabetic, and diabetic plus cilazapril groups fed GLA, the NCV was not significantly different, indicating that dietary GLA also prevented the deficit in the NCV induced by the diabetic state. Analysis of the sciatic nerve endoneurial phospholipid fatty acids revealed a significant reduction in the proportion of GLA and an elevation in the proportion of linoleic acid in the diabetic groups compared with the nondiabetic groups and this was independent of the cilazapril treatment or the dietary lipid supplement. Sciatic nerve myo-inositol content was unaltered while mannose, fructose, glucose, and sorbitol levels were elevated in the diabetic groups and these changes were independent of the cilazapril treatment or the dietary lipid supplement. These results indicate that in the rat, cilazapril treatment or dietary GLA, at the doses tested, are effective in preventing the deficit in the NCV induced by diabetes.
Assuntos
Cilazapril/uso terapêutico , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/prevenção & controle , Condução Nervosa/efeitos dos fármacos , Fosfolipídeos/metabolismo , Nervo Isquiático/fisiopatologia , Ácido gama-Linolênico/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Neuropatias Diabéticas/fisiopatologia , Ácidos Graxos/análise , Masculino , Condução Nervosa/fisiologia , Azeite de Oliva , Fosfolipídeos/análise , Fosfolipídeos/química , Óleos de Plantas , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Ácido gama-Linolênico/administração & dosagemRESUMO
The purpose of this study was to investigate in healthy humans the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake, alone or in combination with dL-alpha-tocopherol acetate (vitamin E) supplements on lipid peroxidation. Eighty men were randomly assigned in a double-blind fashion to take daily for 6 wk either menhaden oil (6.26 g, n-3 fatty acids) or olive oil supplements with either vitamin E (900 IU) or its placebo. Antioxidant vitamins, phospholipid composition, malondialdehyde (MDA), and lipid peroxides were measured in the plasma at baseline and week 6. At the same time, breath alkane output was measured. Plasma alpha-tocopherol concentration increased in those receiving vitamin E (P < 0.0001). In those supplemented with n-3 fatty acids, EPA and DHA increased in plasma phospholipids (P < 0.0001) and plasma MDA and lipid peroxides increased (P < 0.001 and P < 0.05, respectively). Breath alkane output did not change significantly and vitamin E intake did not prevent the increase in lipid peroxidation during menhaden oil supplementation. The results demonstrate that supplementing the diet with n-3 fatty acids resulted in an increase in lipid peroxidation, as measured by plasma MDA release and lipid peroxide products, which was not suppressed by vitamin E supplementation.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Peroxidação de Lipídeos , Vitamina E/administração & dosagem , Adulto , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Etano/metabolismo , Ácidos Graxos/sangue , Óleos de Peixe/administração & dosagem , Glutationa Peroxidase/sangue , Humanos , Peróxidos Lipídicos/sangue , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Pentanos/metabolismo , Fosfolipídeos/sangue , Óleos de Plantas/administração & dosagemRESUMO
Several studies have reported that feeding gamma-linolenic acid (GLA) has resulted in no increase in arachidonic acid (AA) in newborns. This result was ascribed to the eicosapentaenoic acid (EPA)-rich fish oil used in these formulas. Docosahexaenoic acid (DHA) sources with only minor amounts of EPA are now available, thus the addition of GLA to infant formulas might be considered an alternative to AA supplementation. Sixty-six premature infants were randomized to feeding one of four formulas [ST: no GLA, no long-chain polyunsaturated fatty acids; BO: 0.6% GLA (borage oil); BO + FOLOW: 0.6% GLA, 0.3% DHA, 0.06% EPA; BO + FOHIGH: 0.6% GLA, 0.3% DHA, 0.2% EPA] or human milk (HM, nonrandomized) for 4 wk. Anthropometric measures and blood samples were obtained at study entry and after 14 and 28 d. There were no significant differences between groups in anthropometric measures, tocopherol, and retinol status at any of the studied time points. The AA content of plasma phospholipids was similar between groups at study start and decreased significantly until day 28 in all formulafed groups, but not in the breast-fed infants [ST: 6.6 +/- 0.2%, BO: 6.9 +/- 0.3%, BO + FOLOW: 6.9 +/- 0.4%, BO + FOHIGH: 6.7 +/- 0.2%, HM: 8.6 +/- 0.5%, where values are reported as mean +/- standard error; all formulas significantly different (P< 0.05) from HM]. There was no significant influence of GLA or fish oil addition to the diet. GLA had only a very limited effect on AA status which was too small to obtain satisfactory concentrations (concentrations similar to breast-fed babies) under the circumstances tested. The effect of GLA on AA is independent of the EPA and DHA content in the diet within the dose ranges studied.
