The effect of nitric oxide releasing cream on healing pressure ulcers

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Vahid Saidkhani

2016-01-01

Full Text Available Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29 and control (placebo cream; n = 29. In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH. At the outset of the study (before using the cream, the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing between the two groups was statistically significant (P = 0.04. Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future.

The effect of nitric oxide releasing cream on healing pressure ulcers

Science.gov (United States)

Saidkhani, Vahid; Asadizaker, Marziyeh; Khodayar, Mohammad Javad; Latifi, Sayed Mahmoud

2016-01-01

Background: Pressure ulcer is one of the main concerns of nurses in medical centers around the world, which, if untreated, causes irreparable problems for patients. In recent years, nitric oxide (NO) has been proposed as an effective method for wound healing. This study was conducted to determine the effect of nitric oxide on pressure ulcer healing. Materials and Methods: In this clinical trial, 58 patients with pressure ulcer at hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences were homogenized and later divided randomly into two groups of treatment (nitric oxide cream; n = 29) and control (placebo cream; n = 29). In this research, the data collection tool was the Pressure Ulcer Scale for Healing (PUSH). At the outset of the study (before using the cream), the patients' ulcers were examined weekly in terms of size, amount of exudates, and tissue type using the PUSH tool for 3 weeks. By integrating these three factors, wound healing was determined. Data were analyzed using SPSS. Results: Although no significant difference was found in terms of the mean of score size, the amount of exudates, and the tissue type between the two groups, the mean of total score (healing) between the two groups was statistically significant (P = 0.04). Conclusions: Nitric oxide cream seems to accelerate wound healing. Therefore, considering its easy availability and cost-effectiveness, it can be used for treating pressure ulcers in the future. PMID:27186212

Nitric Oxide Release for Improving Performance of Implantable Chemical Sensors - A Review.

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Cha, Kyoung Ha; Wang, Xuewei; Meyerhoff, Mark E

2017-12-01

Over the last three decades, there has been extensive interest in developing in vivo chemical sensors that can provide real-time measurements of blood gases (oxygen, carbon dioxide, and pH), glucose/lactate, and potentially other critical care analytes in the blood of hospitalized patients. However, clot formation with intravascular sensors and foreign body response toward sensors implanted subcutaneously can cause inaccurate analytical results. Further, the risk of bacterial infection from any sensor implanted in the human body is another major concern. To solve these issues, the release of an endogenous gas molecule, nitric oxide (NO), from the surface of such sensors has been investigated owing to NO's ability to inhibit platelet activation/adhesion, foreign body response and bacterial growth. This paper summarizes the importance of NO's therapeutic potential for this application and reviews the publications to date that report on the analytical performance of NO release sensors in laboratory testing and/or during in vivo testing.

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

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Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

Evaluation of antibacterial activity of nitric oxide-releasing polymeric particles against Staphylococcus aureus and Escherichia coli from bovine mastitis.

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Cardozo, Viviane F; Lancheros, Cesar A C; Narciso, Adélia M; Valereto, Elaine C S; Kobayashi, Renata K T; Seabra, Amedea B; Nakazato, Gerson

2014-10-01

Bovine mastitis is a serious veterinary disease that causes great loss to the dairy industry worldwide. It is a major infectious disease and is difficult to manage and control. Furthermore, emerging multidrug resistant bacteria that cause mastitis have complicated such management. The free radical nitric oxide (NO) is a potent antimicrobial agent. Thus, the aims of this study were to prepare and evaluate the antibacterial activity of nitric oxide-releasing polymeric particles against Staphylococcus aureus (MBSA) and Escherichia coli (MBEC), which were isolated from bovine mastitis. Fifteen MBSA isolates and fifteen MBEC were collected from subclinical and clinical bovine mastitis. Biocompatible polymeric particles composed of alginate/chitosan or chitosan/sodium tripolyphosphate (TPP) were prepared and used to encapsulate mercaptosuccinic acid (MSA), which is a thiol-containing molecule. Nitrosation of thiol groups of MSA-containing particles formed S-nitroso-MSA particles, which are NO donors. The NO release kinetics from the S-nitroso-MSA particles showed sustained and controlled NO release over several hours. The antibacterial activity of NO-releasing particles was evaluated by incubating the particles with an MBSA multi-resistant strain, which is responsible for bovine mastitis. The minimum inhibitory concentration for S-nitroso-MSA-alginate/chitosan particles against MBSA ranged from 125 μg/mL to 250 μg/mL. The results indicate that NO-releasing polymeric particles are an interesting approach to combating bacteria resistance in bovine mastitis treatment and prevention. Copyright © 2014. Published by Elsevier B.V.

Functional Layer-by-Layer Thin Films of Inducible Nitric Oxide (NO) Synthase Oxygenase and Polyethylenimine: Modulation of Enzyme Loading and NO-Release Activity.

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Gunasekera, Bhagya; Abou Diwan, Charbel; Altawallbeh, Ghaith; Kalil, Haitham; Maher, Shaimaa; Xu, Song; Bayachou, Mekki

2018-03-07

Nitric oxide (NO) release counteracts platelet aggregation and prevents the thrombosis cascade in the inner walls of blood vessels. NO-release coatings also prevent thrombus formation on the surface of blood-contacting medical devices. Our previous work has shown that inducible nitric oxide synthase (iNOS) films release NO fluxes upon enzymatic conversion of the substrate l-arginine. In this work, we report on the modulation of enzyme loading in layer-by-layer (LbL) thin films of inducible nitric oxide synthase oxygenase (iNOSoxy) on polyethylenimine (PEI). The layer of iNOSoxy is electrostatically adsorbed onto the PEI layer. The pH of the iNOSoxy solution affects the amount of enzyme adsorbed. The overall negative surface charge of iNOSoxy in solution depends on the pH and hence determines the density of adsorbed protein on the positively charged PEI layer. We used buffered iNOSoxy solutions adjusted to pHs 8.6 and 7.0, while saline PEI solution was used at pH 7.0. Atomic force microscopy imaging of the outermost layer shows higher protein adsorption with iNOSoxy at pH 8.6 than with a solution of iNOSoxy at pH 7.0. Graphite electrodes with PEI/iNOSoxy films show higher catalytic currents for nitric oxide reduction mediated by iNOSoxy. The higher enzyme loading translates into higher NO flux when the enzyme-modified surface is exposed to a solution containing the substrate and a source of electrons. Spectrophotometric assays showed higher NO fluxes with iNOSoxy/PEI films built at pH 8.6 than with films built at pH 7.0. Fourier transform infrared analysis of iNOSoxy adsorbed on PEI at pH 8.6 and 7.0 shows structural differences of iNOSoxy in films, which explains the observed changes in enzymatic activity. Our findings show that pH provides a strategy to optimize the NOS loading and enzyme activity in NOS-based LbL thin films, which enables improved NO release with minimum layers of PEI/NOS.

Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

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Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

2012-02-15

Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release

DEFF Research Database (Denmark)

Ollerstam, A.; Skøtt, O.; Ek, J.

2001-01-01

Nitric oxide (NO) produced by neuronal NO-synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7-Nitro indazole (7-NI) inhibits nNOS, and we investigated the effect of short- (4 days) and long-term (4 weeks) 7-NI treatment on blood pressure (BP), plasma renin...... LS rats (107 +/- 15 vs. 56 +/- 1 mGU mL(-1)). Stimulation of PRC in LS rats was further enhanced by 7-NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might...

Arginine, citrulline and nitric oxide metabolism in sepsis

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Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

Role of Nitric Oxide in the Regulation of Renin and Vasopressin Secretion

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Reid, Ian A.

1994-01-01

Research during recent years has established nitric oxide as a unique signaling molecule that plays important roles in the regulation of the cardiovascular, nervous, immune, and other systems. Nitric oxide has also been implicated in the control of the secretion of hormones by the pancreas, hypothalamus, and anterior pituitary gland, and evidence is accumulating that it contributes to the regulation of the secretion of renin and vasopressin, hormones that play key roles in the control of sodium and water balance. Several lines of evidence have implicated nitric oxide in the control of renin secretion. The enzyme nitric oxide synthase is present in vascular and tubular elements of the kidney, particularly in cells of the macula densa, a structure that plays an important role in the control of renin secretion. Guanylyl cyclase, a major target for nitric oxide, is also present in the kidney. Drugs that inhibit nitric oxide synthesis generally suppress renin release in vivo and in vitro, suggesting a stimulatory role for the L-arginine/nitric oxide pathway in the control of renin secretion. Under some conditions, however, blockade of nitric oxide synthesis increases renin secretion. Recent studies indicate that nitric oxide not only contributes to the regulation of basal renin secretion, but also participates in the renin secretory responses to activation of the renal baroreceptor, macula densa, and beta adrenoceptor mechanisms that regulate renin secretion. Histochemical and immunocytochemical studies have revealed the presence of nitric oxide synthase in the supraoptic and paraventricular nuclei of the hypothalamus and in the posterior pituitary gland. Colocalization of nitric oxide synthase and vasopressin has been demonstrated in some hypothalamic neurons. Nitric oxide synthase activity in the hypothalamus and pituitary is increased by maneuvers known to stimulate vasopressin secretion, including salt loading and dehydration, Administration of L-arginine and nitric

Evaluation of the effects of nitric oxide-releasing nanoparticles on plants

International Nuclear Information System (INIS)

Pereira, A E S; Fraceto, L F; Narciso, A M; Seabra, A B

2015-01-01

Nowadays, there are several commercially available products containing nanostructured materials. Meanwhile, despite the many benefits that can be obtained from nanotechnology, it is still necessary to understand the mechanisms in which nanomaterials interact with the environment, and to obtain information concerning their possible toxic effects. In agriculture, nanotechnology has been used in different applications, such as nanosensors to detect pathogens, nanoparticles as controlled release systems for pesticides, and biofilms to deliver nutrients to plants and to protect food products against degradation. Moreover, plants can be used as models to study the toxicity of nanoparticles. Indeed, phytotoxicity assays are required to identify possible negative effects of nanostructured systems, prior to their implementation in agriculture. Nitric oxide (NO) plays a key role in plant growth and defense, and recently, several papers described the beneficial effects due to application of exogenous NO donors in plants. The tripeptide glutathione (GSH) is an important anti-oxidant molecule and is the precursor of the NO donor, S-nitrosoglutathione (GSNO). In this context, the present work investigates the effects of different concentrations of alginate/chitosan nanoparticles, containing either GSH or GSNO, on the development of two test species (Zea mays and Glycine sp.). The results showed that the alginate/chitosan nanoparticles present a size average range from 300 to 550 nm with a polydispersity index of 0.35, and encapsulation efficiency of GSH between 45 - 56%. The NO release kinetics from the alginate/chitosan nanoparticles containing GSNO showed sustained and controlled NO release over several hours. Plant assays showed that at the concentrations tested (1, 5 and 10 mM of GSH or GSNO), polymeric nanoparticles showed no significant inhibitory effects on the development of the species Zea mays and Glycine sp., considering the variables shoot height, root length, and

Evaluation of the effects of nitric oxide-releasing nanoparticles on plants

Science.gov (United States)

Pereira, A. E. S.; Narciso, A. M.; Seabra, A. B.; Fraceto, L. F.

2015-05-01

Nowadays, there are several commercially available products containing nanostructured materials. Meanwhile, despite the many benefits that can be obtained from nanotechnology, it is still necessary to understand the mechanisms in which nanomaterials interact with the environment, and to obtain information concerning their possible toxic effects. In agriculture, nanotechnology has been used in different applications, such as nanosensors to detect pathogens, nanoparticles as controlled release systems for pesticides, and biofilms to deliver nutrients to plants and to protect food products against degradation. Moreover, plants can be used as models to study the toxicity of nanoparticles. Indeed, phytotoxicity assays are required to identify possible negative effects of nanostructured systems, prior to their implementation in agriculture. Nitric oxide (NO) plays a key role in plant growth and defense, and recently, several papers described the beneficial effects due to application of exogenous NO donors in plants. The tripeptide glutathione (GSH) is an important anti-oxidant molecule and is the precursor of the NO donor, S-nitrosoglutathione (GSNO). In this context, the present work investigates the effects of different concentrations of alginate/chitosan nanoparticles, containing either GSH or GSNO, on the development of two test species (Zea mays and Glycine sp.). The results showed that the alginate/chitosan nanoparticles present a size average range from 300 to 550 nm with a polydispersity index of 0.35, and encapsulation efficiency of GSH between 45 - 56%. The NO release kinetics from the alginate/chitosan nanoparticles containing GSNO showed sustained and controlled NO release over several hours. Plant assays showed that at the concentrations tested (1, 5 and 10 mM of GSH or GSNO), polymeric nanoparticles showed no significant inhibitory effects on the development of the species Zea mays and Glycine sp., considering the variables shoot height, root length, and

Synthesis and pharmacological characterization of a novel nitric oxide-releasing diclofenac derivative containing a benzofuroxan moiety.

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de Carvalho, Paulo Sérgio; Maróstica, Marta; Gambero, Alessandra; Pedrazzoli, José

2010-06-01

1-oxy-benzo[1,2,5]oxadiazol-5-ylmethyl [2-(2,6-dichloro-phenylamino)-phenyl]-acetate, a new diclofenac derivative bearing a benzofuroxan heterocyclic moiety in its structure, was prepared by the reaction of sodium diclofenac and 5-bromomethyl-benzo[1,2,5]oxadiazole 1-oxide. Pharmacological characterization of this modified diclofenac maintained the anti-inflammatory activity similar to its parent compound assayed in vitro and in vivo. The ulcerogenic properties of native diclofenac were not observed with this modified compound, despite the inhibition of prostaglandin E2 gastric content. The better gastric tolerability seems to be related to nitric oxide release ability. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Inhibition of Anaerobic Phosphate Release by Nitric Oxide in Activated Sludge

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Van Niel, E. W. J.; Appeldoorn, K. J.; Zehnder, A. J. B.; Kortstee, G. J. J.

1998-01-01

Activated sludge not containing significant numbers of denitrifying, polyphosphate [poly(P)]-accumulating bacteria was grown in a fill-and-draw system and exposed to alternating anaerobic and aerobic periods. During the aerobic period, poly(P) accumulated up to 100 mg of P · g of (dry) weight. When portions of the sludge were incubated anaerobically in the presence of acetate, 80 to 90% of the intracellular poly(P) was degraded and released as orthophosphate. Degradation of poly(P) was mainly catalyzed by the concerted action of polyphosphate:AMP phosphotransferase and adenylate kinase, resulting in ATP formation. In the presence of 0.3 mM nitric oxide (NO) in the liquid-phase release of phosphate, uptake of acetate, formation of poly-β-hydroxybutyrate, utilization of glycogen, and formation of ATP were severely inhibited or completely abolished. In cell extracts of the sludge, adenylate kinase activity was completely inhibited by 0.15 mM NO. The nature of this inhibition was probably noncompetitive, similar to that with hog adenylate kinase. Activated sludge polyphosphate glucokinase was also completely inhibited by 0.15 mM NO. It is concluded that the inhibitory effect of NO on acetate-mediated phosphate release by the sludge used in this study is due to the inhibition of adenylate kinase in the phosphate-releasing organisms. The inhibitory effect of nitrate and nitrite on phosphate release is probably due to their conversion to NO. The lack of any inhibitory effect of NO on adenylate kinase of the poly(P)-accumulating Acinetobacter johnsonii 210A suggests that this type of organism is not involved in the enhanced biological phosphate removal by the sludges used. PMID:9687452

Human nitric oxide biomarker as potential NO donor in conjunction with superparamagnetic iron oxide @ gold core shell nanoparticles for cancer therapeutics.

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Singh, Nimisha; Patel, Khushbu; Sahoo, Suban K; Kumar, Rajender

2018-03-01

Nitric oxide releasing superparamagnetic (Fe 3 O 4 -Au@NTHP) nanoparticles were synthesized by conjugation of human biomarker of nitric oxide, N-nitrosothioproline with iron oxide-gold (Fe 3 O 4 -Au) core shell nanoparticles. The structure and morphology of the prepared nanoparticles were confirmed by ATR-FTIR, HR-TEM, EDAX, XPS, DLS and VSM measurements. N-nitrosothioproline is a natural molecule and nontoxic to humans. Thus, the core shell nanoparticles prepared were highly biocompatible. The prepared Fe 3 O 4 -Au@NTHP nanoparticles also provided an excellent release of nitric oxide in dark and upon light irradiation for cancer treatment. The amount of NO release was controllable with the wavelength of light and time of irradiation. The developed nanoparticles provided efficient cellular uptake and good cytotoxicity in picomolar range when tested on HeLa cancerous cells. These nanoparticles on account of their controllable NO release can also be used to release small amount of NO for killing cancerous cells without any toxic effect. Furthermore, the magnetic and photochemical properties of these nanoparticles provides dual platform for magneto therapy and phototherapy for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The myth of nitric oxide in central cardiovascular control by the nucleus tractus solitarii

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Talman W.T.

1997-01-01

Full Text Available Considerable evidence suggests that nitroxidergic mechanisms in the nucleus tractus solitarii (NTS participate in cardiovascular reflex control. Much of that evidence, being based on responses to nitric oxide precursors or inhibitors of nitric oxide synthesis, has been indirect and circumstantial. We sought to directly determine cardiovascular responses to nitric oxide donors microinjected into the NTS and to determine if traditional receptor mechanisms might account for responses to certain of these donors in the central nervous system. Anesthetized adult Sprague Dawley rats that were instrumented for recording arterial pressure and heart rate were used in the physiological studies. Microinjection of nitric oxide itself into the NTS did not produce any cardiovascular responses and injection of sodium nitroprusside elicited minimal depressor responses. The S-nitrosothiols, S-nitrosoglutathione (GSNO, S-nitrosoacetylpenicillamine (SNAP, and S-nitroso-D-cysteine (D-SNC produced no significant cardiovascular responses while injection of S-nitroso-L-cysteine (L-SNC elicited brisk, dose-dependent depressor and bradycardic responses. In contrast, injection of glyceryl trinitrate elicited minimal pressor responses without associated changes in heart rate. It is unlikely that the responses to L-SNC were dependent on release of nitric oxide in that 1 the responses were not affected by injection of oxyhemoglobin or an inhibitor of nitric oxide synthesis prior to injection of L-SNC and 2 L- and D-SNC released identical amounts of nitric oxide when exposed to brain tissue homogenates. Although GSNO did not independently affect blood pressure, its injection attenuated responses to subsequent injection of L-SNC. Furthermore, radioligand binding studies suggested that in rat brain synaptosomes there is a saturable binding site for GSNO that is displaced from that site by L-SNC. The studies suggest that S-nitrosocysteine, not nitric oxide, may be an

Release by ultraviolet B (u.v.B) radiation of nitric oxide (NO) from human keratinocytes: a potential role for nitric oxide in erythema production

International Nuclear Information System (INIS)

Deliconstantinos, G.; Villiotou, V.; Stravrides, J.C.

1995-01-01

The mechanism of human sunburn is poorly understood but its characteristic features include the development of erythema. In this study we attempted to determine whether human keratinocytes possess a nitric oxide (NO) synthase (NOS), if this enzyme could be activated to release NO following exposure to ultraviolet B (u.v.B) and to define whether this photo-induced response could be involved in the pathogenesis of sunburn erythema. The present results indicate that u.v.B radiation acts as a potent stimulator of NOS in keratinocytes. NO is lipophilic and may diffuse out of the keratinocytes, activating sGC in endothelial cells and neighbouring smooth muscle cells. This may be a major part of the integrated response of the skin leading to vasodilatation and erythema. (author)

[Ultrasound induced the formation of nitric oxide and nitrosonium ions in water and aqueous solutions].

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Stepuro, I I; Adamchuk, R I; Stepuro, V I

2004-01-01

Nitric oxide, nitrosonium ions, nitrites, and nitrates are formed in water saturated with air under the action of ultrasound. Nitrosonium ions react with water and hydrogen peroxide to form nitrites and nitrates in sonicated solution, correspondingly. Nitric oxide is practically completely released from sonicated water into the atmosphere and reacts with air oxygen, forming NOx compounds. The oxidation of nitric oxide in aqueous medium by hydroxyl radicals and dissolved oxygen is a minor route of the formation of nitrites and nitrates in ultrasonic field.

Calcium mobilization in HeLa cells induced by nitric oxide.

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Huang, Yimei; Zheng, Liqin; Yang, Hongqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

2014-01-01

Nitric oxide (NO) has been proposed to be involved in tumor growth and metastasis. However, the mechanism by which nitric oxide modulates cancer cell growth and metastasis on cellular and molecular level is still not fully understood. This work utilized confocal microscopy and fluorescence microplate reader to investigate the effects of exogenous NO on the mobilization of calcium, which is one of the regulators of cell migration, in HeLa cells. The results show that NO elevates calcium in concentration-dependent manner in HeLa cells. And the elevation of calcium induced by NO is due to calcium influx and calcium release from intracellular calcium stores. Moreover, calcium release from intracellular stores is dominant. Furthermore, calcium release from mitochondria is one of the modulation pathways of NO. These findings would contribute to recognizing the significance of NO in cancer cell proliferation and metastasis. © Wiley Periodicals, Inc.

Antibacterial activity of nitric oxide releasing silver nanoparticles

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Seabra, Amedea B.; Manosalva, Nixson; de Araujo Lima, Bruna; Pelegrino, Milena T.; Brocchi, Marcelo; Rubilar, Olga; Duran, Nelson

2017-06-01

Silver nanoparticles (AgNPs) are well known potent antimicrobial agents. Similarly, the free radical nitric oxide (NO) has important antibacterial activity, and due to its instability, the combination of NO and nanomaterials has been applied in several biomedical applications. The aim of this work was to synthesize, characterize and evaluate the antibacterial activity of a new NO-releasing AgNPs. Herein, AgNPs were synthesized by the reduction of silver ions (Ag+) by catechin, a natural polyphenol and potent antioxidant agent, derived from green tea extract. Catechin acts as a reducing agent and as a capping molecule on the surface of AgNPs, minimizing particle agglomeration. The as-synthesized nanoparticles were characterized by different techniques. The results showed the formation of AgNPs with average hydrodynamic size of 44 nm, polydispersity index of 0.21, and zeta potential of -35.9 mV. X-ray diffraction and Fourier transform infrared spectroscopy revealed the presence of the AgNP core and cathecin as capping agent. The low molecular weight mercaptosuccinic acid (MSA), which contain free thiol group, was added on the surface of catechin-AgNPs, leading to the formation of MSA-catechin-AgNPs (the NO precursor nanoparticle). Free thiol groups of MSA-catechin-AgNPs were nitrosated leading to the formation of S-nitroso-mercaptosuccinic acid (S-nitroso-MSA), the NO donor. The amount of 342 ± 16 µmol of NO was released per gram of S-nitroso-MSA-catechin-AgNPs. The antibacterial activities of catechin-AgNPs, MSA-catechin-AgNPs, and S-nitroso-MSA-catechin-AgNPs were evaluated towards different resistant bacterial strains. The results demonstrated an enhanced antibacterial activity of the NO-releasing AgNP. For instance, the minimal inhibitory concentration values for Pseudomonas aeruginosa (ATCC 27853) incubated with AgNPs-catechin, AgNPs-catechin-MSA, and AgNPs-catechin-S-nitroso-MSA were found to be 62, 125 and 3 µg/mL, respectively. While in the case of

Anti-inflammatory effects of nitric oxide-releasing hydrocortisone NCX 1022, in a murine model of contact dermatitis.

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Hyun, Eric; Bolla, Manlio; Steinhoff, Martin; Wallace, John L; Soldato, Piero Del; Vergnolle, Nathalie

2004-11-01

1 The concept that nitric oxide (NO) release can be beneficial in inflammatory conditions has raised more attention in the recent years, particularly with the development of nitric oxide-releasing anti-inflammatory drugs. There is considerable evidence that NO is capable of enhancing the anti-inflammatory benefits of conventional anti-inflammatory drugs. 2 Since hydrocortisone is the most widely used anti-inflammatory drug for the treatment of skin inflammation, we compared the anti-inflammatory effects of hydrocortisone to an NO-releasing derivative of hydrocortisone, NCX 1022, in a murine model of irritant contact dermatitis, induced by epidermal application of benzalkonium chloride. 3 Topical pre- and post-treatment with NCX 1022 (3 nmol) in C57BL6 mice not only reduced ear oedema formation in a dose-dependent manner, but also was significantly more effective than the parent compound during the initial stages of inflammation (from 1 to 5 h). NCX 1022, but not hydrocortisone, significantly inhibited granulocyte recruitment (tissue myeloperoxidase activity). Histological samples of mouse ears treated with NCX 1022 showed significant reduction in both the number of infiltrated cells and disruption of the tissue architecture compared to hydrocortisone-treated tissues. 4 With intravital microscopy, we observed that both pre- and post-treatments with NCX 1022 were more effective than hydrocortisone in terms of inhibiting benzalkonium chloride-induced leukocyte adhesion to the endothelium, without affecting the flux of rolling leukocytes or venule diameter. 5 These results suggest that by releasing NO, NCX 1022 modulates one of the early events of skin inflammation: the recruitment of leukocytes to the site of inflammation. Overall, we have shown that NO-hydrocortisone provided faster and greater protective effects, reducing major inflammatory parameters (leukocyte adhesion and recruitment, oedema formation, tissue disruption) compared to its parental compound.

Vascular nitric oxide: Beyond eNOS

Directory of Open Access Journals (Sweden)

Yingzi Zhao

2015-10-01

Full Text Available As the first discovered gaseous signaling molecule, nitric oxide (NO affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC to produce cyclic guanosine monophosphate (cGMP, although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA or production of cyclic inosine monophosphate (cIMP] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

Nitric oxide donors enhance the frequency dependence of dopamine release in nucleus accumbens.

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Hartung, Henrike; Threlfell, Sarah; Cragg, Stephanie J

2011-08-01

Dopamine (DA) neurotransmission in the nucleus accumbens (NAc) is critically involved in normal as well as maladaptive motivated behaviors including drug addiction. Whether the striatal neuromodulator nitric oxide (NO) influences DA release in NAc is unknown. We investigated whether exogenous NO modulates DA transmission in NAc core and how this interaction varies depending on the frequency of presynaptic activation. We detected DA with cyclic voltammetry at carbon-fiber microelectrodes in mouse NAc in slices following stimuli spanning a full range of DA neuron firing frequencies (1-100 Hz). NO donors 3-morpholinosydnonimine hydrochloride (SIN-1) or z-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA/NONOate) enhanced DA release with increasing stimulus frequency. This NO-mediated enhancement of frequency sensitivity of DA release was not prevented by inhibition of soluble guanylyl cyclase (sGC), DA transporters, or large conductance Ca(2+)-activated K(+) channels, and did not require glutamatergic or GABAergic input. However, experiments to identify whether frequency-dependent NO effects were mediated via changes in powerful acetylcholine-DA interactions revealed multiple components to NO modulation of DA release. In the presence of a nicotinic receptor antagonist (dihydro-β-erythroidine), NO donors increased DA release in a frequency-independent manner. These data suggest that NO in the NAc can modulate DA release through multiple GC-independent neuronal mechanisms whose net outcome varies depending on the activity in DA neurons and accumbal cholinergic interneurons. In the presence of accumbal acetylcholine, NO promotes the sensitivity of DA release to presynaptic activation, but with reduced acetylcholine input, NO will promote DA release in an activity-independent manner through a direct action on dopaminergic terminals.

Sensing nitric oxide with a carbon nanofiber paste electrode modified with a CTAB and nafion composite

International Nuclear Information System (INIS)

Zheng, Dongyun; Liu, Xiaojun; Zhu, Shanying; Cao, Huimin; Chen, Yaguang; Hu, Shengshui

2015-01-01

We describe an electrochemical sensor for nitric oxide that was obtained by modifying the surface of a nanofiber carbon paste microelectrode with a film composed of hexadecyl trimethylammonium bromide and nafion. The modified microelectrode displays excellent catalytic activity in the electrochemical oxidation of nitric oxide. The mechanism was studied by scanning electron microscopy and cyclic voltammetry. Under optimal conditions, the oxidation peak current at a working voltage of 0.75 V (vs. SCE) is related to the concentration of nitric oxide in the 2 nM to 0.2 mM range, and the detection limit is as low as 2 nM (at an S/N ratio of 3). The sensor was successfully applied to the determination of nitric oxide released from mouse hepatocytes. (author)

Enhancement of nitric oxide release and hemocompatibility by surface chirality of D-tartaric acid grafting

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Han, Honghong; Wang, Ke; Fan, Yonghong; Pan, Xiaxin; Huang, Nan; Weng, Yajun

2017-12-01

Nitric Oxide (NO) generation from endogenous NO-donors catalyzed by diselenide modified biomaterials has been reported. Here we reported surface chirality by L-tartaric acid and D-tartaric acid grafting on the outermost showed a significant impact on diselenide modified biomaterials, which modulated protein adsorption, NO release and anti-platelet adhesion properties. D-tartaric acid grafted surface showed more blood protein adsorption than that of L-surfaces by QCM analysis, however, ELISA analysis disclosed less fibrinogen denatured on the D surfaces. Due to the surface ratio of selenium decreasing, NO release catalyzed by L-tartaric acid grafting on the outermost significantly decreased in comparison to that of only selenocystamine immobilized surfaces. While NO release catalyzed by D-tartaric acid grafting on the outermost didn't decrease and was similar with that of selenocystamine immobilized surfaces. Surface chirality combined with NO release had synergetic effects on platelet adhesion, and it showed the lowest number of platelets adhered on the D-tartaric acid grafted surfaces. Thus surface chirality from D-tartaric acid grafting enhanced hemocompatibility of the surface in this study. Our work provides new insights into engineering novel blood contacting biomaterials by taking into account surface chirality.

Liquid-Phase Heat-Release Rates of the Systems Hydrazine-Nitric Acid and Unsymmetrical Dimethylhydrazine-Nitric Acid

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Somogyi, Dezso; Feiler, Charles E.

1960-01-01

The initial rates of heat release produced by the reactions of hydrazine and unsymmetrical dimethylhydrazine with nitric acid were determined in a bomb calorimeter under conditions of forced mixing. Fuel-oxidant weight ratio and injection velocity were varied. The rate of heat release apparently depended on the interfacial area between the propellants. Above a narrow range of injection velocities representing a critical amount of interfacial area, the rates reached a maximum and were almost constant with injection velocity. The maximum rate for hydrazine was about 70 percent greater than that for unsymmetrical dimethylhydrazine. The total heat released did not vary with mixture ratio over the range studied.

Novel Nitric Oxide (NO)-Releasing Polymers and Their Biomedical Applications

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Brisbois, Elizabeth J.

Two common factors that can cause complications with indwelling biomedical devices are thrombus and infection. Nitric oxide (NO) is known to be a potent inhibitor of platelet activation and adhesion. Healthy endothelial cells exhibit a NO flux into the bloodstream of 0.5˜4x10-10 mol cm -2 min-1. In addition, NO that is released within the sinus cavities and by neutrophils/macrophages functions as a potent natural antimicrobial agent. Therefore, polymer materials that release NO are expected to have similar anti-thrombotic and antimicrobial properties. In this dissertation work, two novel approaches to achieving long-term NO release from polymers were studied and evaluated for their potential biomedical applications. In the first approach, S-nitroso-N -acetypenicillamine (SNAP)-doped polymers were studied for potential hemocompatibility. The SNAP-doped Elast-eon E2As (block copolymer of poly(dimethylsiloxane) and polyurethane) creates an inexpensive polymer that can locally deliver physiologically relevant levels of NO (via thermal and photochemical reactions). SNAP was also found to be surprisingly stable in the E2As polymer during shelf-life stability and ethylene oxide sterilization studies. The SNAP/E2As polymer was coated on the inner walls of extracorporeal circulation (ECC) circuits and was found to preserve the platelet count at ˜100% of baseline and reduce thrombus area after 4 h blood flow in a rabbit model. The SNAP/E2As polymer was also used to fabricate NO-releasing catheters that were implanted in sheep veins for 7 d. The SNAP/E2As catheters significantly reduced the amount of thrombus and bacterial adhesion (in comparison to E2As control catheters). In the second approach, the NO release from diazeniumdiolated dibutylhexanediamine (DBHD/N2 O 2)-doped polymers was significantly improved using various poly(lactic-co-glycolic acid) (PLGA) additives. Using acid-capped PLGA additives was found to cause high initial bursts of NO, while using an ester

Role of nitric oxide in methamphetamine neurotoxicity: protection by 7-nitroindazole, an inhibitor of neuronal nitric oxide synthase.

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Di Monte, D A; Royland, J E; Jakowec, M W; Langston, J W

1996-12-01

The role of nitric oxide (NO.) in the neurotoxic effects of methamphetamine (METH) was evaluated using 7-nitroindazole (7-NI), a potent inhibitor of neuronal nitric oxide synthase. Treatment of mice with 7-NI (50 mg/kg) almost completely counteracted the loss of dopamine, 3,4-dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity observed 5 days after four injections of 10 or 7.5 mg/kg METH. With the higher dose of METH, this protection at 5 days occurred despite the fact that combined administration of METH and 7-NI significantly increased lethality and exacerbated METH-induced dopamine release (as indicated by a greater dopamine depletion at 90 min and 1 day). Combined treatment with 4 x 10 mg/kg METH and 7-NI also slightly increased the body temperature of mice as compared with METH alone. Thus, the neuroprotective effects of 7-NI are independent from lethality, are not likely to be related to a reduction of METH-induced dopamine release, and are not due to a decrease in body temperature. These results indicate that NO. formation is an important step leading to METH neurotoxicity, and suggest that the cytotoxic properties of NO. may be directly involved in dopaminergic terminal damage.

Physiological Levels of Nitric Oxide Diminish Mitochondrial Superoxide. Potential Role of Mitochondrial Dinitrosyl Iron Complexes and Nitrosothiols

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Sergey I. Dikalov

2017-11-01

Full Text Available Mitochondria are the major source of superoxide radicals and superoxide overproduction contributes to cardiovascular diseases and metabolic disorders. Endothelial dysfunction and diminished nitric oxide levels are early steps in the development of these pathological conditions. It is known that physiological production of nitric oxide reduces oxidative stress and inflammation, however, the precise mechanism of “antioxidant” effect of nitric oxide is not clear. In this work we tested the hypothesis that physiological levels of nitric oxide diminish mitochondrial superoxide production without inhibition of mitochondrial respiration. In order to test this hypothesis we analyzed effect of low physiological fluxes of nitric oxide (20 nM/min on superoxide and hydrogen peroxide production by ESR spin probes and Amplex Red in isolated rat brain mitochondria. Indeed, low levels of nitric oxide substantially attenuated both basal and antimycin A-stimulated production of reactive oxygen species in the presence of succinate or glutamate/malate as mitochondrial substrates. Furthermore, slow releasing NO donor DPTA-NONOate (100 μM did not change oxygen consumption in State 4 and State 3. However, the NO-donor strongly inhibited oxygen consumption in the presence of uncoupling agent CCCP, which is likely associated with inhibition of the over-reduced complex IV in uncoupled mitochondria. We have examined accumulation of dinitrosyl iron complexes and nitrosothiols in mitochondria treated with fast-releasing NO donor MAHMA NONOate (10 μM for 30 min until complete release of NO. Following treatment with NO donor, mitochondria were frozen for direct detection of dinitrosyl iron complexes using Electron Spin Resonance (ESR while accumulation of nitrosothiols was measured by ferrous-N-Methyl-D-glucamine dithiocarbamate complex, Fe(MGD2, in lysed mitochondria. Treatment of mitochondria with NO-donor gave rise to ESR signal of dinitrosyl iron complexes while ESR

Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

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Timpani, Cara A; Hayes, Alan; Rybalka, Emma

2017-05-25

Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

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Nevzat Selim Gokay

2016-01-01

Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

Improved in vivo performance of amperometric oxygen (PO2) sensing catheters via electrochemical nitric oxide generation/release.

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Ren, Hang; Coughlin, Megan A; Major, Terry C; Aiello, Salvatore; Rojas Pena, Alvaro; Bartlett, Robert H; Meyerhoff, Mark E

2015-08-18

A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of -2 ± 11% and good correlation (R(2) = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of -31 ± 28% and poor correlation (R(2) = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.

Nitric oxide in the rat cerebellum after hypoxia/ischemia.

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Rodrigo, José; Fernández, Ana Patricia; Alonso, David; Serrano, Julia; Fernández-Vizarra, Paula; Martínez-Murillo, Ricardo; Bentura, María Luisa; Martinez, Alfredo

2004-01-01

Nitric oxide is a regulatory biological substance and an important intracellular messenger that acts as a specific mediator of various neuropathological disorders. In mammals and invertebrates, nitric oxide is synthesized from L-arginine in the central and peripheral neural structures by the endothelial, neuronal and inducible enzymatic isoforms of nitric oxide synthase. Nitric oxide may affect the function of various neurotransmitter-specific systems, and is involved in neuromodulation, reproductive function, immune response, and regulation of the cerebral blood circulation. This makes nitric oxide the main candidate in brain responses to brain ischemia/hypoxia. The cerebellum has been reported to be the area of the brain that has the highest nitric oxide synthase activity and the highest concentration of glutamate and aspartate. By glutamate receptors and physiological action of nitric oxide, cyclic guanisine-5'-monophosphate may be rapidly increased. The cerebellum significantly differs with respect to ischemia and hypoxia, this response being directly related to the duration and intensity of the injury. The cerebellum could cover the eventual need for nitric oxide during the hypoxia, boosting the nitric oxide synthase activity, but overall ischemia would require de novo protein synthesis, activating the inducible nitric oxide synthase to cope with the new situation. The specific inhibitors of nitric oxide synthesis show neuroprotective effects.

Association between high risk papillomavirus DNA and nitric oxide release in the human uterine cervix.

Science.gov (United States)

Rahkola, Paivi; Mikkola, Tomi S; Ylikorkala, Olavi; Vaisanen-Tommiska, Mervi

2009-08-01

Local cervical factors may determine the outcome of human papillomavirus (HPV) infection. Nitric oxide (NO) may be one such factor, since it is produced by uterine cervical cells and it takes part in both immunological and carcinogenic reactions. We studied the association between the presence of cervical high risk (hr) HPV DNA and NO in the cervical canal in women. High risk HPV DNA status was assessed from 328 women by using a specific DNA test and the release of cervical NO was assessed as nitrate/nitrite in cervical fluid. Cervical NO was then compared between women showing different status of hr HPV DNA and different cytological and histological findings. High risk HPV DNA was present in 175/328 (53%) women. The cervical NO release in women with hr HPV DNA was 90% higher compared to hr HPV DNA negative women (poral contraception, intrauterine devices, or signs of bacterial vaginosis or candida infection. Cytologically healthy epithelium and epithelium with mild cytological or histological changes showed elevated NO release if hr HPV DNA was present. The presence of hr HPV DNA is associated with an increased release of NO in the human uterine cervix. The clinical significance of this phenomenon remains open.

A Selection of Nitric Oxide-Releasing Materials Incorporating S-Nitrosothiols

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Lutzke, Alec

Nitric oxide (NO) is a diatomic radical that occurs as a crucial component of mammalian biochemistry. As a signaling molecule, NO participates in the regulation of vascular tone and maintains the natural antithrombotic function of the healthy endothelium. Furthermore, NO is produced by phagocytes as part of the immune response, and exhibits both antimicrobial and wound-healing effects. In combination, these beneficial properties have led to the use of exogenous NO as a multifunctional therapeutic agent. However, the comparatively short half-life of NO under physiological conditions often renders systemic administration infeasible. This limitation is addressed by the use of NO-releasing polymeric materials, which permit the localized delivery of NO directly at the intended site of action. Such polymers have been utilized in the development of antithrombotic or antibacterial materials for biointerfacial applications, including tissue engineering and the fabrication of medical devices. NO release from polymers has most frequently been achieved through the incorporation of functional groups that are susceptible to NO-forming chemical decomposition in response to appropriate environmental stimuli. While numerous synthetic sources of NO are known, the S-nitrosothiol (RSNO) functional group occurs naturally in the form of S-nitrosocysteine residues in both proteins and small molecule species such as S-nitrosoglutathione. RSNOs are synthesized directly from thiol precursors, and their NO-forming decay has generally been established to produce the corresponding disulfide as a relatively benign organic byproduct. For these reasons, RSNOs have been conscripted as practical NO donors within a physiological environment. This dissertation describes the synthesis and characterization of RSNO-based NO-releasing polymers derived from the polysaccharides chitin and chitosan, as well as the development of amino acid ester-based NO-releasing biodegradable poly

Double blind, randomized controlled trial, to evaluate the effectiveness of a controlled nitric oxide releasing patch versus meglumine antimoniate in the treatment of cutaneous leishmaniasis [NCT00317629

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Silva Federico A

2006-05-01

Full Text Available Abstract Background Cutaneous Leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. Methods and design A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for Leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be daily administered and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

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Benzing, A; Loop, T; Mols, G; Geiger, K

1999-10-01

Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the

Nitric oxide in the stress axis.

