Environmental Exposure to Methylmercury is Associated with a Decrease in Nitric Oxide Production

Some studies have recently suggested that mercury (Hg)-exposed populations face increased risks of cardiovascular diseases, and experimental data indicate that such risks might be due to reductions in nitric oxide bioavailability. However, no previous study has examined whether Hg exposure affects plasma nitrite concentrations in humans as an indication of nitric oxide production. Here, we investigated whether there is an association between circulating nitrite and Hg concentrations in whole blood, plasma and hair from an exposed methylmercury (MeHg) population. Hair and blood samples were collected from 238 persons exposed to MeHg from fish consumption. Hg concentrations in plasma (PHg), whole blood (BHg) and hair Hg (HHg) were determined by inductively coupled plasma-mass spectrometry. Mean BHg content was 49.8 +/- 35.2 mu g/l, mean PHg was 7.8 +/- 6.9 mu g/l and HHg 14.6 +/- 10.6 mu g/g. Mean plasma nitrite concentration was 253.2 +/- 105.5 nM. No association was found between plasma nitrite concentration and BHg or HHg concentrations in a univariate model. However, multiple regression models adjusted for gender, age and fish consumption showed a significant association between plasma nitrite and plasma Hg concentration (beta = -0.1, p < 0.001). Our findings constitute preliminary clinical evidence that exposure to MeHg may cause inhibitory effects on the production of endothelial nitric oxide.

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.

Phagocytosis and Nitric Oxide Levels in Rheumatic Inflammatory States in Elderly Women

Background Very few studies have investigated, in the elderly, the effect of rheumatic inflammatory states on phagocyte function and free radical production. The objective of this article is to evaluate phagocytosis by neutrophils and the production of nitric oxide (.NO) by monocytes in elderly women recruited among patients of the Brazilian Public Health System. Methods: Forty patients aged more than 60 years with rheumatic inflammatory diseases were studied. Phagocytosis was measured by flow cytometry. .NO production was measured by the total nitrite assay and conventional inflammation markers were determined. Data were analyzed with the Mann Whitney nonparametric test and P<0.05 was considered significant. Results. C-reactive protein levels and white blood cell counts were significantly higher in inflammation than in the control group (P<0.05). The phagocytosis fluorescence intensity per neutrophil and the percentual of neutrophils expressing phagocytosis were significantly higher (P<0.05) in the test than in the control group. Furthermore, there was significant .NO overproduction by monocytes, (P<0.05). Conclusion: Phagocytosis and .NO production are affected by rheumatic states. This suggests that the increased .NO levels may play a part in the increased oxidative stress in rheumatic diseases in elderly women. J. Clin. Lab. Anal. 25:47-51, 2011. (C) 2011 Wiley-Liss, Inc.

Gender-specific vascular effects elicited by chronic ethanol consumption in rats: a role for inducible nitric oxide synthase

Background and purpose: Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Experimental approach: Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. Key results: In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Conclusions and implications: Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS.

Synthesis and characterization of ternary hybrid material based on poly-o-methoxyaniline and poly(ethylene oxide) in mesostructured V(2)O(5)

New hybrid composites based on mesostructured V(2)O(5) containing intercalated poly(ethylene oxide), poly-o-methoxyaniline and poly(ethylene oxide)/poly-o-methoxyaniline were prepared. The results suggest that the polymers were intercalated into the layers of the mesostructured V(2)O(5). Electrochemical studies showed that the presence of both polymers in the mesostructured V(2)O(5) (ternary hybrid) leads to an increase in total charge and stability after several cycles compared with binary hybrid composites. This fact makes this material a potential component as cathode for lithium ion intercalation and further, a promising candidate for applications in batteries.

