Nitric oxide

Batch experiments were carried out to investigate the stoichiometry and kinetics of microbial degradation of toluene under denitrifying conditions. The inoculum originated from a mixture of sludges from sewage treatment plants with alternating nitrification and denitrification. The culture was able to degrade toluene under anaerobic conditions in the presence of nitrate, nitrite, nitric oxide, or nitrous oxide. No degradation occurred in the absence of Noxides. The culture was also able to use oxygen, but ferric iron could not be used as an electron acceptor. In experiments with 14C-labeled toluene, 34% 4-8% of the carbon was incorporated into the biomass, while 53% 4-10% was recovered as t4CO2, and 6% + 2% remained in the medium as nonvolatile water soluble products. The average consumption of nitrate in experiments, where all the reduced nitrate was recovered as nitrite, was 1.3 :t: 0.2 mg of nitrate-N per mg of toluene. This nitrate reduction accounted for 70% of the electrons donated during the oxidation of toluene. When nitrate was reduced to nitrogen gas, the consumption was 0.7 4-0.2 nag per mg of toluene, accounting for 97% of the donated electrons. Since the ammonia concentration decreased during degradation, dissimilatory reduction of nitrate to ammonia was not the reductive process. The degradation of toluene was modelled by classical Monod kinetics. The maximum specific rate of degradation, k, was estimated to be 0.71 mg toluene per mg of protein per hour, and the Monod saturation constant, Ks, to be 0.2 mg toluene/1. The maximum specific growth rate,/~,~ax, was estimated to be 0.1 per hour, and the yield coefficient, Y, was 0.14 mg protein per mg toluene.

Polyphenols are found ubiquitously in plants and their regular consumption has been associated with a reduced risk of a number of chronic diseases, including cancer, cardiovascular disease (CVD) and neurodegenerative disorders. Rather than exerting direct antioxidant effects, the mechanisms by which polyphenols express these beneficial properties appear to involve their interaction with cellular signaling pathways and related machinery that mediate cell function under both normal and pathological conditions. We illustrate that their interactions with two such pathways, the MAP kinase (ERK, JNK, p38) and PI3 kinase/Akt signaling cascades, allow them to impact upon normal and abnormal cell function, thus influencing the cellular processes involved in the initiation and progression of cancer, CVD and neurodegeneration. For example, their ability to activate ERK in neurons leads to a promotion of neuronal survival and cognitive enhancements, both of which influence the progression of Alzheimer's disease, whilst ERK activation by polyphenols in vascular endothelial cells influences nitric oxide production, blood pressure and ultimately CVD risk. The main focus of this review is to provide an overview of the role that polyphenols play in the prevention of cancer, cardiovascular disease and neurodegeneration. We present epidemiological data, human intervention study findings, as well as animal and in vitro studies in support of these actions and in each case we consider how their actions at the cellular level may underpin their physiological effects.

Respiratory distress syndrome is the most common respiratory disorder in preterm infants. Over the last decade, because of improvements in neonatal care and increased use of antenatal steroids and surfactant replacement therapy, mortality from respiratory distress syndrome has dropped substantially. However, respiratory morbidity, primarily bronchopulmonary dysplasia, remains unacceptably high. The management of respiratory distress syndrome in preterm infants is based on various modalities of respiratory support and the application of fundamental principles of neonatal care. To obtain best results, a multidisciplinary approach is crucial. This review discusses surfactant replacement therapy and some of the current strategies in ventilatory management of preterm infants with respiratory distress syndrome. Key words: pediatric, respiratory, pulmonary, respiratory distress syndrome, RDS, surfactant replacement therapy, preterm newborn, bronchopulmonary dysplasia. [Respir Care 2003;48(3):279 -286. © 2003 Daedalus Enterprises] ground-glass appearance of the lung fields, with hypoin-Ricardo J Rodriguez MD is affiliated with the

Peanut testae are potent sources of polyphenols. When the water extracts and acid hydrolysates of five different-colored testae were analyzed by HPLC, chromatograms monitored at 280 nm varied remarkably, whereas two major peaks in the chromatograms monitored at 530 nm were detected only in kernels having completely or partially black color. After acid hydrolysis of the extracts, cyanidin was detected in each of the hydrolysates. By respectively subjecting the black testae of raw and roasted (175°C for 20 min) kernels of a black colored cultivar to water extraction and HPLC analysis, a prominent peak was detected in both extracts. The structure of the substance under those peaks was identified by mass and NMR spectrometry as cyanidin 3-sambubioside in peanut testae for the first time. Subjection of cyanidin 3-sambubioside to antioxidation and anti-inflammation assessments revealed that it was a potent antioxidant and inhibitor of nitric oxide production.