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López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

1998-10-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

21 CFR 862.3080 - Breath nitric oxide test system.

Science.gov (United States)

2010-04-01

... Systems § 862.3080 Breath nitric oxide test system. (a) Identification. A breath nitric oxide test system... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breath nitric oxide test system. 862.3080 Section... fractional nitric oxide concentration in expired breath aids in evaluating an asthma patient's response to...

The role of nitric oxide in reproduction

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McCann S.M.

1999-01-01

Full Text Available Nitric oxide (NO plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH. The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP. NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG.

21 CFR 868.5165 - Nitric oxide administration apparatus.

Science.gov (United States)

2010-04-01

... apparatus. (a) Identification. The nitric oxide administration apparatus is a device used to add nitric oxide to gases that are to be breathed by a patient. The nitric oxide administration apparatus is to be used in conjunction with a ventilator or other breathing gas administration system. (b) Classification...

Nitric oxide-releasing nanoparticles: synthesis, characterization, and cytotoxicity to tumorigenic cells

Energy Technology Data Exchange (ETDEWEB)

Pelegrino, Milena T. [Universidade Federal de São Paulo, Exact and Earth Sciences Department (Brazil); Silva, Letícia C.; Watashi, Carolina M. [Universidade Federal do ABC, UFABC, Center of Natural and Human Sciences (Brazil); Haddad, Paula S. [Universidade Federal de São Paulo, Exact and Earth Sciences Department (Brazil); Rodrigues, Tiago; Seabra, Amedea B., E-mail: amedea.seabra@ufabc.edu.br [Universidade Federal do ABC, UFABC, Center of Natural and Human Sciences (Brazil)

2017-02-15

Nitric oxide (NO) is involved in several biological processes, including toxicity against tumor cells. The aim of this study was to synthesize, characterize, and evaluate the cytotoxicity of NO-releasing chitosan nanoparticles. A thiol-containing molecule, mercaptosuccinic acid (MSA), was encapsulated (encapsulation efficiency of 99%) in chitosan/sodium tripolyphosphate nanoparticles (CS NPs). The obtained nanoparticles showed an average hydrodynamic size of 108.40 ± 0.96 nm and polydispersity index of 0.26 ± 0.01. MSA-CS NPs were nitrosated leading to S-nitroso-MSA-CS NPs, which act as NO donor. The cytotoxicity of CS NPs, MSA-CS NPs, and S-nitroso-MSA-CS NPs were evaluated in several tumor cells, including human hepatocellular carcinoma (HepG2), mouse melanoma (B16F10), and human chronic myeloid leukemia (K562) cell lines and Lucena-1, a vincristine-resistant K562 cell line. Both CS NPs and MSA-CS NPs did not cause toxic effects in these cells, whereas S-nitroso-MSA-CS NPs caused potent cytotoxic effects in all the tested tumor cell lines. The half-maximal inhibitory concentration values of S-nitroso-MSA-CS NPs were 19.7, 10.5, 22.8, and 27.8 μg·mL{sup −1} for HepG2, B16F10, K562, and Lucena-1 cells, respectively. In contrast, S-nitroso-MSA-CS NPs exhibited lower cytotoxic to non-tumorigenic melanocytes (Melan-A) when compared with melanoma B16F10. Therefore, the results highlight the potential use of NO-releasing CS NPs in antitumor chemotherapy.

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

OpenAIRE

van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

2000-01-01

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study,...

Nitric oxide in the psychobiology of mental disorders

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Altan Eşsizoğlu

2009-03-01

Full Text Available Nitric oxide is in a gaseous form and is widespread in the human body. It functions by acting as a secondary messenger in the modulatory activities of neuronal functions of the central nervous system. Nitric oxide is the first identified neurotransmitter of the nontraditional neurotransmitter family.Studies conducted on experimental animals demonstrate that nitric oxide has a neuromodulatory efficacy on the secretions of other neurotransmitters and that it has an effect on learning and memory functions, and on various neuronal mechanisms. Many studies have been conducted to investigate the location of nitric oxide in the central nervous system, its effect on anxiety and depression, its relationship with other neurotransmitters, and also about its role on neurotoxicity. There are clinical studies concerning the level of nitrate, a product of nitric oxide metabolism, and also experimental studies concerning its rewarding effect of alcohol and substance use, in patients with depression and schizophrenia. However, limited studies have been conducted to investigate its relationship with stress, which is an important factor in the etiology of psychiatric disorders. These studies demonstrate that nitric oxide is closely related with stress physiology.Nitric oxide is a neuromodulator, which is frequently being mentioned about nowadays in psychiatry. Clinical and experimental studies play an important role in the psychobiology of psychiatric disorders.

Calcimimetic R-568 and its enantiomer S-568 increase nitric oxide release in human endothelial cells.

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Mario Bonomini

Full Text Available Calcimimetics, such as R-568, are thought to activate G protein-linked Ca(2+-sensing receptor (CaSR by allosterically increasing the affinity of the receptor for Ca(2+ allowing for efficient control of uremic hyperparathyroidism. Several recent studies suggest they possess additional vascular actions. Although it has been postulated that calcimimetics may have a direct effect on CaSR in the blood vessels, further studies are needed to elucidate their vascular CaSR-dependent versus CaSR-independent effects.Focusing on human umbilical vein endothelial cells (HUVECs, we studied the CaSR expression and distribution by Immunofluorescence and Western Blot analysis. CaSR function was evaluated by measuring the potential effect of calcimimetic R-568 and its enantiomer S-568 upon the modulation of intracellular Ca(2+ levels (using a single cell approach and FURA-2AM, in the presence or absence of Calhex-231, a negative modulator of CaSR. To address their potential vascular functions, we also evaluated R- and S-568-stimulated enzymatic release of Nitric Oxide (NO by DAF-2DA, by Nitric Oxide Synthase (NOS radiometric assay (both in HUVECs and in Human Aortic Endothelial Cells and by measuring eNOS-ser1177 phosphorylation levels (Immunoblotting. We show that, although the CaSR protein was expressed in HUVECs, it was mainly distributed in cytoplasm while the functional CaSR dimers, usually localized on the plasma membrane, were absent. In addition, regardless of the presence or absence of Calhex-231, both R- and S-568 significantly increased intracellular Ca(2+ levels by mobilization of Ca(2+ from intracellular stores, which in turn augmented NO release by a time- and Ca(2+-dependent increase in eNOS-ser1177 phosphorylation levels.Taken together, these data indicate that in human endothelium there is no stereoselectivity in the responses to calcimimetics and that CaSR is probably not involved in the action of R- and S-568. This suggests an additional

Ratiometric two-photon excited photoluminescence of quantum dots triggered by near-infrared-light for real-time detection of nitric oxide release in situ

International Nuclear Information System (INIS)

Jin, Hui; Gui, Rijun; Sun, Jie; Wang, Yanfeng

2016-01-01

Probe-donor integrated nanocomposites were developed from conjugating silica-coated Mn"2"+:ZnS quantum dots (QDs) with MoS_2 QDs and photosensitive nitric oxide (NO) donors (Fe_4S_3(NO)_7"−, RBS). Under excitation with near-infrared (NIR) light at 808 nm, the Mn"2"+:ZnS@SiO_2/MoS_2-RBS nanocomposites showed the dual-emissive two-photon excited photoluminescence (TPEPL) that induced RBS photolysis to release NO in situ. NO caused TPEPL quenching of Mn"2"+:ZnS QDs, but it produced almost no impact on the TPEPL of MoS_2 QDs. Hence, the nanocomposites were developed as a novel QDs-based ratiometric TPEPL probe for real-time detection of NO release in situ. The ratiometric TPEPL intensity is nearly linear (R"2 = 0.9901) with NO concentration in the range of 0.01∼0.8 μM, which corresponds to the range of NO release time (0∼15 min). The detection limit was calculated to be approximately 4 nM of NO. Experimental results confirmed that this novel ratiometric TPEPL probe possessed high selectivity and sensitivity for the detection of NO against potential competitors, and especially showed high detection performance for NIR-light triggered NO release in tumor intracellular microenvironments. These results would promote the development of versatile probe-donor integrated systems, also providing a facile and efficient strategy to real-time detect the highly controllable drug release in situ, especially in physiological microenvironments. - Highlights: • Mn"2"+:ZnS@SiO_2/MoS_2-RBS nanocomposites were developed as a novel ratiometric two-photon excited fluorescence probe. • This probe could conduct real-time detection of nitric oxide release in situ. • High feasibility of this probe was confirmed in tumor intracellular microenvironments.

Nitric-phosphoric acid oxidation of solid and liquid organic materials

International Nuclear Information System (INIS)

Pierce, R.A.; Smith, J.R.; Poprik, D.C.

1995-01-01

Nitric-phosphoric acid oxidation has been developed specifically to address issues that face the Savannah River Site, other defense-related facilities, private industry, and small-volume generators such as university and medical laboratories. Initially tested to destroy and decontaminate SRS solid, Pu-contaminated job-control waste, the technology has also exhibited potential for remediating hazardous and mixed-hazardous waste forms. The process is unique to Savannah River and offers a valuable alternative to other oxidation processes that require extreme temperatures and/or elevated pressures. To address the broad categories of waste, many different organic compounds which represent a cross-section of the waste that must be treated have been successfully oxidized. Materials that have been quantitatively oxidized at atmospheric pressure below 180 degrees C include neoprene, cellulose, EDTA, tributylphosphate, and nitromethane. More stable compounds such as benzoic acid, polyethylene, oils, and resins have been completely decomposed below 200 degrees C and 10 psig. The process uses dilute nitric acid in a concentrated phosphoric acid media as the main oxidant for the organic compounds. Phosphoric acid allow nitric acid to be retained in solution well above its normal boiling point. The reaction forms NOx vapors which can be reoxidized and recycled using air and water. The addition of 0.001M Pd(II) reduces CO generation to near 1% of the released carbon gases. The advantages of this process are that it is straightforward, uses relatively inexpensive reagents, operates at relatively low temperature and pressure, and produces final solutions which are compatible with stainless steel equipment. For organic wastes, all carbon, hydrogen, and nitrogen are converted to gaseous products. If interfaced with an acid recovery system which converts NOx back to nitric acid, the net oxidizer would be oxygen from air

Cellular signaling with nitric oxide and cyclic GMP

Directory of Open Access Journals (Sweden)

F. Murad

1999-11-01

Full Text Available During the past two decades, nitric oxide signaling has been one of the most rapidly growing areas in biology. This simple free radical gas can regulate an ever growing list of biological processes. In most instances nitric oxide mediates its biological effects by activating guanylyl cyclase and increasing cyclic GMP synthesis. However, the identification of effects of nitric oxide that are independent of cyclic GMP is also growing at a rapid rate. The effects of nitric oxide can mediate important physiological regulatory events in cell regulation, cell-cell communication and signaling. Nitric oxide can function as an intracellular messenger, neurotransmitter and hormone. However, as with any messenger molecule, there can be too much or too little of the substance and pathological events ensue. Methods to regulate either nitric oxide formation, metabolism or function have been used therapeutically for more than a century as with nitroglycerin therapy. Current and future research should permit the development of an expanded therapeutic armamentarium for the physician to manage effectively a number of important disorders. These expectations have undoubtedly fueled the vast research interests in this simple molecule.

Trigeminocardiac reflex by mandibular extension on rat pial microcirculation: role of nitric oxide.

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Dominga Lapi

Full Text Available In the present study we have extended our previous findings about the effects of 10 minutes of passive mandibular extension in anesthetized Wistar rats. By prolonging the observation time to 3 hours, we showed that 10 minutes mandibular extension caused a significant reduction of the mean arterial blood pressure and heart rate respect to baseline values, which persisted up to 160 minutes after mandibular extension. These effects were accompanied by a characteristic biphasic response of pial arterioles: during mandibular extension, pial arterioles constricted and after mandibular extension dilated for the whole observation period. Interestingly, the administration of the opioid receptor antagonist naloxone abolished the vasoconstriction observed during mandibular extension, while the administration of Nω-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, abolished the vasodilation observed after mandibular extension. Either drug did not affect the reduction of mean arterial blood pressure and heart rate induced by mandibular extension. By qRT-PCR, we also showed that neuronal nitric oxide synthase gene expression was significantly increased compared with baseline conditions during and after mandibular extension and endothelial nitric oxide synthase gene expression markedly increased at 2 hours after mandibular extension. Finally, western blotting detected a significant increase in neuronal and endothelial nitric oxide synthase protein expression. In conclusion mandibular extension caused complex effects on pial microcirculation involving opioid receptor activation and nitric oxide release by both neurons and endothelial vascular cells at different times.

Nitric oxide nanoparticles

Science.gov (United States)

Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

2012-01-01

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections. PMID:22286699

Nitric Oxide Metabolites and Asymmetric Dimethylarginine Concentrations in Breast Milk

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Hakan Öztürk

2017-04-01

Full Text Available Objective: Nitric oxide plays a preventive role in the development of necrotizing enterocolitis. Oral nitrite and nitrate intake has gained importance with the discovery of the conversion of nitrite to nitric oxide in acidic medium out of the synthesis of nitric oxide from L-arginine. Objective of this study was to examine the breast milk concentrations of nitric oxide and asymmetric dimethylarginine which is a competitive inhibitor of nitric oxide and to compare these concentrations in terms of gestational age and maturity of breast milk. Study Design: Forty-one women were included in the study. Milk samples were collected from 3 groups of mothers as term, late preterm and preterm on the postpartum days 3, 7 and 28. Results: When breast milk concentrations of nitric oxide were compared according to the postnatal day of the milk independently from gestational age; nitric oxide concentration was higher in the colostrum than in the transition milk and mature milk (p=0,035; p=0,001; respectively. For the comparison of asymmetric dimethylarginine concentrations among these groups and days; no statistically significant difference was observed in terms of gestational age and maturity of the milk (p=0.865, p=0.115; respectively. Conclusion: The highest nitric oxide concentration was found in the colostrum, suggesting that colostrum is a valuable food for newborns. Plasma concentrations of asymmetric dimethylarginine were negatively correlated with nitric oxide and did not show a correlation with breast milk, suggesting that asymmetric dimethylargininedoesn’t make nitric oxide inhibition in breast milk.

S-nitrosocaptopril nanoparticles as nitric oxide-liberating and transnitrosylating anti-infective technology.

Science.gov (United States)

Mordorski, Breanne; Pelgrift, Robert; Adler, Brandon; Krausz, Aimee; da Costa Neto, Alexandre Batista; Liang, Hongying; Gunther, Leslie; Clendaniel, Alicea; Harper, Stacey; Friedman, Joel M; Nosanchuk, Joshua D; Nacharaju, Parimala; Friedman, Adam J

2015-02-01

Nitric oxide (NO), an essential agent of the innate immune system, exhibits multi-mechanistic antimicrobial activity. Previously, NO-releasing nanoparticles (NO-np) demonstrated increased antimicrobial activity when combined with glutathione (GSH) due to formation of S-nitrosoglutathione (GSNO), a transnitrosylating agent. To capitalize on this finding, we incorporated the thiol-containing ACE-inhibitor, captopril, with NO-np to form SNO-CAP-np, nanoparticles that both release NO and form S-nitrosocaptopril. In the presence of GSH, SNO-CAP-np demonstrated increased transnitrosylation activity compared to NO-np, as exhibited by increased GSNO formation. Escherichia coli and methicillin-resistant Staphylococcus aureus were highly susceptible to SNO-CAP-np in a dose-dependent fashion, with E. coli being most susceptible, and SNO-CAP-np were nontoxic in zebrafish embryos at translatable concentrations. Given SNO-CAP-np's increased transnitrosylation activity and increased E. coli susceptibility compared to NO-np, transnitrosylation rather than free NO is likely responsible for overcoming E. coli's resistance mechanisms and ultimately killing the pathogen. This team of authors incorporated the thiol-containing ACE-inhibitor, captopril, into a nitric oxide releasing nanoparticle system, generating nanoparticles that both release NO and form S-nitrosocaptopril, with pronounced toxic effects on MRSA and E. coli in the presented model system. Copyright © 2015 Elsevier Inc. All rights reserved.

Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

Science.gov (United States)

Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

2017-11-01

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

Nanocarriers for Nitric Oxide Delivery

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Juliana Saraiva

2011-01-01

Full Text Available Nitric oxide (NO is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

Nitric oxide releasing silicone rubbers with improved blood compatibility: preparation, characterization, and in vivo evaluation.

Science.gov (United States)

Zhang, Huiping; Annich, Gail M; Miskulin, Judiann; Osterholzer, Kathryn; Merz, Scott I; Bartlett, Robert H; Meyerhoff, Mark E

2002-03-01

Nitric oxide (NO) releasing silicone rubbers (SR) are prepared via a three-step reaction scheme. A diamino triaminoalkyltrimethoxysilane crosslinker is used to vulcanize hydroxyl terminated polydimethylsiloxane (PDMS) in the presence of ambient moisture and a dibutyltin dilaurate catalyst so that the respective diamine triamine groups are covalently linked to the cured SR structure. These amine sites are then diazeniumdiolated, in situ, when the cured SR is reacted with NO at elevated pressure (80 psi). Although nitrite species are also formed during the NO addition reaction, in most cases the diazeniumdiolated polymer is the major product within the final SR matrix. Temperature appears to be the major driving force for the dissociation of the attached diazeniumdiolate moieties, whereas the presence of bulk water bathing the SR materials has only minimal effect on the observed NO release rate owing to the low water uptake of the SR matrices. The resulting SR films/coatings release NO at ambient or physiological temperature for up to 20 d with average fluxes of at least 4 x 10(10) mol x cm(-2) x min(-1) (coating thickness > or = 600 microm) over first 4 h, comparable to the NO fluxes observed from stimulated human endothelial cells. The NO loading and concomitant NO release flux of the SR material are readily adjustable by altering the diamine triamine loading and film/coating thickness. The new NO releasing SR materials are shown to exhibit improved thromboresistance in vivo, as demonstrated via reduced platelet activation on the surface of these polymers when used to coat the inner walls of SR tubings employed for extracorporeal circulation in a rabbit model.

Manipulation of nitric oxide in an animal model of acute liver injury ...

African Journals Online (AJOL)

We evaluated the impact of altering nitric oxide release on acute liver injury, the associated gut injury and bacterial translocation, at different time intervals. Methods: An acute rat liver injury model induced by D-galactosamine was used. Sprague Dawley rats were divided into four main groups: normal control, acute liver ...

Oral bioavailability, efficacy and gastric tolerability of P2026, a novel nitric oxide-releasing diclofenac in rat.

Science.gov (United States)

Pathan, Asif R; Karwa, Manoj; Pamidiboina, Venu; Deshattiwar, Jagannath J; Deshmukh, Nitin J; Gaikwad, Parikshit P; Mali, Sunil V; Desai, Dattatraya C; Dhiman, Mini; Thanga Mariappan, T; Sharma, Somesh D; Satyam, Apparao; Nemmani, Kumar V S

2010-08-01

The present study was designed to evaluate, P2026 [(2-((2-(nitrooxy)ethyl)disulfanyl)ethyl 2-(2-(2,6-dichlorophenylamino)phenyl)acetate)], a novel NO (nitric oxide) donor prodrug of diclofenac for its ability to release NO and diclofenac, and whether P2026 provides advantage of improved activity/gastric tolerability over diclofenac. Oral bioavailability of P2026 was estimated from plasma concentration of diclofenac and nitrate/nitrite (NOx). Anti-inflammatory activity was evaluated in three different models of inflammation: acute (carrageenan-induced paw oedema), chronic (adjuvant-induced arthritis), and systemic (lipopolysaccharide-induced endotoxic shock). Gastric tolerability was evaluated from compound's propensity to cause gastric ulcers. P2026 exhibited dose-dependent diclofenac and NOx release. Similar to diclofenac, P2026 showed potent anti-inflammatory activity in acute and chronic model, whereas it improved activity in systemic model. Both diclofenac and P2026 inhibited gastric prostaglandin, but only diclofenac produced dose-dependent haemorrhagic ulcers. Thus, the results suggest that coupling of NO and diclofenac contribute to improved gastric tolerability while retaining the anti-inflammatory properties of diclofenac.

Nitric oxide in the stress axis

OpenAIRE

Lopez-Figueroa, M.O.; Day, H.E.W.; Akil, H.; Watson, S.J.

1998-01-01

In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbichypothalamic- ...

Bifunctional effects of fucoidan on the expression of inducible nitric oxide synthase

International Nuclear Information System (INIS)

Yang, Jin Won; Yoon, Se Young; Oh, Soo Jin; Kim, Sang Kyum; Kang, Keon Wook

2006-01-01

Algal fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities including anti-thrombotic and anti-inflammatory effects. This study evaluated the effect of fucoidan on the expression of inducible nitric oxide synthase (iNOS) in a macrophage cell line, RAW264.7. Low concentration range of fucoidan (10 μg/ml) increased the basal expression level of iNOS in quiescent macrophages. However, we found for the first time that fucoidan inhibited the release of nitric oxide (NO) in RAW264.7 cells stimulated with lipopolysaccharide (LPS). Western blot analysis revealed that fucoidan suppressed the LPS-induced expression of the inducible nitric oxide synthase (iNOS) gene. Moreover, the activation of both nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) are key steps in the transcriptional activation of the iNOS gene. Here, it was revealed that fucoidan selectively suppressed AP-1 activation, and that the activation of AP-1 appears to be essential for the induction of iNOS in activated macrophages. This inhibitory effect on AP-1 activation by fucoidan might be associated with its NO blocking and anti-inflammatory effects

Direct Reaction of Amides with Nitric Oxide To Form Diazeniumdiolates

Science.gov (United States)

2015-01-01

We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C=O)NH–N(O)=NO–, with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1–3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base. PMID:25210948

Ratiometric two-photon excited photoluminescence of quantum dots triggered by near-infrared-light for real-time detection of nitric oxide release in situ

Energy Technology Data Exchange (ETDEWEB)

Jin, Hui [Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, College of Chemistry and Chemical Engineering, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Shandong 266071 (China); Gui, Rijun, E-mail: guirijun@qdu.edu.cn [Shandong Sino-Japanese Center for Collaborative Research of Carbon Nanomaterials, Collaborative Innovation Center for Marine Biomass Fiber Materials and Textiles, College of Chemistry and Chemical Engineering, Laboratory of Fiber Materials and Modern Textile, The Growing Base for State Key Laboratory, Qingdao University, Shandong 266071 (China); Sun, Jie; Wang, Yanfeng [Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062 (China)

2016-05-30

Probe-donor integrated nanocomposites were developed from conjugating silica-coated Mn{sup 2+}:ZnS quantum dots (QDs) with MoS{sub 2} QDs and photosensitive nitric oxide (NO) donors (Fe{sub 4}S{sub 3}(NO){sub 7}{sup −}, RBS). Under excitation with near-infrared (NIR) light at 808 nm, the Mn{sup 2+}:ZnS@SiO{sub 2}/MoS{sub 2}-RBS nanocomposites showed the dual-emissive two-photon excited photoluminescence (TPEPL) that induced RBS photolysis to release NO in situ. NO caused TPEPL quenching of Mn{sup 2+}:ZnS QDs, but it produced almost no impact on the TPEPL of MoS{sub 2} QDs. Hence, the nanocomposites were developed as a novel QDs-based ratiometric TPEPL probe for real-time detection of NO release in situ. The ratiometric TPEPL intensity is nearly linear (R{sup 2} = 0.9901) with NO concentration in the range of 0.01∼0.8 μM, which corresponds to the range of NO release time (0∼15 min). The detection limit was calculated to be approximately 4 nM of NO. Experimental results confirmed that this novel ratiometric TPEPL probe possessed high selectivity and sensitivity for the detection of NO against potential competitors, and especially showed high detection performance for NIR-light triggered NO release in tumor intracellular microenvironments. These results would promote the development of versatile probe-donor integrated systems, also providing a facile and efficient strategy to real-time detect the highly controllable drug release in situ, especially in physiological microenvironments. - Highlights: • Mn{sup 2+}:ZnS@SiO{sub 2}/MoS{sub 2}-RBS nanocomposites were developed as a novel ratiometric two-photon excited fluorescence probe. • This probe could conduct real-time detection of nitric oxide release in situ. • High feasibility of this probe was confirmed in tumor intracellular microenvironments.

Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum.

Science.gov (United States)

Faro, Lilian R F; Ferreira Nunes, Brenda V; Alfonso, Miguel; Ferreira, Vania M; Durán, Rafael

2013-09-15

The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5. Administration of GLA to CNQX (500μM) pretreated animals produced an effect that was not significantly different from the one produced in animals not pretreated with CNQX. On the other hand, administration of GLA to l-NAME (100μM) or 7-NI (100μM) pretreated animals, produced increases in dopamine overflow that were ∼80% and ∼75% smaller than those observed in animals not pretreated with these inhibitors. In summary, GLA appears to act, at least in part, through an overstimulation of NMDA (and not AMPA/kainate) receptors with possible NO production to induce in vivo dopamine release. Administration of NMDA receptor antagonists and NOS inhibitors partially blocks the release of dopamine from rat striatum. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

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Anna E. Maciag

2013-01-01

Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

On hydrazine oxidation in nitric acid media

International Nuclear Information System (INIS)

Zil'berman, B.Ya.; Lelyuk, G.A.; Mashkin, A.N.; Yasnovitskaya, A.L.

1988-01-01

Yield of products of radiolytic ( 60 Co gamma radiation) and chemical hydrazine (HZ) oxidation in nitric acid media is studied. Under radiolyte HZ oxidation by nitric acid hydrazoic acid, ammonia and nitrogen appear to be the reaction products. HN 3 yield maximum under HZN oxidation makes up ∼ 0.35 mol per a mol of oxiduzed HZN. Under chemical oxidation HZN is oxidized by HNO 3 according to reaction catalysed by technetium HN 3 yield makes up ∼ 0.35 mol per a mol of oxidized HZN. Radiation-chemical oxidation of HN 3 proceeds up to its complete decomposition, decomposition rate is comparable with HZ oxidation rate. Under the chemical oxidation HN 3 is more stable, it is slowly decomposed after complete HZ decomposition

Synthesis and Biological Evaluation of Novel Furozan-Based Nitric Oxide-Releasing Derivatives of Oridonin as Potential Anti-Tumor Agents

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Hao Cai

2012-06-01

Full Text Available To search for novel nitric oxide (NO releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by a Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high levels of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines was also determined, among which, 9h exhibited the most potential anti-tumor activity with IC₅₀ values of 1.82 µM against K562, 1.81 µM against MGC-803 and 0.86 µM against Bel-7402, respectively. Preliminary structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.

Reproducibility of exhaled nitric oxide measurements in overweight and obese adults

NARCIS (Netherlands)

Thijs, Willemien; de Mutsert, Renée; le Cessie, Saskia; Hiemstra, Pieter S.; Rosendaal, Frits R.; Middeldorp, Saskia; Rabe, Klaus F.

2014-01-01

Exhaled nitric oxide is a noninvasive measure of airway inflammation that can be detected by a handheld device. Obesity may influence the reproducibility of exhaled nitric oxide measurements, by - for instance - decreased expiratory reserve volume. We analyzed triple exhaled nitric oxide

Nitrogen-Based Diazeniumdiolates: Versatile Nitric Oxide-Releasing Compounds for Biomedical Research and Potential Clinical Applications

Science.gov (United States)

Saavedra, Joseph E.; Keefer, Larry K.

2002-12-01

Nitric oxide-generating ions of the nitrogen-diazeniumdiolate class with the general structure R1R2N-[N(O)NO]1 have been prepared by exposing primary, secondary, and polyamines to nitric oxide (NO). The resulting complexes regenerate bioactive NO at physiological pH with half-lives ranging from 2 seconds to 20 hours. An important goal in our research is to deliver NO to a specific organ or cell type where it is needed without affecting other NO-sensitive parts of the anatomy. By taking advantage of the remarkable chemical versatility of diazeniumdiolates, we have developed general strategies to prepare either tissue-selective NO donor drugs or materials containing NO delivery agents that can be physically placed near the target sites. Inhibition of blood coagulation, induction of penile erection, relief of pulmonary hypertension, and reversal of cerebral vasospasm are a few examples of their potential clinical applications. See Featured Molecules.

JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells.

Science.gov (United States)

Udupi, Vidya; Yu, Margaret; Malaviya, Swati; Saavedra, Joseph E; Shami, Paul J

2006-10-01

Nitric oxide (NO) induces differentiation and apoptosis in acute myelogenous leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K induces apoptosis in HL-60 cells by a caspase-dependent mechanism. The purpose of this study was to determine the pathway through which JS-K induces apoptosis. We show that JS-K alters mitochondrial membrane potential (DeltaPsim) and induces cytochrome c release from mitochondria into the cytoplasm. Treatment with JS-K resulted in activation of Caspase (Casp) 9, Casp 3 and Casp 8. JS-K constitutes a promising lead for a new class of anti-leukemic agents.

Nitric oxide synthase gene G298 allele

International Nuclear Information System (INIS)

Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar

2004-01-01

Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

Biocompatibility evaluations and biomedical sensing applications of nitric oxide-releasing/generating polymeric materials

Science.gov (United States)

Wu, Yiduo

Nitric oxide (NO) is a potent signaling molecule secreted by healthy vascular endothelial cells (EC) that is capable of inhibiting the activation and adhesion of platelets, preventing inflammation and inducing vasodilation. Polymeric materials that mimic the EC through the continuous release or generation of NO are expected to exhibit enhanced biocompatibility in vivo. In this dissertation research, the biocompatibility of novel NO-releasing/generating materials has been evaluated via both in vitro and in vivo studies. A new in vitro platelet adhesion assay has been designed to quantify platelet adhesion on NO-releasing/generating polymer surfaces via their innate lactate dehydrogenase (LDH) content. Using this assay, it was discovered that continuous NO fluxes of up to 7.05 x10-10 mol cm-2 min-1 emitted from the polymer surfaces could reduce platelet adhesion by almost 80%. Such an in vitro biocompatibility assay can be employed as a preliminary screening method in the development of new NO-releasing/generating materials. In addition, the first in vivo biocompatibility evaluation of NO-generating polymers was conducted in a porcine artery model for intravascular oxygen sensing catheters. The Cu(I)-catalyzed decomposition of endogenous S-nitrosothiols (RSNOs) generated NO in situ at the polymer/blood interface and offered enhanced biocompatibility to the NO-generating catheters along with more accurate analytical results for intra-arterial measurements of PO2 levels. NO-generating polymers can also be utilized to fabricate electrochemical RSNO sensors based on the amperometric detection of NO generated by the reaction of RSNOs with immobilized catalysts. Unlike conventional methodologies employed to measure labile RSNO, the advantage of the RSNO sensor method is that measurement in whole blood samples is possible and this minimizes sample processing artifacts in RSNO measurements. An electrochemical RSNO sensor with organoselenium crosslinked polyethylenimine (RSe

Nitric oxide-induced interstrand cross-links in DNA.

Science.gov (United States)

Caulfield, Jennifer L; Wishnok, John S; Tannenbaum, Steven R

2003-05-01

The DNA damaging effects of nitrous acid have been extensively studied, and the formation of interstrand cross-links have been observed. The potential for this cross-linking to occur through a common nitrosating intermediate derived from nitric oxide is investigated here. Using a HPLC laser-induced fluorescence (LIF) system, the amount of interstrand cross-link formed on nitric oxide treatment of the 5'-fluorescein-labeled oligomer ATATCGATCGATAT was determined. This self-complimentary sequence contains two 5'-CG sequences, which is the preferred site for nitrous acid-induced cross-linking. Nitric oxide was delivered to an 0.5 mM oligomer solution at 15 nmol/mL/min to give a final nitrite concentration of 652 microM. The resulting concentration of the deamination product, xanthine, in this sample was found to be 211 +/- 39 nM, using GC/MS, and the amount of interstrand cross-link was determined to be 13 +/- 2.5 nM. Therefore, upon nitric oxide treatment, the cross-link is found at approximately 6% of the amount of the deamination product. Using this system, detection of the cross-link is also possible for significantly lower doses of nitric oxide, as demonstrated by treatment of the same oligomer with NO at a rate of 18 nmol/mL/min resulting in a final nitrite concentration of 126 microM. The concentration of interstrand cross-link was determined to be 3.6 +/- 0.1 nM in this sample. Therefore, using the same dose rate, when the total nitric oxide concentration delivered drops by a factor of approximately 5, the concentration of cross-link drops by a factor of about 4-indicating a qausi-linear response. It may now be possible to predict the number of cross-links in a small genome based on the number of CpG sequences and the yield of xanthine derived from nitrosative deamination.

Radiosensitization of hypoxic tumor cells in vitro by nitric oxide

International Nuclear Information System (INIS)

Griffin, Robert J.; Makepeace, Carol M.; Hur, Won-Joo; Song, Chang W.

1996-01-01

Purpose: The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied. Methods and Materials: NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined. Results: Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions. Conclusions: NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated

Mid-Ir Cavity Ring-Down Spectrometer for Biological Trace Nitric Oxide Detection

Science.gov (United States)

Kan, Vincent; Ragab, Ahemd; Stsiapura, Vitali; Lehmann, Kevin K.; Gaston, Benjamin M.

2011-06-01

S-nitrosothiols have received much attention in biochemistry and medicine as donors of nitrosonium ion (NO^+) and nitric oxide (NO) - physiologically active molecules involved in vasodilation and signal transduction. Determination of S-nitrosothiols content in cells and tissues is of great importance for fundamental research and medical applications. We will report on our ongoing development of a instrument to measure trace levels of nitric oxide gas (NO), released from S-nitrosothiols after exposure to UV light (340 nm) or reaction with L-Cysteine+CuCl mixture. The instrument uses the method of cavity ring-down spectroscopy, probing rotationally resolved lines in the vibrational fundamental transition near 5.2 μm. The laser source is a continuous-wave, room temperature external cavity quantum cascade laser. An acousto-optic modulator is used to abruptly turn off the optical power incident on the cavity when the laser and cavity pass through resonance.

NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols

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Ignarro Louis J

2008-02-01

Full Text Available Abstract Background Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. Methods NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP, was studied in cisplatin-sensitive (A2780 WT and cisplatin-resistant (A2780 cDDP cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. Results Cells treated with NCX-4040 (25 μM showed a significant reduction of cell viability (A2780 WT, 34.9 ± 8.7%; A2780 cDDP, 41.7 ± 7.6%; p versus NCX-4040+cisplatin, 26.4 ± 7.6%; p versus NCX-4040+cisplatin, 56.4 ± 7.8%; p Conclusion The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies.

Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.

Science.gov (United States)

Wu, Wen; Perrin-Sarrado, Caroline; Ming, Hui; Lartaud, Isabelle; Maincent, Philippe; Hu, Xian-Ming; Sapin-Minet, Anne; Gaucher, Caroline

2016-10-01

Alginate/chitosan nanocomposite particles (GSNO-acNCPs), i.e. S-nitrosoglutathione (GSNO) loaded polymeric nanoparticles incorporated into an alginate and chitosan matrix, were developed to increase the effective GSNO loading capacity, a nitric oxide (NO) donor, and to sustain its release from the intestine following oral administration. Compared with free GSNO and GSNO loaded nanoparticles, GSNO-acNCPs promoted 2.7-fold GSNO permeation through a model of intestinal barrier (Caco-2 cells). After oral administration to Wistar rats, GSNO-acNCPs promoted NO storage into the aorta during at least 17h, as highlighted by (i) a long-lasting hyporeactivity to phenylephrine (decrease in maximum vasoconstrictive effect of aortic rings) and (ii) N-acetylcysteine (a thiol which can displace NO from tissues)-induced vasodilation of aorxxtic rings preconstricted with phenylephrine. In conclusion, GSNO-acNCPs enhance GSNO intestinal absorption and promote the formation of releasable NO stores into the rat aorta. GSNO-acNCPs are promising carriers for chronic oral application devoted to the treatment of cardiovascular diseases. Copyright © 2016. Published by Elsevier Inc.

Catalytic abatement of nitrous oxide from nitric and production

NARCIS (Netherlands)

Oonk, J.

1998-01-01

Nitric acid production is identified as a main source of nitrous oxide. Options for emission reduction however are not available. TNO and Hydro Agri studied the technological and economic feasibility of catalytic decomposition of nitrous oxide in nitric acid tail-gases. Although in literature

Novel approaches to improving endothelium-dependent nitric oxide-mediated vasodilatation

DEFF Research Database (Denmark)

Simonsen, Ulf; Rodriguez-Rodriguez, Rosalia; Dalsgaard, Thomas

2009-01-01

Endothelial dysfunction, which is defined by decreased endothelium-dependent vasodilatation, is associated with an increased number of cardiovascular events. Nitric oxide (NO) bioavailability is reduced by altered endothelial signal transduction or increased formation of radical oxygen species...... reacting with NO. Endothelial dysfunction is therapeutically reversible and physical exercise, calcium channel blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists improve flow-evoked endothelium-dependent vasodilation in patients with hypertension and diabetes. We have...... the endothelial signal transduction pathways involved in vasorelaxation and NO release induced by an olive oil component, oleanolic acid, and (3) investigated the role of calcium-activated K channels in the release of NO induced by receptor activation. Tempol increases endothelium-dependent vasodilatation...

Constitutive nitric oxide synthase (cNOS activity in Langerhans islets from streptozotocin diabetic rats

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Fonovich de Schroeder T.M.

1998-01-01

Full Text Available Nitric oxide synthase activity was measured in Langerhans islets isolated from control and streptozotocin diabetic rats. The activity of the enzyme was linear up to 150 µg of protein from control rats and was optimal at 0.1 µM calcium, when it was measured after 45 min of incubation at 37oC in the presence of 200 µM arginine. Specific activity of the enzyme was 25 x 10-4 nmol [3H]citrulline 45 min-1 mg protein-1. Streptozotocin diabetic rats exhibited less enzyme activity both in total pancreas homogenate and in isolated Langerhans islets when compared to control animals. Nitric oxide synthase activity measured in control and diabetic rats 15 days after the last streptozotocin injection in the second group of animals corresponded only to a constitutive enzyme since it was not inhibited by aminoguanidine in any of the mentioned groups. Hyperglycemia in diabetic rats may be the consequence of impaired insulin release caused at least in part by reduced positive modulation mediated by constitutive nitric oxide synthase activity, which was dramatically reduced in islets severely damaged after streptozotocin treatment.

Induction of insulin secretion in engineered liver cells by nitric oxide

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Özcan Sabire

2007-10-01

Full Text Available Abstract Background Type 1 Diabetes Mellitus results from an autoimmune destruction of the pancreatic beta cells, which produce insulin. The lack of insulin leads to chronic hyperglycemia and secondary complications, such as cardiovascular disease. The currently approved clinical treatments for diabetes mellitus often fail to achieve sustained and optimal glycemic control. Therefore, there is a great interest in the development of surrogate beta cells as a treatment for type 1 diabetes. Normally, pancreatic beta cells produce and secrete insulin only in response to increased blood glucose levels. However in many cases, insulin secretion from non-beta cells engineered to produce insulin occurs in a glucose-independent manner. In the present study we engineered liver cells to produce and secrete insulin and insulin secretion can be stimulated via the nitric oxide pathway. Results Expression of either human insulin or the beta cell specific transcription factors PDX-1, NeuroD1 and MafA in the Hepa1-6 cell line or primary liver cells via adenoviral gene transfer, results in production and secretion of insulin. Although, the secretion of insulin is not significantly increased in response to high glucose, treatment of these engineered liver cells with L-arginine stimulates insulin secretion up to three-fold. This L-arginine-mediated insulin release is dependent on the production of nitric oxide. Conclusion Liver cells can be engineered to produce insulin and insulin secretion can be induced by treatment with L-arginine via the production of nitric oxide.