Morphological and electrochemical investigation of RuO(2)-Ta(2)O(5) oxide films prepared by the Pechini-Adams method

Preparation methods can profoundly affect the structural and electrochemical properties of electrocatalytic coatings. In this investigation, RuO(2)-Ta(2)O(5) thin films containing between 10 and 90 at.% Ru were prepared by the Pechini-Adams method. These coatings were electrochemically and physically characterized by cyclic voltammetry, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The composition and morphology of the oxide were investigated before and after accelerated life tests (ALT) by EDX and SEM. SEM results indicate typical mud-flat-cracking morphology for the majority of the films. High resolution SEMs reveal that pure oxide phases exhibit nanoporosity while binary compositions display a very compact structure. EDX analyses reveal considerable amounts of Ru in the coating even after total deactivation. XRD indicated a rutile-type structure for RuO(2) and orthorhombic structure for Ta(2)O(5). XPS data demonstrate that the binding energy of Ta is affected by Ru addition in the thin films, but the binding energy of Ru is not likewise influenced by Ta. The stability of the electrodes was evaluated by ALT performed at 750 mA cm(-2) in 80 degrees C 0.5 mol dm(-3) H(2)SO(4). The performance of electrodes prepared by the Pechini-Adams method is 100% better than that of electrodes prepared by standard thermal decomposition.

Synthesis, characterization, and catalytic properties of a mesostructured lamellar xerogel tungsten oxide phase

Cetyltrimethylammonium bromide (CTAB) and n-hexadecylamine (HDA) have been used as template in the synthesis of a mesolamellar xerogel tungsten oxide phase (WO(3)/CTAB/HDA). The catalytic properties of the resulting material were investigated in the oxidation of cis-cyclooctene, styrene, and cyclohexane, using hydrogen peroxide (H(2)O(2)), terc-butyl hydroperoxide (t-BOOH), or m-chlorperbenzoic acid (m-CPBA) as oxygen transfer agent. In general, the catalytic results were comparable to those obtained with related systems, thus suggesting the potential application of this material as catalyst for epoxidation reactions. (C) 2011 Elsevier B.V. All rights reserved.

Effect of mesoporosity of vanadium oxide prepared by sol-gel process as cathodic material evaluated by cyclability during Li(+) insertion/deinsertion

The effect of pore structure on the behavior of lithium intercalation into an electrode containing porous V(2)O(5) film has been investigated and compared with the electrode containing a non-porous V(2)O(5) film. X-ray diffraction patterns indicate a lamellar structure for both materials. Nitrogen adsorption isotherms, t-plot method, and Scanning Electronic Microscopy show that the route employed for the preparation of mesoporous V(2)O(5) was successful. The electrochemical performance of these matrices as lithium intercalation cathode materials was evaluated. The porous material reaches stability after several cycles more easily compared with the V(2)O(5) xerogel. Lithium intercalation into the porous V(2)O(5) film electrode is crucially influenced by pore surface and film surface irregularity, in contrast with the non-porous surface of the V(2)O(5) xerogel.

Comparison of Inhaled Nitric Oxide Versus Oxygen on Hemodynamics in Patients With Mitral Stenosis and Severe Pulmonary Hypertension After Mitral Valve Surgery

Pulmonary hypertension represents an important cause of morbidity and mortality in patients with mitral stenosis who undergo cardiac surgery, especially in the postoperative period. The aim of this study was to test the hypothesis that inhaled nitric oxide (iNO) would improve the hemodynamic effects and short-term clinical outcomes of patients with mitral stenosis and severe pulmonary hypertension who undergo cardiac surgery in a randomized, controlled study. Twenty-nine patients (4 men, 25 women; mean age 46 2 years) were randomly allocated to receive iNO (n = 14) or oxygen (n = 15) for 48 hours immediately after surgery. Hemodynamic data, the use of vasoactive drugs, duration of stay, and short-term complications were assessed. No differences in baseline characteristics were observed between the groups. After 24 and 48 hours, patients receiving iNO had a significantly greater increase in cardiac index compared to patients receiving oxygen (p < 0.0001). Pulmonary vascular resistance was also more significantly reduced in patients receiving iNO versus oxygen (-117 dyne/s/cm(5), 95% confidence interval 34 to 200, vs 40 dyne/s/cm5, 95% confidence interval 34 to 100, p = 0.005) at 48 hours. Patients in the iNO group used fewer systemic vasoactive drugs.(mean 2.1 +/- 0.14 vs 2.6 +/- 0.16, p = 0.046) and had a shorter intensive care unit stay (median 2 days, interquartile range 0.25, vs median 3 days, interquartile range 7, p = 0.02). In conclusion, iNO immediately after surgery in patients with mitral stenosis and severe pulmonary hypertension improves hemodynamics and may have short-term clinical benefits. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1040-1045)