BAY 58-2667 (BAY-58) directly activates soluble guanylyl cyclase without tolerance in a nitric oxide (NO)independent manner, and its haemodynamic effect is similar to that of nitroglycerin. We tested whether BAY-58 could make both rabbit and rat hearts resistant to infarction when given at the end of an ischaemic insult.

Purpose: To date, the exact cause of abnormal exercise response in chronic fatigue syndrome (CFS) remains to be revealed, but evidence addressing intracellular immune deregulation in CFS is growing. Therefore, the aim of this cross-sectional study was to examine the interactions between several intracellular immune variables and exercise performance in CFS patients. Methods: After venous blood sampling, subjects (16 CFS patients) performed a maximal exercise stress test on a bicycle ergometer with continuous monitoring of cardiorespiratory variables. The following immune variables were assessed: the ratio of 37 kDa Ribonuclease (RNase) L to the 83 kDa native RNase L (using a radiolabeled ligand/receptor assay), RNase L enzymatic activity (enzymatic assay), protein kinase R activity assay (comparison Western blot), elastase activity (enzymatic-colorimetric assay), the percent of monocytes, and nitric oxide determination (for monocytes and lymphocytes; flow cytometry, live cell assay). Results: Forward stepwise multiple regression analysis revealed 1) that elastase activity was the only factor related to the reduction in oxygen uptake at a respiratory exchange ratio (RER) of 1.0 (regression model: R 2 ϭ 0.53, F (1,14) ϭ 15.5, P Ͻ 0.002; elastase activity P Ͻ 0.002); 2) that the protein kinase R activity was the principle factor related to the reduction in workload at RER ϭ 1.0; and 3) that elastase activity was the principle factor related to the reduction in percent of target heart rate achieved. Conclusion: These data provide evidence for an association between intracellular immune deregulation and exercise performance in patients with CFS. To establish a causal relationship, further study of these interactions using a prospective longitudinal design is required.

EPR spectroscopic techniques have been developed for the measurement of oxygen and nitric oxide in vivo. Specifically, the methods for in vivo measurement of these molecules has been applied to the study of septic shock, utilising an experimental murine model developed in our laboratory. Oxygen was measured as pO 2 by the particlulate probes Gloxy and LiPc, which were surgically implanted at specific sites in tissues, and the soluble probe Trityl, which was administered intravenously. Nitric oxide was measured as the NO-Fe-(DETC) 2 complex after administration of Fe 2+ and DETC. LPS was seen to significantly decrease liver oxygen measured across the lobule and at the sinusoids by the Gloxy probe; there was a corresponding increase in nitric oxide both in the liver and systemically. The nitric oxide most likely originated from increased iNOS enzyme in the liver as demonstrated by Western blotting and the localisation of nitric oxide to the liver was confirmed with EPR imaging. LPS also caused a decrease in cerebral blood and tissue oxygenation, the rate of which was found to be dependent on the blood oxygenation. The development and applications of these in vivo EPR techniques for biomedical research and diagnostics is discussed.

Arginase 2 (Arg2) is a critical target in atherosclerosis because it controls endothelial nitric oxide, proliferation, fibrosis, and inflammation. Regulators of Arg2 transcription in the endothelium have not been characterized. The goal of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial Arg2 transcription and endothelial function. The HDAC inhibitor trichostatin A increased levels of Arg2 mRNA, protein, and activity in both human aortic endothelial cells and mouse aortic rings. These changes occurred in both time- and dose-dependent patterns and resulted in Arg2-dependent endothelial dysfunction. Trichostatin A and the atherogenic stimulus oxidized low-density lipoprotein enhanced the activity of common promoter regions of Arg2. HDAC inhibition with trichostatin A also decreased endothelial nitric oxide, and these effects were blunted by arginase inhibition. Nonselective class I HDAC inhibitors enhanced Arg2 expres...

