Association between adiposity levels and cognitive impairment in the Chilean older adult population.

Although both obesity and ageing are risk factors for cognitive impairment, there is no evidence in Chile on how obesity levels are associated with cognitive function. Therefore, the aim of the present study was to investigate the association between adiposity levels and cognitive impairment in older Chilean adults. This cross-sectional study includes 1384 participants, over 60 years of age, from the Chilean National Health Survey 2009-2010. Cognitive impairment was evaluated using the Mini-Mental State Examination. BMI and waist circumference (WC) were used as measures of adiposity. Compared with people with a normal BMI, the odds of cognitive impairment were higher in participants who were underweight (OR 4·44; 95 % CI 2·43, 6·45; P < 0·0001), overweight (OR 1·86; 95 % CI 1·06, 2·66; P = 0·031) and obese (OR 2·26; 95 % CI 1·31, 3·21; P = 0·003). The associations were robust after adjustment for confounding variables. Similar results were observed for WC. Low and high levels of adiposity are associated with an increased likelihood of cognitive impairment in older adults in Chile.

Catalase is more sensible to the inhibitory effect of soluble component of tobacco smoke than Glutathione Peroxidase and Superoxide Dismutase / Catalasa es más sensible a los efectos inhibitorios de los componentes solubles del humo de tabaco que Glutatión Peroxidasa y Superóxido Dismutasa

Tobacco smoke causes oxidative damage directly by the effect of their oxidants or indirectly through the induction of endogenously produced oxidants and/or inactivation of antioxidants. The oxidative effect of tobacco smoke depends on many variables: dose, time of exposure, tissue or cell type and endogenous antioxidant status. In an attempt to simplify this complex scenario, we examined the effect of a soluble extract of tobacco smoke on the activity of purified antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) and in human plasma. Our results revealed that catalase and glutathione peroxidase were inhibited with an IC50 of 18 and 80 smoker equivalents (arbitrary units), respectively; meanwhile superoxide dismutase was not affected. A similar effect of soluble extract of tobacco smoke was obtained for antioxidant enzymes in human plasma, where catalase was inhibited, while superoxide dismutase was little affected, and glutathione peroxidase increased 20% its activity. Benzo[a]pyrene, a well-known component of tobacco smoke, was partly responsible for catalase inactivation. Although soluble extract of tobacco smoke and benzo[a]pyrene both induced carbonylation of plasma proteins, we ruled out that catalase inhibition would be caused by carbonylation, since the inhibition was reversed by dialysis. Considering the higher sensitivity of catalase to inhibition induced by soluble extract of tobacco smoke and its important role in peroxide elimination, we conceived that benzo[a]pyrene and other compounds of tobacco smoke extract promote a transient peroxide accumulation which could be one of the factors responsible for the oxidative damage in respiratory tract and other tissues in smokers (AU)

El humo de tabaco causa daño oxidativo directamente por efecto de sus oxidantes o indirectamente por la inducción de la producción de oxidantes endógenos y/o inactivación de antioxidantes. El efecto oxidativo del humo de tabaco depende de varias variables: dosis, tiempo de exposición, tejido o tipo cleular y estado antioxidante. En un intento de simplificar este complejo escenario, examinamos el efecto de un extracto soluble de humo de tabaco en la actividad de tres enzimas antioxidantes en estado purificado y en plasma humano (catalasa, glutatión peroxidasa and superóxido dismutasa). Nuestro resultados revelan que catalasa y glutatión peroxidasa fueron inhibidas con un IC50 de 18 y 80 equivalentes de fumador (unidades arbirtarias), respectivamente; mientras que superóxido dismutasa no fue afectada. Encontramos un efecto similar del extracto soluble de humo de tabaco en las enzimas antioxidantes plasmáticas, donde catalasa fue más inhibida que superóxido dismutasa y glutatión peroxidasa aumentó 20% su actividad. Benzo[a]pireno, un conocido componente del humo de tabaco, fue parcialmente responsable del la inhibicicón de catalasa. Aunque el extracto soluble del humo de tabaco y el benzo[a]pireno indujeron carbonilación de las proteínas plasmáticas, descartamos que esta modificación sera responsable de la inhibición de catalasa, porque la diálisis revertió su efecto. Considerando la alta sensibilidad de catalasa a la inhibición por extracto de humo de tabaco y benzo[a]pireno en particular, concluimos que el extracto de humo de tabaco promueve una acumulación transiente de peróxidos que podría ser uno de los factores responsables del daño oxidativo observado en el tracto respiratorio y en otros tejidos de sujetos fumadores (AU)

Cellular mechanisms against ischemia reperfusion injury induced by the use of anesthetic pharmacological agents.

