Nutritional Status of Zinc in Children with Down Syndrome

Experimental and clinical studies have established that zinc metabolism is altered in individuals with Down syndrome (DS). The present study intends to evaluate the nutritional status of zinc in children with DS by determining their biochemical and dietary parameters. The investigation was carried out on a group of children with DS (n = 35) and compared with a control group (n = 33), both aging between 4 and 11 years. Weight-for-age, height-for-age, and weight-for-height indexes and diet were evaluated by using a 3-day dietary record. Zinc was evaluated in plasma, erythrocytes, and 24-h urine collection by using the method of atomic absorption spectroscopy. The frequency of short stature was higher in children with DS. Both groups presented high protein content, adequate concentrations of lipids and carbohydrates, and deficit in calories. Adequate zinc intake was observed in 40% of children with DS and in 67% of the control group. Zinc concentrations were significantly lower in plasma and urine and higher in erythrocytes of children with DS. The results allowed us to conclude that the altered zinc nutritional status of individuals with Down syndrome contributes to clinical disturbances that usually appear with aging in these patients.

Balloon catheter injury abolishes phenylephrine-induced relaxation in the rat contralateral carotid

BACKGROUND AND PURPOSE The consequences of compensatory responses to balloon catheter injury in rat carotid artery, on phenylephrine-induced relaxation and contraction in the contralateral carotid artery were studied. EXPERIMENTAL APPROACH Relaxation and contraction concentration-response curves for phenylephrine were obtained for contralateral carotid arteries in the presence of indomethacin (COX inhibitor), SC560 (COX-1 inhibitor), SC236 (COX-2 inhibitor) or 4-hydroxytetramethyl-L-piperidine-1-oxyl (tempol; superoxide dismutase mimetic). Reactive oxygen species were measured in carotid artery endothelial cells fluorimetrically with dihydroethidium. KEY RESULTS Phenylephrine-induced relaxation was abolished in contralateral carotid arteries from operated rats (E(max) = 0.01 +/- 0.004 g) in relation to control (E(max) = 0.18 +/- 0.005 g). Phenylephrine-induced contractions were increased in contralateral arteries (E(max) = 0.54 +/- 0.009 g) in relation to control (E(max) = 0.38 +/- 0.014 g). SC236 restored phenylephrine-induced relaxation (E(max) = 0.17 +/- 0.004 g) and contraction (E(max) = 0.34 +/- 0.018 g) in contralateral arteries. Tempol restored phenylephrine-induced relaxation (E(max) = 0.19 +/- 0.012 g) and contraction (E(max) = 0.42 +/- 0.014 g) in contralateral arteries, while apocynin did not alter either relaxation (E(max) = 0.01 +/- 0.004 g) or contraction (E(max) = 0.54 +/- 0.009 g). Dihydroethidium fluorescence was increased in contralateral samples (18 882 +/- 435 U) in relation to control (10 455 +/- 303 U). SC236 reduced the fluorescence in contralateral samples (8250 +/- 365 U). CONCLUSIONS AND IMPLICATIONS Balloon catheter injury abolished phenylephrine-induced relaxation and increased phenylephrine-induced contraction in contralateral carotid arteries, through O(2)(-) derived from COX-2.

3`3-Ditrifluoromethyldiphenyl diselenide: A new organoselenium compound with interesting antigenotoxic and antimutagenic activities

The trace element selenium (Se), once known only for its potential toxicity, is now a well-established essential micronutrient for mammals. The organoselenium compound diphenyl diselenide (DPDS) has shown interesting antioxidant and neuroprotective activities. On the other hand, this compound has also presented pro-oxidant and mutagenic effects. The compound 3`3-ditrifluoromethyldiphenyl diselenide (DFDD), a structural analog of diphenyl diselenide, has proven antipsychotic activity in mice. Nevertheless, as opposed to DPDS, little is known on the biological and toxicological properties of DFDD. In the present study, we report the genotoxic effects of the organoselenium compound DFDD on Salmonella typhimurium, Saccharomyces cerevisiae and Chinese hamster lung fibroblasts (V79 cells). DFDD protective effects against hydrogen peroxide (H(2)O(2))-induced DNA damage in vitro are demonstrated. DFDD did not cause mutagenic effects on S. typhimurium or S. cerevisiae strains; however, it induced DNA damage in V79 cells at doses higher than 25 mu M, as detected by comet assay. DFDD protected S. typhimurium and S. cerevisiae against H(2)O(2)-induced mutagenicity, and, at doses lower than 12.5 mu M, prevented H(2)O(2)-induced genotoxicity in V79 cells. The in vitro assays demonstrated that DFDD mimics catalase activity better than DPDS, but neither presents Superoxide dismutase action. The products of the reactions of DFDD or DPDS with H(2)O(2) were different. as determined by electrospray mass spectrometry analysis (ESI-MS). These results suggest that DFDD is not mutagenic for bacteria or yeast; however, it may induce weak genotoxic effects on mammalian cells. In addition, DFDD has a protective effect against H(2)O(2)-induced damage probably by mimicking catalase activity, and the distinct products of the reaction DFDD with H(2)O(2) probably have a fundamental role in the protective effects of DFDD. (C) 2009 Elsevier B.V. All rights reserved.

Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: the role of oxidative stress

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); prenatal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.

Low level and sub-chronic exposure to methylmercury induces hypertension in rats: nitric oxide depletion and oxidative damage as possible mechanisms

Increased risk of hypertension after methylmercury (MeHg) exposure has been suggested. However, the underlying mechanisms are not well explored. In this paper, we have analyzed whether sub-chronic exposure to MeHg increases systolic blood pressure even at very low levels. In addition, we analyzed if the methylmercury-induced hypertension is associated with a decreased plasmatic nitric oxide levels and with a dysregulation of the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), as well as the levels of MDA and glutathione. For this study, Wistar rats were treated with methylmercury chloride (100 mu g/kg per day) or vehicle. Total treatment time was 100 days. Malondialdehyde (MDA) and circulating NOx levels and superoxide dismutase (SOD) and catalase (CAT) activities were determined in plasma, whereas glutathione levels were determined in erythrocytes. Our results show that long-term treatment at a low level of MeHg affected systolic blood pressure, increasing and reducing the levels of plasmatic MDA and NOx, respectively. However, the activity of SOD did not decrease in the MeHg exposed group when compared to the control. We found a negative correlation between plasmatic nitrite/nitrate (NOx) levels and systolic blood pressure (r = -0.67; P = 0.001), and a positive correlation between MDA and systolic blood pressure (r = 0.61; P = 0.03), thus suggesting increased inhibition of NO formation with the increase of hypertension. In conclusion, long-term exposure to a low dose of MeHg increases the systolic pressure and is associated, at least in part, with increased production of ROS as judged by increased production of malondialdehyde and depressed NO availability.

Protective properties of quercetin against DNA damage and oxidative stress induced by methylmercury in rats

Aim of the study was to find out whether consumption of quercetin (QC), an abundant flavonoid in the human diet, protects against DNA damage caused by exposure to organic mercury. Therefore, rats were treated orally with methylmercury (MeHg) and the flavonoid with doses that reflect the human exposure. The animals received MeHg (30 mu g/kg/bw/day), QC (0.5-50 mg/kg/bw/day), or combinations of both over 45 days. Subsequently, the glutathione levels (GSH) and the activities of glutathione peroxidase (GPx) and catalase (CAT) were determined, and DNA damage was measured in hepatocytes and peripheral leukocytes in single cell gel electrophoresis assays. MeHg decreased the concentration of GSH and the activity of GPx by 17 and 12%, respectively and caused DNA damage to liver and blood cells, while with QC no such effects were seen. When the flavonoid was given in combination with MeHg, the intermediate and the highest concentrations (5.0 and 50.0 mg/kg/bw/day) were found to cause DNA protection; DNA migration was reduced by 54 and 65% in the hepatocytes and by 27 and 36% in the leukocytes; furthermore, the reduction in GSH and GPx levels caused by MeHg treatment was restored. In summary, our results indicate that consumption of QC-rich foods may protect Hg-exposed humans against the adverse health effects of the metal.

Evaluation of protective effects of fish oil against oxidative damage in rats exposed to methylmercury

The present study evaluates a possible protective effect of fish oil against oxidative damage promoted by methylmercury (MeHg) in sub-chronically exposed rats. Reduced glutathione peroxidase and catalase enzyme activity and reduced glutathione levels were observed in MeHg-exposed animals compared to controls. Methylmercury exposure was also associated with DNA damage. Administration of fish oil to the methylmercury-exposed animals did not ameliorate enzyme activity or glutathione levels. On the other hand, a significant DNA protective effect (about 30%) was observed with fish oil treatment. There were no differences in the total mercury concentration in rat liver, kidney, heart or brain after MeHg administration with or without fish oil co-administration. Histopathological analyses showed a significant leukocyte infiltration in rat tissues after MeHg exposure, but this effect was significantly reduced after co-administration of fish oil. Taken together, our findings demonstrate oxidative damage even after low-level MeHg exposure and the protective effect of fish oil. This protection seems not to be related to antioxidant defenses or mercury re-distribution in rat tissues. It is probably due to the anti-inflammatory effects of fish oil. (C) 2010 Elsevier Inc. All rights reserved.