Natural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3carbinol produced multiple effects on the NO level; it signifi cantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. Indole-3-carbinol enhanced lipopolyssaccharide (LPS)-induced NO production in all rat organs. It decreased iNOS gene expression in the brain cortex of animals that did not receive LPS and up-regulated it in the LPS-treated animals. Lycopene increased the iNOS gene transcription rate in the brain cortex of LPS-treated animals. Luteolin did not modify NO production in any organ of LPS-untreated rats, nor did it affect gene expression in the liver. In the brain it slightly decreased iNOS gene expression. Luteolin decreased NO production in the blood of LPS-treated animals and the number of iNOS-positive cells in these animals. Our results suggest that changes in tissue NO levels caused by natural compounds cannot be predicted from their effect on NOS expression or activity obtained in model systems. This stresses the importance of direct measurements of NO and NOS expression in animal tissues. Rostoka E, et al. EFFECTS OF NATURAL COMPOUNDS ON NO AND iNOS Arh Hig Rada Toksikol 2010;61:275-285

Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N -nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K ϩ channel (K ATP channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-␤-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K ATP channels and NO-related mechanisms.

Although numerous studies demonstrate the participation of nitric oxide (NO) in various inflammatory diseases, the precise function of NO in allergic asthma remains unclear. We investigated whether iNOS inhibition could interfere with the kinetics of VLA-4 and Mac-1 expression and adhesion properties of bone marrow and peripheral blood eosinophils of sensitized mice after antigen exposure. Treatment of allergic mice with 1400W (iNOS inhibitor) increased the adhesion of bone marrow eosinophils to ICAM-1, but not blood eosinophils, at 24 h and 48 h after OVA-challenge. Conversely, adhesion of blood eosinophils from 1400W-treated mice to VCAM-1 diminished at 24 h and was almost completely blocked at 48 h. 1400W did not induce any change in the adhesion of bone marrow eosinophils to VCAM-1, at 24 h, but cells collected 48 h after challenge showed significantly lower adherence. Flow cytometry demonstrated that 1400W resulted in a significantly increased Mac-1 expression on bone marrow eosinophils at 24 h, as compared to control mice. However, at 24 h, 1400W significantly decreased Mac-1 and VLA-4 expressions on blood eosinophils. At 48 h, the expressions of both Mac-1 and VLA-4 returned to previous levels. Results show a temporal effect of iNOS upon Mac-1 expression and function, the chief adhesion molecule involved in the eosinophil efflux from the bone marrow at 24 h. In contrast, Mac-1 and VLA-4 were involved in eosinophil mobilization from blood to lungs at 48 h after antigen challenge. Data suggest an important role of the Mac-1 and VLA-4 in the iNOS-modulated migration of eosinophils to the lungs of allergic mice.

Involvement of nitric oxide (NO) in the episodic secretion of prolactin was studied in conscious freely moving adult rats. Prolactin secretion was pulsatile in all animals of either group during the bleeding period (from 10:30 h to 13:30 h). Administration of N ω -nitro-L-arginine ...

Historical perspective Asthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity. Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary disorder characterized by the generalized reversible obstruction of airflow and to define reversibility as a greater than 12% increase in the patient's forced expiratory volume in 1 second (FEV 1) that occurs either spontaneously or with therapy. Airway hyperresponsiveness, an exaggerated bronchospastic response to nonspecific agents such as methacholine and histamine or specific antigens, is the physiologic cornerstone of this disorder. A diagnosis of asthma is established based on a history of recurrent wheeze, cough, or shortness of breath, reversible airway obstruction demonstrated by pulmonary-function testing, and, in cases where questions exist, a methacholine challenge demonstrating airway hyperresponsiveness. It has long been assumed that patients with asthma experience intermittent attacks and have relatively normal lung function during intervening periods. More recent studies have demonstrated that asthma can cause progressive lung impairment and, in some patients, eventuate in partially reversible or irreversible airway obstruction. Any discussion of asthma must take into account the recent increase in its prevalence. Since approximately 1980, the frequency of this disorder has almost doubled. As a result of this "epidemic," asthma now affects approximately 8-10% of the population in the US, is the leading cause of hospitalization among children less than 15 years of age, and costs society billions of dollars annually. This increase in prevalence is not simply due to diagnostic transference or increased diagnostic awareness, since asthma mortality rates have also increased during this interval.