Nitric Oxide and Histamine Signal Attempts to Swallow: A Component of Learning that Food Is Inedible in "Aplysia"

Science.gov (United States)

Katzoff, Ayelet; Miller, Nimrod; Susswein, Abraham J.

2010-01-01

Memory that food is inedible in "Aplysia" arises from training requiring three contingent events. Nitric oxide (NO) and histamine are released by a neuron responding to one of these events, attempts to swallow food. Since NO release during training is necessary for subsequent memory and NO substitutes for attempts to swallow, it was suggested that…

Estimation of the nitric oxide formed from hydroxylamine by Nitrosomonas

Science.gov (United States)

Anderson, J. H.

1965-01-01

1. Nitric oxide that was produced by reducing nitrite with an excess of acidified potassium iodide under nitrogen in Warburg respirometer flasks was rapidly absorbed by a solution of permanganate in sodium hydroxide held in the side arm. A small amount of nitrous oxide (or nitrogen) that was also produced was not absorbed. 2. By using a quantitative method for the recovery of nitrite from samples of the alkaline permanganate, it was found that the sum of the nitrite N formed and the residual nitrous oxide N was equivalent to the nitrite N used to generate the gases. These results showed that alkaline permanganate completely oxidized nitric oxide to nitrite. The method was suitable for determining 0·4–20 μmoles of nitric oxide. 3. The technique was used to determine the nitric oxide content of the nitrogenous gas that was produced anaerobically from hydroxylamine by an extract of the autotrophic nitrifying micro-organism Nitrosomonas in the presence of methylene blue as electron acceptor. PMID:14342235

The Nitric Oxide Donor SNAP-Induced Amino Acid Neurotransmitter Release in Cortical Neurons. Effects of Blockers of Voltage-Dependent Sodium and Calcium Channels

Science.gov (United States)

Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

2014-01-01

Background The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. Findings The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Conclusions Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons. PMID:24598811

The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

Science.gov (United States)

Merino, José Joaquín; Arce, Carmen; Naddaf, Ahmad; Bellver-Landete, Victor; Oset-Gasque, Maria Jesús; González, María Pilar

2014-01-01

The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated. The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA) in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated. Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

The nitric oxide donor SNAP-induced amino acid neurotransmitter release in cortical neurons. Effects of blockers of voltage-dependent sodium and calcium channels.

Directory of Open Access Journals (Sweden)

José Joaquín Merino

Full Text Available The discovery that nitric oxide (NO functions as a signalling molecule in the nervous system has radically changed the concept of neuronal communication. NO induces the release of amino acid neurotransmitters but the underlying mechanisms remain to be elucidated.The aim of this work was to study the effect of NO on amino acid neurotransmitter release (Asp, Glu, Gly and GABA in cortical neurons as well as the mechanism underlying the release of these neurotransmitters. Cortical neurons were stimulated with SNAP, a NO donor, and the release of different amino acid neurotransmitters was measured by HPLC. The involvement of voltage dependent Na+ and Ca2+ channels as well as cGMP in its mechanism of action was evaluated.Our results indicate that NO induces release of aspartate, glutamate, glycine and GABA in cortical neurons and that this release is inhibited by ODQ, an inhibitor of soluble guanylate cyclase. Thus, the NO effect on amino acid neurotransmission could be mediated by cGMP formation in cortical neurons. Our data also demonstrate that the Na+ and Ca2+ voltage- dependent calcium channels are involved in the NO effects on cortical neurons.

The correlation between total antioxidant capacity and nitric oxide ...

African Journals Online (AJOL)

DNA damage was measured by comet assay and nitric oxide concentration was evaluated by Griess assay. TAC was measured in seminal plasma based on the generation of peroxyl radicals from 2,2-azinobis (2-amidino propane) dihydrochlorid (AAPH). Our results show that the means of DNA damage and nitric oxide ...

Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway.

Science.gov (United States)

Achike, Francis I; Kwan, Chiu-Yin

2003-09-01

1. Nitric oxide (NO) is formed enzymatically from l-arginine in the presence of nitric oxide synthase (NOS). Nitric oxide is generated constitutively in endothelial cells via sheer stress and blood-borne substances. Nitric oxide is also generated constitutively in neuronal cells and serves as a neurotransmitter and neuromodulator in non-adrenergic, non-cholinergic nerve endings. Furthermore, NO can also be formed via enzyme induction in many tissues in the presence of cytokines. 2. The ubiquitous presence of NO in the living body suggests that NO plays an important role in the maintenance of health. Being a free radical with vasodilatory properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations, NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death. Thus, diseases can arise in the presence of the extreme ends of the physiological concentrations of NO. 3. The NO signalling pathway has, in recent years, become a target for new drug development. The high level of flavonoids, catechins, tannins and other polyphenolic compounds present in vegetables, fruits, soy, tea and even red wine (from grapes) is believed to contribute to their beneficial health effects. Some of these compounds induce NO formation from the endothelial cells to improve circulation and some suppress the induction of inducible NOS in inflammation and infection. 4. Many botanical medicinal herbs and drugs derived from these herbs have been shown to have effects on the NO signalling pathway. For example, the saponins from ginseng, ginsenosides, have been shown to relax blood vessels (probably contributing to the antifatigue and blood pressure-lowering effects of ginseng) and corpus cavernosum (thus, for the treatment of men suffering from erectile dysfunction; however, the legendary aphrodisiac effect of ginseng may be an overstatement). Many plant extracts or

Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

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Anne Abot

2018-04-01

Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

Cannula sensor for nitric oxide detection

Energy Technology Data Exchange (ETDEWEB)

Glazier, S.A. [National Institute of Standard and Technology, Gaithersburg, MD (United States)

1995-12-31

Nitric oxide (NO) has received much attention because of its numerous roles in mammalian systems. It has been found in the brain and nervous system to act as a neurotransmitter, in blood vessels as a blood pressure regulator, in the immune system to act as a bactericide and tumorcide, and in other postulated roles as well. Nitric oxide is produced in mammalian cells by the enzyme nitric oxide synthetase. Once produced, NO is oxidized or reacts rapidly with components in living systems and hence has a short half-life. Only a few sensors have been constructed which can detect NO at nanomolar to micromolar levels found in these systems. We are currently examining the use of a cannula sensor employing oxyhemoglobin for NO detection. This sensor continuously draws in liquid sample at a low rate and immediately reacts it with oxyhemoglobin. The absorbance changes which accompany the reaction are monitored. The sensor has a linear response range from approximately 50 to 1000 nM of NO in aqueous solution. Its utility in monitoring NO produced by stimulated murine macrophage cells (RAW 264.7) in culture is currently being examined. The sensor design is generic in that it can also employ fluorescence and chemiluminescence detection chemistries which may allow lower detection limits to be achieved. Details of the sensor`s performance will be given.

Exhaled Nitric Oxide is Decreased by Exposure to the Hyperbaric Oxygen Therapy Environment

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Zudin A. Puthucheary

2006-01-01

or 40% oxygen, 1 ATA. In an in vitro study, nitrate/nitrite release decreased after 90 minutes HBOT in airway epithelial (A549 cells. Conclusion. HBO exposure causes a fall in eNO. Inducible nitric oxide synthase (iNOS may cause elevated eNO in patients secondary to inflammation, and inhibition of iNOS may be the mechanism of the reduction of eNO seen with HBOT.

Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after Laser Acupuncture at Bilateral Same-Name Acupoints in Human

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Wan-Ling Jiang

2017-01-01

Full Text Available Objective. The purpose of the study was to examine the effects of laser acupuncture (LA at right Neiguan (RPC6/left Neiguan (LPC6 acupoints on the releases of nitric oxide (NO in the treated and contralateral/nontreated PC6, compared to the nonacupoint control area. Methods. 24 mW LA at RPC6, LPC6, and nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped to the nontreated PC6/nonacupoint during the treatment and immediately taped to the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging compound was injected into the tube for 40 min to absorb the molecular which was tested by spectrophotometry in a blinded fashion. Results. LA-induced NO releases over PC6 acupoints for the nontreated and treated sides all significantly increased after LA removal, but for the nontreated acupoints they did not change during LA stimulation. LA at RPC6 induced the more release of the NO at contralateral side than stimulating LPC6, but not on nonacupoints. The results suggest that LA-induced NO release over contralateral acupoint and NO release resulting from the lateralized specificity all are different and specific to the acupoint within different time course. Conclusions. LA-evoked NO release over acupoints could improve the neurogenic, endothelial activity of the vessel wall to further facilitate microcirculation.

Mechanisms of electrochemical reduction and oxidation of nitric oxide

NARCIS (Netherlands)

Vooys, de A.C.A.; Beltramo, G.L.; Riet, van B.; Veen, van J.A.R.; Koper, M.T.M.

2004-01-01

A summary is given of recent work on the reactivity of nitric oxide on various metal electrodes. The significant differences between the reactivity of adsorbed NO and NO in solution are pointed out, both for the reduction and the oxidation reaction(s). Whereas adsorbed NO can be reduced only to

Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse

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Sophie A. Bradley

2016-01-01

Full Text Available Nitric oxide (NO is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS, new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Huntington’s.

Zeolites as catalyzer to environmental control. Nitric oxide removal

International Nuclear Information System (INIS)

Montes, C.; Zapata N, M; Villa H, A.L.

1995-01-01

Zeolites and the microporous materials related to them are a class of environmental catalysts, it which are used to remove the produced gases in combustion process (as mobile sources). In this work the importance that has catalysis for environment improvement is emphasized. A review of recent progress in the use of certain zeolitic material as catalysts for nitric oxide elimination of combustion systems is presented. More used nitric oxide removal methods are presented, as well as its advantages and disadvantages. Furthermore, it is emphasized on the need of accomplishing more investigation projects on the development of an active catalyst for the decomposition of the nitric oxide in its elements (N and O)

Pu-erh Tea Reduces Nitric Oxide Levels in Rats by Inhibiting Inducible Nitric Oxide Synthase Expression through Toll-Like Receptor 4

Science.gov (United States)

Xu, Yang; Wang, Guan; Li, Chunjie; Zhang, Min; Zhao, Hang; Sheng, Jun; Shi, Wei

2012-01-01

Pu-erh tea undergoes a unique fermentation process and contains theabrownins, polysaccharides and caffeine; although it is unclear about which component is associated with the down regulation of nitric oxide levels or how this process is mediated. To address this question we examined the effects of pu-erh tea on nitric oxide synthase (NOS) genes. Cohorts of rats were separately given four-week treatments of water as control, pu-erh tea, or the tea components: theabrownins, caffeine or polysaccharides. Five experimental groups were injected with lipopolysaccharides (LPS) to induce nitric oxide (NO) production, while the corresponding five control groups were injected with saline as a negative control. The serum and liver NO concentrations were examined and the NOS expression of both mRNA and protein was measured in liver. The results showed that the rats which were fed pu-erh tea or polysaccharides had lower levels of NO which corresponded with the down-regulation of inducible nitric oxide synthase (iNOS) expression. We further demonstrate that this effect is mediated through reduction of Toll-like receptor 4 (TLR4) signaling. Thus we find that the polysaccharide components in pu-erh tea reduce NO levels in an animal model by inhibiting the iNOS expression via signaling through TLR4. PMID:22837686

SOIL NITROUS OXIDE, NITRIC OXIDE, AND AMMONIA EMISSIONS FROM A RECOVERING RIPARIAN ECOSYSTEM IN SOUTHERN APPALACHIA

Science.gov (United States)

The paper presents two years of seasonal nitric oxide, ammonia, and nitrous oxide trace gas fluxes measured in a recovering riparian zone with cattle excluded and in an adjacent riparian zone grazed by cattle. In the recovering riparian zone, average nitric oxide, ammonia, and ni...

Nitric oxide nanoparticles: Pre-clinical utility as a therapeutic for intramuscular abscesses

OpenAIRE

Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

2012-01-01

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine absce...

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China); Zhang, Qunye, E-mail: wz.zhangqy@sdu.edu.cn [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, Shandong (China); Li, Guorong, E-mail: grli@sdnu.edu.cn [Shandong Provincial Key Laboratory of Animal Resistant Biology, School of Life Sciences, Shandong Normal University, Jinan 250014 (China)

2015-03-13

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation.

Flavone inhibits nitric oxide synthase (NOS) activity, nitric oxide production and protein S-nitrosylation in breast cancer cells

International Nuclear Information System (INIS)

Zhu, Wenzhen; Yang, Bingwu; Fu, Huiling; Ma, Long; Liu, Tingting; Chai, Rongfei; Zheng, Zhaodi; Zhang, Qunye; Li, Guorong

2015-01-01

As the core structure of flavonoids, flavone has been proved to possess anticancer effects. Flavone's growth inhibitory functions are related to NO. NO is synthesized by nitric oxide synthase (NOS), and generally increased in a variety of cancer cells. NO regulates multiple cellular responses by S-nitrosylation. In this study, we explored flavone-induced regulations on nitric oxide (NO)-related cellular processes in breast cancer cells. Our results showed that, flavone suppresses breast cancer cell proliferation and induces apoptosis. Flavone restrains NO synthesis by does-dependent inhibiting NOS enzymatic activity. The decrease of NO generation was detected by fluorescence microscopy and flow cytometry. Flavone-induced inhibitory effect on NOS activity is dependent on intact cell structure. For the NO-induced protein modification, flavone treatment significantly down-regulated protein S-nitrosylation, which was detected by “Biotin-switch” method. The present study provides a novel, NO-related mechanism for the anticancer function of flavone. - Highlights: • Flavone inhibits proliferation and induces apoptosis in MCF-7 cells. • Flavone decreases nitric oxide production by inhibiting NOS enzymatic activity in breast cancer cells. • Flavone down-regulates protein S-nitrosylation

Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

NARCIS (Netherlands)

Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

2006-01-01

The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium

Does increased Nitric Oxide production and oxidative stress due to high fat diet affect cardiac function after myocardial infarction?

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Marjan Aghajani

2017-01-01

Full Text Available Background &Objectives: High fat (HF diet by affecting the oxidative stress and nitric oxide (NO production may lead to different effects on function of the heart after myocardial infarction (MI. In the present study we aimed to address the hypothesis that high release of NO by activated macrophages affects LV function after MI.Methods: The animals were randomly divided into four groups comprising each of 10 rats: 1 Sham; 2 MI; 3 Sham+ HF diet; 4 MI+ HF diet. Animals fed with HF diet 30 days before sham and MI surgery. MI was induced by permanent ligation of left anterior descending coronary artery (LAD. Nitric oxide (NO production of peritoneal macrophages, the concentrations of MDA in the heart and the infarct size were measured.Results: Our study indicated that HF has adverse effects on myocardium and it may increase NO production as well as oxidative stress, resulting in augmentation of infarct size.Conclusion: Our results add to our knowledge that HF diet was associated with overproduction of NO by peritoneal macrophages and ROS that lead to development of infarct size and adverse remodeling.

Non-asthmatic patients show increased exhaled nitric oxide concentrations

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Beatriz M. Saraiva-Romanholo

2009-01-01

Full Text Available OBJECTIVE: Evaluate whether exhaled nitric oxide may serve as a marker of intraoperative bronchospasm. INTRODUCTION: Intraoperative bronchospasm remains a challenging event during anesthesia. Previous studies in asthmatic patients suggest that exhaled nitric oxide may represent a noninvasive measure of airway inflammation. METHODS: A total of 146,358 anesthesia information forms, which were received during the period from 1999 to 2004, were reviewed. Bronchospasm was registered on 863 forms. From those, three groups were identified: 9 non-asthmatic patients (Bronchospasm group, 12 asthmatics (Asthma group and 10 subjects with no previous airway disease or symptoms (Control group. All subjects were submitted to exhaled nitric oxide measurements (parts/billion, spirometry and the induced sputum test. The data was compared by ANOVA followed by the Tukey test and Kruskal-Wallis followed by Dunn's test. RESULTS: The normal lung function test results for the Bronchospasm group were different from those of the asthma group (p <0.05. The median percentage of eosinophils in induced sputum was higher for the Asthma [2.46 (0.45-6.83] compared with either the Bronchospasm [0.55 (0-1.26] or the Control group [0.0 (0] (p <0.05; exhaled nitric oxide followed a similar pattern for the Asthma [81.55 (57.6-86.85], Bronchospasm [46.2 (42.0 -62.6] and Control group [18.7 (16.0-24.7] (p< 0.05. CONCLUSIONS: Non-asthmatic patients with intraoperative bronchospasm detected during anesthesia and endotracheal intubation showed increased expired nitric oxide.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells.

Science.gov (United States)

Ugusman, Azizah; Zakaria, Zaiton; Hui, Chua Kien; Nordin, Nor Anita Megat Mohd

2010-07-01

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs). HUVECS WERE DIVIDED INTO FOUR GROUPS: control, treatment with 180 microM hydrogen peroxide (H(2)O(2)), treatment with 150 microg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H(2)O(2) for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Role of nitric oxide in glucose-, fructose and galactose-induced ...

African Journals Online (AJOL)

Previous studies have shown that the infusion of glucose, fructose and galactose resulted in significant increases in intestinal glucose uptake (IGU) and the role of nitric oxide in these responses was not known. The present study was designed to investigate the role of nitric oxide in the observed increases in IGU.

Pain modulation by nitric oxide in the spinal cord.

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Marco Aurelio M Freire

2009-09-01

Full Text Available Nitric oxide (NO is a versatile messenger molecule first associated with endothelial relaxing effects. In the central nervous system (CNS, NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA receptors and has a Janus face, with both beneficial and harmful properties, depending on concentration and the identity of its synthetic enzyme isoform. There are three isoforms of the NO synthesizing enzyme nitric oxide synthase (NOS: neuronal (nNOS, endothelial (eNOS, and inducible nitric oxide synthase (iNOS, each one involved with specific events in the brain. In CNS, nNOS is involved with modulation of synaptic transmission through long-term potentiation in several regions, including nociceptive circuits in the spinal cord. Here, we review the role played by NO on central pain sensitization.

Nitric oxide-related drug targets in headache

DEFF Research Database (Denmark)

Olesen, Jes

2010-01-01

SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so-called del......SUMMARY: Nitric oxide (NO) is a very important molecule in the regulation of cerebral and extra cerebral cranial blood flow and arterial diameters. It is also involved in nociceptive processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in normal volunteers and a so......-called delayed headache that fulfils criteria for migraine without aura in migraine sufferers. Blockade of nitric oxide synthases (NOS) by L-nitromonomethylarginine effectively treats attacks of migraine without aura. Similar results have been obtained for chronic the tension-type headache and cluster headache....... Inhibition of the breakdown of cyclic guanylate phosphate (cGMP) also provokes migraine in sufferers, indicating that cGMP is the effector of NO-induced migraine. Similar evidence suggests an important role of NO in the tension-type headache and cluster headache. These very strong data from human...

Influence of nitric oxide on histamine and carbachol – induced ...

African Journals Online (AJOL)

The study aimed to determine the influence of nitric oxide (NO) on the action of histamine and carbachol on acid secretion in the common African toad – Bufo regularis. Gastric acidity was determined by titration method. The acid secretion was determined when nitric oxide was absent following administration of NO synthase ...

Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

International Nuclear Information System (INIS)

Curtis, Brandon M.; Leix, Kyle Alexander; Ji, Yajing; Glaves, Richard Samuel Elliot; Ash, David E.; Mohanty, Dillip K.

2014-01-01

Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well

Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

Energy Technology Data Exchange (ETDEWEB)

Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

2014-07-18

Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

A plasma needle generates nitric oxide

International Nuclear Information System (INIS)

Stoffels, E; Gonzalvo, Y Aranda; Whitmore, T D; Seymour, D L; Rees, J A

2006-01-01

Generation of nitric oxide (NO) by a plasma needle is studied by means of mass spectrometry. The plasma needle is an atmospheric glow generated by a radio-frequency excitation in a mixture of helium and air. This source is used for the treatment of living tissues, and nitric oxide may be one of the most important active agents in plasma therapy. Efficient NO generation is of particular importance in the treatment of cardiovascular diseases. Mass spectrometric measurements have been performed under various plasma conditions; gas composition in the plasma and conversion of feed gases (nitrogen and oxygen) into other species has been studied. Up to 30% of the N 2 and O 2 input is consumed in the discharge, and NO has been identified as the main conversion product

Light-Induced Acid Generation on a Gatekeeper for Smart Nitric Oxide Delivery.

Science.gov (United States)

Choi, Hyung Woo; Kim, Jihoon; Kim, Jinhwan; Kim, Yonghwi; Song, Hyun Beom; Kim, Jeong Hun; Kim, Kimoon; Kim, Won Jong

2016-04-26

We report herein the design of a light-responsive gatekeeper for smart nitric oxide (NO) delivery. The gatekeeper is composed of a pH-jump reagent as an intermediary of stimulus and a calcium phosphate (CaP) coating as a shielding layer for NO release. The light irradiation and subsequent acid generation are used as triggers for uncapping the gatekeeper and releasing NO. The acids generated from a light-activated pH-jump agent loaded in the mesoporous nanoparticles accelerated the degradation of the CaP-coating layers on the nanoparticles, facilitating the light-responsive NO release from diazeniumdiolate by exposing a NO donor to physiological conditions. Using the combination of the pH-jump reagent and CaP coating, we successfully developed a light-responsive gatekeeper system for spatiotemporal-controlled NO delivery.

Production of nitric oxide using a microwave plasma torch and its application to fungal cell differentiation

International Nuclear Information System (INIS)

Na, Young Ho; Kang, Min-Ho; Cho, Guang Sup; Choi, Eun Ha; Park, Gyungsoon; Uhm, Han Sup; Kumar, Naresh

2015-01-01

The generation of nitric oxide by a microwave plasma torch is proposed for its application to cell differentiation. A microwave plasma torch was developed based on basic kinetic theory. The analytical theory indicates that nitric oxide density is nearly proportional to oxygen molecular density and that the high-temperature flame is an effective means of generating nitric oxide. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimeters per minute. The apparent length of the torch flame increases as the oxygen input increases. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the mole fraction of oxygen gas, and the microwave power. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to a model microbial cell (Neurospora crassa: non-pathogenic fungus). Germination and hyphal differentiation of fungal cells were not dramatically changed but there was a significant increase in spore formation after treatment with nitric oxide. In addition, the expression level of a sporulation related gene acon-3 was significantly elevated after 24 h upon nitric oxide treatment. Increase in the level of nitric oxide, nitrite and nitrate in water after nitric oxide treatment seems to be responsible for activation of fungal sporulation. Our results suggest that nitric oxide generated by plasma can be used as a possible activator of cell differentiation and development. (paper)

Relationship between nitric oxide- and calcium-dependent signal transduction pathways in growth hormone release from dispersed goldfish pituitary cells.

Science.gov (United States)

Chang, John P; Sawisky, Grant R; Davis, Philip J; Pemberton, Joshua G; Rieger, Aja M; Barreda, Daniel R

2014-09-15

Nitric oxide (NO) and Ca(2+) are two of the many intracellular signal transduction pathways mediating the control of growth hormone (GH) secretion from somatotropes by neuroendocrine factors. We have previously shown that the NO donor sodium nitroprusside (SNP) elicits Ca(2+) signals in identified goldfish somatotropes. In this study, we examined the relationships between NO- and Ca(2+)-dependent signal transduction mechanisms in GH secretion from primary cultures of dispersed goldfish pituitary cells. Morphologically identified goldfish somatotropes stained positively for an NO-sensitive dye indicating they may be a source of NO production. In 2h static incubation experiments, GH release responses to the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) were attenuated by CoCl2, nifedipine, verapamil, TMB-8, BHQ, and KN62. In column perifusion experiments, the ability of SNP to induce GH release was impaired in the presence of TMB-8, BHQ, caffeine, and thapsigargin, but not ryanodine. Caffeine-elicited GH secretion was not affected by the NO scavenger PTIO. These results suggest that NO-stimulated GH release is dependent on extracellular Ca(2+) availability and voltage-sensitive Ca(2+) channels, as well as intracellular Ca(2+) store(s) that possess BHQ- and/or thapsigargin-inhibited sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases, as well as TMB-8- and/or caffeine-sensitive, but not ryanodine-sensitive, Ca(2+)-release channels. Calmodulin kinase-II also likely participates in NO-elicited GH secretion but caffeine-induced GH release is not upstream of NO production. These findings provide insights into how NO actions many integrate with Ca(2+)-dependent signalling mechanisms in goldfish somatotropes and how such interactions may participate in the GH-releasing actions of regulators that utilize both NO- and Ca(2+)-dependent transduction pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Piper sarmentosum increases nitric oxide production in oxidative stress: a study on human umbilical vein endothelial cells

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Azizah Ugusman

2010-01-01

Full Text Available OBJECTIVE: Nitric oxide produced by endothelial nitric oxide synthase (eNOS possesses multiple anti-atherosclerotic properties. Hence, enhanced expression of eNOS and increased Nitric oxide levels may protect against the development of atherosclerosis. Piper sarmentosum is a tropical plant with antioxidant and anti-inflammatory activities. This study aimed to investigate the effects of Piper sarmentosum on the eNOS and Nitric oxide pathway in cultured human umbilical vein endothelial cells (HUVECs. METHODS: HUVECs were divided into four groups: control, treatment with 180 μM hydrogen peroxide (H2O2, treatment with 150 μg/mL aqueous extract of Piper sarmentosum, and concomitant treatment with aqueous extract of PS and H2O2 for 24 hours. Subsequently, HUVECs were harvested and eNOS mRNA expression was determined using qPCR. The eNOS protein level was measured using ELISA, and the eNOS activity and Nitric oxide level were determined by the Griess reaction. RESULTS: Human umbilical vein endothelial cells treated with aqueous extract of Piper sarmentosum showed a marked induction of Nitric oxide. Treatment with PS also resulted in increased eNOS mRNA expression, eNOS protein level and eNOS activity in HUVECs. CONCLUSION: Aqueous extract of Piper sarmentosum may improve endothelial function by promoting NO production in HUVECs.

Growth inhibition and chemosensitization of exogenous nitric oxide released from NONOates in glioma cells in vitro.

Science.gov (United States)

Weyerbrock, Astrid; Baumer, Brunhilde; Papazoglou, Anna

2009-01-01

Exogenous nitric oxide (NO) from NO donors has cytotoxic, chemosensitizing, and radiosensitizing effects, and increases vascular permeability and blood flow in tumors. Yet little is known about whether these cytotoxic and chemosensitizing effects can be observed in glioma cells at doses that alter tumor physiological characteristics in vivo and whether these effects are tumor selective. The effect of NO released from proline NONOate, diethylamine NONOate, spermine NONOate, and sodium nitrite on cell proliferation, apoptosis, and chemosensitivity to carboplatin of cultured glioma cells was studied in C6, U87 glioma cells, human glioblastoma cells, and human astrocytes and fibroblasts. Although proline NONOate failed to induce cell death, the other NO donors induced growth arrest when present in high concentrations (10(-2) M) in all cell lines. Chemosensitization was observed after concomitant incubation with spermine NONOate and carboplatin in C6 and human glioblastoma cells. There is strong evidence that cell death occurs primarily by necrosis and to a lesser degree by apoptosis. The NO doses, which altered tumor physiology in vivo, were not cytotoxic, indicating that NO alters vascular permeability and cell viability in vivo by different mechanisms. The authors found that NO-generating agents at high concentrations are potent growth inhibitors and might also be useful as chemosensitizers in glioma cells. These data corroborate the theory that the use of NOgenerating agents may play a role in the multimodal treatment of malignant gliomas but that the NO release must be targeted more specifically to tumor cells to improve selectivity and efficacy.

Pharmacological hypothesis: Nitric oxide-induced inhibition of ADAM-17 activity as well as vesicle release can in turn prevent the production of soluble endothelin-converting enzyme.

Science.gov (United States)

Kuruppu, Sanjaya; Rajapakse, Niwanthi W; Parkington, Helena C; Smith, Ian

2017-10-01

Endothelin-1 (ET-1) and nitric oxide (NO) are two highly potent vasoactive molecules with opposing effects on the vasculature. Endothelin-converting enzyme (ECE) and nitric oxide synthase (NOS) catalyse the production of ET-1 and NO, respectively. It is well established that these molecules play a crucial role in the initiation and progression of cardiovascular diseases and have therefore become targets of therapy. Many studies have examined the mechanism(s) by which NO regulates ET-1 production. Expression and localization of ECE-1 is a key factor that determines the rate of ET-1 production. ECE-1 can either be membrane bound or be released from the cell surface to produce a soluble form. NO has been shown to reduce the expression of both membrane-bound and soluble ECE-1. Several studies have examined the mechanism(s) behind NO-mediated inhibition of ECE expression on the cell membrane. However, the precise mechanism(s) behind NO-mediated inhibition of soluble ECE production are unknown. We hypothesize that both exogenous and endogenous NO, inhibits the production of soluble ECE-1 by preventing its release via extracellular vesicles (e.g., exosomes), and/or by inhibiting the activity of A Disintegrin and Metalloprotease-17 (ADAM17). If this hypothesis is proven correct in future studies, these pathways represent targets for the therapeutic manipulation of soluble ECE-1 production. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.

OpenAIRE

Mariotto, S; Cuzzolin, L; Adami, A; Del Soldato, P; Suzuki, H; Benoni, G

1995-01-01

A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils.

Hyperbaric oxygen therapy may overcome nitric oxide blockage during cyanide intoxication

DEFF Research Database (Denmark)

Polzik, Peter; Hansen, Marco Bo; Olsen, Niels Vidiendal

2017-01-01

PURPOSE: To determine the effects of a blockade of nitric oxide (NO) synthesis on hyperbaric oxygen (HBO₂) therapy during cyanide (CN) intoxication. METHODS: 39 anesthetized female Sprague-Dawley rats were exposed to CN intoxication (5.4 mg/kg intra-arterially) with or without previous nitric oxide...

Resveratrol and Endothelial Nitric Oxide

Directory of Open Access Journals (Sweden)

Ning Xia

2014-10-01

Full Text Available Nitric oxide (NO derived from the endothelial NO synthase (eNOS has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors.

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion.

Science.gov (United States)

Masini, E.; Lupini, M.; Mugnai, L.; Raspanti, S.; Mannaioni, P. F.

1995-01-01

1. Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2. In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration-dependent fashion. At the highest concentration studied (10(-6) M), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3. The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NG-monomethyl-L-arginine (L-NMMA, 10(-4) M), an inhibitor of nitric oxide synthase (NOS). 4. The endothelium-dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10(-4) M). 5. In guinea-pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6. Reperfusion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7. The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed. PMID:7582482

Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

Science.gov (United States)

Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

2016-09-15

Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. Copyright © 2016 Elsevier Inc. All rights reserved.

Nitric oxide scavenging by hemoglobin or nitric oxide synthase inhibition by N-Nitro-L-arginine induces cortical spreading ischemia when K+0+ is increased in the subarachnoid space

DEFF Research Database (Denmark)

Dreier, J.P.; Körner, K.; Ebert, Nathalie

1998-01-01

Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)......Cerebral blood flow, nitric oxide, potassium, spreading depression, vasospasm, migraine, migrainous stroke, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)...

Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.

Science.gov (United States)

Mariotto, S; Cuzzolin, L; Adami, A; Del Soldato, P; Suzuki, H; Benoni, G

1995-01-01

A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils. PMID:7542530

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection by Trypanosoma cruzi.

Science.gov (United States)

Triquell, María Fernanda; Díaz-Luján, Cintia; Romanini, María Cristina; Ramirez, Juan Carlos; Paglini-Oliva, Patricia; Schijman, Alejandro Gabriel; Fretes, Ricardo Emilio

2018-03-25

The innate immune response of the placenta may participate in the congenital transmission of Chagas disease through releasing reactive oxygen and nitrogen intermediates. Placental explants were cultured with 1 × 10 6 and 1 × 10 5 trypomastigotes of Tulahuen and Lucky strains and controls without parasites, and with the addition of nitric oxide synthase inhibitor Nω-Nitro-l-arginine methyl ester (l-NAME) and N-acetyl cysteine (NAC) as the reactive oxygen species (ROS) scavenger. Detachment of the syncytiotrophoblast (STB) was examined by histological analysis, and the nitric oxide synthase, endothelial (eNOS), and nitrotyrosine expressions were analyzed by immunohistochemistry, as well as the human chorionic gonadotrophin (hCG) levels in the culture supernatant through ELISA assays. Parasite load with qPCR using Taqman primers was quantified. The higher number of T. cruzi (10 6 ) increased placental infection, eNOS expression, nitrosative stress, and STB detachment, with the placental barrier being injured by oxidative stress. The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Continuous determination of nitric oxide and nitrogen dioxide in the atmosphere

Energy Technology Data Exchange (ETDEWEB)

Yanagisawa, S; Yamate, N; Mitsuzawa, S; Mori, M

1966-10-01

Continuous determinations of nitric oxide and nitrogen dioxide in that atmospheric air by the use of a modified Saltzman reagent is described. Measurement was made intermittently, once every 30 min., by an automatic continuous analyzer equipped with a single-path colorimeter. The response of the analyzer was obtained as an average of the concentration of nitrogen oxides over a period of 25 min. Two bubblers were used for absorbing nitrogen oxides into the modified Saltzman reagent, whose transmittance was measured for the determination. One bubbler was designed to absorb nitrogen dioxide, and the other, nitric oxide plus nitrogen dioxide after the oxidation of the nitric oxide by permanganate. The oxidizing efficiency of the permanganate was 96-100%. The acetic acid in the Saltzman reagent was replaced with n-propyl alcohol in the modified Saltzman reagent; the spontaneous coloration and corrosive quality of the reagent was decreased by this substitution. The concentration of nitric oxide was obtained from the difference between the two responses of the analyzer, while the concentration of nitrogen dioxide could be read directly from the indication of the recorder. The transmittance ratio method was applied to the measurements, accurate determinations were possible, even at high blank values. Therefore, the reagent was used repeatedly by cycling it on the basis of measuring the difference in the coloration of the reagent before and after the absorption of nitrogen oxides. The analyzer could be used for a long period without changing the reagent.

Oxygen, nitric oxide and articular cartilage

Directory of Open Access Journals (Sweden)

B Fermor

2007-04-01

Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

Measurement of IL-13-induced iNOS-derived gas phase nitric oxide in human bronchial epithelial cells.

Science.gov (United States)

Suresh, Vinod; Mih, Justin D; George, Steven C

2007-07-01

Exhaled nitric oxide (NO) is altered in numerous diseases including asthma, and is thought broadly to be a noninvasive marker of inflammation. However, the precise source of exhaled NO has yet to be identified, and the interpretation is further hampered by significant inter-subject variation. Using fully differentiated normal human bronchial epithelial (NHBE) cells, we sought to determine (1) the rate of NO release (flux, pl.s(-1.)cm(-2)) into the gas; (2) the effect of IL-13, a prominent mediator of allergic inflammation, on NO release; and (3) inter-subject/donor variability in NO release. NHBE cells from three different donors were cultured at an air-liquid interface and stimulated with different concentrations of IL-13 (0, 1, and 10 ng/ml) for 48 h. Gas phase NO concentrations in the headspace over the cells were measured using a chemiluminescence analyzer. The basal NO flux from the three donors (0.05 +/- 0.03) is similar in magnitude to that estimated from exhaled NO concentrations, and was significantly increased by IL-13 in a donor-specific fashion. The increase in NO release was strongly correlated with inducible nitric oxide synthase (iNOS) gene and protein expression. There was a trend toward enhanced production of nitrate relative to nitrite as an end product of NO metabolism in IL-13-stimulated cells. NO release from airway epithelial cells can be directly measured. The rate of release in response to IL-13 is strongly dependent on the individual donor, but is primarily due to the expression of iNOS.

Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

Science.gov (United States)

Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

2017-08-01

Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N   G -nitro-l-arginine methyl ester (eNOS inhibitor; P preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P preeclampsia women had lower STBEV-eNOS expression compared with that from NP women ( P preeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

A possible way to assess tidal exhaled nitric oxide in neonates and infants treated with nasal continuous positive airway pressure

DEFF Research Database (Denmark)

Schmidt, Birgitte Johanne; Reim, Pauline Schibler; Pedersen, Ole Find

2018-01-01

The endogenous compound nitric oxide (NO) is released into the airways via inducible NO synthase (1),which has the capacity to produce NO when up-regulated by pro-inflammatory cytokines or exogenous factors, like hypoxia, bacterial toxins and viruses (2). Prematurely born infants are susceptible...

Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania.

Science.gov (United States)

Chan, Marion Man-Ying; Adapala, Naga Suresh; Fong, Dunne

2005-04-01

Upon Leishmania infection, macrophages are activated to produce nitrogen and oxygen radicals simultaneously. It is well established that the infected host cells rely on nitric oxide (NO) as the major weapon against the intracellular parasite. In India where leishmaniasis is endemic, the spice turmeric is used prolifically in food and for insect bites. Curcumin, the active principle of turmeric, is a scavenger of NO. This report shows that curcumin protects promastigotes and amastigotes of the visceral species, Leishmania donovani, and promastigotes of the cutaneous species, L. major, against the actions of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and DETANONOate, which release NO, 3-morpholino-sydnonimine hydrochloride (SIN-1), which releases NO and superoxide, and peroxynitrite, which is formed from the reaction of NO with superoxide. Thus, curcumin, as an antioxidant, is capable of blocking the action of both NO and NO congeners on the Leishmania parasite.

The role of nitric oxide in regulation of the cardiovascular system in reptiles.

Science.gov (United States)

Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias

2005-10-01

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

STORAGESEVER

2010-05-24

May 24, 2010 ... chronic periodontitis (CP), 31 with gingivitis (G) and 50 healthy controls. Probing depth ..... Periodontal disease in pregnancy I. Prevalence and severity. ... endothelial nitric oxide synthase gene in premenopausal women with.

Studies on nitric oxide removal in simulated gas compositions under plasma-dielectric/catalytic discharges

International Nuclear Information System (INIS)

Rajanikanth, B.S.; Rout, Satyabrata

2001-01-01

Application of pulsed electrical discharges for gas cleaning is gaining prominence, mainly from the energy consideration point of view. This present paper presents recent work on applying the electrical discharge plasma technology for treating gaseous pollutants, in general, and nitric oxide, in particular, as this is one of the major contributors to air pollution. The present work focuses attention on pulsed electrical discharge technique for nitric oxide removal from simulated gas compositions and study of effect of packed dielectric pellets, with and without a coating of catalyst, on the removal process. Experiments were conducted in a cylindrical corona reactor energized by repetitive high voltage pulses. The effects of various parameters, viz. pulse voltage magnitude, pulse frequency, initial nitric oxide concentration and gas mixture composition on nitric oxide removal efficiency, are discussed. When the reactors were filled with different dielectric pellets like, barium titanate, alumina, and alumina coated with palladium catalyst, the improvement in nitric oxide removal efficiency is studied and discussed. The power dissipated in the reactor and the energy consumed per nitric oxide molecule removed was calculated. Further results and comparative study of various cases are presented in the paper

Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

Science.gov (United States)

Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

Flavonoids as scavengers of nitric oxide radical.

NARCIS (Netherlands)

van Acker, S.A.B.E.; Tromp, M.N.J.L.; Haenen, G.R.M.M.; van der Vijgh, W.J.F.; Bast, A.

1995-01-01

Flavonoids are a group of naturally occurring compounds used, e.g., in the treatment of vascular endothelial damage. They are known to be excellent scavengers of oxygen free radicals. Since the nitric oxide radical (

Interactions between cytokines and nitric oxide.