Petrographic and isotope constraints on the origin of authigenic carbonate minerals and the associated fluid evolution in Late Permian coal measures, Bowen Basin (Queensland), Australia

Authigenic carbonate minerals are ubiquitous throughout the Late Permian coal measures of the Bowen Basin, Queensland, Australia. In the northern Bowen Basin, carbonates include the following assemblages: siderite I (delta O-18(SMOW) = +11.4 to + 17%, delta C-13(PDB) = - 5.3 to + 120), Fe-Mg calcite-ankerite-siderite II mineral association (delta O-18(SMOW) = +7.2 to + 10.20, delta C-13(PDB) = 10.9 to - 1.80 for ankerite) and a later calcite (delta O-18(SMOW) = +5.9 to + 14.60, delta C-13(PDB) = -11.4 to + 4.40). In the southern Bowen Basin, the carbonate phase consists only of calcite (delta O-18(SMOW) = +12.5 to + 14.80, delta C-13(PDB) = -19.4 to + 0.80), where it occurs extensively throughout all stratigraphic levels. Siderite I occurs in mudrocks and sandstones and predates all other carbonate minerals. This carbonate phase is interpreted to have formed as an early diagenetic mineral from meteoric waters under cold climate and reducing conditions. Fe-Mg calcite-ankerite-siderite Il occur in sandstones as replacement of volcanic rock fragments. Clay minerals (illite-smectite, chlorite and kaolinite) postdate Ca-Fe-Mg carbonates, and precipitation of the later calcite is associated with clay mineral formation. The Ca-Fe-Mg carbonates and later calcite of the northern Bowen Basin are regarded as having formed as a result of hydrothermal activity during the latest Triassic extensional tectonic event which affected this part of the basin, rather than deep burial diagenesis during the Middle to Late Triassic as previously reported. This hypothesis is based on the timing relationships of the authigenic mineral phases and the low delta O-18 values of ankerite and calcite, together with radiometric dating of illitic clays and recently published regional geological evidence. Following the precipitation of the Ca-Fe-Mg carbonates from strongly O-18-depleted meteoric-hydrothermal fluids, continuing fluid circulation and water-rock interaction resulted in dissolution of these carbonate phases as well as labile fragments of volcaniclastic rocks. Subsequently, the later calcite and day minerals precipitated from relatively evolved (O-18-enriched) fluids. The nearly uniform delta O-18 values of the southern Bowen Basin calcite have been attributed to very low water/rock ratio in the system, where the fluid isotropic composition was buffered by the delta O-18 values of rocks. (C) 2000 Elsevier Science B.V. All rights reserved.

Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and alpha-lipoic acid

The purpose of these experiments was to examine the effects of dietary antioxidant supplementation with vitamin E (VE) and alpha -lipoic acid (alpha -LA) on biochemical and physiological responses to in vivo myocardial ischemia-reperfusion (I-R) in aged rats. Male Fischer-334 rats (18 mo old) were assigned to either 1) a control diet (CON) or 2) a VE and alpha -LA supplemented diet (ANTIOX). After a 14-wk feeding period, animals in each group underwent an in vivo I-R protocol (25 min of myocardial ischemia and 15 min of reperfusion). During reperfusion, peak arterial pressure was significantly higher (P < 0.05) in ANTIOX animals compared with CON diet animals. I-R resulted in a significant increase (P < 0.05) in myocardial lipid peroxidation in CON diet animals but not in ANTIOX animals. Compared with ANTIOX animals, heart homogenates from CON animals experienced significantly less (P < 0.05) oxidative damage when exposed to five different in vitro radical producing systems. These data indicate that dietary supplementation with VE and -LA protects the aged rat heart from I-R-induced lipid peroxidation by scavenging numerous reactive oxygen species. Importantly, this protection is associated with improved cardiac performance during reperfusion.