The aim of this study was to evaluate the negative effects of the Pringle maneuver on pancreatic tissue with respect to the time of performing the maneuver. Moreover, the efficacy of octreotide therapy on pancreatic changes at the time of the Pringle maneuver was assessed. Fifty male Wistar Albino rats were randomized into 5 groups. The groups were formed as follows: Group A: sham operation, Group B: Pringle maneuver for 30 min plus octreotide (PM30-OCT), Group C: Pringle maneuver for 60 min plus octreotide (PM60-OCT) and Group D: Pringle maneuver for 30 min plus 0.9 % saline solution (PM30-SS), Pringle maneuver for 60 min plus 0.9 % saline solution (PM60-SS, Group E). Blood samples for the evaluation of both amylase and lipase levels were taken via the portal vein. Levels of glutathione, glutathione reductase, catalase, myeloperoxidase, nitric oxide, xanthine oxidase, malondialdehyde, tumour necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) were assessed in the ...

Protozoan parasites of genus Leishmania cause a number of important human diseases including cutaneous, mucocutaneous and visceral leishmaniasis. During their digenetic life cycle, these parasites alternate between an extracellular promastigote stage and an intracellular amastigote stage that reside within the phagolysosome compartment of macrophages in mammalian hosts (Descoteaux and Turco, 2002; Handman and Bullen, 2002). One of the key determinants of parasite infectivity and survival in these environments is the glycoconjugate lipophosphoglycan (LPG). LPG from all Leishmania species has same structure and composed of a repeating phosphorylated disaccharide unit attached via a phosphosaccharide core to the phosphatidylinositol, 1-O-alkyl-2-lysophosphatidylinositol (McConville et al., 1992; Turco and Descoteaux, 1992). New strategies for control of leishmaniasis are needed since chemotherapy such as antimonial drugs is prolonged, expensive, associated with side effects and relapses. Vector control has limitations and a vaccine which may be the best approach is not available. LPG has several functions and has been implicated in binding of parasites to epithelial cells of the sandfly

Osteoarthritis is a progressive joint disease and a major cause of disability for which no curative therapies are yet available. To identify compounds with potential anti-osteoarthritic properties, in this study, we screened one sesquiterpene, E-caryophyllene, and two monoterpene, myrcene and limonene, hydrocarbon compounds for anti-inflammatory, anti-catabolic and pro-anabolic activities in human chondrocytes. At non-cytotoxic concentrations, myrcene and limonene inhibited IL-1β-induced nitric oxide production (IC50=37.3μg/ml and 85.3µg/ml, respectively), but E-caryophyllene was inactive. Myrcene, and limonene to a lesser extent, also decreased IL-1β-induced NF-κB, JNK and p38 activation and the expression of inflammatory (iNOS) and catabolic (MMP-1 and MMP-13) genes, while increasing the expression of anti-catabolic genes (TIMP-1 and -3 by myrcene and TIMP-1 by limonene). Limonene increased ERK1/2 activation by 30%, while myrcene decreased it by 26%, relative to IL-1β-treated cell...

Nitric oxide (NO) and reactive oxygen species (ROS) are emerging as important regulators of angiogenesis. NO enhances VEGF synthesis in several cell types and is required for execution of VEGF angiogenic effect in endothelial cells. Similarly, hydrogen peroxide induces VEGF synthesis and recent studies indicate the involvement of ROS in signaling downstream of VEGF stimulation. VEGF synthesis can not only be enhanced by gene transfer of VEGF but also by overexpression of NO synthase genes. Here, we examined the possibility of augmentation of VEGF production by gene transfer of copper/zinc superoxide dismutase (CuZnSOD, SOD1). Overexpression of human SOD1 in mouse NIH 3T3 fibroblasts increased SOD activity, enhanced intracellular generation of H 2 O 2 and significantly stimulated VEGF production as determined by increase in VEGF promoter activity, VEGF mRNA expression and VEGF protein synthesis. The stimulatory effect on VEGF synthesis induced by SOD1 gene transfer was reverted by overexpression of human catalase. The effect of H 2 O 2 produced by engineered cells is mediated by activation of hypoxia-inducible factor response element (HRE) as well as Sp1 recognition site of VEGF promoter. This data suggest the feasibility of stimulation of angiogenesis by overexpression of SOD1. (Mol Cell Biochem 264: [169][170][171][172][173][174][175][176][177][178][179][180][181] 2004)