Science.gov (United States)

Liew, F Y

1995-01-01

There is now an impressive range of evidence supporting the important role of cytokines in sleep regulation (see Krueger et al., 1995; De Simoni et al., 1995). It has also been reported that inhibition of nitric oxide (NO) synthesis suppresses sleep in rabbits (Kapás et al., 1994). This is not surprising, since NO is closely involved in neurotransmission (Garthwaite, 1991; Schuman and Madison, 1994) and cytokines are the major inducers of NO synthesis (Hibbs et al., 1990). Further, it is now clear that NO plays an important role in modulating immune responses, possibly through the differential regulation of cytokine synthesis (Taylor-Robinson et al., 1994). In this article, I will provide evidence for the interactions between cytokines and nitric oxide, and discuss their implications in the regulation of immune responses. I shall illustrate these mainly with results from my coworkers and I, from our laboratory rather than attempting an exhaustive review of the subject.

Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

DEFF Research Database (Denmark)

Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina

2000-01-01

We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused...... a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis...

A nitric oxide donor (nitroglycerin) triggers genuine migraine attacks

DEFF Research Database (Denmark)

Thomsen, L L; Kruuse, C; Iversen, Helle Klingenberg

1994-01-01

Supersensitivity to induction of headache and arterial dilatation by a donor of nitric oxide (nitroglycerin) has recently been demonstrated in migraine sufferers. The aims of the present study were to examine whether the nitric oxide donor nitroglycerin may induce a typical migraine attack......, to exclude placebo-related effects and to describe the relation between middle cerebral artery dilatation and provoked migraine. Nitroglycerin (0.5 μg/kg/min for 20 min) or placebo was infused into 12 migraine patients in a double-blind cross-over trial. Blood velocity in the middle cerebral artery...

Chemical kinetic models for combustion of hydrocarbons and formation of nitric oxide

Science.gov (United States)

Jachimowski, C. J.; Wilson, C. H.

1980-01-01

The formation of nitrogen oxides NOx during combustion of methane, propane, and a jet fuel, JP-4, was investigated in a jet stirred combustor. The results of the experiments were interpreted using reaction models in which the nitric oxide (NO) forming reactions were coupled to the appropriate hydrocarbon combustion reaction mechanisms. Comparison between the experimental data and the model predictions reveals that the CH + N2 reaction process has a significant effect on NO formation especially in stoichiometric and fuel rich mixtures. Reaction models were assembled that predicted nitric oxide levels that were in reasonable agreement with the jet stirred combustor data and with data obtained from a high pressure (5.9 atm (0.6 MPa)), prevaporized, premixed, flame tube type combustor. The results also suggested that the behavior of hydrocarbon mixtures, like JP-4, may not be significantly different from that of pure hydrocarbons. Application of the propane combustion and nitric oxide formation model to the analysis of NOx emission data reported for various aircraft gas turbines showed the contribution of the various nitric oxide forming processes to the total NOx formed.

Curcumin longa extract-loaded nanoemulsion improves the survival of endotoxemic mice by inhibiting nitric oxide-dependent HMGB1 release.

Science.gov (United States)

Ahn, Min Young; Hwang, Jung Seok; Lee, Su Bi; Ham, Sun Ah; Hur, Jinwoo; Kim, Jun Tae; Seo, Han Geuk

2017-01-01

High mobility group box 1 (HMGB1) is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. The murine macrophage RAW264.7 cells were treated with lipopolysaccharide (LPS) and/or a C. longa extract-loaded nanoemulsion (CLEN). The levels of released HMGB1, nitric oxide (NO) production, inducible NO synthase (iNOS) expression, and phosphorylation of mitogen-activated protein kinases were analyzed in RAW264.7 macrophages. The effects of CLEN on survival of endotoxemic model mice, circulating HMGB1 levels, and tissue iNOS expression were also evaluated. We have shown that a nanoemulsion loaded with an extract from the C. longa rhizome regulates cellular inflammatory responses and LPS-induced systemic inflammation by suppressing the release of HMGB1 by macrophages. First, treatment of RAW264.7 macrophages with the nanoemulsion significantly attenuated their LPS-induced release of HMGB1: this effect was mediated by inhibiting c-Jun N-terminal kinase activation, which in turn suppressed the NO production and iNOS expression of the cells. The nanoemulsion did not affect LPS-induced p38 or extracellular signal-regulated kinase activation. Second, intraperitoneal administration of the nanoemulsion improved the survival rate of LPS-injected endotoxemic mice. This associated with marked reductions in circulating HMGB1 levels and tissue iNOS expression. The present study shows for the first time the mechanism by which C. longa ameliorates sepsis, namely, by suppressing NO signaling and thereby inhibiting the release of the proinflammatory cytokine HMGB1. These observations suggest that identification of

Curcumin longa extract-loaded nanoemulsion improves the survival of endotoxemic mice by inhibiting nitric oxide-dependent HMGB1 release

Directory of Open Access Journals (Sweden)

Min Young Ahn

2017-09-01

Full Text Available Background High mobility group box 1 (HMGB1 is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. Methods The murine macrophage RAW264.7 cells were treated with lipopolysaccharide (LPS and/or a C. longa extract-loaded nanoemulsion (CLEN. The levels of released HMGB1, nitric oxide (NO production, inducible NO synthase (iNOS expression, and phosphorylation of mitogen-activated protein kinases were analyzed in RAW264.7 macrophages. The effects of CLEN on survival of endotoxemic model mice, circulating HMGB1 levels, and tissue iNOS expression were also evaluated. Results We have shown that a nanoemulsion loaded with an extract from the C. longa rhizome regulates cellular inflammatory responses and LPS-induced systemic inflammation by suppressing the release of HMGB1 by macrophages. First, treatment of RAW264.7 macrophages with the nanoemulsion significantly attenuated their LPS-induced release of HMGB1: this effect was mediated by inhibiting c-Jun N-terminal kinase activation, which in turn suppressed the NO production and iNOS expression of the cells. The nanoemulsion did not affect LPS-induced p38 or extracellular signal-regulated kinase activation. Second, intraperitoneal administration of the nanoemulsion improved the survival rate of LPS-injected endotoxemic mice. This associated with marked reductions in circulating HMGB1 levels and tissue iNOS expression. Discussion The present study shows for the first time the mechanism by which C. longa ameliorates sepsis, namely, by suppressing NO signaling and thereby inhibiting the release of the proinflammatory cytokine HMGB1

Nitric oxide as a mediator of gastrointestinal mucosal injury?—Say it ain't so

Directory of Open Access Journals (Sweden)

Paul Kubes

1995-01-01

Full Text Available Nitric oxide has been suggested as a contributor to tissue injury in various experimental models of gastrointestinal inflammation. However, there is overwhelming evidence that nitric oxide is one of the most important mediators of mucosal defence, influencing such factors as mucus secretion, mucosal blood flow, ulcer repair and the activity of a variety of mucosal immunocytes. Nitric oxide has the capacity to down-regulate inflammatory responses in the gastrointestinal tract, to scavenge various free radical species and to protect the mucosa from injury induced by topical irritants. Moreover, questions can be raised regarding the evidence purported to support a role for nitric oxide in producing tissue injury. In this review, we provide an overview of the evidence supporting a role for nitric oxide in protecting the gastrointestinal tract from injury.

Comparison Between the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Sildenafil

Directory of Open Access Journals (Sweden)

Ronald W. Day

2015-03-01

Full Text Available Objective. Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. The acute pulmonary vascular effect of inhaled nitric oxide is frequently used to identify patients who will respond favorably to vasodilator therapy. This study sought to determine whether the acute pulmonary vascular effects of oxygen with nitric oxide and intravenous sildenafil are similar. Methods. A retrospective, descriptive study of 13 individuals with pulmonary hypertension who underwent heart catheterization and acute vasodilator testing was performed. The hemodynamic measurements during five phases (21% to 53% oxygen, 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21% to 51% oxygen, and 21% to 51% oxygen with 0.05 mg/kg to 0.29 mg/kg intravenous sildenafil of the procedures were compared.Results. Mean pulmonary arterial pressure and pulmonary vascular resistance acutely decreased with 100% oxygen with nitric oxide, and 21% to 51% oxygen with sildenafil. Mean pulmonary arterial pressure (mm Hg, mean ± standard error of the mean was 38 ± 4 during 21% to 53% oxygen, 32 ± 3 during 100% oxygen, 29 ± 2 during 100% oxygen with nitric oxide, 37 ± 3 during 21% to 51% oxygen, and 32 ± 2 during 21% to 51% oxygen with sildenafil. There was not a significant correlation between the percent change in pulmonary vascular resistance from baseline with oxygen and nitric oxide, and from baseline with sildenafil (r2 = 0.011, p = 0.738. Conclusions. Oxygen with nitric oxide and sildenafil decreased pulmonary vascular resistance. However, the pulmonary vascular effects of oxygen and nitric oxide cannot be used to predict the acute response to sildenafil. Additional studies are needed to determine whether the acute response to sildenafil can be used to predict the long-term response to treatment with an oral phosphodiesterase V inhibitor.

Tyrosine nitration in blood vessels occurs with increasing nitric oxide concentration

OpenAIRE

Amirmansour, Charles; Vallance, Patrick; Bogle, Richard G

1999-01-01

Experiments were designed to explore the effects of nitric oxide (NO) donors on generation of superoxide (O2.−) and peroxynitrite (ONOO−) in rabbit aortic rings.Following inhibition of endogenous superoxide dismutase (SOD), significant basal release of O2.− was revealed (0.9±0.01×10−12 mol min−1 mg−1 tissue). Generation of O2.− increased in a concentration-dependent manner in response to NADH or NADPH (EC50=2.34±1.18×10−4 and 6.21±1.79×10−3 M respectively, n=4). NADH-stimulated O2.− chemilumi...

Measurement of IL-13–Induced iNOS-Derived Gas Phase Nitric Oxide in Human Bronchial Epithelial Cells

Science.gov (United States)

Suresh, Vinod; Mih, Justin D.; George, Steven C.

2007-01-01

Exhaled nitric oxide (NO) is altered in numerous diseases including asthma, and is thought broadly to be a noninvasive marker of inflammation. However, the precise source of exhaled NO has yet to be identified, and the interpretation is further hampered by significant inter-subject variation. Using fully differentiated normal human bronchial epithelial (NHBE) cells, we sought to determine (1) the rate of NO release (flux, pl·s−1.cm−2) into the gas; (2) the effect of IL-13, a prominent mediator of allergic inflammation, on NO release; and (3) inter-subject/donor variability in NO release. NHBE cells from three different donors were cultured at an air–liquid interface and stimulated with different concentrations of IL-13 (0, 1, and 10 ng/ml) for 48 h. Gas phase NO concentrations in the headspace over the cells were measured using a chemiluminescence analyzer. The basal NO flux from the three donors (0.05 ± 0.03) is similar in magnitude to that estimated from exhaled NO concentrations, and was significantly increased by IL-13 in a donor-specific fashion. The increase in NO release was strongly correlated with inducible nitric oxide synthase (iNOS) gene and protein expression. There was a trend toward enhanced production of nitrate relative to nitrite as an end product of NO metabolism in IL-13–stimulated cells. NO release from airway epithelial cells can be directly measured. The rate of release in response to IL-13 is strongly dependent on the individual donor, but is primarily due to the expression of iNOS. PMID:17347445

Glufosinate ammonium stimulates nitric oxide production through N-methyl D-aspartate receptors in rat cerebellum.

Science.gov (United States)

Nakaki, T; Mishima, A; Suzuki, E; Shintani, F; Fujii, T

2000-09-01

Glufosinate ammonium, a structural analogue of glutamate, is an active herbicidal ingredient. The neuronal activities of this compound were investigated by use of a microdialysis system that allowed us to measure nitric oxide production in the rat cerebellum in vivo. Kainate (0.3-30 nmol/10 microliter), N-methyl-D-aspartate (NMDA) (3-300 nmol/10 microliter) and glufosinate ammonium (30-3000 nmol/10 microliter), which were administered through the microdialysis probe at a rate of 1 microliter/min for 10 min, stimulated nitric oxide production. The glufosinate ammonium-elicited increase in nitric oxide production was suppressed by an inhibitor of nitric oxide synthase and was antagonized by NMDA receptor antagonists, but not by a kainate/(+/-)-alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist. These results suggest that glufosinate ammonium stimulates nitric oxide production through NMDA receptors.

The endogenous nitric oxide mediates selenium-induced phytotoxicity by promoting ROS generation in Brassica rapa.

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Yi Chen

Full Text Available Selenium (Se is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO in the root of Brassica rapa under Se(IV stress. Se(IV-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR- and nitric oxide synthase (NOS-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

DNA sequence changes induced by two nitric oxide donor drugs in the supF assay

Energy Technology Data Exchange (ETDEWEB)

Routledge, M.N.; Dipple, A. [ABL-Basic Research Program, Frederick, MD (United States); Wink, D.A.; Keefer, L.K. [National Cancer Institute, Frederick, MD (United States)

1994-09-01

To refine our understanding of the mutational spectra one might expect on exposure of human cells to nitric oxide (NO), we have treated the plasmid pSP189 at pH 7.4 with two compounds that generate NO spontaneously in solution, and then sequenced the mutations found when the treated plasmid was transfected into human Ad293 cells and allowed to replicate. G{center_dot}C {yields} A{center_dot}T transitions were the most abundant mutation observed with these NO donor drugs, whereas in previous work, A{center_dot}T {yields} G{center_dot}C transitions predominated when nitric oxide gas was bubbled through the plasmid solution under otherwise identical conditions. A difference in reactive intermediates formed in solution- versus gas-phase NO exposure was demonstrated by treating buffered 2,2{prime}-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) or ferrocyanide, in the presence or absence of azide, aerobically with preformed solutions of NO, with solutions of the two NO-releasing compounds, or with gaseous mixtures of equimolar NO/O{sub 2} in air; oxidation of these substrates was extensive with the gas-phase NO source whether azide was present or not, while azide almost completely quenched the oxidation pathway in the solution-phase reactions.

Increase of hepatic nitric oxide levels in a nutritional model of fatty ...

African Journals Online (AJOL)

GREGORY

2010-08-30

Aug 30, 2010 ... (MDA) and protein carbonyl (PC), and also nitric oxide (NO) in over fed broiler breeder hens, 198 hens. (30 weeks old) .... The total protein in the liver tissue was determined by a method ... Table 1. Egg production and LHS in broiler breeder hens .... trations of nitric oxide metabolites (nitrates-nitrites) in rat.

Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

Directory of Open Access Journals (Sweden)

Giovanna Romano

Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

Light-controlled relaxation of the rat penile corpus cavernosum using NOBL-1, a novel nitric oxide releaser

Directory of Open Access Journals (Sweden)

Yuji Hotta

2016-05-01

Full Text Available Purpose: To investigate whether relaxation of the rat penile corpus cavernosum could be controlled with NOBL-1, a novel, lightcontrollable nitric oxide (NO releaser. Materials and Methods: Fifteen-week-old male Wistar-ST rats were used. The penile corpus cavernosum was prepared and used in an isometric tension study. After noradrenaline (10−5 M achieved precontraction, the penile corpus cavernosum was irradiated by light (470–500 nm with and without NOBL-1 (10−6 M. In addition, we noted rats’ responses to light with vardenafil (10−6 M, a phosphodiesterase-5 (PDE-5 inhibitor. Next, responses to light in the presence of a guanylate cyclase inhibitor, ODQ (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M, were measured. All measurements were performed in pretreated L-NAME (10−4 M conditions to inhibit endogenous NO production. Results: Corpus cavernosal smooth muscle, precontracted with noradrenaline, was unchanged by light irradiation in the absence of NOBL-1. However, in the presence of NOBL-1, corpus cavernosal smooth muscle, precontracted with noradrenaline, relaxed in response to light irradiation. After blue light irradiation ceased, tension returned. In addition, the light response was obviously enhanced in the presence of a PDE-5 inhibitor. Conclusions: This study showed that rat corpus cavernosal smooth muscle relaxation can be light-controlled using NOBL-1, a novel, light sensitive NO releaser. Though further in vivo studies are needed to investigate possible usefulness, NOBL-1 may be prove to be a useful tool for erectile dysfunction therapy, specifically in the field of penile rehabilitation.

Modulation of cholinergic airway reactivity and nitric oxide production by endogenous arginase activity

NARCIS (Netherlands)

Meurs, Herman; Hamer, M.A M; Pethe, S; Vadon-Le Goff, S; Boucher, J.-L; Zaagsma, Hans

1 Cholinergic airway constriction is functionally antagonized by agonist-induced constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO). Since cNOS and arginase, which hydrolyzes L-arginine to L-ornithine and urea, use L-arginine as a common substrate, competition between both enzymes

Nitric-phosphoric acid oxidation of organic waste materials

International Nuclear Information System (INIS)

Pierce, R.A.; Smith, J.R.

1995-01-01

A wet chemical oxidation technology has been developed to address issues facing defense-related facilities, private industry, and small-volume generators such as university and medical laboratories. Initially tested to destroy and decontaminate a heterogenous mixture of radioactive-contaminated solid waste, the technology can also remediate other hazardous waste forms. The process, unique to Savannah River, offers a valuable alternative to incineration and other high-temperature or high-pressure oxidation processes. The process uses nitric acid in phosphoric acid; phosphoric acid allows nitric acid to be retained in solution well above its normal boiling point. The reaction converts organics to carbon dioxide and water, and generates NO x vapors which can be recycled using air and water. Oxidation is complete in one to three hours. In previous studies, many organic compounds were completely oxidized, within experimental error, at atmospheric pressure below 180 degrees C; more stable compounds were decomposed at 200 degrees C and 170 kPa. Recent studies have evaluated processing parameters and potential throughputs for three primary compounds: EDTA, polyethylene, and cellulose. The study of polyvinylchloride oxidation is incomplete at this time

Nitric oxide levels in the anterior chamber of vitrectomized eyes with silicon oil

Directory of Open Access Journals (Sweden)

Paulo Escarião

2013-10-01

Full Text Available PURPOSE: To investigate the nitric oxide levels in the anterior chamber of eyes who underwent pars plana vitrectomy (PPV with silicone oil. METHODS: Patients who underwent PPV with silicon oil injection, from february 2005 to august 2007, were selected. Nine patients (nine eyes participated in the study (five women and four men. Nitric oxide concentration was quantified after the aspiration of aqueous humor samples during the procedure of silicon oil removal. Data such as: oil emulsification; presence of oil in the anterior chamber; intraocular pressure and time with silicone oil were evaluated. Values of p <0.05 were considered to be statistically significant. RESULTS: A positive correlation between nitric oxide concentration and time with silicon oil in the vitreous cavity (r=0.799 was observed. The nitric oxide concentration was significantly higher (p=0.02 in patients with silicon oil more than 24 months (0.90µmol/ml ± 0.59, n=3 in the vitreous cavity comparing to patients with less than 24 months (0.19µmol/ml ± 0.10, n=6. CONCLUSION: A positive correlation linking silicone oil time in the vitreous cavity with the nitric oxide concentration in the anterior chamber was observed.

Nitric oxide and Na,K-ATPase activity in rat skeletal muscle

DEFF Research Database (Denmark)

Juel, Carsten

2016-01-01

Aim: It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. Method: The study used...... isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Results: Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles...... activity was depressed by oxidized glutathione. Conclusion: NO and cGMP stimulate the Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely...

Carboxyhemoglobin formation secondary to nitric oxide therapy in the setting of interstitial lung disease and pulmonary hypertension.

Science.gov (United States)

Ruisi, Phillip; Ruisi, Michael

2011-01-01

Carbon monoxide (CO) has been widely recognized as an exogenous poison, although endogenous mechanisms for its formation involve heme-oxygenase (HO) isoforms, more specifically HO-1, in the setting of oxidative stress such as acute respiratory distress syndrome, sepsis, trauma, and nitric oxide use have been studied. In patients with refractory hypoxemia, inhaled nitric oxide (iNO) therapy is used to selectively vasodilate the pulmonary vasculature and improve ventilation-perfusion match. Inhaled nitric oxide is rapidly inactivated on binding to hemoglobin in the formation of nitrosyl- and methemoglobin in the pulmonary vasculature. Hence, inhaled nitric oxide has minimal systemic dissemination. Several experimental design studies involving lab rats have demonstrated increased levels of carboxyhemoglobin and exhaled CO as a result of nitric oxide HO-1 induction.

Role of inducible nitric oxide synthase-derived nitric oxide in lipopolysaccharide plus interferon-γ-induced pulmonary inflammation

International Nuclear Information System (INIS)

Zeidler, Patti C.; Millecchia, Lyndell M.; Castranova, Vincent

2004-01-01

Exposure of mice to lipopolysaccharide (LPS) plus interferon-γ (IFN-γ) increases nitric oxide (NO) production, which is proposed to play a role in the resulting pulmonary damage and inflammation. To determine the role of inducible nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT) mice to aspirated LPS + IFN-γ were compared. Male mice (8-10 weeks) were exposed to LPS (1.2 mg/kg) + IFN-γ (5000 U/mouse) or saline. At 24 or 72 h postexposure, lungs were lavaged with saline and the acellular fluid from the first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction of the total BAL was used to determine alveolar macrophage (AM) and polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN-γ were characterized by significantly decreased TAC, increased BAL AMs and PMNs, LDH, albumin, TNF-α, and MIP-2, and enhanced AM-CL to the same extent in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however, significant differences were found between WT and iNOS KO mice. iNOS KO mice demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs, LDH, albumin, TNF-α, and MIP-2, and an enhanced AM-CL compared to the WT. These data suggest that the role of iNOS-derived NO in the pulmonary response to LPS + IFN-γ is anti-inflammatory, and this becomes evident over time

Enhancement of vascular targeting by inhibitors of nitric oxide synthase

International Nuclear Information System (INIS)

Davis, Peter D.; Tozer, Gillian M.; Naylor, Matthew A.; Thomson, Peter; Lewis, Gemma; Hill, Sally A.

2002-01-01

Purpose: This study investigates the enhancement of the vascular targeting activity of the tubulin-binding agent combretastatin A4 phosphate (CA4P) by various inhibitors of nitric oxide synthases. Methods and Materials: The syngeneic tumors CaNT and SaS growing in CBA mice were used for this study. Reduction in perfused vascular volume was measured by injection of Hoechst 33342 24 h after drug administration. Necrosis (hematoxylin and eosin stain) was assessed also at 24 h after treatment. Combretastatin A4 phosphate was synthesized by a modification of the published procedure and the nitric oxide synthase inhibitors L-NNA, L-NMMA, L-NIO, L-NIL, S-MTC, S-EIT, AMP, AMT, and L-TC, obtained from commercial sources. Results: A statistically significant augmentation of the reduction in perfused vascular volume by CA4P in the CaNT tumor was observed with L-NNA, AMP, and AMT. An increase in CA4P-induced necrosis in the same tumor achieved significance with L-NNA, L-NMMA, L-NIL, and AMT. CA4P induced little necrosis in the SaS tumor, but combination with the inhibitors L-NNA, L-NMMA, L-NIO, S-EIT, and L-TC was effective. Conclusions: Augmentation of CA4P activity by nitric oxide synthase inhibitors of different structural classes supports a nitric oxide-related mechanism for this effect. L-NNA was the most effective inhibitor studied

Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway

Directory of Open Access Journals (Sweden)

Kim Vriens

2017-01-01

Full Text Available Amphotericin B (AmB induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections.

Processes regulating nitric oxide emissions from soils

DEFF Research Database (Denmark)

Pilegaard, Kim

2013-01-01

, the net result is complex and dependent on several factors such as nitrogen availability, organic matter content, oxygen status, soil moisture, pH and temperature. This paper reviews recent knowledge on processes forming NO in soils and the factors controlling its emission to the atmosphere. Schemes......Nitric oxide (NO) is a reactive gas that plays an important role in atmospheric chemistry by influencing the production and destruction of ozone and thereby the oxidizing capacity of the atmosphere. NO also contributes by its oxidation products to the formation of acid rain. The major sources...

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

Science.gov (United States)

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-08

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

ORIGINAL ARTICLE Relationship between endothelial nitric oxide ...

African Journals Online (AJOL)

salah

The haplotype analysis confirmed ... hand, no consistent association was shown between the two SNPs and SBP or. DBP. ... Endothelial nitric oxide synthase gene polymorphisms and risk of MI .... type (-786T*+894G), the haplotypes ... Tests adjusted for age, BMI, diabetes, current smoking and alcohol consumption.

Endothelial nitric oxide synthase gene polymorphisms associated ...

African Journals Online (AJOL)

Endothelial nitric oxide synthase (NOS3) is involved in key steps of immune response. Genetic factors predispose individuals to periodontal disease. This study's aim was to explore the association between NOS3 gene polymorphisms and clinical parameters in patients with periodontal disease. Genomic DNA was obtained ...

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

Energy Technology Data Exchange (ETDEWEB)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G., E-mail: bipin@amrita.edu

2016-08-15

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

International Nuclear Information System (INIS)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G.

2016-01-01

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Caveolin versus calmodulin. Counterbalancing allosteric modulators of endothelial nitric oxide synthase.

Science.gov (United States)

Michel, J B; Feron, O; Sase, K; Prabhakar, P; Michel, T

1997-10-10

Nitric oxide is synthesized in diverse mammalian tissues by a family of calmodulin-dependent nitric oxide synthases. The endothelial isoform of nitric oxide synthase (eNOS) is targeted to the specialized signal-transducing membrane domains termed plasmalemmal caveolae. Caveolin, the principal structural protein in caveolae, interacts with eNOS and leads to enzyme inhibition in a reversible process modulated by Ca2+-calmodulin (Michel, J. B., Feron, O., Sacks, D., and Michel, T. (1997) J. Biol. Chem. 272, 15583-15586). Caveolin also interacts with other structurally distinct signaling proteins via a specific region identified within the caveolin sequence (amino acids 82-101) that appears to subserve the role of a "scaffolding domain." We now report that the co-immunoprecipitation of eNOS with caveolin is completely and specifically blocked by an oligopeptide corresponding to the caveolin scaffolding domain. Peptides corresponding to this domain markedly inhibit nitric oxide synthase activity in endothelial membranes and interact directly with the enzyme to inhibit activity of purified recombinant eNOS expressed in Escherichia coli. The inhibition of purified eNOS by the caveolin scaffolding domain peptide is competitive and completely reversed by Ca2+-calmodulin. These studies establish that caveolin, via its scaffolding domain, directly forms an inhibitory complex with eNOS and suggest that caveolin inhibits eNOS by abrogating the enzyme's activation by calmodulin.

Nitric oxide and TGF-β1 inhibit HNF-4α function in HEPG2 cells

International Nuclear Information System (INIS)

Lucas, Susana de; Lopez-Alcorocho, Juan Manuel; Bartolome, Javier; Carreno, Vicente

2004-01-01

This study analyzes if the profibrogenic factors nitric oxide and transforming growth factor-β1 (TGF-β1) affect hepatocyte nuclear factor-4α (HNF-4α) function. For this purpose, HepG2 cells were treated with TGF-β1 or with a nitric oxide donor to determine mRNA levels of coagulation factor VII and HNF-4α. Treatment effect on factor VII gene promoter was assessed by chloramphenicol acetyl-transferase assays in cells transfected with the pFVII-CAT plasmid. HNF-4α binding and protein levels were determined by gel shift assays and Western blot. TGF-β1 and nitric oxide downregulated factor VII mRNA levels by inhibiting its gene promoter activity. This inhibition is caused by a decrease in the DNA binding of HNF-4α. TGF-β1 induces degradation of HNF-4α in the proteasome while nitric oxide provokes nitrosylation of cysteine residues in this factor. TGF-β1 and nitric oxide inhibit HNF-4α activity. These findings may explain the loss of liver functions that occurs during fibrosis progression

Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

Science.gov (United States)

Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

2007-09-01

In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

Carbon monoxide releasing molecule induces endothelial nitric oxide synthase activation through a calcium and phosphatidylinositol 3-kinase/Akt mechanism.

Science.gov (United States)

Yang, Po-Min; Huang, Yu-Ting; Zhang, Yu-Qi; Hsieh, Chia-Wen; Wung, Being-Sun

2016-12-01

The production of nitric oxide (NO) by endothelial NO synthase (eNOS) plays a major role in maintaining vascular homeostasis. This study elucidated the potential role of carbon monoxide (CO)-releasing molecules (CORMs) in NO production and explored the underlying mechanisms in endothelial cells. We observed that 25μM CORM-2 could increase NO production and stimulate an increase in the intracellular Ca 2+ level. Furthermore, ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetra acetic acid caused CORM-2-induced NO production, which was abolished by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM), indicating that intracellular Ca 2+ release plays a major role in eNOS activation. The inhibition of the IP3 receptor diminished the CORM-2-induced intracellular Ca 2+ increase and NO production. Furthermore, CORM-2 induced eNOS Ser 1179 phosphorylation and eNOS dimerization, but it did not alter eNOS expression. CORM-2 (25μM) also prolonged Akt phosphorylation, lasting for at least 12h. Pretreatment with phosphatidylinositol 3-kinase inhibitors (wortmannin or LY294002) inhibited the increases in NO production and phosphorylation but did not affect eNOS dimerization. CORM-2-induced eNOS Ser 1179 phosphorylation was intracellularly calcium-dependent, because pretreatment with an intracellular Ca 2+ chelator (BAPTA-AM) inhibited this process. Although CORM-2 increases intracellular reactive oxygen species (ROS), pretreatment with antioxidant enzyme catalase and N-acetyl-cysteine did not abolish the CORM-2-induced eNOS activity or phosphorylation, signifying that ROS is not involved in this activity. Hence, CORM-2 enhances eNOS activation through intracellular calcium release, Akt phosphorylation, and eNOS dimerization. Copyright © 2016 Elsevier Inc. All rights reserved.

Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

OpenAIRE

Gladwin, Mark T.; Schechter, Alan N.; Shelhamer, James H.; Pannell, Lewis K.; Conway, Deirdre A.; Hrinczenko, Borys W.; Nichols, James S.; Pease-Fye, Margaret E.; Noguchi, Constance T.; Rodgers, Griffin P.; Ognibene, Frederick P.

1999-01-01

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain cysteine 93, raise the possibilty of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P50, did not respo...

Iron(II) porphyrins induced conversion of nitrite into nitric oxide: A computational study.

Science.gov (United States)

Zhang, Ting Ting; Liu, Yong Dong; Zhong, Ru Gang

2015-09-01

Nitrite reduction to nitric oxide by heme proteins was reported as a protective mechanism to hypoxic injury in mammalian physiology. In this study, the pathways of nitrite reduction to nitric oxide mediated by iron(II) porphyrin (P) complexes, which were generally recognized as models for heme proteins, were investigated by using density functional theory (DFT). In view of two type isomers of combination of nitrite and Fe(II)(P), N-nitro- and O-nitrito-Fe(II)-porphyrin complexes, and two binding sites of proton to the different O atoms of nitrite moiety, four main pathways for the conversion of nitrite into nitric oxide mediated by iron(II) porphyrins were proposed. The results indicate that the pathway of N-bound Fe(II)(P)(NO2) isomer into Fe(III)(P)(NO) and water is similar to that of O-bound isomer into nitric oxide and Fe(III)(P)(OH) in both thermodynamical and dynamical aspects. Based on the initial computational studies of five-coordinate nitrite complexes, the conversion of nitrite into NO mediated by Fe(II)(P)(L) complexes with 14 kinds of proximal ligands was also investigated. Generally, the same conclusion that the pathways of N-bound isomers are similar to those of O-bound isomer was obtained for iron(II) porphyrin with ligands. Different effects of ligands on the reduction reactions were also found. It is notable that the negative proximal ligands can improve reactive abilities of N-nitro-iron(II) porphyrins in the conversion of nitrite into nitric oxide compared to neutral ligands. The findings will be helpful to expand our understanding of the mechanism of nitrite reduction to nitric oxide by iron(II) porphyrins. Copyright © 2015 Elsevier Inc. All rights reserved.

Endothelial nitric oxide synthase polymorphism G298T in ...

Indian Academy of Sciences (India)

Supplementary data: Endothelial nitric oxide synthase polymorphism G298T in association with oxidative DNA damage in coronary atherosclerosis. Rajesh G. Kumar, Mrudula K. Spurthi, Kishore G. Kumar, Sanjib K. Sahu and Surekha H. Rani. J. Genet. 91, 349–352. Table 1. The demographic and clinical data of the CHD ...

Inducible nitric oxide synthase catalyzes ethanol oxidation to α-hydroxyethyl radical and acetaldehyde

International Nuclear Information System (INIS)

Porasuphatana, Supatra; Weaver, John; Rosen, Gerald M.

2006-01-01

The physiologic function of nitric oxide synthases, independent of the isozyme, is well established, metabolizing L-arginine to L-citrulline and nitric oxide (NO). This enzyme can also transfer electrons to O 2 , affording superoxide (O 2 · - ) and hydrogen peroxide (H 2 O 2 ). We have demonstrated that NOS1, in the presence of L-arginine, can biotransform ethanol (EtOH) to α-hydroxyethyl radical (CH 3 ·CHOH). We now report that a competent NOS2 with L-arginine can, like NOS1, oxidize EtOH to CH 3 ·CHOH. Once this free radical is formed, it is metabolized to acetaldehyde as shown by LC-ESI-MS/MS and HPLC analysis. These observations suggest that NOS2 can behave similarly to cytochrome P-450 in the catalysis of acetaldehyde formation from ethanol via the generation of α-hydroxyethyl radical when L-arginine is present

Intracellular conversion of environmental nitrate and nitrite to nitric oxide with resulting developmental toxicity to the crustacean Daphnia magna.

Directory of Open Access Journals (Sweden)

Bethany R Hannas

2010-08-01

Full Text Available Nitrate and nitrite (jointly referred to herein as NO(x are ubiquitous environmental contaminants to which aquatic organisms are at particularly high risk of exposure. We tested the hypothesis that NO(x undergo intracellular conversion to the potent signaling molecule nitric oxide resulting in the disruption of endocrine-regulated processes.These experiments were performed with insect cells (Drosophila S2 and whole organisms Daphnia magna. We first evaluated the ability of cells to convert nitrate (NO(3(- and nitrite (NO(2(- to nitric oxide using amperometric real-time nitric oxide detection. Both NO(3(- and NO(2(- were converted to nitric oxide in a substrate concentration-dependent manner. Further, nitric oxide trapping and fluorescent visualization studies revealed that perinatal daphnids readily convert NO(2(- to nitric oxide. Next, daphnids were continuously exposed to concentrations of the nitric oxide-donor sodium nitroprusside (positive control and to concentrations of NO(3(- and NO(2(-. All three compounds interfered with normal embryo development and reduced daphnid fecundity. Developmental abnormalities were characteristic of those elicited by compounds that interfere with ecdysteroid signaling. However, no compelling evidence was generated to indicate that nitric oxide reduced ecdysteroid titers.Results demonstrate that nitrite elicits developmental and reproductive toxicity at environmentally relevant concentrations due likely to its intracellular conversion to nitric oxide.

The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults

DEFF Research Database (Denmark)

Karam, O; Gebistorf, F; Wetterslev, J

2017-01-01

on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity......Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration......% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may...

Nitric oxide enhances osmoregulation of tobacco ( Nicotiana ...

African Journals Online (AJOL)

This study was carried out to investigate the effect of the intracellular signaling molecule nitric oxide (NO) on osmoregulation of tobacco cells under osmotic stress caused by phenylethanoid glycosides 6000 (PEG 6000). The results show that the PEG stress induced a specific pattern of endogenous NO production with two ...

Inhibition of Inducible Nitric Oxide Synthase, Cycleooxygenase-2 ...

African Journals Online (AJOL)

HP

Won Chung, Jin Uk Oh, Sehyung Lee and Sung-Jin Kim* ... was determined by Western blot analysis for iNOS and COX-2 expression in LPS-stimulated RAW ..... Nitric oxide-scavenging and antioxidant effects ofUraria crinite root. Food.

Lack of endothelial nitric oxide synthase aggravates murine accelerated anti-glomerular basement membrane glomerulonephritis

NARCIS (Netherlands)

Heeringa, P; van Goor, H; Itoh-Lindstrom, Y; Maeda, N; Falk, RJ; Assmann, KJM; Kallenberg, CGM; Jennette, JC

Nitric oxide (NO) radicals generated by endothelial nitric oxide synthase (eNOS) are involved in the regulation of vascular tone. In addition, NO radicals derived from eNOS inhibit platelet aggregation and leukocyte adhesion to the endothelium and, thus, may have anti-inflammatory effects. To study

Mechanism of vasoconstriction induced by chronic inhibition of nitric oxide in rats.

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Bank, N; Aynedjian, H S; Khan, G A

1994-09-01

Either acute or chronic inhibition of nitric oxide synthesis by L-arginine analogues results in increases in mean arterial pressure and reductions in renal blood flow. The role of endogenous vasoconstrictors in mediating these effects is not entirely clear. In the present study, nitric oxide was inhibited in male Sprague-Dawley rats by oral administration of nitro-L-arginine for 3 weeks. At the end of this time, mean arterial pressure was 30 to 40 mm Hg higher than in normal controls, renal blood flow and glomerular filtration rate were 25% to 30% lower, and renal vascular resistance was markedly increased. Intravenous infusion of receptor antagonists for angiotensin II, thromboxane, epinephrine, and endothelin-1 had no significant effect on the hypertension. Inhibition of prostaglandin synthesis and furosemide-induced diuresis in the presence of angiotensin blockade also had no effect on blood pressure. Renal vascular resistance was also unaffected by these interventions, except that saralasin did reduce renal resistance in both control and nitric oxide-inhibited groups. However, the absolute level of renal vascular resistance remained higher in the latter group. Calcium channel blockade partially corrected blood pressure and renal resistance, but the levels remained significantly higher than in control animals. The findings are consistent with the view that the increase in vascular smooth muscle tone caused by inhibition of nitric oxide synthesis cannot be accounted for by overexpression of common endogenous vasoconstrictors. Rather, the generalized increase in vascular smooth muscle tone appears to be due to a direct effect of reduced nitric oxide availability, which may lead to an increase in intracellular calcium concentration or sensitivity.

Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major

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Septiana Nur Qurbani

2017-06-01

Full Text Available Background Hemolysis and repeated blood transfusions in children with thalassemia major cause iron overload in various organs, including the brain, and may lead to neurodegeneration. Hemolysis also causes decreased levels of nitric oxide, which serves as a volume transmitter and slow dynamic modulation, leading to cognitive impairment. Objective To assess for correlations between serum ferritin as well as nitric oxide levels and cognitive function in children with thalassemia major.  Methods This analytical study with cross-sectional design on 40 hemosiderotic thalassemia major patients aged 6−14 years, was done at the Thalassemia Clinic in Dr. Hasan Sadikin Hospital, Bandung, West Java, from May to June 2015. Serum ferritin measurements were performed by an electrochemiluminescence immunoassay; serum nitric oxide was assayed by a colorimetric procedure based on Griess reaction; and cognitive function was assessed by the Wechsler Intelligence Scale for Children test. Statistical analysis was done using Spearman’s Rank correlation, with a significance value of 0.05. Results Abnormal values in verbal, performance, and full scale IQ were found in 35%, 57.5% and 57.5%, respectively. Serum nitric oxide level was significantly correlated with performance IQ (P=0.022, but not with verbal IQ (P=0.359 or full scale IQ (P=0.164. There were also no significant correlations between serum ferritin level and full scale, verbal, or performance IQ (P=0.377, 0.460, and 0.822, respectively. Conclusion Lower serum nitric oxide level is significantly correlated to lower cognitive function, specifically in the performance IQ category. However, serum ferritin level has no clear correlation with cognitive function.