Assuntos
Ácido Araquidônico/sangue , Óleos de Peixe/farmacologia , Alimentos Infantis , Recém-Nascido Prematuro , Óleos de Plantas/farmacologia , Antioxidantes/farmacologia , Aleitamento Materno , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/química , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Humanos , Lactente , Recém-Nascido , Leite Humano , Fosfolipídeos/sangue , Vitamina E/sangue , Vitamina E/farmacologia , alfa-Tocoferol/sangue , alfa-Tocoferol/farmacologia , Ácido gama-Linolênico/química , Ácido gama-Linolênico/farmacologiaRESUMO
Our objective was to develop a suitable probe to study metabolism of polyunsaturated fatty acids by 13C nuclear magnetic resonance (NMR) in the suckling rat pup. [3-13C] gamma-Linolenic acid was chemically synthesized, and a 20 mg (Experiment 1) or 5 mg (Experiment 2) dose was injected into the stomachs of 6-10-day-old suckling rat pups that were then killed over a 192 h (8 d) time course. 13C NMR showed that 13C in gamma-linolenate peaked in liver total lipids by 12-h post-dosing and that [5-13C]-arachidonic acid peaked in both brain and liver total lipids 48-96 h post-dosing. 13C enrichment in brain gamma-linolenic acid was not detected by NMR, but gas chromatography-combustion-isotope ratio mass spectrometry showed that its mass enrichment in brain phospholipids at 48-96 h post-dosing was 1-2% of that in brain arachidonic acid. 13C was present in liver and brain cholesterol and in perchloric acid-extractable water-soluble metabolites in the brain, liver and carcass. We conclude that low but measurable amounts of exogenous gamma-linolenic acid do access the suckling rat brain in vivo. The slow time course of [5-13C] arachidonic acid appearance in the brain suggests most of it was probably transported there after synthesis elsewhere, probably in the liver. Some carbon from gamma-linolenic acid is also incorporated into lipid products other than n-6 long-chain polyunsaturated fatty acids.
Assuntos
Ácido Araquidônico/biossíntese , Espectroscopia de Ressonância Magnética/métodos , Ácido alfa-Linolênico , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Radioisótopos de Carbono , Fígado/metabolismo , Espectroscopia de Ressonância Magnética/instrumentação , Ratos , Fatores de TempoRESUMO
Cancer and cardiovascular disease are still the number one and two killer diseases in most developed countries. There is justified hope that beta-carotene will be proven efficacious in the prevention and/or delaying of the onset of these chronic diseases. Chronic disease prevention through better nutrition, judicious use of supplements and better lifestyles will assume added importance in the coming years as the proportion of the population over 65 years increases.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Carotenoides/uso terapêutico , Neoplasias/prevenção & controle , Humanos , beta CarotenoAssuntos
Colágeno/farmacologia , Agregação Plaquetária , Animais , Fenômenos Químicos , Química , Cobaias , Conformação Molecular , CoelhosAssuntos
Testes Respiratórios , Gorduras Insaturadas na Dieta/farmacologia , Etano/análise , Ácidos Graxos Ômega-3/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Pentanos/análise , Vitamina E/farmacologia , Adulto , Ácido Araquidônico/sangue , Gorduras Insaturadas na Dieta/administração & dosagem , Método Duplo-Cego , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Insaturados/sangue , Humanos , Malondialdeído/sangue , Vitamina E/administração & dosagem , Vitamina E/sangueRESUMO
In the past few years interest in the use of fish oil as a dietetic approach in the management of thromboarteriosclerotic diseases has increased. This is based on epidemiological studies which indicate that people living mainly on a fish diet have a low incidence of coronary heart disease (CHD). The beneficial effect is attributed to the high content of polyunsaturated n-3 fatty acids (PUFA), especially eicosapentaenoic acid (C20:5n-3) (EPA), in the marine diet. These fatty acids are built into the phospholipids of various cell membranes, changing their biological reactivity. EPA and docosahexaenoic acid (C22:6n-3) are also metabolized into specific eicosanoids (e.g. prostaglandin I3, thromboxane A3 and leukotriene B5). In contrast to the mediators originating from the n-6 fatty acids, these n-3 autocoids exhibit stronger antiaggregant, vasodilatory and anti-inflammatory activities. When given to volunteers, n-3 PUFAs inhibit platelet aggregation and lower plasma triglycerides. However, first clinical studies in patients with angina pectoris are equivocal. Furthermore, restenosis of coronary arteries in patients after PTCA was not clearly reduced. Therefore, more prospective clinical studies are needed to establish the efficacy of these fish oils before their use in thromboarteriosclerotic CHD can be recommended.
Assuntos
Arteriosclerose/prevenção & controle , Óleos de Peixe/uso terapêutico , Trombose/prevenção & controle , Animais , Ácidos Graxos/metabolismo , Óleos de Peixe/farmacologia , Humanos , Lipídeos/sangue , Agregação Plaquetária/efeitos dos fármacosRESUMO
We investigated the possible mechanisms involved in the positive inotropic activity of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a structurally novel cardiotonic agent with vasodilating properties. The positive inotropic response to Ro 13-6438 of the isolated guinea pig papillary muscle was accompanied by inhibition of myocardial phosphodiesterase (PDE) activity and elevation of intracellular cyclic AMP (cAMP) levels Ro 13-6438 had no effect on Na+,K+-stimulated or Ca2+-stimulated ATPase activity and did not influence the rate of 45Ca uptake in cardiac membrane vesicles. Ro 13-6438 caused a concentration-dependent increase in the upstroke velocity, overshoot, and duration of slow action potentials evoked in partially depolarized papillary muscles. Pretreatment of guinea pigs with reserpine did not prevent the effects of Ro 13-6438 on slow action potentials, but slightly decreased its positive inotropic activity. The muscarinic agonist carbachol reversed the Ro 13-6438-induced enhancement of contractility and changes in the slow action potential in an atropine-sensitive manner. These results indicate that the positive inotropic effects of Ro 13-6438 are correlated with PDE inhibition, increased cAMP levels, and an increase of the slow action potential in ventricular myocardium. It is suggested that the elevated cAMP levels resulting from the Ro 13-6438-induced inhibition of PDE enhance the slow inward Ca2+ current.