State-resolved two-pulse correlation measurement is useful to study the time scale and mechanism of photo-induced desorption as well as electronic structures of admolecules before desorption. In photodesorption of nitric oxide molecules from Pt(1 1 1) at 250 K induced by 80 fs, 620 nm laser pulses, the yields and translational temperatures reached a maximum at zero delay time. In contrast, the rotational temperature of X ¼ 3=2 molecules reached a maximum at a delay time of AE1 ps, while that of X ¼ 1=2 molecules was enhanced at around zero delay. In addition, the ratio of total yields of X ¼ 1=2 molecules to that of X ¼ 3=2 molecules increased at short delay times. All of these results can be explained by the model of rotational heating, including spin-orbit (SO) coupling, where the difference in the correlation time was found to be due to the SO structure in the adsorbed phase. : S 0 0 3 9 -6 0 2 8 ( 0 2 ) 0 1 6 5 9 -X

Nitric oxide is a metastable radical, reacts with oxygen to produce toxic nitrogen oxides (N2O3, ONOO−) which damage DNA. Occupational exposure to nitric oxide leads to increased frequency of chromosomal aberrations in humans. In the present study the DNA damage among the jewellery workers occupationally exposed to nitric oxide was analyzed using buccal cell comet assay. The result of this study shows increased levels of DNA damage among jewellery workers. The habit of cigarette smoking among the jewellery workers has a synergistic effect on inducing DNA damage.

Cereals are an important part of diets for hypercholesterolemic patients. However, some of these patients are allergic to these natural products. The purpose of the current study was to compare oatmeal with equal in nutritional values two allergy-free amaranth meals to determine whether this pseudocereal can be a substitute for allergic to cereals individuals. The total phenols of the samples were determined with the Folin-Chocalteu reagent, anthocyanins, and flavonoids spectrophotometrically. The antioxidant activities were estimated with nitric oxide scavenging radical (NO) and by ␤-carotene bleaching (␤-carotene). It was found that the contents of different protein fractions, antioxidant compounds, and the antioxidant activities of oatmeal were significantly higher than those of the two amaranth samples. The results of kinetic reactions showed that samples differed in their capacities to quench these radicals, and oats have shown more antioxidant activity than amaranth. High correlation was observed between antioxidant activities and phenols (R 2 ϭ 0.99). In the in vivo part of the investigation, 60 male Wistar rats were divided into five diet groups of 12 animals each; these groups were designated as Control, Chol, Chol/Oat, Chol/AmarI, and Chol/AmarII. The rats of the Control group were fed basal diet (BD) only. To the BD of the four other groups were added the following: 1% of cholesterol (Chol), 10% of oat meal and 1% of cholesterol (Chol/Oat), 10% of amaranth I meal, and 1% of cholesterol (Chol/AmarI) and 10% of amaranth II meal and 1% of cholesterol (Chol/AmarII). After 32 days of different feeding, diets supplemented with oat meal and, to lesser degree, with amaranth I and amaranth II hindered the rise in the plasma lipids: a) TC: 3.14 vs. 4.57 mmol/L, Ϫ 31.3%; 3.31 vs. 4.57 mmol/L Ϫ 27.6%; and 3.40 vs. 4.57, Ϫ 25.6%, respectively b) LDL-C: 1.69 vs. 3.31 mmol/L, Ϫ 49.9%; 2.05 vs. 3.31 mmol/L, Ϫ 38.1%; and 2.16 vs. 3.31 mmol/L, Ϫ 34.8%, respectively; c) TG: 0.73 vs. 0.88 mmol/L, Ϫ 17.1%; 0.75 vs. 0.88 mmol/L, Ϫ 14.8%; and 0.79 vs. 0.88 mmol/L, Ϫ10.2%, respectively. The HDL-PH was increased as follows: 0.79 vs. 0.63 mmol/L, Ϫ25.3%; 0.75 vs. 0.63 mmol/L, Ϫ23.0%; and 0.71 vs. 0.63 mmol/L, Ϫ12