Inhibition of Pancreatic Intraepithelial Neoplasia Progression to Carcinoma by Nitric Oxide-Releasing Aspirin in p48Cre/+-LSL-KrasG12D/+ Mice

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Chinthalapally V. Rao

2012-09-01

Full Text Available Nitric oxide-releasing aspirin (NO-aspirin represents a novel class of promising chemopreventive agents. Unlike conventional nonsteroidal anti-inflammatory drugs, NO-aspirin seems to be free of adverse effects while retaining the beneficial activities of its parent compound. The effect of NO-aspirin on pancreatic carcinogenesis was investigated by assessing the development of precursor pancreatic lesions and adenocarcinomas in KrasG12D/+ transgenic mice that recapitulate human pancreatic cancer progression. Six-week-old male p48Cre/+-LSL-KrasG12D/+ transgenic mice (20 per group were fed diets containing 0, 1000, or 2000 ppm NO-aspirin. The development of pancreatic tumors was monitored by positron emission tomography imaging. All mice were killed at the age of 41 weeks and assessed for pancreatic intraepithelial neoplasia (PanIN and pancreatic ductal adenocarcinoma (PDAC and for molecular changes in the tumors. Our results reveal that NO-aspirin at 1000 and 2000 ppm significantly suppressed pancreatic tumor weights, PDAC incidence, and carcinoma in situ (PanIN-3 lesions. The degree of inhibition of PanIN-3 and carcinoma was more pronounced with NO-aspirin at 1000 ppm (58.8% and 48%, respectively than with 2000 ppm (47% and 20%, respectively. NO-aspirin at 1000 ppm significantly inhibited the spread of carcinoma in the pancreas (∼97%; P < .0001. Decreased expression of cyclooxygenase (COX; with ∼42% inhibition of total COX activity, inducible nitric oxide synthase, proliferating cell nuclear antigen, Bcl-2, cyclin D1, and β-catenin was observed, with induction of p21, p38, and p53 in the pancreas of NO-aspirin-treated mice. These results suggest that low-dose NO-aspirin possesses inhibitory activity against pancreatic carcinogenesis by modulating multiple molecular targets.

Critical evaluation of pressurized microwave-assisted digestion efficiency using nitric acid oxidizing systems (M7)

International Nuclear Information System (INIS)

Matusiewicz, H.

2002-01-01

Full text: The possibilities of enhancement of a medium-pressure microwave-assisted digestion system for sample preparation in trace element analysis of biological material was investigated. Based on optimal digestion conditions for oxidizing systems with nitric acid, different digestion procedures were examined to minimize residual carbon. The substitution of nitric acid and the addition of hydrogen peroxide and ozone to nitric acid was evaluated. The residual carbon content of the digestate was determined coulometrically. Addition of hydrogen peroxide during organic oxidation reactions does not lower the resolved carbon in the solution. Ozone was tested as an additional, potentially non-contaminating, digestion/oxidation system to the nitric acid used in the sample preparation method. (author)

Involvement of beta 3-adrenoceptor in altered beta-adrenergic response in senescent heart: role of nitric oxide synthase 1-derived nitric oxide.

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Birenbaum, Aurélie; Tesse, Angela; Loyer, Xavier; Michelet, Pierre; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno; Amour, Julien

2008-12-01

In senescent heart, beta-adrenergic response is altered in parallel with beta1- and beta2-adrenoceptor down-regulation. A negative inotropic effect of beta3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that beta3-adrenoceptor plays a role in beta-adrenergic dysfunction in senescent heart. beta-Adrenergic responses were investigated in vivo (echocardiography-dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and beta-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline +/- SD. An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 +/- 23 vs. 162 +/- 16%; P < 0.05) and in vitro (127 +/- 10 vs. 179 +/- 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor N-nitro-L-arginine methylester (L-NAME; 183 +/- 19%), the selective NOS1 inhibitor vinyl-L-N-5(1-imino-3-butenyl)-L-ornithine (L-VNIO; 172 +/- 13%), or the selective NOS2 inhibitor 1400W (183 +/- 19%). In the senescent group, in parallel with beta3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by L-NAME (151 +/- 8%; P < 0.05) and L-VNIO (149 +/- 7%; P < 0.05) but not by 1400W (132 +/- 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific beta3-adrenoceptor agonist BRL 37344 (167 +/- 10 vs. 142 +/- 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. In senescent cardiomyopathy, beta3-adrenoceptor overexpression plays an important role in the

Fluorescence-based detection of nitric oxide in aqueous and methanol media using a copper(II) complex.

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Mondal, Biplab; Kumar, Pankaj; Ghosh, Pokhraj; Kalita, Apurba

2011-03-14

The quenched fluorescent intensity of a copper(II) complex, 1, of a fluorescent ligand, in degassed methanol or aqueous (buffered at pH 7.2) solution, was found to reappear on exposure to nitric oxide. Thus, it can function as a fluorescence based nitric oxide sensor. It has been found that the present complex can be used to sense nanomolar quantities of nitric oxide in both methanol and pH 7.2 buffered-water medium.

Regulation and control of nitric oxide (NO) in macrophages

DEFF Research Database (Denmark)

Kovacevic, Zaklina; Sahni, Sumit; Lok, K.H.

2017-01-01

We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores and transp......We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione-S-transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MØ) models from large quantities of endogenous NO. This system stores...... be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MØs, to tumor cell targets....

Quantum dots-hyperbranched polyether hybrid nanospheres towards delivery and real-time detection of nitric oxide

DEFF Research Database (Denmark)

Liu, Shuiping; Gu, Tianxun; Fu, Jiajia

2014-01-01

In this work, novel hybrid nanosphere vehicles were synthesized for nitric oxide (NO) donating and real-time detection. The hybrid nanosphere vehicles consist of cadmium selenide quantum dots (CdSe QDs) as NO fluorescent probes, and the modified hyperbranched polyether (mHP)-based diazeniumdiolates...... as NO donors, respectively. The nanospheres have spherical outline with dimension of ~ 127 nm. The data of systematic characterization demonstrated that the mHP-based hybrid nanosphere vehicles (QDs-mHP-NO) can release and real-time detect NO with the low limit of 25 nM, based on fluorescence quenching...

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

Science.gov (United States)

Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

2016-01-01

Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

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Elena Lima-Cabello

2016-01-01

Full Text Available Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases

DEFF Research Database (Denmark)

Reimers, J I; Bjerre, U; Mandrup-Poulsen, T

1994-01-01

Substantial in vitro evidence suggests that nitric oxide may be a major mediator of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction in the initial events leading to insulin-dependent diabetes mellitus. Using NG-nitro-L-arginine methyl ester, an inhibitor of both...

Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain.

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Yokom, Adam L; Morishima, Yoshihiro; Lau, Miranda; Su, Min; Glukhova, Alisa; Osawa, Yoichi; Southworth, Daniel R

2014-06-13

Nitric-oxide synthase (NOS) is required in mammals to generate NO for regulating blood pressure, synaptic response, and immune defense. NOS is a large homodimer with well characterized reductase and oxygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize l-arginine and generate NO. Ca(2+)-calmodulin (CaM) binds between the reductase and oxygenase domains to activate NO synthesis. Although NOS has long been proposed to adopt distinct conformations that alternate between interflavin and FMN-heme electron transfer steps, structures of the holoenzyme have remained elusive and the CaM-bound arrangement is unknown. Here we have applied single particle electron microscopy (EM) methods to characterize the full-length of the neuronal isoform (nNOS) complex and determine the structural mechanism of CaM activation. We have identified that nNOS adopts an ensemble of open and closed conformational states and that CaM binding induces a dramatic rearrangement of the reductase domain. Our three-dimensional reconstruction of the intact nNOS-CaM complex reveals a closed conformation and a cross-monomer arrangement with the FMN domain rotated away from the NADPH-FAD center, toward the oxygenase dimer. This work captures, for the first time, the reductase-oxygenase structural arrangement and the CaM-dependent release of the FMN domain that coordinates to drive electron transfer across the domains during catalysis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

On EPR detection of nitric oxide in vivo

NARCIS (Netherlands)

van Faassen, E.E.H.

2008-01-01

Nitric oxide (NO ) is a peculiar radical: Ground state is not paramagnetic (g = 0 since orbital and spin magnetic moments cancel); low reactivity with other molecules except superoxide (O2 ); thermodynamically unstable; dimerizes to N2O2; difficult to detect in-vivo.

Arginine affects appetite via nitric oxide in ducks.

Science.gov (United States)

Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

2014-08-01

The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. © Poultry Science Association Inc.

Upregulation of cyclooxygenase-2 expression in porcine macula densa with chronic nitric oxide synthase inhibition.

Science.gov (United States)

Kommareddy, M; McAllister, R M; Ganjam, V K; Turk, J R; Laughlin, M Harold

2011-11-01

The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.

Nitric Oxide - Its Importance in Swallowing, Inflammatory Bowel Disease and Cirrhotic Cardiomyopathy

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ABR Thomson

2001-01-01

Full Text Available Nitric oxide is a neurotransmitter found in the central and peripheral nervous systems. Nitric oxide synthase (NOS is localized in the central nervous system, including the nucleus of the solitary tract, nucleus ambiguus and dorsal motor nucleus of the vagus. These are regions that are implicated in the central control of swallowing and esophageal motility. In rats and rabbits, NOS has been shown to be present in the nucleus subcentralis of the nucleus of the solitary tract, and is thought to be responsible for the central programming of the striated muscle component of esophageal peristalsis. Beyak and co-workers from the University of Toronto, Toronto, Ontario provided evidence that the L-arginine-nitric oxide pathway is implicated in the central control of swallowing and esophageal motility. They studied oropharyngeal swallowing as well as esophageal peristalsis, and determined the functional role of brain stem nitric oxide by examining the effects of blockade of central nervous system NOS on swallowing, and on primary and secondary peristalsis. Administering NOS inhibitors intravenously or intracerebroventricularly into the fourth ventricle produced a number of oropharyngeal swallows and induced primary peristalsis in the smooth muscle portion of the esophageal body. NOS reduced the number of oropharyngeal swallows and the incidence of primary peristalsis in both smooth and striated muscle, and reduced the amplitude of peristalsis and smooth muscle contraction. This suggests that nitric oxide is a functional neurotransmitter in the central pattern generator responsible for swallowing and the central control of esophageal peristalsis. Peripherally administered NOS inhibitor can access structures within the blood-brain barrier to affect neuronal activity and physiological function. The central pattern generated for swallowing and esophageal peristalsis is suggested to be a serial network of linked neurons within the nucleus of the solitary

DMPD: Regulation of nitric oxide synthesis and apoptosis by arginase and argininerecycling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17513437 Regulation of nitric oxide synthesis and apoptosis by arginase and arginin...tion of nitric oxide synthesis and apoptosis by arginase and argininerecycling. A...erecycling. Mori M. J Nutr. 2007 Jun;137(6 Suppl 2):1616S-1620S. (.png) (.svg) (.html) (.csml) Show Regulation of nitric oxide synthe...sis and apoptosis by arginase and argininerecycling. PubmedID 17513437 Title Regula

Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

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Sorokin, Andrey

2016-01-01

The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.

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Stamler, J S; Jaraki, O; Osborne, J; Simon, D I; Keaney, J; Vita, J; Singel, D; Valeri, C R; Loscalzo, J

1992-01-01

We have recently shown that nitric oxide or authentic endothelium-derived relaxing factor generated in a biologic system reacts in the presence of specific protein thiols to form S-nitrosoprotein derivatives that have endothelium-derived relaxing factor-like properties. The single free cysteine of serum albumin, Cys-34, is particularly reactive toward nitrogen oxides (most likely nitrosonium ion) under physiologic conditions, primarily because of its anomalously low pK; given its abundance in plasma, where it accounts for approximately 0.5 mM thiol, we hypothesized that this plasma protein serves as a reservoir for nitric oxide produced by the endothelial cell. To test this hypothesis, we developed a methodology, which involves UV photolytic cleavage of the S--NO bond before reaction with ozone for chemiluminescence detection, with which to measure free nitric oxide, S-nitrosothiols, and S-nitrosoproteins in biologic systems. We found that human plasma contains approximately 7 microM S-nitrosothiols, of which 96% are S-nitrosoproteins, 82% of which is accounted for by S-nitroso-serum albumin. By contrast, plasma levels of free nitric oxide are only in the 3-nM range. In rabbits, plasma S-nitrosothiols are present at approximately 1 microM; 60 min after administration of NG-monomethyl-L-arginine at 50 mg/ml, a selective and potent inhibitor of nitric oxide synthetases, S-nitrosothiols decreased by approximately 40% (greater than 95% of which were accounted for by S-nitrosoproteins, and approximately 80% of which was S-nitroso-serum albumin); this decrease was accompanied by a concomitant increase in mean arterial blood pressure of 22%. These data suggest that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-nitroso-serum albumin. This abundant, relatively long-lived adduct likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitric oxide can be

Endothelial and Neuronal Nitric Oxide Activate Distinct Pathways on Sympathetic Neurotransmission in Rat Tail and Mesenteric Arteries.

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Joana Beatriz Sousa

Full Text Available Nitric oxide (NO seems to contribute to vascular homeostasis regulating neurotransmission. This work aimed at assessing the influence of NO from different sources and respective intracellular pathways on sympathetic neurotransmission, in two vascular beds. Electrically-evoked [3H]-noradrenaline release was assessed in rat mesenteric and tail arteries in the presence of NO donors or endothelial/neuronal nitric oxide synthase (NOS inhibitors. The influence of NO on adenosine-mediated effects was also studied using selective antagonists for adenosine receptors subtypes. Location of neuronal NOS (nNOS was investigated by immunohistochemistry (with specific antibodies for nNOS and for Schwann cells and Confocal Microscopy. Results indicated that: 1 in mesenteric arteries, noradrenaline release was reduced by NO donors and it was increased by nNOS inhibitors; the effect of NO donors was only abolished by the adenosine A1 receptors antagonist; 2 in tail arteries, noradrenaline release was increased by NO donors and it was reduced by eNOS inhibitors; adenosine receptors antagonists were devoid of effect; 3 confocal microscopy showed nNOS staining in adventitial cells, some co-localized with Schwann cells. nNOS staining and its co-localization with Schwann cells were significantly lower in tail compared to mesenteric arteries. In conclusion, in mesenteric arteries, nNOS, mainly located in Schwann cells, seems to be the main source of NO influencing perivascular sympathetic neurotransmission with an inhibitory effect, mediated by adenosine A1 receptors activation. Instead, in tail arteries endothelial NO seems to play a more relevant role and has a facilitatory effect, independent of adenosine receptors activation.

Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

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Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

2016-01-01

Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors.

Science.gov (United States)

Vozzi, Federico; Bianchi, Francesca; Ahluwalia, Arti; Domenici, Claudio

2014-01-01

Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of heat shock protein 90 and endothelial nitric oxide synthase during early anesthetic and ischemic preconditioning.

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Amour, Julien; Brzezinska, Anna K; Weihrauch, Dorothee; Billstrom, Amie R; Zielonka, Jacek; Krolikowski, John G; Bienengraeber, Martin W; Warltier, David C; Pratt, Philip F; Kersten, Judy R

2009-02-01

Nitric oxide is known to be essential for early anesthetic preconditioning (APC) and ischemic preconditioning (IPC) of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, the authors tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning within 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pretreatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or N-nitro-L-arginine methyl ester, a nonspecific nitric oxide synthase NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or N-nitro-L-arginine methyl ester. Interactions between Hsp90 and eNOS, and eNOS activation, were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. APC and IPC decreased infarct size (by 50% and 59%, respectively), and this action was abolished by Hsp90 inhibitors. N-nitro-L-arginine methyl ester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes, and eNOS was below the level of detection. The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signaling during APC.

Ruthenium release from thermally overheated nitric acid solution containing ruthenium nitrosyl nitrate and sodium nitrate to solidify

Energy Technology Data Exchange (ETDEWEB)

Sawada, Kayo; Ueda, Yasuyuki; Enokida, Youichi [Nuclear Chemical Engineering Laboratory, Nagoya University, Nagoya 4648603 (Japan)

2016-07-01

Radioactive ruthenium (Ru) is one of the dominant elemental species released into the environment from a fuel reprocessing plant in a hypothetical design accident due to its relatively higher fission yield and longer half-life. After the hypothetical accident assuming the loss of all electric power and cooling functions, high-level liquid waste (HLLW) may be overheated by the energetic decays of many fission products in it, and Ru may be oxidized to the volatile tetroxide, RuO{sub 4}, which is released through the off-gas pathway. At a reprocessing plant in Japan, alkaline solution from the solvent scrubbing stream is sometimes mixed with the HLLW followed by vitrification, which can be influenced by the addition of sodium nitrate to a simulated HLLW containing ruthenium nitrosyl nitrate that was experimentally evaluated on a small scale using the overheated nitric acid solution of 2 mol/dm{sup 3}, which was kept at 180 Celsius degrees in a glass evaporator placed in a thermostatic bath. The release fraction of Ru increased by approximately 30% by the addition of sodium nitrate. This may be partially explained by the existence of relatively highly concentrated nitrate ions in the liquid phase that oxidize the ruthenium species to RuO{sub 4} during the drying process. (authors)

Role of nitric oxide in pheromone-mediated intraspecific communication in mice.

Science.gov (United States)

Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique

2009-12-07

Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-NAME, 100mg/kg) blocks the innate preference displayed by female mice for sexual pheromones contained in male-soiled bedding, with a lower dose of the drug (50mg/kg) having no effect. Animals treated with the high dose of L-NAME show no reduction of olfactory discrimination of male urine in a habituation-dishabituation test, thus suggesting that the effect of the drug on the preference for male pheromones is not due to an inability to detect male urine. Alternatively, it may result from an alteration in processing the reinforcing value of pheromones as sexual signals. These results add a new piece of evidence to our understanding of the neurochemistry of intraspecific chemical communication in rodents, and suggest that the role of nitric oxide in socio-sexual behaviours should be re-evaluated taking into account the involvement of this neuromodulator in the processing of chemical signals.

Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

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Bruno P. Carreira

2015-01-01

Full Text Available Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO. In these conditions, NO promotes proliferation of neural stem cells (NSC in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA induced seizure mouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.

Nitric oxide and neopterin in bipolar affective disorder

NARCIS (Netherlands)

Hoekstra, R.; Fekkes, D.; Pepplinkhuizen, L.; Loonen, A.J.M.; Tuinier, S.; Verhoeven, W.M.A.

2006-01-01

Background: There is an increasing interest in the role of nitric oxide (NO) and pterines in the pathophysiology of neuropsychiatric disorders. The results so far show an inconsistent pattern. Methods: In the present study, neopterin and a measure of NO synthesis in plasma of symptomatic and

Nitric oxide-releasing flurbiprofen reduces formation of proinflammatory hydrogen sulfide in lipopolysaccharide-treated rat

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Anuar, Farhana; Whiteman, Matthew; Siau, Jia Ling; Kwong, Shing Erl; Bhatia, Madhav; Moore, Philip K

2006-01-01

The biosynthesis of both nitric oxide (NO) and hydrogen sulfide (H2S) is increased in lipopolysaccharide (LPS)-injected mice and rats but their interaction in these models is not known. In this study we examined the effect of the NO donor, nitroflurbiprofen (and the parent molecule flurbiprofen) on NO and H2S metabolism in tissues from LPS-pretreated rats. Administration of LPS (10 mg kg−1, i.p.; 6 h) resulted in an increase (PFlurbiprofen (21 mg kg−1, i.p.) was without effect. These results show for the first time that nitroflurbiprofen downregulates the biosynthesis of proinflammatory H2S and suggest that such an effect may contribute to the augmented anti-inflammatory activity of this compound. These data also highlight the existence of ‘crosstalk' between NO and H2S in this model of endotoxic shock. PMID:16491094

NITRIC OXIDE AND ENDOTHELIN-1 IN CHILDREN WITH DIGESTIVE DISORDERS

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I. V. Panova

2012-01-01

Full Text Available The important part in the group of biological compounds, participating in the regulation of the functions of the gastro-intestinal tract, is assigned to endothelial factors because of their impact on the majority of physiological and pathophysiological processes of the digestive system. The article provides information about physiological role of nitric oxide and endothelin-1 and presents a review of scientific data on the participation of nitric oxide and endothelin-1 in the pathogenesis of many digestive system diseases, emphasizing chronic inflammatory disorders of the upper gastrointestinal tract. The authors accentuate the importance of endothelium endocrine function research in children with esophagogastroduodenal disorders at the beginning of puberty, which is the critical period of ontogenesis.

Stimulation of nitric oxide synthesis by the aqueous extract of Panax ginseng root in RAW 264.7 cells.

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Friedl, R; Moeslinger, T; Kopp, B; Spieckermann, P G

2001-12-01

1. In this study, we investigated the effect of Panax ginseng root aqueous extracts upon inducible nitric oxide synthesis in RAW 264.7 cells. Panax ginseng root extract has been used in the Asian world for centuries as a traditional herb to enhance physical strength and resistance and is becoming more and more popular in Europe and North America. 2. Incubation of murine macrophages (RAW 264.7 cells) with increasing amounts of aqueous extracts of Panax ginseng (0.05 - 0.8 microg microl(-1)) showed a dose dependent stimulation of inducible nitric oxide synthesis. 3. Polysaccharides isolated from Panax ginseng showed strong stimulation of inducible nitric oxide synthesis, whereas a triterpene-enriched fraction from an aqueous extract of Panax ginseng did not show any stimulation. 4. Inducible nitric oxide synthase protein expression was enhanced in a dose dependent manner as revealed by immunoblotting when cells were incubated with increasing amounts of Panax ginseng extract. This was associated with an incline in inducible nitric oxide synthase mRNA-levels as determined by semiquantitative polymerase chain reaction and electromobility shift assay studies indicated enhanced nuclear factor-kappaB DNA binding activity. 5. As nitric oxide plays an important role in immune function, Panax ginseng treatment could modulate several aspects of host defense mechanisms due to stimulation of the inducible nitric oxide synthase.

Treatment Of Sunitinib-Induced Hypertension In Solid Tumors By Nitric Oxid Donors

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Luís A. Leon

2015-08-01

Hypertension (HT is one of the most common adverse effects of angiogenesis inhibitors. Hypertension observed in clinical trials appears to correlate with the potency of VEGF kinase inhibitor against VEGFR-2: agents with higher potency are associated with a higher incidence of hypertension. Although the exact mechanism by TKIs induce hypertension has not yet been completely clarified, two key hypotheses have been postulated. First, some studies have pointed to a VEGF inhibitors-induced decrease in nitric oxide synthase (NOS and nitric oxide (NO production, that can result in vasoconstriction and increased blood pressure. VEGF, mediated by PI3K/Akt and MAPK pathway, upregulates the endothelial nitric oxide synthase enzyme leading to up-regulation of NO production. So inhibition of signaling through the VEGF pathway would lead to a decrease in NO production, resulting in an increase in vascular resistance and blood pressure. Secondly a decrease in the number of microvascular endothelial cells and subsequent depletion of normal microvessel density (rarefaction occurs upon VEGF signaling inhibition.

Effect of nanoparticles binding ß-amyloid peptide on nitric oxide production by cultured endothelial cells and macrophages

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Orlando A

2013-04-01

Full Text Available Antonina Orlando,1 Francesca Re,1 Silvia Sesana,1 Ilaria Rivolta,1 Alice Panariti,1 Davide Brambilla,2 Julien Nicolas,2 Patrick Couvreur,2 Karine Andrieux,2 Massimo Masserini,1 Emanuela Cazzaniga1 1Department of Health Sciences, University of Milano-Bicocca, Monza, Italy; 2Institut Galien Paris Sud, University Paris-Sud, Châtenay-Malabry, France Background: As part of a project designing nanoparticles for the treatment of Alzheimer’s disease, we have synthesized and characterized a small library of nanoparticles binding with high affinity to the β-amyloid peptide and showing features of biocompatibility in vitro, which are important properties for administration in vivo. In this study, we focused on biocompatibility issues, evaluating production of nitric oxide by cultured human umbilical vein endothelial cells and macrophages, used as models of cells which would be exposed to nanoparticles after systemic administration. Methods: The nanoparticles tested were liposomes and solid lipid nanoparticles carrying phosphatidic acid or cardiolipin, and PEGylated poly(alkyl cyanoacrylate nanoparticles (PEG-PACA. We measured nitric oxide production using the Griess method as well as phosphorylation of endothelial nitric oxide synthase and intracellular free calcium, which are biochemically related to nitric oxide production. MTT viability tests and caspase-3 detection were also undertaken. Results: Exposure to liposomes did not affect the viability of endothelial cells at any concentration tested. Increased production of nitric oxide was detected only with liposomes carrying phosphatidic acid or cardiolipin at the highest concentration (120 µg/mL, together with increased synthase phosphorylation and intracellular calcium levels. Macrophages exposed to liposomes showed a slightly dose-dependent decrease in viability, with no increase in production of nitric oxide. Exposure to solid lipid nanoparticles carrying phosphatidic acid decreased viability in

Nitric oxide in health and disease of the respiratory system

NARCIS (Netherlands)

Ricciardolo, Fabio L. M.; Sterk, Peter J.; Gaston, Benjamin; Folkerts, Gert

2004-01-01

During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO

[Studies on the oxidation reaction of octanol-2 with nitric acid by infrared spectroscopy].

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Zhang, G; Zhao, G; Wang, Y; Zhang, Q; Zhang, S; Lu, F

1998-04-01

In this paper, the reaction process of oxidation of octanol-2 with nitric acid has been studied by IR spectroscopy. It is found that the main components of non-sapoifiable matter are different in different oxidation degrees. The relation between oxidation products and the amount of nitric acid are investigated,the reaction mechanism has also been studied. Experimental results show that the oxidation process of octanol-2 is as follows: first, octanol-2 is oxidated to octanone-2, or to nitrate, nitrite and nitrile copmpounds, then these compounds are reoxidated to caproic acid in the meantime some by-products, such as valeric, enanthic acids are also found in oxidated products.

Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice.

Science.gov (United States)

Gawali, Nitin B; Chowdhury, Amrita A; Kothavade, Pankaj S; Bulani, Vipin D; Nagmoti, Dnyaneshwar M; Juvekar, Archana R

2016-01-05

In view of the reports that nitric oxide modulates the neurotransmitters implicated in obsessive-compulsive disorder (OCD), patients with OCD exhibit higher plasma nitrate levels, and drugs useful in OCD influence nitric oxide. Agmatine is a polyamine and widely distributed in mammalian brain which interacts with nitrergic systems. Hence, the present study was carried out to understand the involvement of nitrergic systems in the anticompulsive-like effect of agmatine. We used marble-burying behaviour (MBB) of mice as the animal model of OCD, and nitric oxide levels in hippocampus (HC) and cortex homogenate were measured. Results revealed that, agmatine (20 and 40mg/kg, i.p) significantly inhibited the MBB. Intraperitoneal administration of nitric oxide enhancers viz. nitric oxide precursor - l-arginine (l-ARG) (400mg/kg and 800mg/kg) increased MBB as well as brain nitrites levels, whereas treatment with N(G)-nitro-l-arginine methyl ester (l-NAME) neuronal nitric oxide synthase inhibitor (30mg/kg and 50mg/kg, i.p.) and 7-nitroindazole (7-NI) (20mg/kg and 40mg/kg) attenuated MBB and nitrites levels in brain. Further, in combination studies, the anticompulsive-like effect of agmatine (20mg/kg, ip) was exacerbated by prior administration of l-ARG (400mg/kg) and conversely l-NAME (15mg/kg) or 7-NI (10.0mg/kg) attenuated OCD-like behaviour with HC and cortex changes in the levels of NO. None of the above treatment had any significant influence on locomotor activity. In conclusion, Agmatine is effective in ameliorating the compulsive-like behaviour in mice which appears to be related to nitric oxide in brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Total Glucosides of Paeonia lactiflora Pall Suppress Nitric Oxide ...

African Journals Online (AJOL)

iNOS) expression and ... Keywords: Total glucosides, Paeonia lactiflora, Nitric oxide, iNOs, Nuclear factor-κB. Tropical Journal of Pharmaceutical Research ... Nuclear factor (NF)-κB is the key transcriptional factor regulating iNOS gene transcription.

Experience with inhaled nitric oxide therapy in hypoxic respiratory failure of the newborn.

Science.gov (United States)

Sehgal, Arvind; Callander, Ian; Stack, Jacqueline; Momsen, Tracey; Sterling-Levis, Katy

2005-01-01

Respiratory diseases are the commonest cause of morbidity and mortality in newborns. Inhaled nitric oxide (iNO) has been shown to be effective in the management of persistent pulmonory hypertension of newborn (PPHN). To retrospectively analyse data to determine the effectiveness of inhaled nitric oxide (iNO) in the management of newborns with PPHN in terms of survival and changes in oxygenation status. Neo-natal data since inception of iNO therapy at the unit (past six years) was reviewed. Pertinent demographic and clinical information was collected from medical records of newborns that received inhaled nitric oxide therapy during their stay. Details of underlying illnesses, other therapeutic modalities, arterial blood gas, ventilatory and nitric oxide parameters were assessed and analysed to ascertain efficacy of iNO. A total of 36 babies (gestational age ranging from 24-41 weeks) received iNO during this period; two were excluded from final analysis. Overall survival rate was 80 percent. There was a statistically significant increase in systemic oxygenation (PaO2) from 41.1 +/- 2.1 mmHg to 128.5 +/- 13.2 mmHg and a decline in oxygenation index (OI) from 49.4 +/- 5.9 to 17.3 +/- 2.5, when assessed after four hours (P < 0.001). Mean duration of iNO therapy was 63 +/- 7.3 hours and the maximum methaemoglobin levels were noted to be 2.1 percent. Inhaled nitric oxide appears to be an effective rescue therapy for the management of PPHN associated with hypoxic respiratory failure. It is safe and well tolerated with no evidence of clinical or biochemical side effects.

Nitric Oxide in Astrocyte-Neuron Signaling

Energy Technology Data Exchange (ETDEWEB)

Li, Nianzhen [Iowa State Univ., Ames, IA (United States)

2002-01-01

Astrocytes, a subtype of glial cell, have recently been shown to exhibit Ca²⁺ elevations in response to neurotransmitters. A Ca²⁺ elevation can propagate to adjacent astrocytes as a Ca²⁺ wave, which allows an astrocyte to communicate with its neighbors. Additionally, glutamate can be released from astrocytes via a Ca²⁺-dependent mechanism, thus modulating neuronal activity and synaptic transmission. In this dissertation, the author investigated the roles of another endogenous signal, nitric oxide (NO), in astrocyte-neuron signaling. First the author tested if NO is generated during astrocytic Ca²⁺ signaling by imaging NO in purified murine cortical astrocyte cultures. Physiological concentrations of a natural messenger, ATP, caused a Ca²⁺-dependent NO production. To test the roles of NO in astrocytic Ca²⁺ signaling, the author applied NO to astrocyte cultures via addition of a NO donor, S-nitrosol-N-acetylpenicillamine (SNAP). NO induced an influx of external Ca²⁺, possibly through store-operated Ca²⁺ channels. The NO-induced Ca²⁺ signaling is cGMP-independent since 8-Br-cGMP, an agonistic analog of cGMP, did not induce a detectable Ca²⁺ change. The consequence of this NO-induced Ca²⁺ influx was assessed by simultaneously monitoring of cytosolic and internal store Ca²⁺ using fluorescent Ca²⁺ indicators x-rhod-1 and mag-fluo-4. Blockage of NO signaling with the NO scavenger PTIO significantly reduced the refilling percentage of internal stores following ATP-induced Ca²⁺ release, suggesting that NO modulates internal store refilling. Furthermore, locally photo-release of NO to a single astrocyte led to a Ca²⁺ elevation in the stimulated astrocyte and a subsequent Ca²⁺ wave to neighbors. Finally, the author tested the role of NO inglutamate-mediated astrocyte-neuron signaling by

Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

Science.gov (United States)

Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

2016-06-01

Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species.

Science.gov (United States)

Maeng, Oky; Kim, Yong Chan; Shin, Han-Jae; Lee, Jie-Oh; Huh, Tae-Lin; Kang, Kwang-il; Kim, Young Sang; Paik, Sang-Gi; Lee, Hayyoung

2004-04-30

Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.

Inducible nitric oxide inhibitors block NMDA antagonist-stimulated motoric behaviors and medial prefrontal cortical glutamate efflux

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Hadley C Bergstrom

2015-12-01

Full Text Available Nitric oxide (NO plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS for studying the neurobehavioral effects of noncompetitive NMDA-antagonist stimulants such as dizocilpine (MK-801 and phencyclidine (PCP. This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS aminoguanidine (AG and (--epigallocatechin-3-gallate (EGCG in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG or vehicle prior to receiving NMDA antagonists MK-801, PCP or a conventional psychostimulant (cocaine and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated medial prefrontal cortical glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in green tea and chocolate may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.

Inhaled nitric oxide for the adjunctive therapy of severe malaria: Protocol for a randomized controlled trial

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Lavery James V

2011-07-01

Full Text Available Abstract Background Severe malaria remains a major cause of global morbidity and mortality. Despite the use of potent anti-parasitic agents, the mortality rate in severe malaria remains high. Adjunctive therapies that target the underlying pathophysiology of severe malaria may further reduce morbidity and mortality. Endothelial activation plays a central role in the pathogenesis of severe malaria, of which angiopoietin-2 (Ang-2 has recently been shown to function as a key regulator. Nitric oxide (NO is a major inhibitor of Ang-2 release from endothelium and has been shown to decrease endothelial inflammation and reduce the adhesion of parasitized erythrocytes. Low-flow inhaled nitric oxide (iNO gas is a US FDA-approved treatment for hypoxic respiratory failure in neonates. Methods/Design This prospective, parallel arm, randomized, placebo-controlled, blinded clinical trial compares adjunctive continuous inhaled nitric oxide at 80 ppm to placebo (both arms receiving standard anti-malarial therapy, among Ugandan children aged 1-10 years of age with severe malaria. The primary endpoint is the longitudinal change in Ang-2, an objective and quantitative biomarker of malaria severity, which will be analysed using a mixed-effects linear model. Secondary endpoints include mortality, recovery time, parasite clearance and neurocognitive sequelae. Discussion Noteworthy aspects of this trial design include its efficient sample size supported by a computer simulation study to evaluate statistical power, meticulous attention to complex ethical issues in a cross-cultural setting, and innovative strategies for safety monitoring and blinding to treatment allocation in a resource-constrained setting in sub-Saharan Africa. Trial Registration ClinicalTrials.gov Identifier: NCT01255215

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

Energy Technology Data Exchange (ETDEWEB)

Gallo, Annemarie; Mani, Gopinath, E-mail: Gopinath.Mani@usd.edu

2013-08-15

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

A stent for co-delivering paclitaxel and nitric oxide from abluminal and luminal surfaces: Preparation, surface characterization, and in vitro drug release studies

International Nuclear Information System (INIS)

Gallo, Annemarie; Mani, Gopinath

2013-01-01

Most drug-eluting stents currently available are coated with anti-proliferative drugs on both abluminal (toward blood vessel wall) and luminal (toward lumen) surfaces to prevent neointimal hyperplasia. While the abluminal delivery of anti-proliferative drugs is useful for controlling neointimal hyperplasia, the luminal delivery of such drugs impairs or prevents endothelialization which causes late stent thrombosis. This research is focused on developing a bidirectional dual drug-eluting stent to co-deliver an anti-proliferative agent (paclitaxel – PAT) and an endothelial cell promoting agent (nitric oxide – NO) from abluminal and luminal surfaces of the stent, respectively. Phosphonoacetic acid, a polymer-free drug delivery platform, was initially coated on the stents. Then, the PAT and NO donor drugs were co-coated on the abluminal and luminal stent surfaces, respectively. The co-coating of drugs was collectively confirmed by the surface characterization techniques such as Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), 3D optical surface profilometry, and contact angle goniometry. SEM showed that the integrity of the co-coating of drugs was maintained without delamination or cracks formation occurring during the stent expansion experiments. In vitro drug release studies showed that the PAT was released from the abluminal stent surfaces in a biphasic manner, which is an initial burst followed by a slow and sustained release. The NO was burst released from the luminal stent surfaces. Thus, this study demonstrated the co-delivery of PAT and NO from abluminal and luminal stent surfaces, respectively. The stent developed in this study has potential applications in inhibiting neointimal hyperplasia as well as encouraging luminal endothelialization to prevent late stent thrombosis.

Premotor nitric oxide synthase immunoreactive pathway connecting lumbar segments with the ventral motor nucleus of the cervical enlargement in the dog.

Science.gov (United States)

Marsala, Jozef; Lukácová, Nadezda; Cízková, Dása; Lukác, Imrich; Kuchárová, Karolína; Marsala, Martin

2004-03-01

In this study we investigate the occurrence and origin of punctate nitric oxide synthase immunoreactivity in the neuropil of the ventral motor nucleus in C7-Th1 segments of the dog spine, which are supposed to be the terminal field of an ascending premotor propriospinal nitric oxide synthase-immunoreactive pathway. As the first step, nitric oxide synthase immunohistochemistry was used to distinguish nitric oxide synthase-immunoreactive staining of the ventral motor nucleus. Dense, punctate nitric oxide synthase immunoreactivity was found on control sections in the neuropil of the ventral motor nucleus. After hemisection at Th10-11, axotomy-induced retrograde changes consisting in a strong upregulation of nitric oxide synthase-containing neurons were found mostly unilaterally in lamina VIII, the medial part of lamina VII and in the pericentral region in all segments of the lumbosacral enlargement. Concurrently, a strong depletion of the punctate nitric oxide synthase immunopositivity in the neuropil of the ventral motor nucleus ipsilaterally with the hemisection was detected, thus revealing that an uncrossed ascending premotor propriospinal pathway containing a fairly high number of nitric oxide synthase-immunoreactive fibers terminates in the ventral motor nucleus. Application of the retrograde fluorescent tracer Fluorogold injected into the ventral motor nucleus and analysis of alternate sections processed for nitric oxide synthase immunocytochemistry revealed the presence of Fluorogold-labeled and nitric oxide synthase-immunoreactive axons in the ventrolateral funiculus and in the lateral and medial portions of the ventral column throughout the thoracic and upper lumbar segments. A noticeable number of Fluorogold-labeled and nitric oxide synthase-immunoreactive somata detected on consecutive sections were found in the lumbosacral enlargement, mainly in laminae VIII-IX, the medial part of lamina VII and in the pericentral region (lamina X), ipsilaterally with the

In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla.

Science.gov (United States)

Kim, N Y; Pae, H O; Ko, Y S; Yoo, J C; Choi, B M; Jun, C D; Chung, H T; Inagaki, M; Higuchi, R; Kim, Y C

1999-10-01

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.

Nitric oxide inhibits glycogen synthesis in isolated rat hepatocytes

NARCIS (Netherlands)

Sprangers, F.; Sauerwein, H. P.; Romijn, J. A.; van Woerkom, G. M.; Meijer, A. J.

1998-01-01

There is increasing evidence for the existence of intrahepatic regulation of glucose metabolism by Kupffer cell products. Nitric oxide (NO) is known to inhibit gluconeogenic flux through pyruvate carboxylase and phosphoenolpyruvate carboxykinase. However, NO may also influence glucose metabolism at

Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75

OpenAIRE

Cáceres, Lucía; Necakov, Aleksandar S.; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J.H.; Krause, Henry M.

2011-01-01

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer part...

Radiation, nitric oxide and cellular death

International Nuclear Information System (INIS)

Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

1997-01-01

The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone.