Ischemia-reperfusion (IR) cycle in the myocardium is associated with activation of an injurious cascade, thus leading to new myocardial challenges, which account for up to 50% of infarct size. Some evidence implicates reactive oxygen species (ROS) as a probable cause of myocardial injury in prooxidant clinical settings. Damage occurs during both ischemia and post-ischemic reperfusion in animal and human models. The mechanisms that contribute to this damage include the increase in cellular calcium (Ca(2+)) concentration and induction of ROS sources during reperfusion. Pharmacological preconditioning, which includes pharmacological strategies that counteract the ROS burst and Ca(2+) overload followed to IR cycle in the myocardium, could be effective in limiting injury. Currently widespread evidence supports the use of anesthetics agents as an important cardioprotective strategy that act at various levels such as metabotropic receptors, ion channels or mitochondrial level. Their administration before a prolonged ischemic episode is known as anesthetic preconditioning, whereas when given at the very onset of reperfusion, is termed anesthetic postconditioning. Both types of anesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. This review focuses on cellular and pathophysiological concepts on the myocardial damage induced by IR and how anesthetic pharmacological agents commonly used could attenuate the functional and structural effects induced by oxidative stress in cardiac tissue.

Vitamin C transporters

Vitamin C is a wide spectrum antioxidant essential for humans, which are unableto synthesize the vitamin and must obtain it from dietary sources. There are two biologicallyimportant forms of vitamin C, the reduced form, ascorbic acid, and the oxidizedform, dehydroascorbic acid. Vitamin C exerts most of its biological functionsintracellularly and is acquired by cells with the participation of specific membranetransporters. This is a central issue because even in those species capable of synthesizingvitamin C, synthesis is restricted to the liver (and pancreas) from which is distributedto the organism. Most cells express two different transporter systems for vitaminC; a transporter system with absolute specificity for ascorbic acid and a secondsystem that shows absolute specificity for dehydroascorbic acid. The dehydroascorbicacid transporters are members of the GLUT family of facilitative glucose transporters,of which at least three isoforms, GLUT1, GLUT3 and GLUT4, are dehydroascorbicacid transporters. Ascorbic acid is transported by the SVCT family ofsodium-coupled transporters, with two isoforms molecularly cloned, the transportersSVCT1 y SVCT2, that show different functional properties and differentialcell and tissue expression. In humans, the maintenance of a low daily requirement ofvitamin C is attained through an efficient system for the recycling of the vitamininvolving the two families of vitamin C transporters (AU)

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Vitamin C transporters.

Vitamin C is a wide spectrum antioxidant essential for humans, which are unable to synthesize the vitamin and must obtain it from dietary sources. There are two biologically important forms of vitamin C, the reduced form, ascorbic acid, and the oxidized form, dehydroascorbic acid. Vitamin C exerts most of its biological functions intracellularly and is acquired by cells with the participation of specific membrane transporters. This is a central issue because even in those species capable of synthesizing vitamin C, synthesis is restricted to the liver (and pancreas) from which is distributed to the organism. Most cells express two different transporter systems for vitamin C; a transporter system with absolute specificity for ascorbic acid and a second system that shows absolute specificity for dehydroascorbic acid. The dehydroascorbic acid transporters are members of the GLUT family of facilitative glucose transporters, of which at least three isoforms, GLUT1, GLUT3 and GLUT4, are dehydroascorbic acid transporters. Ascorbic acid is transported by the SVCT family of sodium-coupled transporters, with two isoforms molecularly cloned, the transporters SVCT1 y SVCT2, that show different functional properties and differential cell and tissue expression. In humans, the maintenance of a low daily requirement of vitamin C is attained through an efficient system for the recycling of the vitamin involving the two families of vitamin C transporters.