Within the CNS and under normal conditions, nitric oxide ('NO) appears to be an important physiological signalling molecule. Its ability to increase cyclic GMP concentration suggests that 'No is implicated in the regulation of important metabolic pathways in the brain. Under certain circumstances N0 synthesis may be excessive and N0 may become neurotoxic. Excessive glutamatereceptor stimulation may lead to neuronal death through a mechanism implicating synthesis of both 'No and superoxide (02') and hence peroxynitrite (ONOO ) formation. In response to lipopolysaccharide and cytokines, glial cells may also be induced to synthesize large amounts of 'No, which may be deleterious to the neighbouring neurones and oligodendrocytes. The precise mechanism of 'No neurotoxicity is not fully understood. One possibility is that it may involve neuronal energy deficiency. This may occur by ONOO interfering with key enzymes of the tricarboxylic acid cycle, the mitochondrial respiratory chain, mitochondrial calcium metabolism, or DNA damage with subsequent activation of the energy-consuming pathway involving poly(ADPribose) synthetase. Possible mechanisms whereby ONOO impairs the mitochondrial respiratory chain and the relevance for neurotoxicity are discussed. The intracellular content of reduced glutathione also appears important in determining the sensitivity of cells to ONOOproduction. lt is concluded that neurotoxicity elicited by excessive 'NO production may be mediated by mitochondrial dysfunction leading to an energy deficiency state.

Reduction of nitrite (NO 2 Ϫ ) provides a major source of nitric oxide (NO) in the circulation, especially in hypoxemic conditions. Our previous studies suggest that xanthine oxidoreductase (XOR) is an important nitrite reductase in the heart and kidney. Herein, we have demonstrated that conversion of nitrite to NO by blood vessels and RBCs was enhanced in the presence of the XOR substrate xanthine (10 mol/L) and attenuated by the XOR inhibitor allopurinol (100 mol/L) in acidic and hypoxic conditions only. Whereas endothelial nitric oxide synthase (eNOS) inhibition had no effect on vascular nitrite reductase activity, in RBCs L-NAME, L-NMMA, and L-arginine inhibited nitrite-derived NO production by Ͼ50% (PϽ0.01) at pH 7.4 and 6.8 under hypoxic conditions. Western blot and immunohistochemical analysis of RBC membranes confirmed the presence of eNOS and abundant XOR on whole RBCs. Thus, XOR and eNOS are ideally situated on the membranes of RBCs and blood vessels to generate intravascular vasodilator NO from nitrite during ischemic episodes. In addition to the proposed role of deoxyhemoglobin, our findings suggest that the nitrite reductase activity within the circulation, under hypoxic conditions (at physiological pH), is mediated by eNOS; however, as acidosis develops, a substantial role for XOR becomes evident. (Circ Res. 2008;103:957-964.)

Information on sCD200 (OX-2), 25-Hydroxyvitamin-D(25(OH)D), homocysteine (hcy), eosinophil cationic peptid (ECP), d-dimer (DD), CXCL8, fractional exhale nitric oxide concentrations (FeNO) status all together among patients with allergy in mediterranean region in comparison of climatic conditions have not been well established yet. Blood samples were taken on May and June during the highest air pollination. Hence, this study was undertaken to compare these serum biomolecules’ levels in allergic patients and matched controls, to evaluate disease characteristics. The study participants (n=129) included 25 healthy individuals (controls) and 104 allergic patients. Consecutive patients with allergic disease (Group II,III,IV,V) above the age of 18 years, managed. In the control group there was a significant positive correlation between ECP and BMI. Positive correlations between ECP, IgE and OX-2 were detected in group IV. For group V patients, positive correlations between age and IgE and ...

Neuronal nitric oxide synthase (nNOS) in the medial preoptic area (MPOA) has been implicated in various physiological functions, including male rat copulation. Based on their apparent sensitivity to gonadal steroid manipulation, we hypothesized that nNOS cells contain steroid receptors, and the testosterone-induced restoration of nNOS-immunoreactivity in castrates should accompany the restoration of copulation. In Experiment 1, we investigated co-localization of nNOS with the androgen receptor (AR) and the estrogen receptor alpha (ERa) using immunocytochemistry. We found regionally specific co-localizations of nNOS-AR and nNOS-ERa. In Experiment 2, we investigated the relationship between MPOA nNOS-immunoreactivity (ir) and copulatory measures in the testosterone-induced restoration paradigm in castrates. The restoration of various copulatory measures was accompanied by an increase in optical density of nNOS-ir, but not in the number of nNOS-ir cells. These data provide additional evidence supporting the role of MPOA nitric oxide in male rat copulation. D 2005 Elsevier B.V. All rights reserved.