Differential responses of antioxidant enzymes in pioneer and late-successional tropical tree species grown under sun and shade conditions

To investigate the ability of pioneer and late-successional species to adapt to a strong light environment in a reforestation area, we examined the activities of antioxidant enzymes in relation to photosystem chlorophyll a fluorescence and photosynthetic pigment concentration for eight tropical tree species grown under 100% (sun) and 10% (shade) sunlight irradiation. The pioneer (early-succession) species (PS) were Cecropia pachystachya, Croton urucurana, Croton floribundus and Schinus terebinthifolius. The non-pioneer (late succession) species (LS) were Hymenaea courbaril L var. stilbocarpa, Esenbeckia leiocarpa, Cariniana legalis and Tabebuia roseo-alba. We observed a greater decline in the ratio of variable to maximum chlorophyll a fluorescence (F(v)/F(m)) under full sunlight irradiation in the late-successional species than in the pioneer species. The LS species most sensitive to high irradiance were C. legalis and H. courbaril. In LS species, chlorophyll a, chlorophyll b and total chlorophyll concentrations were higher in the shade-grown plants than in plants that developed under full sunlight, but in the PS species C. floribundus and C. pachystachya, we did not observe significant changes in chlorophyll content when grown in the two contrasting environments. The carotenoids/total chlorophyll ratio increased significantly when plants developed under high-sunlight irradiation, but this response was not observed in the PS species S. terebinthifolius and C. pachystachya. The improved performance of the pioneer species in high sunlight was accompanied by an increase in superoxide dismutase (SOD. EC 1.15.1.1) activity, though no light-dependent increase in the activity of ascorbate peroxidase (APX. EC 1.11.1.11) was observed. The activity of catalase (CAT, EC 1.11.1.6) was reduced by high irradiation in both pioneer and late-successional species. Our results show that pioneer species perform better under high-sunlight irradiation than late-successional species, as indicated by increased SOD activity and a higher F IF,, ratio. C. legalis was the LS species most susceptible to photoinhibition under full sunlight conditions. These results suggest that pioneer plants have more potential tolerance to photo-oxidative damage than late-successional species associated with the higher SOD activity found in pioneer species. Reduced photoinhibition in pioneer species probably results from their higher photosynthetic capacities, as has been observed in a previous survey carried out by our group. (C) 2010 Elsevier B.V. All rights reserved.

Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function

Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A individuals, compared with -9% in G/G individuals (p = 0.024). When considering TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.

Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge

Amyloid-beta peptide (A beta) is pivotal to the pathogenesis of Alzheimer disease. Here we report the formation of a toxic A beta-Cu2+ complex formed via a histidine-bridged dimer, as observed at Cu2+/ peptide ratios of > 0.6:1 by EPR spectroscopy. The toxicity of the A beta-Cu2+ complex to cultured primary cortical neurons was attenuated when either the pi- or tau-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Toxicity did not correlate with the ability to form amyloid or perturb the acyl-chain region of a lipid membrane as measured by diphenyl- 1,3,5-hexatriene anisotropy, but did correlate with lipid peroxidation and dityrosine formation. P-31 magic angle spinning solid-state NMR showed that A beta and A beta-Cu2+ complexes interacted at the surface of a lipid membrane. These findings indicate that the generation of the A beta toxic species is modulated by the Cu2+ concentration and the ability to form an intermolecular His bridge.

Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity

Background: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. Methods: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. Results: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-gamma, TNF-alpha and IL-10 were not different between the groups. Conclusion: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke. Copyright (C) 2011 S. Karger AG, Basel

Effect of IIb-IIIa Glycoprotein Inhibitors in a Partial Limb Amputation Model Submitted to Warm Ischemia in Rats

Viability and functional results of a segment replantation depend on the prevention of deleterious effects of ischemia. Prolonged ischemia leads to alterations in the microcirculation: thrombosis, edema, production of oxygen free radicals, and platelet aggregation. The effect of IIb-IIIa glycoprotein inhibitors was tested in a partial limb amputation model submitted to warm ischemia. The male Wistar rats were divided into four groups: G1 with 0 hours of ischemia and saline (n = 20), G2 with 6 hours of ischemia and saline (n = 24), G3 with 6 hours of ischemia and abciximab (n = 23), and G4 with 6 hours of ischemia and tirofiban (n = 29). The limbs were observed for 7 days and classified as viable or nonviable. Viability, and mortality rates were obtained and analyzed by Q-square and Fisher exact tests (p < 0.05). The viability rates were 100% (G1), 30% (G2), 77.78% (G3), and 80.95% (G4). G2 was statistically different from G1, G3, and G4. G1, G3, and G4 were not statistically different. Transoperative and postoperative mortalities were not statistically different. The administration of abciximab and tirofiban improved limb salvage after ischemia and reperfusion and did not modify mortality rates significantly.

Self-organization with traveling waves: A case for a convective torus

A traveling wave of BaSO4 in the chlorite-thiourea reaction has shown concentric precipitation patterns upon being triggered by the autocatalyst HOCl. The precipitation patterns show circular rings of alternate null and full precipitation regions. This self-organization appears to be the result of the formation of a convective torus. The formation of the convective torus can be described as a Benard-Marangoni instability with lateral heating.