Exhaled nitric oxide as a predictor of exacerbation in children with moderate-to-severe asthma: a prospective, 5-month study

Background: Inhaled corticosteroids (ICSs) are recommended as the first line of treatment in children with moderate-to-severe asthma. Exhaled nitric oxide (ENO) has been proposed as a clinically useful marker of control that might help identify patients in whom ICS dose may be safely reduced. Objective: To evaluate the ability of ENO to predict future asthma exacerbations in children with moderate-to-severe asthma undergoing ICS tapering. Methods: This is an observational study with no control group. ENO was measured biweekly for 14 weeks in 32 children with moderate-to-severe asthma who were undergoing ICS tapering. Clinical evaluations and spirometry were performed concomitantly, and families kept daily diaries to record symptoms between visits. We used generalized estimating equations to model the In (odds) of an asthma exacerbation in the subsequent 2-week interval as a function of ENO level at the start of the interval while adjusting for age, sex, asthma severity, and current medication use. Results: We were able to successfully lower ICS doses in 10 (56%) of the 18 children with moderate asthma and in 3 (21%) of the 14 children with severe asthma. In 83 of the 187 follow-up clinical evaluations, children were determined to have had an exacerbation during the preceding 2 weeks. ENO levels, whether expressed as a continuous variable or dichotomized, were not associated with future risk for exacerbations in either unadjusted or adjusted models. Conclusion: ENO was not a useful clinical predictor of future asthma exacerbations for children with moderate-to-severe asthma undergoing ICS tapering. Ann Allergy Asthma Immunol. 2009; 103:206-211.

Effects of dobutamine on gut mucosal nitric oxide production during endotoxic shock in rabbits

Background: Dobutamine is the agent of choice for increasing cardiac output during myocardial depression in humans with septic shock. Studies have shown that beta-adrenoceptor agonists influence nitric oxide generation, probably by modulating cyclic adenosine monophosphate. We investigated the effects of dobutamine on the systemic and luminal gut release of nitric oxide during endotoxic shock in rabbits. Materials/Methods: Twenty anesthetized and ventilated New Zealand rabbits received placebo or intravenous lipopolysaccharide with or without dobutamine (5 mu g/kg/min). Ultrasonic flow probes placed around the superior mesenteric artery and the abdominal aorta continously estimated the flow. A segment from the ileum was isolated and perfused, and scrum nitrate/nitrite levels were measured in the perfusate solution and the serum every hour. Results: The mean arterial pressure decreased with statistical significance in the lipopolysaccharide group but not in the lipopolysaccharide/dobutamine group. The abdominal aortic flow decreased statistically significantly after lipopolysaccharide administration in both groups but recovered to base-line in the lipopolysaccharide/dobutamine group. The flow in the superior mesenteric artery was statistically significantly higher in the lipopolysaccharide/dobutamine group than in the lipopolysaccharide group at 2 hours. The serum nitrate/nitrite levels were higher in the lipopolysaccharide group and lower in the lipopolysaccharide/dobutamine group than those in the control group. The gut luminal perfusate serum nitrate/nitric level was higher in the lipopolysaccharide group than in the lipopolysaccharide/dobutamine group. Conclusions: Dobutamine can decrease total and intestinal nitric oxide production in vivo. Those effects seem to be inversely proportional to the changes in blood flow.

Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks: Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P=0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

Effect of Isolated Fractions of Harpagophytum procumbens DC (Devil`s Claw) on COX-1, COX-2 Activity and Nitric Oxide Production on Whole-Blood Assay

The present study evaluates the effect of isolated fractions of Harpagophytum procumbens (devil`s claw) on cyclooxygenase (COX-1 and COX-2) activities and NO production using a whole blood assay. The activity of COX-1 was quantified as platelet thromboxane B(2) production in blood clotting and COX-2 as prostaglandin E(2) production in LPS-stimulated whole blood. Total NO(2)(-)/NO(3)(-) concentration was determined by Griess reaction in LPS stimulated blood. Assays were performed by incubation of isolated fractions obtained by flash chromatography monitored with HPLC, TLC and identified by (1)HNMR, containing different amounts of harpagoside with blood from healthy donors. Indomethacin and etoricoxib were the positive controls of COX-1 and COX-2 Inhibition. Data shows that fraction containing the highest concentration of harpagoside inhibited indistinctively COX-1 and COX-2 (37.2 and 29.5% respectively) activity and greatly inhibited NO production (66%). In contrast the fraction including iridoid pool increased COX-2 and did not alter NO and COX-1 activities. The fraction containing cinnamic acid was able to reduce only NO production (67%). Our results demonstrated that the harpagoside fraction is the main responsible for the effect of devils claw on these enzyme activities. However, other components from devil`s claw crude extract could antagonize or increase the synthesis of inflammatory mediators. Copyright (C) 2010 John Wiley & Sons, Ltd.

Nitric oxide modulates lipopolysaccharide-induced endothelial platelet endothelial cell adhesion molecule expression via interleukin-10

We have shown previously that nitric oxide (NO) controls platelet endothelial cell adhesion molecule (PECAM-1) expression on both neutrophils and endothelial cells under physiological conditions. Here, the molecular mechanism by which NO regulates lipopolysaccharide (LPS)-induced endothelial PECAM-1 expression and the role of interleukin (IL)-10 on this control was investigated. For this purpose, N-(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg/day for 14 days dissolved in drinking water) was used to inhibit both constitutive (cNOS) and inducible nitric oxide (iNOS) synthase activities in LPS-stimulated Wistar rats (5 mg/kg, intraperitoneally). This treatment resulted in reduced levels of serum NO. Under this condition, circulating levels of IL-10 was enhanced, secreted mainly by circulating lymphocytes, dependent on transcriptional activation, and endothelial PECAM-1 expression was reduced independently on reduced gene synthesis. The connection between NO, IL-10 and PECAM-1 expression was examined by incubating LPS-stimulated (1 mu g/ml) cultured endothelial cells obtained from naive rats with supernatant of LPS-stimulated lymphocytes, which were obtained from blood of control or L-NAME-treated rats. Supernatant of LPS-stimulated lymphocytes obtained from L-NAME-treated rats, which contained higher levels of IL-10, reduced LPS-induced PECAM-1 expression by endothelial cells, and this reduction was reversed by adding the anti-IL-10 monoclonal antibody. Therefore, an association between NO, IL-10 and PECAM-1 was found and may represent a novel mechanism by which NO controls endothelial cell functions.

Characterization of Superparamagnetic Iron Oxide Coated with Silicone Used as Contrast Agent for Magnetic Resonance Image for the Gastrointestinal Tract

The present work is a report of the characterization of superparamagnetic iron oxide nanoparticles coated with silicone used as a contrast agent in magnetic resonance imaging of the gastrointestinal tract. The hydrodynamic size of the contrast agent is 281.2 rim, where it was determined by transmission electron microscopy and a Fe(3)O(4) crystalline structure was identified by X-ray diffraction, also confirmed by Mossbauer Spectroscopy. The blocking temperature of 190 K was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above the blocking temperature. Ferromagnetic resonance analysis indicated the superparamagnetic nature of the nanoparticles and a strong temperature dependence of the peak-to-peak linewidth Delta H(pp), giromagnetic factor g, number of spins N(S) and relaxation time T(2) were observed. This behavior can be attributed to an increase in the superexchange interaction.