The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dosetitration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg −1 day −1 . In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg −1 day −1 ) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological

Five new meroterpenoids, purpurogenolides A-E (1-5), and four known metabolites (6-9) were isolated from the solid substrate fermentation cultures of the fungus Penicillium purpurogenum MHz 111. The structures of the new meroterpenoids were elucidated by analysis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The absolute configurations of 1 and 5 were determined by single-crystal X-ray crystallographic analysis, and those of 2-4 were elucidated on the basis of experimental and calculated electronic circular dichroism spectra. Compounds 2-4 and 6 showed inhibition of nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 0.8-30.0 μM.

Since the discovery that the therapeutic efficacy of antipsychotic drugs was significantly correlated to their ability to block dopamine D 2 receptors, abnormal dopamine transmission in the forebrain has been postulated to underlie psychosis in schizophrenia. In the past 15 years, an impressive amount of clinical and basic research aimed at the study of schizophrenia has indicated that prefrontal and temporal cortical abnormalities may be more important in the etiology of many of the symptoms of schizophrenia, including psychosis. However, the cortical systems that appear to have structural and/or metabolic abnormalities in schizophrenia patients potently regulate forebrain dopamine transmission through a number of mechanisms. In turn, dopamine modulates excitatory transmission mediated by frontal and temporal cortical projections to the basal ganglia and other regions. The present review summarizes the multiple interactions between forebrain DA systems and frontal and temporal corticostriatal transmission. It then examines the role of these interactions in normal behaviors and the psychopa

Background Cow's milk allergy (CMA) has been found to be associated with an increased incidence of asthma at school age. However, prospective population-based studies of CMA and the development of airway inflammation and bronchial hyperresponsivess (BHR) are lacking. Objective The aims of this study was to evaluate CMA as a risk factor for BHR and airway inflammation presented later in childhood. Methods We followed prospectively 118 children with CMA and invited them to a clinical visit at a mean age of 8.6 years including the measurement of exhaled nitric oxide (FE NO) and bronchial challenge with histamine. Ninety-four patients and 80 control subjects from the same cohort participated. Results At school age, children with a history of CMA had higher FE NO levels (P = 0.0009) and more pronounced responsiveness to histamine (P = 0.027) than their controls. Stratified analysis showed a significant difference only in IgE-positive CMA. Multinomial logistic regression analysis showed that IgE-positive CMA [odds ratio (OR) 3.51; 95% confidence intervals (CI) 1.56-7.90; P = 0.002] and a history of wheeze during the first year of life (OR 2.81; 95% CI 1.16-6.84; P = 0.023) were independent explanatory factors for increased FE NO , and IgE-positive CMA (OR 3.37; 95% CI 1.03-10.97; P = 0.044) and parental smoking (OR 3.41; 95% CI 1.14-10.22; P = 0.028) for increased BHR, whereas for IgE-negative CMA, no associations with FE NO or BHR were found. In the CMA group, those exposed to CM very early at the maternity hospital, had less BHR (P = 0.002). Conclusions Compared with their controls, children with a history of IgE-positive CMA show signs of airway inflammation, expressed as higher FE NO , and more pronounced bronchial responsiveness to histamine at school age. In contrast to IgE-negative CMA, IgE-positive CMA is a significant predictor of increased FE NO and BHR at school age. Very early exposure to CM was associated with less BHR.

Use of probiotics, alone or as adjunct to other established therapies, has been reported to have potential benefits. Recently, we have reported protective potential of probiotic against Salmonella-induced liver injury. However, co-supplementation with prebiotics did not result in meaningful synergism at systemic level. Owing to the action of probiotics at the mucosal level and of arginine at systemic level, the present study was designed to evaluate the effect of Lactobacillus plantarum alone or in conjunction with arginine to combat endotoxin-mediated liver injury in rats. Bacterial endotoxin/lipopolysaccharide (LPS) was injected intraperitoneally and animals were sacrificed 8h post-challenge. Efficacy of L. plantarum alone or in conjunction with l-arginine was determined on the basis of enzyme markers, histology, levels of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) in addition to identification of amino acids by paper chromatography. Prior supplementation of LPS-cha...