Science.gov (United States)

Arnold, Robyn E; Weigent, Douglas A

2003-01-01

Growth hormone (GH) is produced by immunocompetent cells and has been implicated in the regulation of a multiplicity of functions in the immune system involved in growth and activation. However, the actions of endogenous or lymphocyte GH and its contribution to immune reactivity when compared with those of serum or exogenous GH are still unclear. In the present study, we overexpressed lymphocyte GH in EL4 lymphoma cells, which lack the GH receptor (GHR), to determine the role of endogenous GH in nitric oxide (NO) production and response to genotoxic stress. Western blot analysis demonstrated that the levels of GH increased approximately 40% in cells overexpressing GH (GHo) when compared with cells with vector alone. The results also show a substantial increase in NO production in cells overexpressing GH that could be blocked by N(G)-monomethyl-L-arginine (L-NMMA), an L-arginine analogue that competitively inhibits all three isoforms of nitric oxide synthase (NOS). No evidence was obtained to support an increase in peroxynitrite in cells overexpressing GH. Overexpression of GH increased NOS activity, inducible nitric oxide synthase (iNOS) promoter activity, and iNOS protein expression, whereas endothelial nitric oxide synthase and neuronal nitric oxide synthase protein levels were essentially unchanged. In addition, cells overexpressing GH showed increased arginine transport ability and intracellular arginase activity when compared with control cells. GH overexpression appeared to protect cells from the toxic effects of the DNA alkylating agent methyl methanesulfonate. This possibility was suggested by maintenance of the mitochondrial transmembrane potential in cells overexpressing GH when compared with control cells that could be blocked by L-NMMA. Taken together, the data support the notion that lymphocyte GH, independently of the GH receptor, may play a key role in the survival of lymphocytes exposed to stressful stimuli via the production of NO.

Triazine herbicides inhibit relaxin signaling and disrupt nitric oxide homeostasis

Energy Technology Data Exchange (ETDEWEB)

Park, Si Eun; Lim, Sa Rang; Choi, Hyung-kyoon; Bae, Jeehyeon, E-mail: jeehyeon@cau.ac.kr

2016-09-15

Triazines are herbicides that are widely used worldwide, and we previously observed that the maternal exposure of mice to simazine (50 or 500 μg/kg) resulted in smaller ovaries and uteri of their female offspring. Here, we investigated the underlying mechanism that may account for the reproductive dysfunction induced by simazine. We found that following maternal exposure, simazine is transmitted to the offspring, as evidenced by its presence in the offspring ovaries. Analyses of the simazine-exposed offspring revealed that the expression of the relaxin hormone receptor, relaxin-family peptide receptor 1 (RXFP1), prominently decreased in their ovaries and uteri. In addition, downstream target genes of the relaxin pathway including nitric oxide (NO) synthase 2 (Nos2), Nos3, matrix metallopeptidase 9 (Mmp9), and vascular endothelial growth factor (Vegf) were downregulated in their ovaries. Moreover, AKT and extracellular signal-regulated kinases (ERK) levels and their phosphorylated active forms decreased in simazine-exposed ovaries. In vitro exposure of the human ovarian granulosa cells (KGN) and uterine endometrium cells (Hec-1A) to very low concentrations (0.001 to 1 nM) of triazines including atrazine, terbuthylazine, and propazine repressed NO production with a concurrent reduction in RXFP1, NOS2, and NOS3. The inhibitory action of triazines on NO release was dependent on RXFP1, phosphoinositol 3-kinase (PI3K)/AKT, and ERK. Radioligand-binding assay also confirmed that triazines competitively inhibited the binding of relaxin to its receptor. Therefore, the present study suggests that triazine herbicides act as endocrine disrupters by interfering with relaxin hormone signaling. Thus, further evaluation of their impact on human health is imperative. - Highlights: • Triazines downregulate critical molecules involved in the relaxin signaling pathway. • Triazines act as potent antagonists of binding of relaxin to its receptor. • Triazines disrupt nitric oxide

NITRIC OXIDE IMPLICATION IN THE CONTROL OF SEED DORMANCY AND GERMINATION

Directory of Open Access Journals (Sweden)

Erwann eArc

2013-09-01

Full Text Available Germination ability is regulated by a combination of environmental and endogenous signals with both synergistic and antagonistic effects. Nitric oxide (NO is a potent dormancy-releasing agent in many species, including Arabidopsis, and has been suggested to behave as an endogenous regulator of this physiological blockage. Distinct reports have also highlighted a positive impact of NO on seed germination under sub-optimal conditions. However, its molecular mode of action in the context of seed biology remains poorly documented. This review aims to focus on the implications of this radical in the control of seed dormancy and germination. The consequences of NO chemistry on the investigations on both its signaling and its targets in seeds are discussed. NO-dependant protein post-translational modifications are proposed as a key mechanism underlying NO signalling during early seed germination.

Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

Directory of Open Access Journals (Sweden)

Erickson Michelle A

2011-10-01

Full Text Available Abstract Background Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO, cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1, a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-β peptide. Methods Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results Lipopolysaccharide (LPS induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif ligand (CCL-3, and CCL-4. Pericyte expressions of both subunits of

Modulation of glucose uptake in adipose tissue by nitric oxide ...

Indian Academy of Sciences (India)

Madhu

ion-dependent breakdown and trans-nitrosation reactions are ... [McGrowder D, Ragoobirsingh D and Brown P 2006 Modulation of glucose uptake in adipose tissue by nitric oxide-generating ... Briefly, nicotinamide (Sigma Chemical Co.,.

Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin

NARCIS (Netherlands)

Lechner, Matthias; Lirk, Philipp; Rieder, Josef

2005-01-01

Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid l-arginine. iNOS-derived NO plays an important role in numerous physiological (e.g. blood pressure regulation, wound repair and host defence mechanisms) and pathophysiological

Nitric oxide in the nervous system: biochemical, developmental, and neurobiological aspects.

Science.gov (United States)

Cossenza, Marcelo; Socodato, Renato; Portugal, Camila C; Domith, Ivan C L; Gladulich, Luis F H; Encarnação, Thaísa G; Calaza, Karin C; Mendonça, Henrique R; Campello-Costa, Paula; Paes-de-Carvalho, Roberto

2014-01-01

Nitric oxide (NO) is a very reactive molecule, and its short half-life would make it virtually invisible until its discovery. NO activates soluble guanylyl cyclase (sGC), increasing 3',5'-cyclic guanosine monophosphate levels to activate PKGs. Although NO triggers several phosphorylation cascades due to its ability to react with Fe II in heme-containing proteins such as sGC, it also promotes a selective posttranslational modification in cysteine residues by S-nitrosylation, impacting on protein function, stability, and allocation. In the central nervous system (CNS), NO synthesis usually requires a functional coupling of nitric oxide synthase I (NOS I) and proteins such as NMDA receptors or carboxyl-terminal PDZ ligand of NOS (CAPON), which is critical for specificity and triggering of selected pathways. NO also modulates CREB (cAMP-responsive element-binding protein), ERK, AKT, and Src, with important implications for nerve cell survival and differentiation. Differences in the regulation of neuronal death or survival by NO may be explained by several mechanisms involving localization of NOS isoforms, amount of NO being produced or protein sets being modulated. A number of studies show that NO regulates neurotransmitter release and different aspects of synaptic dynamics, such as differentiation of synaptic specializations, microtubule dynamics, architecture of synaptic protein organization, and modulation of synaptic efficacy. NO has also been associated with synaptogenesis or synapse elimination, and it is required for long-term synaptic modifications taking place in axons or dendrites. In spite of tremendous advances in the knowledge of NO biological effects, a full description of its role in the CNS is far from being completely elucidated. © 2014 Elsevier Inc. All rights reserved.

Reduction of nitric oxide catalyzed by hydroxylamine oxidoreductase from an anammox bacterium.

Science.gov (United States)

Irisa, Tatsuya; Hira, Daisuke; Furukawa, Kenji; Fujii, Takao

2014-12-01

The hydroxylamine oxidoreductase (HAO) from the anammox bacterium, Candidatus Kuenenia stuttgartiensis has been reported to catalyze the oxidation of hydroxylamine (NH2OH) to nitric oxide (NO) by using bovine cytochrome c as an oxidant. In contrast, we investigated whether the HAO from anammox bacterium strain KSU-1 could catalyze the reduction of NO with reduced benzyl viologen (BVred) and the NO-releasing reagent, NOC 7. The reduction proceeded, resulting in the formation of NH2OH as a product. The oxidation rate of BVred was proportional to the concentration of BVred itself for a short period in each experiment, a situation that was termed quasi-steady state. The analyses of the states at various concentrations of HAO allowed us to determine the rate constant for the catalytic reaction, (2.85 ± 0.19) × 10(5) M(-1) s(-1), governing NO reduction by BVred and HAO, which was comparable to that reported for the HAO from the ammonium oxidizer, Nitrosomonas with reduced methyl viologen. These results suggest that the anammox HAO functions to adjust anammox by inter-conversion of NO and NH2OH depending on the redox potential of the physiological electron transfer protein in anammox bacteria. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Reactive oxygen species and nitric oxide signaling in bystander cells.

Science.gov (United States)

Jella, Kishore Kumar; Moriarty, Roisin; McClean, Brendan; Byrne, Hugh J; Lyng, Fiona M

2018-01-01

It is now well accepted that radiation induced bystander effects can occur in cells exposed to media from irradiated cells. The aim of this study was to follow the bystander cells in real time following addition of media from irradiated cells and to determine the effect of inhibiting these signals. A human keratinocyte cell line, HaCaT cells, was irradiated (0.005, 0.05 and 0.5 Gy) with γ irradiation, conditioned medium was harvested after one hour and added to recipient bystander cells. Reactive oxygen species, nitric oxide, Glutathione levels, caspase activation, cytotoxicity and cell viability was measured after the addition of irradiated cell conditioned media to bystander cells. Reactive oxygen species and nitric oxide levels in bystander cells treated with 0.5Gy ICCM were analysed in real time using time lapse fluorescence microscopy. The levels of reactive oxygen species were also measured in real time after the addition of extracellular signal-regulated kinase and c-Jun amino-terminal kinase pathway inhibitors. ROS and glutathione levels were observed to increase after the addition of irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). Caspase activation was found to increase 4 hours after irradiated cell conditioned media treatment (0.005, 0.05 and 0.5 Gy ICCM) and this increase was observed up to 8 hours and there after a reduction in caspase activation was observed. A decrease in cell viability was observed but no major change in cytotoxicity was found in HaCaT cells after treatment with irradiated cell conditioned media (0.005, 0.05 and 0.5 Gy ICCM). This study involved the identification of key signaling molecules such as reactive oxygen species, nitric oxide, glutathione and caspases generated in bystander cells. These results suggest a clear connection between reactive oxygen species and cell survival pathways with persistent production of reactive oxygen species and nitric oxide in bystander cells following exposure to irradiated cell

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by ...

African Journals Online (AJOL)

Inhibition of Nitric Oxide and Prostaglandin E 2 Expression by Methanol Extract of Polyopes affinis in Lipopolysaccharide-stimulated BV2 Microglial Cells through Suppression of Akt-dependent NF-kB Activity and MAPK Pathway.

Long-term treatment of anterior pituitary cells with nitric oxide induces programmed cell death.

Science.gov (United States)

Velardez, Miguel Omar; Poliandri, Ariel Hernán; Cabilla, Jimena Paula; Bodo, Cristian Carlos Armando; Machiavelli, Leticia Inés; Duvilanski, Beatriz Haydeé

2004-04-01

Nitric oxide (NO) plays a complex role in modulating programmed cell death. It can either protect the cell from apoptotic death or mediate apoptosis, depending on its concentration and the cell type and/or status. In this study, we demonstrate that long-term exposition to NO induces cell death of anterior pituitary cells from Wistar female rats. DETA NONOate (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate, 1 mm], a NO donor that releases NO for an extended period of time, decreased cellular viability and prolactin release from primary cultures of anterior pituitary cells. Morphological studies showed an increase in the number of cells with chromatin condensation and nuclear fragmentation at 24 and 48 h after DETA/NO exposure. DNA internucleosomal fragmentation was also observed at the same time. Reversibility of the NO effect on cellular viability and prolactin release was observed only when the cells were incubated with DETA/NO for less than 6 h. Most apoptotic cells were immunopositive for prolactin, suggesting a high susceptibility of lactotrophs to the effect of NO. The cytotoxic effect of NO is dependent of caspase-9 and caspase-3, but seems to be independent of oxidative stress or nitrosative stress. Our results show that the exposition of anterior pituitary cells to NO for long periods induces programmed cell death of anterior pituitary cells.

Isoxazole derivatives as new nitric oxide elicitors in plants

Directory of Open Access Journals (Sweden)

Anca Oancea

2017-04-01

Full Text Available Several 3,5-disubstituted isoxazoles were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I iodide. Effects of 3,5-disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators.

Nitric oxide turnover in permeable river sediment

DEFF Research Database (Denmark)

Schreiber, Frank; Stief, Peter; Kuypers, Marcel M M

2014-01-01

We measured nitric oxide (NO) microprofiles in relation to oxygen (O2) and all major dissolved N-species (ammonium, nitrate, nitrite, and nitrous oxide [N2O]) in a permeable, freshwater sediment (River Weser, Germany). NO reaches peak concentrations of 0.13 μmol L-1 in the oxic zone and is consumed......-nitroso-N-acetylpenicillamine (SNAP) (1) confirmed denitrification as the main NO consumption pathway, with N2O as its major product, (2) showed that denitrification combines one free NO molecule with one NO molecule formed from nitrite to produce N2O, and (3) suggested that NO inhibits N2O reduction....

Localization of nitric oxide synthase in human skeletal muscle

DEFF Research Database (Denmark)

Frandsen, Ulrik; Lopez-Figueroa, M.; Hellsten, Ylva

1996-01-01

The present study investigated the cellular localization of the neuronal type I and endothelial type III nitric oxide synthase in human skeletal muscle. Type I NO synthase immunoreactivity was found in the sarcolemma and the cytoplasm of all muscle fibres. Stronger immunoreactivity was expressed...

Water vapour and carbon dioxide decrease nitric oxide readings

NARCIS (Netherlands)

vanderMark, TW; Kort, E; Meijer, RJ; Postma, DS; Koeter, GH

Measurement of nitric oxide levels in exhaled ah-is commonly performed using a chemiluminescence detector. However, water vapour and carbon dioxide affect the chemiluminescence process, The influence of these gases at the concentrations present in exhaled air has not vet been studied. For this in

Study of Nitric Oxide production by murine peritoneal macrophages induced by Brucella Lipopolysaccharide

Directory of Open Access Journals (Sweden)

Kavoosi G

2001-07-01

Full Text Available Brueclla is a gram negative bacteria that causes Brucellosis. Lipopolysaccharide (LPS ", the pathogenic agent of Brucella is composed of O-chain, core oligosaccharide and lipid A. in addition, the structural and biological properties of different LPS extracted from different strains are not identical. The first defense system against LPS is nonspecific immunity that causes macrophage activation. Activated macrophages produce oxygen and nitrogen radicals that enhance the protection against intracellular pathogens.In this experiment LPS was extracted by hot phenol- water procedure and the effect of various LPSs on nitric oxide prodution by peritoneal mouse macrophages was examined.Our results demonstrated that the effect of LPS on nitric oxide production is concentration-dependent we observed the maximum response in concentration of 10-20 microgram per milliliter. Also our results demonstrate that LPS extracted from vaccine Brucella abortus (S 19 had a highe effect on nitric oxide production than the LPS from other strains

Fe-Chlorophyllin Promotes the Growth of Wheat Roots Associated with Nitric Oxide Generation

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Hui Jiang

2010-12-01

Full Text Available : Effects of Fe-chlorophyllin on the growth of wheat root were investigated in this study. We found that Fe-chlorophyllin can promote root growth. The production of nitric oxide in wheat root was detected using DAF-2DA fluorescent emission. The intensity of fluorescent in the presence of 0.1 mg/L Fe-chlorophyllin was near to that observed with the positive control of sodium nitroprusside (SNP, the nitric oxide donor. IAA oxidase activity decreased with all treatments of Fe-chlorophyllin from 0.01 to 10 mg/L. At the relatively lower Fe-chlorophyllin concentration of 0.1 mg/L, the activity of IAA oxidase displayed a remarkable decrease, being 40.1% lower than the control. Meanwhile, Fe-chlorophyllin treatment could increase the activities of reactive oxygen scavenging enzymes, such as superoxide dismutase (SOD and peroxidase (POD, as determined using non-denaturing polyacrylamide gel electrophoresis. These results indicate that Fe-chlorophyllin contributes to the growth of wheat root associated with nitric oxide generation.

Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

Science.gov (United States)

Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

2012-08-01

Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

The role of nitrite in nitric oxide homeostasis

DEFF Research Database (Denmark)

Jensen, Frank Bo

2009-01-01

Nitrite is endogenously produced as an oxidative metabolite of nitric oxide, but it also functions as a NO donor that can be activated by a number of cellular proteins under hypoxic conditions. This article discusses the physiological role of nitrite and nitrite-derived NO in blood flow regulation...... mechanisms. Nitrite reduction to NO provides cytoprotection in tissues during ischemia-reperfusion events by inhibiting mitochondrial respiration and limiting reactive oxygen species. It is argued that the study of hypoxia-tolerant lower vertebrates and diving mammals may help evaluate mechanisms and a full...

Platelet content of nitric oxide synthase 3 phosphorylated at Serine 1177 is associated with the functional response of platelets to aspirin.

Directory of Open Access Journals (Sweden)

Javier Modrego

Full Text Available OBJECTIVE: To analyse if platelet responsiveness to aspirin (ASA may be associated with a different ability of platelets to generate nitric oxide (NO. PATIENTS/METHODS: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26 and ASA-resistant (n = 24 using a platelet functionality test (PFA-100. RESULTS: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3 was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2 isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786 → C in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser(1177, an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177 phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018 of NOS3 phosphorylation at Ser(1177. On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177. During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. CONCLUSIONS: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177.

Nitric oxide synthase in the gill of Atlantic salmon: colocalization with and inhibition of Na+,K+-ATPase

DEFF Research Database (Denmark)

Ebbesson, Lars O E; Tipsmark, Christian K; Holmqvist, Bo

2005-01-01

We investigated the relationship between nitric oxide (NO) and Na(+),K(+)-ATPase (NKA) in the gill of anadromous Atlantic salmon. Cells containing NO-producing enzymes were revealed by means of nitric oxide synthase (NOS) immunocytochemistry and nicotinamide adenine dinucleotide phosphate diaphor...

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

Science.gov (United States)

Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

Science.gov (United States)

Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Thermal-grating contributions to degenerate four-wave mixing in nitric oxide

International Nuclear Information System (INIS)

Danehy, P.M.; Paul, P.H.; Farrow, R.L.

1995-01-01

We report investigations of degenerate four-wave mixing (DFWM) line intensities in the A 2 Σ + left-arrow X 2 Π electronic transitions of nitric oxide. Contributions from population gratings (spatially varying perturbations in the level populations of absorbing species) and thermal gratings (spatially varying perturbations in the overall density) were distinguished and compared by several experimental and analytical techniques. For small quantities of nitric oxide in a strongly quenching buffer gas (carbon dioxide), we found that thermal-grating contributions dominated at room temperature for gas pressures of ∼0.5 atm and higher. In a nearly nonquenching buffer (nitrogen) the population-grating mechanism dominated at pressures of ∼1.0 atm and lower. At higher temperatures in an atmospheric-pressure methane/air flame, population gratings of nitric oxide also dominated. We propose a simple model for the ratio of thermal- to population-grating scattering intensities that varies as P 4 T -4.4 . Preliminary investigations of the temperature dependence and detailed studies of the pressure dependence are in agreement with this model. Measurements of the temporal evolution and the peak intensity of isolated thermal-grating signals are in detailed agreement with calculations based on a linearized hydrodynamic model [J. Opt. Soc. Am. B 12, 384 (1995)]. copyright 1995 Optical Society of America

Cellular inactivation of nitric oxide induces p53-dependent ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1595-1603 ... Cellular inactivation of nitric oxide induces p53-dependent apoptosis in ... apoptosis induced by a selective iNOS inhibitor, N-[(3-aminomethyl) benzyl] acetamidine (1400W), .... and nitrate. ... Nitrite production was measured in culture media.

Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise

DEFF Research Database (Denmark)

Boushel, Robert Christopher; Langberg, Henning; Gemmer, Carsten

2002-01-01

The vascular endothelium is an important mediator of tissue vasodilatation, yet the role of the specific substances, nitric oxide (NO) and prostaglandins (PG), in mediating the large increases in muscle perfusion during exercise in humans is unclear. Quadriceps microvascular blood flow......, respectively (P exercise in humans. These findings demonstrate an important synergistic role of NO and PG for skeletal muscle vasodilatation and hyperaemia during muscular contraction....... was quantified by near infrared spectroscopy and indocyanine green in six healthy humans during dynamic knee extension exercise with and without combined pharmacological inhibition of NO synthase (NOS) and PG by L-NAME and indomethacin, respectively. Microdialysis was applied to determine interstitial release...

Heterogeneous reduction of nitric oxide on synthetic coal chars

Energy Technology Data Exchange (ETDEWEB)

C. Pevida; A. Arenillas; F. Rubiera; J.J. Pis [Instituto Nacional del Carbon (CSIC), Oviedo (Spain)

2005-12-01

Model compounds, with a controlled heteroatoms content and well-defined functionalities, were used to study the release of nitrogen compounds from char combustion. In the present work, the mechanisms involved in NO-char heterogeneous reduction were studied with a synthetic coal (SC) char as carbon source. Another synthetic char (SN) without any nitrogen in its composition was also employed in these studies. Temperature programmed reduction (TPR) tests with a gas mixture of 400 ppm NO in argon and with isotopically labelled nitric oxide, {sup 15}NO (500 ppm {sup 15}NO in argon), were carried out. The gases produced were quantitatively determined by means of MS and FTIR analysers. Under the conditions of this work the main products of the NO-C reaction were found to be N{sub 2} and CO{sub 2}. The main path of reaction involves the formation of surface nitrogen compounds that afterwards react with nitrogen from the reactive gas to form N{sub 2}. It was observed that fuel-N also participates in the overall heterogeneous reduction reaction, although to a lesser extent.

Nitric oxide and Na,K-ATPase activity in rat skeletal muscle.

Science.gov (United States)

Juel, C

2016-04-01

It has been suggested that nitric oxide (NO) stimulates the Na,K-ATPase in cardiac myocytes. Therefore, the aims of this study were to investigate whether NO increases Na,K-ATPase activity in skeletal muscle and, if that is the case, to identify the underlying mechanism. The study used isolated rat muscle, muscle homogenates and purified membranes as model systems. Na,K-ATPase activity was quantified from phosphate release due to ATP hydrolysis. Exposure to the NO donor spermine NONOate (10 μm) increased the maximal Na,K-ATPase activity by 27% in isolated glycolytic muscles, but had no effect in oxidative muscles. Spermine NONOate increased the maximal Na,K-ATPase activity by 58% (P Na,K-ATPase α-isoform. Incubation with cGMP (1 mm) increased the maximal Na,K-ATPase activity in homogenates from glycolytic muscle by 16% (P Na,K-ATPase in glycolytic skeletal muscle. Direct S-nitrosylation and interference with S-glutathionylation seem to be excluded. In addition, phosphorylation of phospholemman at serine 68 is not involved. Most likely, the NO/cGMP/protein kinase G signalling pathway is involved. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Exercise promotes collateral artery growth mediated by monocytic nitric oxide.

Science.gov (United States)

Schirmer, Stephan H; Millenaar, Dominic N; Werner, Christian; Schuh, Lisa; Degen, Achim; Bettink, Stephanie I; Lipp, Peter; van Rooijen, Nico; Meyer, Tim; Böhm, Michael; Laufs, Ulrich

2015-08-01

Collateral artery growth (arteriogenesis) is an important adaptive response to hampered arterial perfusion. It is unknown whether preventive physical exercise before limb ischemia can improve arteriogenesis and modulate mononuclear cell function. This study aimed at investigating the effects of endurance exercise before arterial occlusion on MNC function and collateral artery growth. After 3 weeks of voluntary treadmill exercise, ligation of the right femoral artery was performed in mice. Hindlimb perfusion immediately after surgery did not differ from sedentary mice. However, previous exercise improved perfusion restoration ≤7 days after femoral artery ligation, also when exercise was stopped at ligation. This was accompanied by an accumulation of peri-collateral macrophages and increased expression of endothelial nitric oxide synthase and inducible nitric oxide synthase (iNOS) in hindlimb collateral and in MNC of blood and spleen. Systemic monocyte and macrophage depletion by liposomal clodronate but not splenectomy attenuated exercise-induced perfusion restoration, collateral artery growth, peri-collateral macrophage accumulation, and upregulation of iNOS. iNOS-deficient mice did not show exercise-induced perfusion restoration. Transplantation of bone marrow-derived MNC from iNOS-deficient mice into wild-type animals inhibited exercise-induced collateral artery growth. In contrast to sedentary controls, thrice weekly aerobic exercise training for 6 months in humans increased peripheral blood MNC iNOS expression. Circulating mononuclear cell-derived inducible nitric oxide is an important mediator of exercise-induced collateral artery growth. © 2015 American Heart Association, Inc.

Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

Science.gov (United States)

Hyde, Embriette R; Andrade, Fernando; Vaksman, Zalman; Parthasarathy, Kavitha; Jiang, Hong; Parthasarathy, Deepa K; Torregrossa, Ashley C; Tribble, Gena; Kaplan, Heidi B; Petrosino, Joseph F; Bryan, Nathan S

2014-01-01

The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO) homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis.

Directory of Open Access Journals (Sweden)

Embriette R Hyde

Full Text Available The microbiota of the human lower intestinal tract helps maintain healthy host physiology, for example through nutrient acquisition and bile acid recycling, but specific positive contributions of the oral microbiota to host health are not well established. Nitric oxide (NO homeostasis is crucial to mammalian physiology. The recently described entero-salivary nitrate-nitrite-nitric oxide pathway has been shown to provide bioactive NO from dietary nitrate sources. Interestingly, this pathway is dependent upon oral nitrate-reducing bacteria, since humans lack this enzyme activity. This pathway appears to represent a newly recognized symbiosis between oral nitrate-reducing bacteria and their human hosts in which the bacteria provide nitrite and nitric oxide from nitrate reduction. Here we measure the nitrate-reducing capacity of tongue-scraping samples from six healthy human volunteers, and analyze metagenomes of the bacterial communities to identify bacteria contributing to nitrate reduction. We identified 14 candidate species, seven of which were not previously believed to contribute to nitrate reduction. We cultivated isolates of four candidate species in single- and mixed-species biofilms, revealing that they have substantial nitrate- and nitrite-reduction capabilities. Colonization by specific oral bacteria may thus contribute to host NO homeostasis by providing nitrite and nitric oxide. Conversely, the lack of specific nitrate-reducing communities may disrupt the nitrate-nitrite-nitric oxide pathway and lead to a state of NO insufficiency. These findings may also provide mechanistic evidence for the oral systemic link. Our results provide a possible new therapeutic target and paradigm for NO restoration in humans by specific oral bacteria.

Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions

Science.gov (United States)

Halasa, Salaheldin; Dickinson, Eva

2014-02-01

From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.

Modeling the solar cycle change in nitric oxide in the thermosphere and upper mesosphere

International Nuclear Information System (INIS)

Fuller-Rowell, T.J.

1993-01-01

Measurements from the Solar Mesosphere Explorer (SME) satellite have shown that low-latitude nitric oxide densities at 110 km decrease by about a factor of 8 from January 1982 to April 1985. This time period corresponds to the descending phase of the last solar cycle where the monthly smoothed sunspot number decreased from more than 150 to less than 25. In addition, nitric oxide was observed to vary by a factor of 2 over a solar rotation, during high solar activity. A one-dimensional, globally averaged model of the thermosphere and upper mesosphere has been used to study the height distribution of nitric oxide (NO) and its response to changes in the solar extreme ultraviolet radiation (EUV) through the solar cycle and over a solar rotation. The primary source of nitric oxide is the reaction of excited atomic nitrogen, N( 2 D), with molecular oxygen. The atomic nitrogen is created by a number of ion-neutral reactions and by direct dissociation of molecular nitrogen by photons and photoelectrons. The occurrence of the peak nitric oxide density at or below 115 km is a direct consequence of ionization and dissociation of molecular nitrogen by photoelectrons, which are produced by the solar flux below 30.0 nm (XUV). Nitric oxide is shown to vary over the solar cycle by a factor of 7 at low latitudes in the lower thermosphere E region, due to the estimated change in the solar EUV flux, in good agreement with the SME satellite observations. The NO density is shown to be strongly dependent on the temperature profile in the lower thermosphere and accounts for the difference between the current model and previous work. Wavelengths less than 1.8 nm have little impact on the NO profile. A factor of 3 change in solar flux below 5.0 nm at high solar activity produced a factor of 2 change in the peak NO density, consistent with SME observations over a solar rotation; this change also lowered the peak to 100 km, consistent with rocket data. 52 refs., 10 figs., 5 tabs

Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric oxide.

Science.gov (United States)

Gupta, N; Bhargava, V K; Pandhi, P

2000-05-01

The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited by its capacity to induce tolerance and dependence. A means of preventing or minimizing the tolerance and dependence inducing properties is required. Here the role of nitric oxide in preventing the development of tolerance and withdrawal hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg i.p. twice daily produced tolerance to its anticonvulsant action in 28 days. After sudden cessation of therapy it produced hyperexcitability. Tolerance was shown by a decrease in seizure threshold to near control value while withdrawal hyperexcitability was evidenced by a significant decrease in seizure threshold below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L-arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam. Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug therapy. Electroshock was used as a model of epilepsy and seizure thresholds were determined by an up and down method of Kimball et al. L-Arginine was found to inhibit the development tolerance as well as withdrawal hyperexcitability when administered with clonazepam while N omega-L-arginine did not prevent either the development of tolerance or withdrawal hyperexcitability in the electroshock model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant action and withdrawal hyperexcitability while inhibition of nitric oxide synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

Detection of nitric acid and nitric oxides in the terrestrial atmosphere in the middle-infrared spectral region

Directory of Open Access Journals (Sweden)

M. I. Blecka

1996-11-01

Full Text Available A proposal for combined space and ground-based observations of the vertical distributions and the column densities of nitric acid and nitric oxide concentrations in the earth's atmosphere is discussed. We focus on the aspects that are particular to the idea of correlative measurements: geometrical considerations, simulations of the solar absorption spectra in the middle-infrared region corresponding to the different observational geometries, and the associated retrieval methods. These studies are done specifically for the Belgian-French experiment MIRAS (MIR Infrared Atmospheric Spectrometer onboard the Russian Space Station MIR and correlative ground-based FTIR measurements in the Tatra mountains.

Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

2013-05-01

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

Protein Nanocage-Based Photo-Controlled Nitric Oxide Releasing Platform.

Science.gov (United States)

Li, Xiao; Zhang, Yajie; Sun, Jian; Chen, Weijian; Wang, Xuewei; Shao, Fenli; Zhu, Yuyu; Feng, Fude; Sun, Yang

2017-06-14

A photoactive NO releasing system was constructed by incorporation of NO-bound Fe-S clusters into horse spleen apoferritin cavities with high loading efficacy. The composites retained intact core-shell structure and indicated advantages such as enhanced stability, reduced cytotoxicity, efficient cellular uptake, and photocontrolled NO releasing property.

Nitric oxide and chronic colitis

Directory of Open Access Journals (Sweden)

Matthew B Grisham

1996-01-01

Full Text Available Nitric oxide (NO is thought to play an important role in modulating the inflammatory response by virtue of its ability to affect bloodflow, leukocyte function and cell viability. The objective of this study was to assess the role that NO may play in mediating the mucosal injury and inflammation in a model of chronic granulomatous colitis using two pharmacologically different inhibitors of nitric oxide synthase (NOS. Chronic granulomatous colitis with liver and spleen inflammation was induced in female Lewis rats via the subserosal (intramural injection of peptidoglycan/polysaccharide (PG/PS derived from group A streptococci. Chronic NOS inhibition by oral administration of NG-nitro-L-arginine methyl ester (L-NAME (15 µmol/kg/day or amino-guanidine (AG (15 µmol/ kg/day was found to attenuate the PG/PS-induced increases in macroscopic colonic inflammation scores and colonic myeloperoxidase activity. Only AG -- not L-NAME – attenuated the PG/PS-induced increases in colon dry weight. Both L-NAME and AG significantly attenuated the PG/PS-induced increases in spleen weight whereas neither was effective at significantly attenuating the PG/PS-induced increases in liver weight. Although both L-NAME and AG inhibited NO production in vivo, as measured by decreases in plasma nitrite and nitrate levels, only AG produced significantly lower values (38±3 versus 83±8 µM, respectively, P<0.05. Finally, L-NAME, but not AG, administration significantly increased mean arterial pressure from 83 mmHg in colitic animals to 105 mmHg in the PG/PS+ L-NAME-treated animals (P<0.05. It is concluded that NO may play an important role in mediating some of the pathophysiology associated with this model of chronic granulomatous colitis.

Nitric oxide radical scavenging potential of some Elburz medicinal ...

African Journals Online (AJOL)

Some plants scavenge nitric oxide (NO) with high affinity. For this purpose, forty extracts from 26 medicinal plants, growing extensively in Elburz mountains, were evaluated for their NO scavenging activity. Total phenolic and flavonoid contents of these extracts were also measured by Folin Ciocalteu and AlCl3 colorimetric ...

How to protect liver graft with nitric oxide

Institute of Scientific and Technical Information of China (English)

Hassen Ben Abdennebi; Mohamed Amine Zaoualí; Izabel Alfany-Fernandez; Donia Tabka; Joan Roselló-Catafau

2011-01-01

Organ preservation and ischemia reperfusion injury associated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is endothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-protective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regulating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidence to support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subsequent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation.

Direct and controllable nitric oxide delivery into biological media and living cells by a pin-to-hole spark discharge (PHD) plasma

Energy Technology Data Exchange (ETDEWEB)

Dobrynin, D; Friedman, G [Electrical and Computer Engineering Department, College of Engineering, Drexel University, Philadelphia, PA (United States); Arjunan, K; Clyne, A Morss [School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA (United States); Fridman, A, E-mail: alisam@coe.drexel.edu [Department of Mechanical Engineering and Mechanics, College of Engineering, Drexel University, Philadelphia, PA (United States)

2011-02-23

Nitric oxide has great potential for improving wound healing through both inflammatory and vascularization processes. Nitric oxide can be produced in high concentrations by atmospheric pressure thermal plasmas. We measured the physical characteristics and nitric oxide production of a pin-to-hole spark discharge (PHD) plasma, as well as plasma-produced nitric oxide delivery into liquid and endothelial cells. The plasma temperature was calculated as 9030 {+-} 320 K by the Boltzmann method, which was adequate to produce nitric oxide, although the average gas temperature was near room temperature. The plasma produced significant UV radiation and hydrogen peroxide, but these were prevented from reaching the cells by adding a straight or curved tube extension to the plasma device. Plasma-produced nitric oxide in gas reached 2000 ppm and rapidly diffused into liquid and cells. Cells remained viable following plasma treatment and showed a linear increase in cGMP concentration with plasma treatment, indicating an intracellular functional response to PHD plasma NO. These data suggest that this plasma may provide a novel method for delivering NO locally and directly for enhanced wound healing.

Direct and controllable nitric oxide delivery into biological media and living cells by a pin-to-hole spark discharge (PHD) plasma

International Nuclear Information System (INIS)

Dobrynin, D; Friedman, G; Arjunan, K; Clyne, A Morss; Fridman, A

2011-01-01

Nitric oxide has great potential for improving wound healing through both inflammatory and vascularization processes. Nitric oxide can be produced in high concentrations by atmospheric pressure thermal plasmas. We measured the physical characteristics and nitric oxide production of a pin-to-hole spark discharge (PHD) plasma, as well as plasma-produced nitric oxide delivery into liquid and endothelial cells. The plasma temperature was calculated as 9030 ± 320 K by the Boltzmann method, which was adequate to produce nitric oxide, although the average gas temperature was near room temperature. The plasma produced significant UV radiation and hydrogen peroxide, but these were prevented from reaching the cells by adding a straight or curved tube extension to the plasma device. Plasma-produced nitric oxide in gas reached 2000 ppm and rapidly diffused into liquid and cells. Cells remained viable following plasma treatment and showed a linear increase in cGMP concentration with plasma treatment, indicating an intracellular functional response to PHD plasma NO. These data suggest that this plasma may provide a novel method for delivering NO locally and directly for enhanced wound healing.

Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance.

Science.gov (United States)

Chakraborty, Jayashree B; Mahato, Sanjit K; Joshi, Kalpana; Shinde, Vaibhav; Rakshit, Srabanti; Biswas, Nabendu; Choudhury Mukherjee, Indrani; Mandal, Labanya; Ganguly, Dipyaman; Chowdhury, Avik A; Chaudhuri, Jaydeep; Paul, Kausik; Pal, Bikas C; Vinayagam, Jayaraman; Pal, Churala; Manna, Anirban; Jaisankar, Parasuraman; Chaudhuri, Utpal; Konar, Aditya; Roy, Siddhartha; Bandyopadhyay, Santu

2012-01-01

Alcoholic extract of Piper betle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxy-chavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings. © 2011 Japanese Cancer Association.

Continuous electrochemical monitoring of nitric oxide production in murine macrophage cell line RAW 264.7

Czech Academy of Sciences Publication Activity Database

Pekarová, Michaela; Králová, Jana; Kubala, Lukáš; Číž, Milan; Lojek, Antonín; Gregor, Č.; Hrbáč, J.

2009-01-01

Roč. 394, č. 5 (2009), s. 1497-1504 ISSN 1618-2642 R&D Projects: GA AV ČR(CZ) 1QS500040507 Grant - others:GA ČR(CZ) GP524/05/P135 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : nitric oxide * macrophage s RAW 264.7 * nitric oxide sensor Subject RIV: BO - Biophysics Impact factor: 3.480, year: 2009

Lipopolysaccharide-induced dopaminergic cell death in rat midbrain slice cultures: role of inducible nitric oxide synthase and protection by indomethacin.

Science.gov (United States)

Shibata, Haruki; Katsuki, Hiroshi; Nishiwaki, Mayumi; Kume, Toshiaki; Kaneko, Shuji; Akaike, Akinori

2003-09-01

Glial cell activation associated with inflammatory reaction may contribute to pathogenic processes of neurodegenerative disorders, through production of several cytotoxic molecules. We investigated the consequences of glial activation by interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) in rat midbrain slice cultures. Application of IFN-gamma followed by LPS caused dopaminergic cell death and accompanying increases in nitrite production and lactate dehydrogenase release. Aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), or SB203580, an inhibitor of p38 mitogen-activated protein kinase, prevented dopaminergic cell loss as well as nitrite production. SB203580 also suppressed expression of iNOS and cyclooxygenase-2 (COX-2) induced by IFN-gamma/LPS. A COX inhibitor indomethacin protected dopaminergic neurons from IFN-gamma/LPS-induced injury, whereas selective COX-2 inhibitors such as NS-398 and nimesulide did not. Notably, indomethacin was able to attenuate neurotoxicity of a nitric oxide (NO) donor. Neutralizing antibodies against tumour necrosis factor-alpha and interleukin-1beta did not inhibit dopaminergic cell death caused by IFN-gamma/LPS, although combined application of these antibodies blocked lactate dehydrogenase release and decrease in the number of non-dopaminergic neurons. These results indicate that iNOS-derived NO plays a crucial role in IFN-gamma/LPS-induced dopaminergic cell death, and that indomethacin exerts protective effect by mechanisms probably related to NO neurotoxicity rather than through COX inhibition.

Estriol-induced fibrinolysis due to the activation of plasminogen to plasmin by nitric oxide synthesis in platelets.

Science.gov (United States)

Jana, Pradipta; Maiti, Smarajit; Kahn, Nighat N; Sinha, Asru K

2015-04-01

Estriol, an oestrogen, at 0.6 nmol/l was reported to inhibit ADP-induced platelet aggregation through nitric oxide synthesis. As nitric oxide has been reported to cause fibrinolysis due to the activation of plasminogen to plasmin, the role of estriol as a fibrinolytic agent was investigated. Also, the mechanism of estriol-induced nitric oxide synthesis in anucleated platelets was investigated. The estriol-induced lysis of platelet-rich plasma (PRP) clot was determined by photography of the clot lysis and by the assay of fibrin degradation products in the lysate and was obtained by SDS-PAGE. Nitric oxide was determined by methemoglobin method. The platelet membrane protein was isolated from the platelets by using Triton X-100 (0.05% v/v). The binding of estriol to the protein was determined by Scatchard plot by using an ELISA for estriol. Estriol at 0.6 nmol/l was found to lyse the clotted PRP due to fibrinolysis that produced fibrin degradation products in the lysate. The amino acid analysis of the platelet membrane protein, which resembles with nitric oxide synthase (NOS) activity, was activated nearly 10-fold over the control in the presence of estriol and was identified to be a human serum albumin precursor (Mr. 69 kDa) that binds to estriol with Kd1 of 6.0 × 10 mol/l and 39 ± 2 molecules of estriol bound the NOS molecule. The estriol-induced nitric oxide is capable of inducing fibrinolysis of the clotted PRP. The binding of estriol to platelet membrane NOS activated the enzyme in the absence of DNA in the platelet.