Xanthine oxidase released from reperfused hind limbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock.

We have shown previously that rats subjected to tourniquet shock develop an acute form of remote organ injury of the liver that is both Kupffer cell (KC) and polymorphonuclear (PMN) leukocyte dependent. Circulating plasma xanthine oxidase (XO) has been shown to be responsible for the development of endothelial dysfunction and for remote organ injury of the lung and intestine after ischemia-reperfusion protocols. We now hypothesize that XO is released from rat hind limbs upon reperfusion and that it is responsible for KC and PMN leukocyte activation in this shock model. Our results show that about 30% of rat gastrocnemius muscle xanthine dehydrogenase (XD) is converted to XO during the 5-h tourniquet period and that it is released into the femoral vein within 10 min of reperfusion. Total muscle xanthine oxidoreductase activity (XO + XD) decreases within 30 min of reperfusion and is paralleled by a corresponding increase in femoral vein lactic dehydrogenase. In addition, liver tissue XO increases significantly within 30 min of reperfusion without a corresponding conversion of endogenous XD. Conversion of hepatic XD becomes evident 60 min after reperfusion is initiated, as does XO, and alanine aminotransferase (ALT) release into the hepatic vein, presumably from damaged hepatocytes as a consequence of oxidative stress. Tissue myeloperoxidase activity also increases significantly after the 60-min reperfusion period. That XO mediates KC and PMN activation is supported by the following observations: a) the close relationships between plasma XO and the time courses of tumor necrosis factor-alpha TNFalpha release into the hepatic vein and colloidal carbon clearance by KCs; b) that colloidal carbon clearance, TNFalpha and ALT release, loss of tissue free thiols, lipid peroxidation (TBARS), and liver infiltration by PMN neutrophils can also be induced by the administration of exogenous XO to normal rats; and c) pretreatment of rats with allopurinol inhibits KC activation and liver leukocyte infiltration. These results suggest that XO, released from the ischemic limb on reperfusion, is taken up by the liver were it mediates KC and PMN neutrophil activation and thus contributes to the development of multiple system organ failure after hind limb reperfusion.

Role of Küpffer cells and PMN leukocytes in hepatic and systemic oxidative stress in rats subjected to tourniquet shock.

Küpffer cells (KCs) have been implicated in leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs and polymorphonuclear (PMN) leukocytes on the oxidative stress elicited in the liver as a consequence of hind limb reperfusion in rats subjected to tourniquet shock, a shock model that differs from other models in that hepatic injury is a consequence of remote organ damage. Colloidal carbon clearance from blood and its incorporation into KCs demonstrate that these cells are activated after the 2 h hind limb reperfusion period and that they are responsible for the observed oxidative stress and for PMN leukocyte recruitment and activation. Liver oxidative stress in this model is evidenced by increased liver tissue GSSG/GSH ratio, thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, and a significant loss in total tissue superoxide dismutase (SOD) activity. Mean arterial blood pressure (MAP), as well as plasma levels of alanine aminotransferase (ALT), an index of hepatic tissue injury, total SOD activity, plasma levels of alpha-tocopherol and beta-carotene, and total plasma nitrite are also affected as a consequence of KC activation after the 2 h hind limb reperfusion period. Inhibition of KC activity by gadolinium chloride (GdCl3) reverted most of the above alterations to values that do no differ from those found in control animals. These results support the hypothesis that hepatic and systemic oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock is both KC and PMN leukocyte dependent.

Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock.

The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.

Quantitative electroencephalographic studies of the effects of ethanol in rabbits= I. Interaction between ethanol and reserpine.

At a dose of 1 g/kg i.v. ethanol induced in the cortical EEG of rabbits a synchronization which lasted 2-3 hours. Thereafter a pronounced hyper-stimulation occurred which persisted up to 4 hours. Pre-treatment of the animals with reserpine reduced markedly the initial synchronization and abolished the delayed stimulant effect. These findings are discussed in terms of possible interaction between acetaldehyde and biogenic amines.