Experimental autoimmune encephalomyelitis (EAE) is a well-established cell-mediated autoimmune inflammatory disease of the CNS, which has been used as a model of the human demyelinating disease. EAE is characterized by infiltration of the CNS by lymphocytes and mononuclear cells, microglial and astrocytic hypertrophy, and demyelination which cumulatively contribute to clinical expression of the disease. EAE was induced in female Sprague-Dawley rats, 3 months old (300 g ± 20 g), by immunization with myelin basic protein (MBP) in combination with Complete Freund's adjuvant (CFA). The animals were divided into 7 groups: control, EAE, CFA, EAE + aminoguanidine (AG), AG, EAE + N-acetyl-L-cysteine (NAC) and NAC. The animals were sacrificed 15 days after EAE induction, and the level of nitric oxide (NO(·)) production was determined by measuring nitrite and nitrate concentrations in 10% homogenate of cerebellum and spinal cord. Obtained results showed that the level of NO(·) was significantly increased in all examined tissues of the EAE rats compared to the control and CFA groups. Also, AG and NAC treatment decreased the level of NO(·) in all tissues compared to the EAE group. The level of NO(·) is increased significantly in the spinal cord compared to the cerebellum. The clinical course of the EAE was significantly decreased in the EAE groups treated with AG and NAC during the development of the disease compared to EAE group and its correlates with the NO(·) level in cerebellum and spinal cord. The findings of our work suggest that NO(·) and its derivatives play an important role in multiple sclerosis (MS). It may be the best target for new therapies in human demyelinating disease and recommend the new therapeutic approaches based on a decreased level of NO(·) during the course of MS.

The aim of the current study was to determine the impact and interaction of important influencing factors on the fraction of exhaled nitric oxide (FeNO). FeNO was measured in a population-based sample of 1250 middle-aged subjects from the KORA F4 cohort (Augsburg, Germany). Analysis of covariance models was performed including the factors age, height, FVC, FEV(1), sex, current smoking status, recent respiratory tract infection, and respiratory allergy. Geometric mean (SD as factor; 95% confidence interval as factor) FeNO was 13.9 (1.9; 1.033) ppb. FeNO significantly depended on age, height, smoking, infection and allergy. Smoking reduced FeNO by 21%, while infection and allergy led to increases by 9 and 11%, respectively. Increases in age by 10 years and in height by 10 cm were associated with increases of FeNO by 15 and 10%, respectively. Non-smokers demonstrated independent multiplicative superposition of factors affecting FeNO while the effect of allergy was virtually eliminated ...

Aims: To investigate the protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in rats. Main methods: Bilateral renal ischemia was induced for 30 min followed by reperfusion for 24 h. Cannabidiol (5 mg/kg, i.v.) was given 1 h before and 12 h following the procedure. Key findings: Ischemia/reperfusion caused significant elevations of serum creatinine and renal malondialdehyde and nitric oxide levels, associated with a significant decrease in renal reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters induced by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced kidney damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in ischemic/reperfused kidney tissue. Significance: Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent a potential therapeutic option to protect against ischemia/reperfusion renal injury.

Introduction The change in light intensity that takes place when an ambient air sample is drawn into the detection chamber of a chemiluminescence monitor generates changes in the concentrations of several species, such as NO 2 , NO and O 3 . Although this phenomenon has been known for several decades, there is still no commonly accepted approach on when or how to correct for it in NO 2 and O 3 readings. Discussion In this work, we have assessed the expanded uncertainty of two chemiluminescence NO x analysers commercially available according to EN 14211:2005, with the aim of establishing the maximum allowable standard uncertainty due to the reaction between NO and O 3 in the sampling system.

Potassium currents play a critical role in action potential repolarization, setting of the resting membrane potential, control of neuronal ®ring rates, and regulation of neurotransmitter release. The diversity of the potassium channels that generate these currents is nothing less than staggering. This diversity is generated by multiple genes (as many as 100 and perhaps more in some creatures) encoding the pore-forming channel a subunits, alternative splicing of channel gene transcripts, formation of heteromultimeric channels, participation of auxiliary (non-pore-forming) b and other subunits, and modulation of channel properties by post-translational modi®cations and other mechanisms. Prominent among the potassium channels are several families of calcium activated potassium channels, which are highly selective for potassium ions as their charge carrier, and require intracellular calcium for channel gating. The modulation of one of these families, that of the large conductance calcium activated and voltage-dependent potassium channels, has been especially widely studied. In this review we discuss a few selected examples of the modulation of these channels, to illustrate some of the molecular mechanisms and physiological consequences of ion channel modulation.