Variation of nitric oxide levels in imported Plasmodium falciparum ...

African Journals Online (AJOL)

SERVER

2008-03-18

Mar 18, 2008 ... Nitric oxide (NO) has been recognized during the past two decades as one of the most versatile players in the immune system. Even though the molecular mechanisms responsible by the naturally acquired immunity against malaria are still to be clarified, the production of NO seems to play an important role.

Melatonin inhibits endothelin-1 and induces endothelial nitric oxide ...

African Journals Online (AJOL)

Although, I/R augmented the endothelin-1 (ET-1) gene expression and the level of big endothelin-1 (big ET-1) in liver tissue, melatonin attenuated these increases. Conversely, non-significant decrease in endothelial nitric oxide synthase (eNOS) mRNA expression in I/R group was significantly elevated by melatonin in ...

Caffeic acid, a phenol found in white wine, modulates endothelial nitric oxide production and protects from oxidative stress-associated endothelial cell injury.

Directory of Open Access Journals (Sweden)

Massimiliano Migliori

Full Text Available Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF, an active component with known antioxidant activities.The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury.CAF increased basal as well as acetylcholine-induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration.The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

Analysis of genetic variation of inducible nitric oxide synthase and ...

African Journals Online (AJOL)

The genetic diversity of 100 Malaysian native chickens was investigated using polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) for two candidate genes: inducible nitric oxide synthase (INOS) and natural resistance-associated macrophage protein 1 (NRAMP1). The two genes were selected ...

Effect of nitric oxide-releasing derivative of indomethacin on Prevotella intermedia lipopolysaccharide-induced production of proinflammatory mediators in murine macrophages.

Science.gov (United States)

Choe, So-Hui; Choi, Eun-Young; Hyeon, Jin-Yi; Choi, In Soon; Kim, Sung-Jo

2017-10-14

The purpose of this study was to investigate the influences of NCX 2121, a nitric oxide (NO)-releasing derivative of indomethacin, upon the generation of proinflammatory mediators using murine macrophages activated by lipopolysaccharide (LPS) isolated from Prevotella intermedia, which is one of the pathogens implicated in periodontal diseases. Inducible NO synthase (iNOS)-derived NO, IL-1β and IL-6 as well as their relevant mRNA were significantly attenuated by NCX 2121 in RAW264.7 cells activated by P. intermedia LPS. NCX 2121 was much more effective than the parental compound indomethacin in reducing these proinflammatory mediators. NCX 2121 triggered induction of heme oxygenase-1 (HO-1) in cells exposed to P. intermedia LPS, and its inhibitory influence upon P. intermedia LPS-elicited NO generation was notably blocked by SnPP treatment. NCX 2121 attenuated NF-κB-dependent SEAP release induced by P. intermedia LPS. NCX 2121 did not display inhibitory action towards IκB-α degradation triggered by LPS. Instead, it significantly diminished nuclear translocation as well as DNA-binding action of NF-κB p50 subunit elicited by P. intermedia LPS. Further, NCX 2121 significantly up-regulated SOCS1 mRNA expression in cells challenged with P. intermedia LPS. In summary, NCX 2121 down-regulates P. intermedia LPS-elicited generation of NO, IL-1β and IL-6 in murine macrophages in a mechanism that involves anti-inflammatory HO-1 induction as well as decrement of NF-κB activation, which may be associated with SOCS1 expression. NCX 2121 may have potential benefits as a host immunomodulatory agent for the therapy of periodontal disease. Copyright © 2017 Elsevier Inc. All rights reserved.

The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.

Science.gov (United States)

Maciag, Anna E; Saavedra, Joseph E; Chakrapani, Harinath

2009-09-01

Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O(2)-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O(2)-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.

Nitric oxide and HSV vaginal infection in BALB/c mice

International Nuclear Information System (INIS)

Benencia, Fabian; Gamba, Gisela; Cavalieri, Hernan; Courreges, Maria Cecilia; Benedetti, Ruben; Villamil, Soledad Maria; Massouh, Ernesto Jorge

2003-01-01

Here we study the role of nitric oxide in the vaginal infection of Balb/c mice with herpes simplex virus type 2. Inducible nitric oxide synthase (iNOS) mRNA was detected by RT-PCR in vaginal tissue and inguinal lymph nodes early postinfection. iNOS was also found to be activated in cells recovered from vaginal washings of infected animals. Animals treated with aminoguanidine (AG), an iNOS inhibitor, showed a dose-dependent increase in vaginal pathology after viral infection compared to controls. Viral titers in vaginal washings and vaginas were higher in AG-treated mice. Treated animals presented higher PMN counts in vaginal washings compared to controls. Histopathology studies revealed a profound inflammatory exudate in vaginal tissue of treated animals. Finally, RT-PCR analysis showed increased expression of the chemokines MIP-2 and RANTES in vaginal tissue and inguinal lymph nodes of these animals

UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

International Nuclear Information System (INIS)

Arimoto-Kobayashi, Sakae; Sano, Kayoko; Machida, Masaki; Kaji, Keiko; Yakushi, Keiko

2010-01-01

We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in φX174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and NDMA. A significant linear correlation between the optical density of N-dialkynitrosamines at 340 nm and NO formation in each irradiated solution was revealed by ANOVA. We would like to propose the hypothesis that the N-nitroso moiety of N-dialkylnitrosamines absorbs UVA photons, UVA-photolysis of N-dialkylnitrosamines brings release of nitric oxide, and subsequent production of alkyl radical cations and active oxygen species follow as secondary events, which cause DNA strand breaks, oxidative and

UVA activation of N-dialkylnitrosamines releasing nitric oxide, producing strand breaks as well as oxidative damages in DNA, and inducing mutations in the Ames test

Energy Technology Data Exchange (ETDEWEB)

Arimoto-Kobayashi, Sakae [Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530 (Japan); Sano, Kayoko; Machida, Masaki; Kaji, Keiko; Yakushi, Keiko [Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima, Okayama 700-8530 (Japan)

2010-09-10

We investigated the photo-mutagenicity and photo-genotoxicity of N-dialkylnitrosamines and its mechanisms of UVA activation. With simultaneous irradiation of UVA, photo-mutagenicity of seven N-dialkylnitrosamines was observed in Ames bacteria (Salmonella typhimurium TA1535) in the absence of metabolic activation. Mutagenicity of pre-irradiated N-dialkylnitrosamines was also observed with S. typhimurium hisG46, TA100, TA102 and YG7108 in the absence of metabolic activation. UVA-mediated mutation with N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) decreased by adding either the NO or OH radical scavenger. When superhelical DNA was irradiated with N-dialkylnitrosamines, nicked circular DNA appeared. Ten N-dialkylnitrosamines examined produced strand breaks in the treated DNA in the presence of UVA. The level of single-strand breaks in {phi}X174 DNA mediated by N-nitrosomorpholine (NMOR) and UVA decreased by adding either a radical scavenger or superoxide dismutase. When calf thymus DNA was treated with N-dialkylnitrosamines (NDMA, NDEA, NMOR, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP)) and UVA, the ratio of 8-oxodG/dG in the DNA increased. Action spectra were obtained to determine if nitrosamine acts as a sensitizer of UVA. Both mutation frequency and NO formation were highest at the absorption maximum of nitrosamines, approximately 340 nm. The plots of NO formation and mutation frequency align with the absorption curve of NPYR, NMOR and NDMA. A significant linear correlation between the optical density of N-dialkynitrosamines at 340 nm and NO formation in each irradiated solution was revealed by ANOVA. We would like to propose the hypothesis that the N-nitroso moiety of N-dialkylnitrosamines absorbs UVA photons, UVA-photolysis of N-dialkylnitrosamines brings release of nitric oxide, and subsequent production of alkyl radical cations and active oxygen species follow as secondary events, which cause DNA strand breaks, oxidative and

Synthesis of N-(Methoxycarbonylthienylmethylthioureas and Evaluation of Their Interaction with Inducible and Neuronal Nitric Oxide Synthase

Directory of Open Access Journals (Sweden)

Michael D. Threadgill

2010-04-01

Full Text Available Two isomeric N-(methoxycarbonylthienylmethylthioureas were synthesised by a sequence of radical bromination of methylthiophenecarboxylic esters, substitution with trifluoroacetamide anion, deprotection, formation of the corresponding isothiocyanates and addition of ammonia. The interaction of these new thiophene-based thioureas with inducible and neuronal nitric oxide synthase was evaluauted. These novel thienylmethylthioureas stimulated the activity of inducible Nitric Oxide Synthase (iNOS.

Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms.

Science.gov (United States)

Amour, Julien; Brzezinska, Anna K; Jager, Zachary; Sullivan, Corbin; Weihrauch, Dorothee; Du, Jianhai; Vladic, Nikolina; Shi, Yang; Warltier, David C; Pratt, Phillip F; Kersten, Judy R

2010-03-01

Endothelial nitric oxide synthase activity is regulated by (6R-)5,6,7,8-tetrahydrobiopterin (BH4) and heat shock protein 90. The authors tested the hypothesis that hyperglycemia abolishes anesthetic preconditioning (APC) through BH4- and heat shock protein 90-dependent pathways. Myocardial infarct size was measured in rabbits in the absence or presence of APC (30 min of isoflurane), with or without hyperglycemia, and in the presence or absence of the BH4 precursor sepiapterin. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells cultured in normal (5.5 mm) or high (20 mm) glucose conditions, with or without sepiapterin (10 or 100 microm). APC decreased myocardial infarct size compared with control experiments (26 +/- 6% vs. 46 +/- 3%, respectively; P < 0.05), and this action was blocked by hyperglycemia (43 +/- 4%). Sepiapterin alone had no effect on infarct size (46 +/- 3%) but restored APC during hyperglycemia (21 +/- 3%). The beneficial actions of sepiapterin to restore APC were blocked by the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (47 +/- 2%) and the BH4 synthesis inhibitor N-acetylserotonin (46 +/- 3%). Isoflurane increased nitric oxide production to 177 +/- 13% of baseline, and this action was attenuated by high glucose concentrations (125 +/- 6%). Isoflurane increased, whereas high glucose attenuated intracellular BH4/7,8-dihydrobiopterin (BH2) (high performance liquid chromatography), heat shock protein 90-endothelial nitric oxide synthase colocalization (confocal microscopy) and endothelial nitric oxide synthase activation (immunoblotting). Sepiapterin increased BH4/BH2 and dose-dependently restored nitric oxide production during hyperglycemic conditions (149 +/- 12% and 175 +/- 9%; 10 and 100 microm, respectively). The results indicate that tetrahydrobiopterin and heat shock protein 90-regulated endothelial nitric oxide synthase activity play a central

Chronic deficit in nitric oxide elicits oxidative stress and augments T-type calcium-channel contribution to vascular tone of rodent arteries and arterioles

DEFF Research Database (Denmark)

Howitt, Lauren; Kuo, Ivana Y; Ellis, Anthie

2013-01-01

arteries in vitro and skeletal muscle arterioles in vivo to study the contribution of L-type (1 µmol/L nifedipine) and T-type (1 µmol/L mibefradil, 3 µmol/L NNC 55-0396) calcium channels to vascular tone, following acute or chronic inhibition of nitric oxide. Acute inhibition with l-NAME (10 µmol...... was reversed by acute scavenging of superoxide with tempol (1 mmol/L), or inhibition of NADPH oxidase with apocynin (500 µmol/L) or DPI (5 µmol/L). CONCLUSION: We conclude that nitric oxide deficit produces a significant increase in the contribution of Cav3.1 and Cav3.2 T-type calcium channels to vascular tone......, by regulating the bioavailability of reactive oxygen species produced by NADPH oxidase. Our data provide evidence for a novel causal link between nitric oxide deficit, oxidative stress, and T-type calcium channel function....

Nanomaterials-based electrochemical sensors for nitric oxide

International Nuclear Information System (INIS)

Dang, Xueping; Hu, Hui; Wang, Shengfu; Hu, Shengshui

2015-01-01

Electrochemical sensing has been demonstrated to represent an efficient way to quantify nitric oxide (NO) in challenging physiological environments. A sensing interface based on nanomaterials opens up new opportunities and broader prospects for electrochemical NO sensors. This review (with 141 refs.) gives a general view of recent advances in the development of electrochemical sensors based on nanomaterials. It is subdivided into sections on (i) carbon derived nanomaterials (such as carbon nanotubes, graphenes, fullerenes), (ii) metal nanoparticles (including gold, platinum and other metallic nanoparticles); (iii) semiconductor metal oxide nanomaterials (including the oxides of titanium, aluminum, iron, and ruthenium); and finally (iv) nanocomposites (such as those formed from carbon nanomaterials with nanoparticles of gold, platinum, NiO or TiO 2 ). The various strategies are discussed, and the advances of using nanomaterials and the trends in NO sensor technology are outlooked in the final section. (author)

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

patients after intra-articular injection of sodium hyaluronate, while the effect is insignificant in severe patients. Thus, sodium hyaluronate can effectively improve nitric oxide levels in synovial fluid, reduce ..... Modern Med Health, 2014; 1:.

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid in Osteoarthritis Patients ... Tropical Journal of Pharmaceutical Research ... and moderate phase patients after intra-articular injection of sodium hyaluronate, while the effect ...

THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

Science.gov (United States)

Sawicka, Ewa; Piwowar, Agnieszka; Musiala, Tomasz; Dlugosz, Anna

2017-05-01

The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

Dysfunctional nitric oxide signalling increases risk of myocardial infarction.

Science.gov (United States)

Erdmann, Jeanette; Stark, Klaus; Esslinger, Ulrike B; Rumpf, Philipp Moritz; Koesling, Doris; de Wit, Cor; Kaiser, Frank J; Braunholz, Diana; Medack, Anja; Fischer, Marcus; Zimmermann, Martina E; Tennstedt, Stephanie; Graf, Elisabeth; Eck, Sebastian; Aherrahrou, Zouhair; Nahrstaedt, Janja; Willenborg, Christina; Bruse, Petra; Brænne, Ingrid; Nöthen, Markus M; Hofmann, Per; Braund, Peter S; Mergia, Evanthia; Reinhard, Wibke; Burgdorf, Christof; Schreiber, Stefan; Balmforth, Anthony J; Hall, Alistair S; Bertram, Lars; Steinhagen-Thiessen, Elisabeth; Li, Shu-Chen; März, Winfried; Reilly, Muredach; Kathiresan, Sekar; McPherson, Ruth; Walter, Ulrich; Ott, Jurg; Samani, Nilesh J; Strom, Tim M; Meitinger, Thomas; Hengstenberg, Christian; Schunkert, Heribert

2013-12-19

Myocardial infarction, a leading cause of death in the Western world, usually occurs when the fibrous cap overlying an atherosclerotic plaque in a coronary artery ruptures. The resulting exposure of blood to the atherosclerotic material then triggers thrombus formation, which occludes the artery. The importance of genetic predisposition to coronary artery disease and myocardial infarction is best documented by the predictive value of a positive family history. Next-generation sequencing in families with several affected individuals has revolutionized mutation identification. Here we report the segregation of two private, heterozygous mutations in two functionally related genes, GUCY1A3 (p.Leu163Phefs*24) and CCT7 (p.Ser525Leu), in an extended myocardial infarction family. GUCY1A3 encodes the α1 subunit of soluble guanylyl cyclase (α1-sGC), and CCT7 encodes CCTη, a member of the tailless complex polypeptide 1 ring complex, which, among other functions, stabilizes soluble guanylyl cyclase. After stimulation with nitric oxide, soluble guanylyl cyclase generates cGMP, which induces vasodilation and inhibits platelet activation. We demonstrate in vitro that mutations in both GUCY1A3 and CCT7 severely reduce α1-sGC as well as β1-sGC protein content, and impair soluble guanylyl cyclase activity. Moreover, platelets from digenic mutation carriers contained less soluble guanylyl cyclase protein and consequently displayed reduced nitric-oxide-induced cGMP formation. Mice deficient in α1-sGC protein displayed accelerated thrombus formation in the microcirculation after local trauma. Starting with a severely affected family, we have identified a link between impaired soluble-guanylyl-cyclase-dependent nitric oxide signalling and myocardial infarction risk, possibly through accelerated thrombus formation. Reversing this defect may provide a new therapeutic target for reducing the risk of myocardial infarction.

Ribavirin in Cancer Immunotherapies: Controlling Nitric Oxide Augments Cytotoxic Lymphocyte Function

Directory of Open Access Journals (Sweden)

Richard E. Kast

2003-01-01

Full Text Available Either ribavirin (RBV or cyclophosphamide (CY can shift an immune response from Th2 toward a Thi cytokine profile. CY is used in this role in various current cancer immunotherapy attempts but with mixed success. More potent and reliable immunoadjuvants and Th1 response biasing methods are needed. RBV is used today mainly to augment interferon-alpha treatment of hepatitis C. RBV shifts an immune response from Th2 toward Th1 more effectively than CY and may be a safe and useful adjuvant for current cancer immunotherapeutic efforts. RBV is thought to act by inhibition of tetrahydrobiopterin synthesis. Tetrahydrobiopterin is an essential cofactor for all known isoforms of nitric oxide synthase. Lowered nitric oxide favors Th1 development as high levels favor Th2 weighting.

Enhanced biogenic emissions of nitric oxide and nitrous oxide following surface biomass burning

Science.gov (United States)

Anderson, Iris C.; Levine, Joel S.; Poth, Mark A.; Riggan, Philip J.

1988-01-01

Recent measurements indicate significantly enhanced biogenic soil emissions of both nitric oxide (NO) and nitrous oxide (N2O) following surface burning. These enhanced fluxes persisted for at least six months following the burn. Simultaneous measurements indicate enhanced levels of exchangeable ammonium in the soil following the burn. Biomass burning is known to be an instantaneous source of NO and N2O resulting from high-temperature combustion. Now it is found that biomass burning also results in significantly enhanced biogenic emissions of these gases, which persist for months following the burn.

Nitric oxide heme interactions in nitrophorin from Cimex lectularius

Energy Technology Data Exchange (ETDEWEB)

Christmann, R.; Auerbach, H., E-mail: auerbach@physik.uni-kl.de [University of Kaiserslautern, Department of Physics (Germany); Berry, R. E.; Walker, F. A. [The University of Arizona, Department of Chemistry and Biochemistry (United States); Schünemann, V. [University of Kaiserslautern, Department of Physics (Germany)

2016-12-15

The nitrophorin from the bedbug Cimex lectularius (cNP) is a nitric oxide (NO) carrying protein. Like the nitrophorins (rNPs) from the kissing bug Rhodnius prolixus, cNP forms a stable heme Fe(III)-NO complex, where the NO can be stored reversibly for a long period of time. In both cases, the NPs are found in the salivary glands of blood-sucking bugs. The insects use the nitrophorins to transport the NO to the victim’s tissues, resulting in vasodilation and reduced blood coagulation. However, the structure of cNP is significantly different to those of the rNPs from Rhodnius prolixus. Furthermore, the cNP can bind a second NO molecule to the proximal heme cysteine when present at higher concentrations. High field Mössbauer spectroscopy on {sup 57}Fe enriched cNP complexed with NO shows reduction of the heme iron and formation of a ferrous nitric oxide (Fe(II)-NO) complex. Density functional theory calculations reproduce the experimental Mössbauer parameters and confirm this observation.

Requirement of argininosuccinate lyase for systemic nitric oxide production.

Science.gov (United States)

Erez, Ayelet; Nagamani, Sandesh C S; Shchelochkov, Oleg A; Premkumar, Muralidhar H; Campeau, Philippe M; Chen, Yuqing; Garg, Harsha K; Li, Li; Mian, Asad; Bertin, Terry K; Black, Jennifer O; Zeng, Heng; Tang, Yaoping; Reddy, Anilkumar K; Summar, Marshall; O'Brien, William E; Harrison, David G; Mitch, William E; Marini, Juan C; Aschner, Judy L; Bryan, Nathan S; Lee, Brendan

2011-11-13

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.

Investigation of the direct and indirect electrochemical oxidation of hydrazine in nitric acid medium on platinum

International Nuclear Information System (INIS)

Cames, B.

1997-01-01

In nuclear fuel processing by the PUREX process, the purification of plutonium in nitric acid medium requires the oxidation of Pu(III) to Pu(IV), and of hydrazinium nitrate to nitrogen. The study helped to characterize the electrochemical behavior of the oxidation of hydrazinium nitrate and the reduction of nitric acid to nitrous acid, a compound which can chemically oxidize hydrazinium nitrate and Pu(III). Electro-analytical studies on polycrystalline platinum showed that hydrazine is oxidized in two potential zones, which depend on the surface texture of the platinum anode. Electrolysis in separate compartments, carried out in medium-acid media (2 and 4 mo/l) in the potential zone where these processes take place, showed that, at 0.9 V/ECS, the hydrazine oxidation reactions involved are: a four-electron process (75 %) with nitrogen formation and a one-electron process (25 %) with formation of nitrogen and ammonium ion. By contrast, electrolysis carried out at 0.65 V/ECS (with reactivation of the electrode at - 0.2 V/ECS to remove the poison from the platinum) allowed the selective oxidation of hydrazine to nitrogen by the four-electron reaction. Nitric acid can only be reduced to nitrous acid in the absence of hydrazine. For medium-acid media (≤ 6 mol/l), this reaction takes place at potentials below - 0.2 V/ECS. However, the production rate of nitrous acid (partial order 0 with respect to nitric acid) is very low compared with the values obtained for strongly-acid media (6 to 10 mol/l) at the potential of - 0.1 V/ECS. Note that, in concentrated nitric medium, the selectivity of the reduction reaction is 47 to 85 % for nitrous acid, depending on the nitric acid concentration (6 to 10 mol/l) and the potential imposed (- 0.1 ≤ E ≤ 0.6 V/ECS). A kinetic study helped to determine the hydrazine oxidation rates as a function of the operating conditions. In all cases, the reaction rate is of partial order 0 with respect to hydrazine. These studies accordingly

Lithium-Vanadium bronzes as model catalysts for the selective reduction of nitric oxide

NARCIS (Netherlands)

Bosch, H.; Bongers, Annemie; Enoch, Gert; Snel, Ruud; Ross, Julian R.H.

1989-01-01

The effect of alkali metals on the selective reduction of nitric oxide with ammonia has been studied on bulk iron oxide and bulk vanadium oxide. The influence of additions of LiOH, NaOH and KOH on the activity was screened by pulse experiments carried out in the absence of gaseous oxygen; FTIR

Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling*#

Science.gov (United States)

Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

2016-01-01

Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H2O2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato’s response to chilling stress. PMID:27921397

Nitric oxide induced by polyamines involves antioxidant systems against chilling stress in tomato (Lycopersicon esculentum Mill.) seedling.

Science.gov (United States)

Diao, Qian-Nan; Song, Yong-Jun; Shi, Dong-Mei; Qi, Hong-Yan

Polyamines (PAs) and nitric oxide (NO) are vital signals in modulating plant response to abiotic stress. However, to our knowledge, studies on the relationship between NO and PAs in response to cold stress in tomato are limited. Accordingly, in this study, we investigated the effects of putrescine (Put) and spermidine (Spd) on NO generation and the function of Spd-induced NO in the tolerance of tomato seedling under chilling stress. Spd increased NO release via the nitric oxide synthase (NOS)-like and nitrate reductase (NR) enzymatic pathways in the seedlings, whereas Put had no such effect. Moreover, H 2 O 2 might act as an upstream signal to stimulate NO production. Both exogenous NO donor (sodium nitroprusside (SNP)) and Spd enhanced chilling tolerance in tomato, thereby protecting the photosynthetic system from damage. Compared to chilling treatment alone, Spd enhanced the gene expressions of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and their enzyme activities in tomato leaves. However, a scavenger or inhibitor of NO abolished Spd-induced chilling tolerance and blocked the increased expression and activity due to Spd of these antioxidant enzymes in tomato leaves under chilling stress. The results showed that NO induced by Spd plays a crucial role in tomato's response to chilling stress.

Variation of nitric oxide levels in imported Plasmodium falciparum ...

African Journals Online (AJOL)

SERVER

2008-03-18

Mar 18, 2008 ... ISSN 1684–5315 © 2008 Academic Journals. Full Length Research Paper. Variation of nitric oxide levels in imported Plasmodium falciparum malaria episodes. De Sousa, Karina*, Silva, Marcelo S. and Tavira, Luís T. Instituto de Higiene e Medicina Tropical, Centro de Malária e outras Doenças Tropicais, ...

Serum Iron and Nitric Oxide Production in Trypanosoma brucei ...

African Journals Online (AJOL)

JTEkanem

reduction in the serum iron status and a modulation of nitric oxide synthase activity of T. brucei infected rats. ... inflammation and tissue damage15. ... The serum iron level was determined ... concentration or of total nitrate and nitrite ... 15. 16. 17. 18. Days. S e ru m iro n lev e l mg. /ml. Infected treated. Infected untreated. 0.

Osteopontin protects against hyperoxia-induced lung injury by inhibiting nitric oxide synthases.

Science.gov (United States)

Zhang, Xiang-Feng; Liu, Shuang; Zhou, Yu-Jie; Zhu, Guang-Fa; Foda, Hussein D

2010-04-05

Exposure of adult mice to more than 95% O(2) produces a lethal injury by 72 hours. Nitric oxide synthase (NOS) is thought to contribute to the pathophysiology of murine hyperoxia-induced acute lung injury (ALI). Osteopontin (OPN) is a phosphorylated glycoprotein produced principally by macrophages. OPN inhibits inducible nitric oxide synthase (iNOS), which generates large amounts of nitric oxide production. However, the relationship between nitric oxide and endogenous OPN in lung tissue during hyperoxia-induced ALI has not yet been elucidated, thus we examined the role that OPN plays in the hyperoxia-induced lung injury and its relationships with NOS. One hundred and forty-four osteopontin knock-out (KO) mice and their matched wild type background control (WT) were exposed in sealed cages > 95% oxygen or room air for 24- 72 hours, and the severity of lung injury was assessed; expression of OPN, endothelial nitric oxide synthase (eNOS) and iNOS mRNA in lung tissues at 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry (IHC) was performed for the detection of iNOS, eNOS, and OPN protein in lung tissues. OPN KO mice developed more severe acute lung injury at 72 hours of hyperoxia. The wet/dry weight ratio increased to 6.85 +/- 0.66 in the KO mice at 72 hours of hyperoxia as compared to 5.31 +/- 0.92 in the WT group (P < 0.05). iNOS mRNA (48 hours: 1.04 +/- 0.08 vs. 0.63 +/- 0.09, P < 0.01; 72 hours: 0.89 +/- 0.08 vs. 0.72 +/- 0.09, P < 0.05) and eNOS mRNA (48 hours: 0.62 +/- 0.08 vs. 0.43 +/- 0.09, P < 0.05; 72 hours: 0.67 +/- 0.08 vs. 0.45 +/- 0.09, P < 0.05) expression was more significantly increased in OPN KO mice than their matched WT mice when exposed to hyperoxia. IHC study showed higher expression of iNOS (20.54 +/- 3.18 vs. 12.52 +/- 2.46, P < 0.05) and eNOS (19.83 +/- 5.64 vs. 9.45 +/- 3.82, P < 0.05) in lung tissues of OPN KO mice at 72 hours of hyperoxia. OPN can protect against

L-arginine increases nitric oxide and attenuates pressor and heart ...

African Journals Online (AJOL)

olayemitoyin

heart rate responses to change in posture in sickle cell anemia subjects. 1 .... the standing position and measurements made immediately. Arterial ... pressure was the difference between systolic and diastolic ... Table 3. Effect of L-Arginine Supplementation on Blood Pressure Parameters, Plasma L-Arginine and Nitric Oxide.

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa.

Science.gov (United States)

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-08-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors.

The changes of nitric oxide production during the growth of Microcystis aerugrinosa

Energy Technology Data Exchange (ETDEWEB)

Tang Xiang; Chen Juan; Wang Wenhua; Liu Tingwu; Zhang Jun; Gao Yahui [Key Laboratory for Subtropical Wetland Ecosystem Research of Ministry of Education of China, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Pei Zhenming [School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); Department of Biology, Duke University, Durham, NC 27708 (United States); Zheng Hailei, E-mail: zhenghl@xmu.edu.cn [Key Laboratory for Subtropical Wetland Ecosystem Research of Ministry of Education of China, Xiamen University, Xiamen, Fujian 361005 (China); School of Life Sciences, Xiamen University, Xiamen, Fujian 361005 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005 (China)

2011-12-15

This study characterized the changes of nitric oxide (NO) production during the growth of Microcystis aerugrinosa, a cyanobacterium which usually cause cyanobacterial blooms. Results showed a drastic NO release accompanying with cell density and Chl-a content sharp rises when M. aerugrinosa grew from fifth day to sixth day. Moreover, high N:P ratio accelerated the cyanobacterial growth and NO burst. Sodium nitroprusside, an exogenous NO donor, promoted M. aerugrinosa growth with the optimal concentration of 0.1 mg/L. Experiments by supplementing with sodium nitrite and L-arginine demonstrated NO production in M. aerugrinosa cells was mainly through nitrate reductase (NR) pathway while minorly through NO synthase pathway. All these data suggested M. aerugrinosa produced increasing NO during its growth mainly by NR pathway, during which NO positively regulated the growth of M. aerugrinosa. - Highlights: > We study NO release during M. aerugrinosa growth. > A drastic NO release from M. aerugrinosa accompanies with cell density and Chl-a sharp rise. > High N:P ratio accelerates the sharp increase of cell density, Chl-a content and NO burst. > NO donor promotes M. aerugrinosa growth with the optimal concentration of 0.1 mg/L. > NO production in M. aerugrinosa cells is mainly through nitrate reductase pathway. - NO produced by M. aerugrinosa has an promoting effect on cyanobacterial growth.

Rocuronium Bromide Inhibits Inflammation and Pain by Suppressing Nitric Oxide Production and Enhancing Prostaglandin E2 Synthesis in Endothelial Cells.

Science.gov (United States)

Baek, Sang Bin; Shin, Mal Soon; Han, Jin Hee; Moon, Sang Woong; Chang, Boksoon; Jeon, Jung Won; Yi, Jae Woo; Chung, Jun Young

2016-12-01

Rocuronium bromide is a nondepolarizing neuromuscular blocking drug and has been used as an adjunct for relaxation or paralysis of the skeletal muscles, facilitation of endotracheal intubation, and improving surgical conditions during general anesthesia. However, intravenous injection of rocuronium bromide induces injection pain or withdrawal movement. The exact mechanism of rocuronium bromide-induced injection pain or withdrawal movement is not yet understood. We investigated whether rocuronium bromide treatment is involved in the induction of inflammation and pain in vascular endothelial cells. For this study, calf pulmonary artery endothelial (CPAE) cells were used, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot, nitric oxide detection, and prostaglandin E 2 immunoassay were conducted. Rocuronium bromide treatment inhibited endothelial nitric oxide synthase and suppressed nitric oxide production in CPAE cells. Rocuronium bromide activated cyclooxygenase-2, inducible nitric oxide synthase and increased prostaglandin E 2 synthesis in CPAE cells. Rocuronium bromide induced inflammation and pain in CPAE cells. Suppressing nitric oxide production and enhancing prostaglandin E 2 synthesis might be associated with rocuronium bromide-induced injection pain or withdrawal movement.

Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

Science.gov (United States)

Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

Immune-relevant thrombocytes of common carp undergo parasite-induced nitric oxide-mediated apoptosis.

Science.gov (United States)

Fink, Inge R; Ribeiro, Carla M S; Forlenza, Maria; Taverne-Thiele, Anja; Rombout, Jan H W M; Savelkoul, Huub F J; Wiegertjes, Geert F

2015-06-01

Common carp thrombocytes account for 30-40% of peripheral blood leukocytes and are abundant in the healthy animals' spleen, the thrombopoietic organ. We show that, ex vivo, thrombocytes from healthy carp express a large number of immune-relevant genes, among which several cytokines and Toll-like receptors, clearly pointing at immune functions of carp thrombocytes. Few studies have described the role of fish thrombocytes during infection. Carp are natural host to two different but related protozoan parasites, Trypanoplasma borreli and Trypanosoma carassii, which reside in the blood and tissue fluids. We used the two parasites to undertake controlled studies on the role of fish thrombocytes during these infections. In vivo, but only during infection with T. borreli, thrombocytes were massively depleted from the blood and spleen leading to severe thrombocytopenia. Ex vivo, addition of nitric oxide induced a clear and rapid apoptosis of thrombocytes from healthy carp, supporting a role for nitric oxide-mediated control of immune-relevant thrombocytes during infection with T. borreli. The potential advantage for parasites to selectively deplete the host of thrombocytes via nitric oxide-induced apoptosis is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exhaled nitric oxide in paediatric asthma and cystic fibrosis.

Science.gov (United States)

Lundberg, J O; Nordvall, S L; Weitzberg, E; Kollberg, H; Alving, K

1996-01-01

Nitric oxide (NO) is present in exhaled air of humans. This NO is mostly produced in the upper airways, whereas basal NO excretion in the lower airways is low. Children with Kartagener's syndrome have an almost total lack of NO in nasally derived air, whereas adult asthmatics have increased NO in orally exhaled air. NO excretion was measured in the nasal cavity and in orally exhaled air in 19 healthy children, in 36 age matched subjects with asthma, and in eight children with cystic fibrosis. NO levels in orally exhaled air were similar in controls and in children with cystic fibrosis, at 4.8 (SD 1.2) v 5.8 (0.8) parts per billion (ppb), but were increased in asthmatic children who were untreated or were being treated only with low doses of inhaled steroids (13.8 (2.5) ppb). Nasal NO levels were reduced by about 70% in children with cystic fibrosis compared to controls and asthmatics. Measurements of airway NO release in different parts of the airways may be useful in non-invasive diagnosis and monitoring of inflammatory airway diseases. PMID:8984919

Inhibition of DNA repair by whole body irradiation induced nitric oxide leads to higher radiation sensitivity in lymphocytes

International Nuclear Information System (INIS)

Sharma, Deepak; Santosh Kumar, S.; Raghu, Rashmi; Maurya, D.K.; Sainis, K.B.

2007-01-01

Full text: It is well accepted that the sensitivity of mammalian cells is better following whole body irradiation (WBI) as compared to that following in vitro irradiation. However, the underlying mechanisms are not well understood. Following WBI, the lipid peroxidation and cell death were significantly higher in lymphocytes as compared to that in vitro irradiated lymphocytes. Further, WBI treatment of tumor bearing mice resulted in a significantly higher inhibition of EL-4 cell proliferation as compared to in vitro irradiation of EL-4 cells. The DNA repair was significantly slower in lymphocytes obtained from WBI treated mice as compared to that in the cells exposed to same dose of radiation in vitro. Generation of nitric oxide following irradiation and also its role in inhibition of DNA repair have been reported, hence, its levels were estimated under both WBI and in vitro irradiation conditions. Nitric oxide levels were significantly elevated in the plasma of WBI treated mice but not in the supernatant of in vitro irradiated cells. Addition of sodium nitroprusside (SNP), a nitric oxide donor to in vitro irradiated cells inhibited the repair of DNA damage and sensitized cells to undergo cell death. It also enhanced the radiation-induced functional impairment of lymphocytes as evinced from suppression of mitogen-induced IL-2, IFN-γ and bcl-2 mRNA expression. Administration of N G -nitro-L-arginine-methyl-ester(L-NAME), a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. Our results indicated that nitric oxide plays a role in the higher radiosensitivity of lymphocytes in vivo by inhibiting repair of DNA damage

Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.

Science.gov (United States)

Cáceres, Lucía; Necakov, Aleksandar S; Schwartz, Carol; Kimber, Sandra; Roberts, Ian J H; Krause, Henry M

2011-07-15

Nitric oxide gas acts as a short-range signaling molecule in a vast array of important physiological processes, many of which include major changes in gene expression. How these genomic responses are induced, however, is poorly understood. Here, using genetic and chemical manipulations, we show that nitric oxide is produced in the Drosophila prothoracic gland, where it acts via the nuclear receptor ecdysone-induced protein 75 (E75), reversing its ability to interfere with its heterodimer partner, Drosophila hormone receptor 3 (DHR3). Manipulation of these interactions leads to gross alterations in feeding behavior, fat deposition, and developmental timing. These neuroendocrine interactions and consequences appear to be conserved in vertebrates.

Electrochemical reduction of oxygen and nitric oxide at low temperature on La1−xSrxMnO3+δ cathodes

DEFF Research Database (Denmark)

Kammer Hansen, Kent

2013-01-01

in the nitric oxide containing atmosphere compared to the activity in the oxygen containing atmosphere at 200°C. At 300 and 400°C the activity in the nitric oxide and oxygen containing atmospheres were similar. The highest ratio between the cathodic current densities in the nitric oxide and oxygen containing......Six La1−xSrxMnO3+δ (x=0, 0.05, 0.15, 0.25, 0.35, 0.50) perovskites were synthesised and characterised by powder XRD and cyclic voltammetry on cone-shaped electrodes in 10% oxygen in argon or 1% nitric oxide in argon at 200, 300 and 400°C. The activity of the manganite based perovskites were highest...

Nitric oxide amplifies the rat electroretinogram.

Science.gov (United States)

Vielma, Alex; Delgado, Luz; Elgueta, Claudio; Osorio, Rodrigo; Palacios, Adrián G; Schmachtenberg, Oliver

2010-11-01

It is well established that nitric oxide (NO) participates in retinal signal processing through stimulation of its receptor enzyme, soluble guanylyl cyclase (sGC). However, under pathological conditions such as uveoretinitis, diabetic or ischemic retinopathy, elevated NO concentrations may cause protein S-nitrosation and peroxynitrite formation in the retina, promoting cellular injury and apoptosis. Previous electroretinogram (ERG) studies demonstrated deleterious effects of NO on the retinal light response, but showed no evidence for a role in normal signal processing. To better understand the function of NO in ocular physiology, we investigated the effects of exogenous NO, produced by NO donors with different release kinetics, on the flash ERG of the rat. Within a limited concentration range, NO strongly amplified ERG a- and b-waves, oscillatory potentials, and the scotopic threshold response. Amplification exceeded 100% under dark adaptation, whereas the photopic ERG and the isolated cone response were increased by less than 50%. Blocking photoreceptor-bipolar cell synapses by AP-4 demonstrated a significant increase of the isolated a-wave by NO, and modeling the ERG generator PIII supported photoreceptors as primary NO targets. The sGC inhibitors ODQ and NS2028 did not reduce NO-dependent ERG amplification, ruling out an involvement of the classical NO effector cyclic GMP. Using immunohistochemistry, we show that illumination and exogenous NO altered the S-nitrosation level of the photoreceptor layer, suggesting that direct protein modifications caused by elevated levels of NO may be responsible for the observed phenomenon. Copyright © 2010 Elsevier Ltd. All rights reserved.

The protective role of nitric oxide and nitric oxide synthases in whole-body hyperthermia-induced hepatic injury in rats.

Science.gov (United States)

Chen, Chao-Fuh; Wang, David; Leu, Fur-Jiang; Chen, Hsing I

2012-01-01

The present study was designed to elucidate the role of endothelial nitric oxide (NO) synthase (eNOS), inducible NOS (iNOS)-derived NO and heat-shock protein (Hsp70) in a rat model of whole-body hyperthermia (WBH)-induced liver injury. Real-time polymerase chain reaction, immunohistochemistry and western blot were used to observe the mRNA and protein expression of eNOS, iNOS and Hsp70. Rats were exposed to hyperthermia by immersion for 60 min at a conscious state in a water bath maintained at 41°C. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used to assess liver injury 15 h after the hyperthermia challenge. Nitrosative and oxidative mediators, particularly NO and hydroxyl radical were measured. Plasma AST, ALT, hydroxyl radical, and NO were significantly increased after WBH. There were 4.14 ± 0.42, 2.82 ± 0.34 and 2.91 ± 0.16-fold increases in the mRNA expression of eNOS, iNOS and Hsp70. Immunohistochemistry and western blot showed up-regulation of eNOS, iNOS and Hsp70 protein. An eNOS inhibitor (N(ω)-nitro-L-arginine methyl ester (L-NAME)), or an iNOS inhibitor (aminoguanidine (AG)), significantly aggravated the liver injury. On the contrary, administration of NO precursor, L-arginine (L-ARG), attenuated the liver injury. Hsp70 inhibitor quercetin reduced Hsp70, while aggravating the WBH-induced hepatic changes. WBH induces increases in eNOS, iNOS and Hsp70 expression with increase in NO release. The deleterious effects of L-NAME and AG and the protective effects of L-ARG and Hsp70 inhibitor on the liver function and pathology suggest that NO and heat shock protein play a beneficial role in the WBH-induced hepatic injury.

Daily life negative mood and exhaled nitric oxide in asthma.

Science.gov (United States)

Ritz, Thomas; Kullowatz, Antje; Bill, Michelle N; Rosenfield, David

2016-07-01

Psychosocial stress and negative affect have been linked to asthma exacerbations, but longitudinal studies demonstrating a daily life association between negative affect and airway nitric oxide are missing. The longitudinal association between negative mood fluctuations, exhaled nitric oxide, and lung function in asthma was examined. Self-assessments of the fraction of exhaled nitric oxide (FeNO), spirometry (forced expiratory volume in the first second, FEV1), negative mood, and daily activities were obtained from 20 patients with asthma for 2 months, resulting in 1108 assessments for the analyses (approximately 55 per patient). Concurrent and prospective associations between FeNO, FEV1, and negative mood were analyzed using mixed effects regression models for longitudinal data. Negative mood was positively associated with changes in FeNO during the same day, and to a stronger extent when prior day negative mood was included in the prediction. FeNO and negative mood were positively associated with same-day FEV1, with the latter relation being partially mediated by changes in FeNO. Associations between FeNO and FEV1 were stronger in younger patients, with earlier onset of asthma, or with lower asthma control. Findings were not changed when controlling for physical activity, medication, cold symptoms, air pollution, and hours spent outside. Daily life changes of negative mood in asthma are positively associated with FeNO changes and FeNO increases are associated with a mild bronchodilation. These findings indicate that psychological influences need to be considered when using FeNO as indicator of airway inflammation and guide for treatment decisions. Copyright © 2016 Elsevier B.V. All rights reserved.

JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.

Science.gov (United States)

McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M

2011-04-01

Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

Nitric oxide synthase isoforms in spontaneous and salt hypertension

Czech Academy of Sciences Publication Activity Database

Hojná, Silvie; Kuneš, Jaroslav; Zicha, Josef

2007-01-01

Roč. 25, Suppl. 2 (2007), S 338-S 338 ISSN 0263-6352. [European Meeting on Hypertension /17./. 15.06.2007-19.06.2007, Milan] R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : nitric oxide synthase isoforms * spontaneous and salt hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

Comparison of nitric oxide binding to different pure and mixed protoporphyrin IX monolayers

NARCIS (Netherlands)

Knoben, W.; Crego-Calama, M.; Brongersma, S.H.

2012-01-01

The nitric oxide (NO) binding properties of monolayers of four different protoporphyrins IX adsorbed on aluminum oxide surfaces have been investigated. XPS and AFM results are consistent with the presence of a monolayer of porphyrins, bound to the surface by their carboxylic acid groups and with the

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption.

Science.gov (United States)

van't Hof, R J; Armour, K J; Smith, L M; Armour, K E; Wei, X Q; Liew, F Y; Ralston, S H

2000-07-05

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFkappaB and in NFkappaB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFkappaB in osteoclast precursors.

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

Science.gov (United States)

van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

2000-01-01

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

Kinetic analysis of nitric oxide reduction using biogas as reburning fuel

African Journals Online (AJOL)

STORAGESEVER

2009-05-18

May 18, 2009 ... Emission of nitric oxide (NO) from coal combustion continues to be a significant ... mass has been focused as a renewable fuel without CO2 addition, and researches ..... Giles DE, Som S, Aggarwal SK (2006). NOx emission ...

Variations in exhaled nitric oxide concentration after three types of dives

NARCIS (Netherlands)

van Ooij, Pieter-Jan; Houtkooper, Antoinette; van Hulst, Rob

2010-01-01

An increase in exhaled nitric oxide concentration (FENO) occurs during an exacerbation of chronic obstructive lung disease or other inflammatory processes of the airway. Raised FENO levels are also observed during normobaric, mild hyperoxic exposures, whereas after hyperbaric hyperoxic exposure the

Nitric oxide mediates insect cellular immunity via phospholipase A2 activation

Science.gov (United States)

After infection or invasion is recognized, biochemical mediators act in signaling insect immune functions. These include biogenic amines, insect cytokines, eicosanoids and nitric oxide (NO). Treating insects or isolated hemocyte populations with different mediators often leads to similar results. Se...

Nitric oxide synthase inhibition and cerebrovascular regulation

DEFF Research Database (Denmark)

Iadecola, C; Pelligrino, D A; Moskowitz, M A

1994-01-01

tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large......There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular...

Nitric Oxide Ameliorates Zinc Oxide Nanoparticles Phytotoxicity in Wheat Seedlings: Implication of the Ascorbate–Glutathione Cycle

Science.gov (United States)

Tripathi, Durgesh K.; Mishra, Rohit K.; Singh, Swati; Singh, Samiksha; Vishwakarma, Kanchan; Sharma, Shivesh; Singh, Vijay P.; Singh, Prashant K.; Prasad, Sheo M.; Dubey, Nawal K.; Pandey, Avinash C.; Sahi, Shivendra; Chauhan, Devendra K.

2017-01-01

The present study investigates ameliorative effects of nitric oxide (NO) against zinc oxide nanoparticles (ZnONPs) phytotoxicity in wheat seedlings. ZnONPs exposure hampered growth of wheat seedlings, which coincided with reduced photosynthetic efficiency (Fv/Fm and qP), due to increased accumulation of zinc (Zn) in xylem and phloem saps. However, SNP supplementation partially mitigated the ZnONPs-mediated toxicity through the modulation of photosynthetic activity and Zn accumulation in xylem and phloem saps. Further, the results reveal that ZnONPs treatments enhanced levels of hydrogen peroxide and lipid peroxidation (as malondialdehyde; MDA) due to severely inhibited activities of the following ascorbate–glutatione cycle (AsA–GSH) enzymes: ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase, and its associated metabolites ascorbate and glutathione. In contrast to this, the addition of SNP together with ZnONPs maintained the cellular functioning of the AsA–GSH cycle properly, hence lesser damage was noticed in comparison to ZnONPs treatments alone. The protective effect of SNP against ZnONPs toxicity on fresh weight (growth) can be reversed by 2-(4carboxy-2-phenyl)-4,4,5,5-tetramethyl- imidazoline-1-oxyl-3-oxide, a NO scavenger, and thus suggesting that NO released from SNP ameliorates ZnONPs toxicity. Overall, the results of the present study have shown the role of NO in the reducing of ZnONPs toxicity through the regulation of accumulation of Zn as well as the functioning of the AsA–GSH cycle. PMID:28220127

Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

DEFF Research Database (Denmark)

Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri

2014-01-01

BACKGROUND AND AIM: Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-rela...

Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

Directory of Open Access Journals (Sweden)

Zeliha Selamoglu-Talas

2015-10-01

Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

OpenAIRE

Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

1996-01-01

Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

Extracellular Protein Kinase A Modulates Intracellular Calcium/Calmodulin-Dependent Protein Kinase II, Nitric Oxide Synthase, and the Glutamate-Nitric Oxide-cGMP Pathway in Cerebellum. Differential Effects in Hyperammonemia.

Science.gov (United States)

Cabrera-Pastor, Andrea; Llansola, Marta; Felipo, Vicente

2016-12-21

Extracellular protein kinases, including cAMP-dependent protein kinase (PKA), modulate neuronal functions including N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation. NMDA receptor activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO), which activates guanylate cyclase, increasing cGMP, which is released to the extracellular fluid, allowing analysis of this glutamate-NO-cGMP pathway in vivo by microdialysis. The function of this pathway is impaired in hyperammonemic rats. The aims of this work were to assess (1) whether the glutamate-NO-cGMP pathway is modulated in cerebellum in vivo by an extracellular PKA, (2) the role of phosphorylation and activity of calcium/calmodulin-dependent protein kinase II (CaMKII) and NOS in the pathway modulation by extracellular PKA, and (3) whether the effects are different in hyperammonemic and control rats. The pathway was analyzed by in vivo microdialysis. The role of extracellular PKA was analyzed by inhibiting it with a membrane-impermeable inhibitor. The mechanisms involved were analyzed in freshly isolated cerebellar slices from control and hyperammonemic rats. In control rats, inhibiting extracellular PKA reduces the glutamate-NO-cGMP pathway function in vivo. This is due to reduction of CaMKII phosphorylation and activity, which reduces NOS phosphorylation at Ser1417 and NOS activity, resulting in reduced guanylate cyclase activation and cGMP formation. In hyperammonemic rats, under basal conditions, CaMKII phosphorylation and activity are increased, increasing NOS phosphorylation at Ser847, which reduces NOS activity, guanylate cyclase activation, and cGMP. Inhibiting extracellular PKA in hyperammonemic rats normalizes CaMKII phosphorylation and activity, NOS phosphorylation, NOS activity, and cGMP, restoring normal function of the pathway.

Ultra-low power thin film transistors with gate oxide formed by nitric acid oxidation method

International Nuclear Information System (INIS)

Kobayashi, H.; Kim, W. B.; Matsumoto, T.

2011-01-01

We have developed a low temperature fabrication method of SiO 2 /Si structure by use of nitric acid, i.e., nitric acid oxidation of Si (NAOS) method, and applied it to thin film transistors (TFT). A silicon dioxide (SiO 2 ) layer formed by the NAOS method at room temperature possesses 1.8 nm thickness, and its leakage current density is as low as that of thermally grown SiO 2 layer with the same thickness formed at ∼900 deg C. The fabricated TFTs possess an ultra-thin NAOS SiO 2 /CVD SiO 2 stack gate dielectric structure. The ultrathin NAOS SiO 2 layer effectively blocks a gate leakage current, and thus, the thickness of the gate oxide layer can be decreased from 80 to 20 nm. The thin gate oxide layer enables to decrease the operation voltage to 2 V (cf. the conventional operation voltage of TFTs with 80 nm gate oxide: 12 V) because of the low threshold voltages, i.e., -0.5 V for P-ch TFTs and 0.5 V for N-ch TFTs, and thus the consumed power decreases to 1/36 of that of the conventional TFTs. The drain current increases rapidly with the gate voltage, and the sub-threshold voltage is ∼80 mV/dec. The low sub-threshold swing is attributable to the thin gate oxide thickness and low interface state density of the NAOS SiO 2 layer. (authors)

Inhibition of nitric oxide synthesis by systemic N(G)-monomethyl-L-arginine administration in humans

DEFF Research Database (Denmark)

Frandsen, U; Bangsbo, J; Langberg, Henning

2000-01-01

(controls) and with prior N(G)-nitro-L-arginine methyl ester (L-NAME) infusion (4 mg/kg, intravenously). Samples from the interstitial fluid were obtained at rest, during exercise and after exercise with the microdialysis technique. Interstitial adenosine in controls increased (p0.05) to controls. The 6......-keto-prostaglandin F1alpha concentration in controls was 1.17+/-0.20 ng/ml at rest and increased (p0.05) in L-NAME. The interstitial K(+) concentration in controls increased (p......We examined whether the formation or the release of the vasodilators adenosine, prostacyclin (PGI(2)) and potassium (K(+)) increase in skeletal muscle interstitium in response to nitric oxide synthase (NOS) inhibition. Five subjects performed one-legged knee extensor exercise at 30 W without...

The effect of energetic electron precipitation on the nitric oxide density in the lower thermosphere

International Nuclear Information System (INIS)

Saetre, Camilla

2006-12-01

The objective of this thesis has been the study of the chemical effects of the electron precipitation in the upper atmosphere, and mainly the increase of thermospheric nitric oxide (NO). NO plays an important role in the temperature balance for the mesosphere and thermosphere.In this project auroral electron precipitation data, derived from the Polar Ionospheric X-ray Imaging Experiment (PIXIE) and the Ultraviolet Imager (UVI) on board the Polar satellite, have been used together with NO density measurements from the Student Nitric Oxide Explorer (SNOE)

Inhibition of inducible nitric oxide synthesis by azathioprine in a macrophage cell line.

Science.gov (United States)

Moeslinger, Thomas; Friedl, Roswitha; Spieckermann, Paul Gerhard

2006-06-20

Azathioprine is used as an anti-inflammatory agent. Although there are numerous data demonstrating cytotoxic and immunosuppressive properties of azathioprine and its metabolite 6-mercaptopurine, the mechanism of the anti-inflammatory action of azathioprine has not yet been fully clarified. During our study, we investigated the effects of azathioprine on the inducible nitric oxide synthase (iNOS) in lipopolysaccharide stimulated murine macrophages (RAW 264.7) by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), and NO production (nitrite levels). Azathioprine (0-210 muM) induces a concentration dependent inhibition of inducible nitric oxide synthesis (IC50: 33.5 muM). iNOS protein expression showed a concentration dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of azathioprine. Azathioprine decreases iNOS mRNA levels as shown by semiquantitative competitive RT-PCR. In contrast, 6-mercaptopurine showed no inhibition of inducible nitric oxide synthesis. Azathioprine did not reduce iNOS mRNA stability after the addition of actinomycin D. Enzymatic activity assays with increasing concentrations of azathioprine (0-210 muM) showed no statistically significant inhibition of iNOS enzyme activity compared to cell lysates without azathioprine. Nuclear translocation of NF-kappaB p65 subunit and binding of NF-kappaB p50 subunit from nuclear extracts to a biotinylated-consensus sequence was unaffected by azathioprine treatment. iNOS inhibition by azathioprine was associated with a decreased expression of IRF-1 (interferon regulatory factor 1) and IFN-beta (beta-interferon) mRNA. Azathioprine induced iNOS inhibition seems to be associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic anti-inflammatory agents by replacing the 6-mercaptopurine component of azathioprine with other substituents. The inhibition of

Neuronal Nitric-Oxide Synthase Deficiency Impairs the Long-Term Memory of Olfactory Fear Learning and Increases Odor Generalization

Science.gov (United States)

Pavesi, Eloisa; Heldt, Scott A.; Fletcher, Max L.

2013-01-01

Experience-induced changes associated with odor learning are mediated by a number of signaling molecules, including nitric oxide (NO), which is predominantly synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current study, we investigated the role of nNOS in the acquisition and retention of conditioned olfactory fear. Mice…

Inhaled Nitric Oxide for the Prevention of Impaired Arterial Oxygenation during Myocardial Revascularization with Extracorporeal Circulation

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I. A. Kozlov

2011-01-01

Full Text Available Objective: to study the efficacy of inhaled nitric oxide used intraoperatively to prevent lung oxygenating dysfunction in patients with coronary heart disease after myocardial revascularization under extracorporeal circulation (EC. Subjects and methods. Thirty-two patients aged 55.0±2.0 years were examined. The inclusion criteria were the standard course of surgical intervention (the absence of hemorrhage, acute cardiovascular insufficiency, perioperative myocardial infarction, etc., a pulmonary artery wedge pressure of less than 15 – mm Hg throughout the study, and the baseline arterial partial oxygen tension/inspired mixture oxygen fraction (PaO2/FiO2 ratio of at least 350 mm Hg. There was a control group (n=21; Group 1 that used no special measures to prevent and/or to correct lung oxygenating dysfunction and Group 2 (n=11 that received inhaled nitric oxide. Ihe administration of inhaled nitric oxide at a concentration of 10 ppm was initiated after water anesthesia, stopped during EC, and resumed in the postperfusion period. Results. At the end, PaO2/FiO2 and intrapulmonary shunt fraction did not differ between the groups (p>0.05. Before EC, the patients receiving inhaled nitric oxide had a lower intrapulmonary blood shunting (8.9±0.7 and 11.7±1.0%; p<0.05. There were no intergroup differences in the values of PaO2/FiO2 at this stage. In the earliest postperfusion period, PaO2/FiO2 was higher in Group 2 than that in Group 1. At the end of operations, Groups 1 and 2 had a PaO2/FiO2 of 336.0±16.8 and 409.0±24.3 mm Hg, respectively (p<0.05 and an intrapulmonary shunt fraction of 14.5±1.0 and 10.4±1.0% (p<0.05. At the end of surgery, the rate of a reduction in PaO2/FiO2 to the level below 350 mm Hg was 52.4±11.1% in Group 1 and 18.2±11.6% in Group 2 (p<0.05. Six hours after surgery, PaO2/FiO2 values less than 300 mm Hg were diagnosed in 61.9±10.5% of Group 1 patients and in 27.3±13.4% of Group 2 ones (p<0.05. Conclusion. The

Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli.

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Zengli Yu

2008-05-01

Full Text Available Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS and nitric oxide (NO determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx/atrogin-1 and muscle RING finger-1 (MuRF1, in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

Quantum dots-hyperbranched polyether hybrid nanospheres towards delivery and real-time detection of nitric oxide

Energy Technology Data Exchange (ETDEWEB)

Liu, Shuiping; Gu, Tianxun; Fu, Jiajia [Key Laboratory of Eco-Textiles, Ministry of Education (Jiangnan University), Wuxi 214122 (China); College of Textile and Clothing, Jiangnan University, Wuxi 214122 (China); Li, Xiaoqiang, E-mail: leecaiwei@163.com [Key Laboratory of Eco-Textiles, Ministry of Education (Jiangnan University), Wuxi 214122 (China); College of Textile and Clothing, Jiangnan University, Wuxi 214122 (China); Technical University of Denmark, DTU Food, Søltofts plads, B227, 2800 Kgs. Lyngby (Denmark); Chronakis, Ioannis S. [Technical University of Denmark, DTU Food, Søltofts plads, B227, 2800 Kgs. Lyngby (Denmark); Ge, Mingqiao [Key Laboratory of Eco-Textiles, Ministry of Education (Jiangnan University), Wuxi 214122 (China); College of Textile and Clothing, Jiangnan University, Wuxi 214122 (China)

2014-12-01

In this work, novel hybrid nanosphere vehicles were synthesized for nitric oxide (NO) donating and real-time detection. The hybrid nanosphere vehicles consist of cadmium selenide quantum dots (CdSe QDs) as NO fluorescent probes, and the modified hyperbranched polyether (mHP)-based diazeniumdiolates as NO donors, respectively. The nanospheres have spherical outline with dimension of ∼ 127 nm. The data of systematic characterization demonstrated that the mHP-based hybrid nanosphere vehicles (QDs-mHP-NO) can release and real-time detect NO with the low limit of 25 nM, based on fluorescence quenching mechanism. The low cell-toxicity of QDs-mHP-NO nanospheres was verified by means of MTT assay on L929 cells viability. The QDs-mHP-NO nanospheres provide perspectives for designing a new class of biocompatible NO donating and imaging systems. - Highlights: • QDs-mHP-NO fluorescent probe was prepared. • The QDs-mHP-NO probe is capable of releasing NO. • The QDs-mHP-NO probe can quantitatively detecting the release of NO in real time. • The low cell-toxicity of QDs-mHP-NO nanospheres was verified.

Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

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Ketab E. Al-Otaibi

2012-01-01

Full Text Available Contrast media- (CM- induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN. Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels and myeloperoxidase (MPO and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

Reduction of nitric oxide by arc vaporized carbons (AVC)

Energy Technology Data Exchange (ETDEWEB)

Tsang, S C; Chen, Y K; Green, M L.H. [The Catalysis Centre, Inorganic Chemistry Laboratory, University of Oxford, Oxford (United Kingdom)

1996-07-04

The reduction of nitric oxide by arc vaporized carbons (AVC) including the compound C{sub 6}0, fullerene soot and carbon nanotubes, giving dinitrogen and carbon oxides has been studied. It is found that the AVC carbons are more active towards oxidation by NO than by oxygen gas at low temperatures (300-400C). In contrast, conventional carbons such as graphite and microporous carbons are more readily oxidised by oxygen than by NO. The addition of copper salts and to a lesser extent, cobalt salts, to fullerene soot substantially promote NO reduction. The high intrinsic activity for NO reduction by AVC carbons compared to graphitic carbons is attributed to the presence of five membered carbon rings in the AVC carbons

Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide

DEFF Research Database (Denmark)

Randsøe, Thomas; Hyldegaard, O

2014-01-01

. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i......INTRODUCTION: Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving...

The Effect of Central Amygdala Nitric Oxide in Expression Of Drug Seeking Behaviors

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Mahnaz Rahimpour

2011-11-01

Full Text Available Introduction: Previous studies shows L-arginin (nitric oxide precursor increases conditioned place preference and drug seeking behaviors whereas LG-nitro-arginine methyl ester L-NAME( as nitric oxide synthase inhibitor decreases this process. In this project, effects of intra-central amygdale bilateral injection of nitric oxide agents on drug-seeking behaviors including rearing, sniffing and compartment entrance were investigated. Method: animals were wistar male rats (200-250 g which allowed to be recovered after they’re being suffered from a surgery by strereotaxis apparatus to be cannulated in coordination of central amygdale nucleus (CeA. CPP was conducted using a five-day schedule of unbiased procedure. Findings: morphine (2.5-10 mg/kg s.c induced significant drug-seeking behaviors. Naloxone (0.1-0.4 mg/kg i.p injection pretesting (after conditioning by morphine 7.5 mg/kg decreased the expression of behaviors. When L-arginine (0.3-3 µgr/rat injected intra–CeA prior to naloxone (0.4 mg/kg, increased behaviors but L-NAME (0.3-3 µgr/rat intra–CeA injections prior to L-arginine (0.3 µgr/rat pretesting, caused significant decreasement of L-arginine response. Conclusion: NO in the CeA may play an important role in the drug seeking behaviors induced of morphine.

Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate.

Science.gov (United States)

Dey, Anupa; Lang, Richard J; Exintaris, Betty

2012-06-01

We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Conventional intracellular microelectrode and tension recording techniques were used. The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA pguinea pig prostates (Student paired t test pproduction. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Oxidation of urate by a therapeutic nitric oxide/air mixture

International Nuclear Information System (INIS)

Hicks, M.; Nguyen, L.; Day, R.; Rogers, P.

1996-01-01

Full text: Little is known about the potential toxicological consequences of therapeutic exposure of lung tissue to inhaled nitric oxide (NO). This route of administration is currently being successfully employed for the treatment of pulmonary hypertension and other lung pathologies including acute reperfusion injury in lung transplant patients. The toxicity of NO lies in its ability to act as an oxidant either in its own right or in concert with oxygen or with the superoxide free radical. One important interaction may be the reaction of these products with protective antioxidants in the lung epithelial lining fluid. One such antioxidant found in significant concentrations in both upper and lower airways is uric acid. In the present study, urate solutions (30μM) were exposed to a therapeutic concentration of NO gas, (35 ppm in air), for up to 90 minutes. Oxidative changes were followed spectrophotometrically and by HPLC. Significant loss of uric acid was observed with a concomitant formation of nitrite and allantoin, the stable oxidation product of NO and the major oxidation product of uric acid, respectively. No oxidation of urate was observed in the presence of air alone or when urate was incubated with nitrite. Uric acid oxidation could also be prevented by passing the NO / air stream through 10% KOH before the uric acid solution. This strategy removed trace amounts of higher oxides of nitrogen, (especially NO 2 ), from the NO / air stream. Thus, therapeutic inhalation of NO may deplete soluble antioxidants such as uric acid, especially during long-term chronic exposure unless care is taken to minimise formation of higher oxides of nitrogen

Nitric oxide nanoparticles: pre-clinical utility as a therapeutic for intramuscular abscesses.

Science.gov (United States)

Schairer, David; Martinez, Luis R; Blecher, Karin; Chouake, Jason; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M; Nosanchuk, Joshua D; Friedman, Adam

2012-01-01

Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections.

Arginase expression modulates nitric oxide production in Leishmania (Leishmania) amazonensis.

Science.gov (United States)

Acuña, Stephanie Maia; Aoki, Juliana Ide; Laranjeira-Silva, Maria Fernanda; Zampieri, Ricardo Andrade; Fernandes, Juliane Cristina Ribeiro; Muxel, Sandra Marcia; Floeter-Winter, Lucile Maria

2017-01-01

Arginase is an enzyme that converts L-arginine to urea and L-ornithine, an essential substrate for the polyamine pathway supporting Leishmania (Leishmania) amazonensis replication and its survival in the mammalian host. L-arginine is also the substrate of macrophage nitric oxide synthase 2 (NOS2) to produce nitric oxide (NO) that kills the parasite. This competition can define the fate of Leishmania infection. The transcriptomic profiling identified a family of oxidoreductases in L. (L.) amazonensis wild-type (La-WT) and L. (L.) amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. We highlighted the identification of an oxidoreductase that could act as nitric oxide synthase-like (NOS-like), due to the following evidences: conserved domain composition, the participation of NO production during the time course of promastigotes growth and during the axenic amastigotes differentiation, regulation dependence on arginase activity, as well as reduction of NO amount through the NOS activity inhibition. NO quantification was measured by DAF-FM labeling analysis in a flow cytometry. We described an arginase-dependent NOS-like activity in L. (L.) amazonensis and its role in the parasite growth. The increased detection of NO production in the mid-stationary and late-stationary growth phases of La-WT promastigotes could suggest that this production is an important factor to metacyclogenesis triggering. On the other hand, La-arg- showed an earlier increase in NO production compared to La-WT, suggesting that NO production can be arginase-dependent. Interestingly, La-WT and La-arg- axenic amastigotes produced higher levels of NO than those observed in promastigotes. As a conclusion, our work suggested that NOS-like is expressed in Leishmania in the stationary growth phase promastigotes and amastigotes, and could be correlated to metacyclogenesis and amastigotes growth in a dependent way to the internal pool of L-arginine and arginase activity.

Reduction Rates for Higher Americium Oxidation States in Nitric Acid

Energy Technology Data Exchange (ETDEWEB)

Grimes, Travis Shane [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mincher, Bruce Jay [Idaho National Lab. (INL), Idaho Falls, ID (United States); Schmitt, Nicholas C [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2015-09-30

The stability of hexavalent americium was measured using multiple americium concentrations and nitric acid concentrations after contact with the strong oxidant sodium bismuthate. Contrary to our hypotheses Am(VI) was not reduced faster at higher americium concentrations, and the reduction was only zero-order at short time scales. Attempts to model the reduction kinetics using zero order kinetic models showed Am(VI) reduction in nitric acid is more complex than the autoreduction processes reported by others in perchloric acid. The classical zero-order reduction of Am(VI) was found here only for short times on the order of a few hours. We did show that the rate of Am(V) production was less than the rate of Am(VI) reduction, indicating that some Am(VI) undergoes two electron-reduction to Am(IV). We also monitored the Am(VI) reduction in contact with the organic diluent dodecane. A direct comparison of these results with those in the absence of the organic diluent showed the reduction rates for Am(VI) were not statistically different for both systems. Additional americium oxidations conducted in the presence of Ce(IV)/Ce(III) ions showed that Am(VI) is reduced without the typical growth of Am(V) observed in the systems sans Ce ion. This was an interesting result which suggests a potential new reduction/oxidation pathway for Am in the presence of Ce; however, these results were very preliminary, and will require additional experiments to understand the mechanism by which this occurs. Overall, these studies have shown that hexavalent americium is fundamentally stable enough in nitric acid to run a separations process. However, the complicated nature of the reduction pathways based on the system components is far from being rigorously understood.

of endothelial nitric oxide synthase gene and serum level of vascular ...

African Journals Online (AJOL)

uwerhiavwe

Davignon and Ganz, 2004). NO is synthe- sized via a reaction that includes the conversion of L- arginine to L-citruline catalyzed by endothelial nitric oxide synthase (eNOS), which is one of the three isoforms of the enzyme (Mayer and Hemmens, 1997) ...

Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase

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Kao Ming-Ching

2011-02-01

Full Text Available Abstract Background Hyperbaric oxygen therapy (HBOT is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS, is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.

Nitric oxide and plant iron homeostasis.

Science.gov (United States)

Buet, Agustina; Simontacchi, Marcela

2015-03-01

Like all living organisms, plants demand iron (Fe) for important biochemical and metabolic processes. Internal imbalances, as a consequence of insufficient or excess Fe in the environment, lead to growth restriction and affect crop yield. Knowledge of signals and factors affecting each step in Fe uptake from the soil and distribution (long-distance transport, remobilization from old to young leaves, and storage in seeds) is necessary to improve our understanding of plant mineral nutrition. In this context, the role of nitric oxide (NO) is discussed as a key player in maintaining Fe homeostasis through its cross talk with hormones, ferritin, and frataxin and the ability to form nitrosyl-iron complexes. © 2015 New York Academy of Sciences.

Cycling above rather than below lactate threshold is more effective for nitric oxide release and post-exercise blood pressure reduction in individuals with type-2 diabetes

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Ricardo Yukio Asano

2013-09-01

Full Text Available The purposes of this study were to analyze and compare the effects of exercise performed in different intensities, above and below lactate threshold (LT on post-exercise blood pressure (BP and nitric oxide (NO responses in individuals with type 2 diabetes (T2D. For this, 11 T2D underwent the following sessions: 1 control session; 2 20-min of moderate cycling (80% LT; and 3 20-min of high intensity cycling (120%LT on a cycle ergometer. Plasma NO and BP measurements were carried out at rest and at 15 and 45 min of post-sessions. When compared to rest, only the exercise session performed at 120%LT elicited an increase of NO (from 7.2 to 9.5 µM, p<0.05, as well as a decrease in systolic BP (from 126.6±7.9 to 118.7±3.9 mmHg, p<0.05 during the post-exercise period. In conclusion, the results suggest that NO release and post-exercise BP decrease are intensity-dependent for individuals with T2D.

The role of nitric oxide radicals in removal of hyper-radiosensitivity by priming irradiation

International Nuclear Information System (INIS)

Edin, Nina Jeppesen; Sandvik, Joe Alexander; Pettersen, Erik Olai; Vollan, Hilde Synnove; Reger, Katharina; Görlach, Agnes

2013-01-01

In this study, a mechanism in which low-dose hyper-radiosensitivity (HRS) is permanently removed, induced by low-dose-rate (LDR) (0.2 - 0.3 Gy/h for 1 h) but not by high-dose-rate priming (0.3 Gy at 40 Gy/h) was investigated. One HRS-negative cell line (NHIK 3025) and two HRS-positive cell lines (T-47D, T98G) were used. The effects of different pretreatments on HRS were investigated using the colony assay. Cell-based ELISA was used to measure nitric oxide synthase (NOS) levels, and microarray analysis to compare gene expression in primed and unprimed cells. The data show how permanent removal of HRS, previously found to be induced by LDR priming irradiation, can also be induced by addition of nitric oxide (NO)-donor DEANO combined with either high-dose-rate priming or exposure to prolonged cycling hypoxia followed by reoxygenation, a treatment not involving radiation. The removal of HRS appears not to involve DNA damage induced during priming irradiation as it was also induced by LDR irradiation of cell-conditioned medium without cells present. The permanent removal of HRS in LDR-primed cells was reversed by treatment with inducible nitric oxide synthase (iNOS) inhibitor 1400W. Furthermore, 1400W could also induce HRS in an HRS-negative cell line. The data suggest that LDR irradiation for 1 h, but not 15 min, activates iNOS, and also that sustained iNOS activation is necessary for the permanent removal of HRS by LDR priming. The data indicate that nitric oxide production is involved in the regulatory processes determining cellular responses to low-dose-rate irradiation. (author)

The effect of weight loss on serum concentrations of nitric oxide induced by short - term exercise in obese women

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M Olszanecka-Glinianowicz

2009-07-01

Full Text Available Objective: The aim of present study was to examine the effect of weight loss comprising regular moderate physical activity on resting serum concentrations of nitric oxide metabolites and exercise induced NO release. Materials and Methods: The study was carried out in 43 obese women without additional diseases (age 41.8±11.9y, body weight 94.5±15.1kg, BMI 36.5±4.6kg/m2. All obese patients participated in a 3-month weight reduction programme that consisted of 1 a group instruction in behavioural and dietary methods of weight control every two weeks; 2 1000-1400kcal/day balanced diet, and 3 moderate physical exercises (30 minutes, 3 times a week. Before and after treatment body mass and height were measured, body mass index (BMI was calculated. Body composition was determined by impedance analysis using a Bodystat analyser. The serum concentration of nitric oxide metabolites before and after exercise was measured using spectrophotometry method by Griess. The serum concentrations of lactate before and after exercise were measured with the use of strip test (ACCUSPORT analyzer. Serum concentration of insulin was measured with the use of RIA. Plasma glucose, cholesterol, HDL cholesterol and triglicerydes were determined by enzymatic procedure. Results: The mean weight loss during treatment was 8.3±4.3 kg. We did not observe differences between resting serum concentrations of NO and lactate before and after weight loss. During exercise serum NO concentrations increased significantly both before and after weight loss treatment. After the weight reduction treatment, the time of exercise test increased significantly P<0.005, but there were no significant differences between the value of NO before and after weight loss. Conclusion: 3 – month regular physical activity and weight loss did not influence exercise-induced nitric oxide production.

Platelet-activating factor dilates efferent arterioles through glomerulus-derived nitric oxide.

Science.gov (United States)

Arima, S; Ren, Y; Juncos, L A; Ito, S

1996-01-01

Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation is poorly understood. It was recently reported that at picomolar concentrations, PAF dilates isolated microperfused afferent arterioles (Af-Art) via nitric oxide (NO). The present study tested the hypothesis that PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were perfused from the distal end (retrograde perfusion [RP]) to eliminate the influence of the glomerulus, or through the glomerulus from the end of the Af-Art (orthograde perfusion [OP]) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with norepinephrine and increasing doses of PAF were added to both the arteriolar perfusate and bath. Only with OP did PAF at picomolar concentrations cause significant dilation: at 400 pmol, the diameter increased by 64 +/- 11% from the preconstricted level (N = 6, P Art. At nanomolar concentrations, PAF constricted Ef-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P OP (10 +/- 2%, N = 6; P Art; and (2) at nanomolar concentrations, PAF constricts the Ef-Art partly through release of cyclooxygenase metabolites. Thus, PAF may play a role in glomerular hemodynamics under various physiological and pathological conditions.

JS-K, a Nitric Oxide Prodrug, Has Enhanced Cytotoxicity in Colon Cancer Cells with Knockdown of Thioredoxin Reductase 1

Science.gov (United States)

Edes, Kornelia; Cassidy, Pamela; Shami, Paul J.; Moos, Philip J.

2010-01-01

Background The selenoenzyme thioredoxin reductase 1 has a complex role relating to cell growth. It is induced as a component of the cellular response to potentially mutagenic oxidants, but also appears to provide growth advantages to transformed cells by inhibiting apoptosis. In addition, selenocysteine-deficient or alkylated forms of thioredoxin reductase 1 have also demonstrated oxidative, pro-apoptotic activity. Therefore, a greater understanding of the role of thioredoxin reductase in redox initiated apoptotic processes is warranted. Methodology The role of thioredoxin reductase 1 in RKO cells was evaluated by attenuating endogenous thioredoxin reductase 1 expression with siRNA and then either inducing a selenium-deficient thioredoxin reductase or treatment with distinct redox challenges including, hydrogen peroxide, an oxidized lipid, 4-hydroxy-2-nonenol, and a nitric oxide donating prodrug. Thioredoxin redox status, cellular viability, and effector caspase activity were measured. Conclusions/Significance In cells with attenuated endogenous thioredoxin reductase 1, a stably integrated selenocysteine-deficient form of the enzyme was induced but did not alter either the thioredoxin redox status or the cellular growth kinetics. The oxidized lipid and the nitric oxide donor demonstrated enhanced cytotoxicity when thioredoxin reductase 1 was knocked-down; however, the effect was more pronounced with the nitric oxide prodrug. These results are consistent with the hypothesis that attenuation of the thioredoxin-system can promote apoptosis in a nitric oxide-dependent manner. PMID:20098717

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase.

Science.gov (United States)

Xiao, Ran; Li, Shan; Cao, Qian; Wang, Xiuling; Yan, Qiujin; Tu, Xiaoning; Zhu, Ying; Zhu, Fan

2017-06-01

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

JS-K, a glutathione/glutathione S-transferase-activated nitric oxide releasing prodrug inhibits androgen receptor and WNT-signaling in prostate cancer cells.

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Laschak, Martin; Spindler, Klaus-Dieter; Schrader, Andres J; Hessenauer, Andrea; Streicher, Wolfgang; Schrader, Mark; Cronauer, Marcus V

2012-03-30

Nitric oxide (NO) and its oxidative reaction products have been repeatedly shown to block steroid receptor function via nitrosation of zinc finger structures in the DNA-binding domain (DBD). In consequence NO-donors could be of special interest for the treatment of deregulated androgen receptor(AR)-signaling in castration resistant prostate cancer (CRPC). Prostate cancer (PCa) cells were treated with JS-K, a diazeniumdiolate derivate capable of generating large amounts of intracellular NO following activation by glutathione S-transferase. Generation of NO was determined indirectly by the detection of nitrate in tissue culture medium or by immunodetection of nitrotyrosine in the cytoplasm. Effects of JS-K on intracellular AR-levels were determined by western blotting. AR-dimerization was analyzed by mammalian two hybrid assay, nuclear translocation of the AR was visualized in PCa cells transfected with a green fluorescent AR-Eos fusion protein using fluorescence microscopy. Modulation of AR- and WNT-signalling by JS-K was investigated using reporter gene assays. Tumor cell proliferation following JS-K treatment was measured by MTT-Assay. The NO-releasing compound JS-K was shown to inhibit AR-mediated reporter gene activity in 22Rv1 CRPC cells. Inhibition of AR signaling was neither due to an inhibition of nuclear import nor to a reduction in AR-dimerization. In contrast to previously tested NO-donors, JS-K was able to reduce the intracellular concentration of functional AR. This could be attributed to the generation of extremely high intracellular levels of the free radical NO as demonstrated indirectly by high levels of nitrotyrosine in JS-K treated cells. Moreover, JS-K diminished WNT-signaling in AR-positive 22Rv1 cells. In line with these observations, castration resistant 22Rv1 cells were found to be more susceptible to the growth inhibitory effects of JS-K than the androgen dependent LNCaP which do not exhibit an active WNT-signaling pathway. Our results

Involvement of the nitric oxide in melatonin-mediated protection against injury.

Science.gov (United States)

Fan, Wenguo; He, Yifan; Guan, Xiaoyan; Gu, Wenzhen; Wu, Zhi; Zhu, Xiao; Huang, Fang; He, Hongwen

2018-05-01

Melatonin is a hormone mainly synthesized by the pineal gland in vertebrates and known well as an endogenous regulator of circadian and seasonal rhythms. It has been demonstrated that melatonin is involved in many physiological and pathophysiological processes showing antioxidant, anti-apoptotic and anti-inflammatory properties. Nitric oxide (NO) is a free radical gas in the biological system, which is produced by nitric oxide synthase (NOS) family. NO acts as a biological mediator and plays important roles in different systems in humans. The NO/NOS system exerts a broad spectrum of signaling functions. Accumulating evidence has clearly revealed that melatonin regulates NO/NOS system through multiple mechanisms that may influence physiological and pathophysiological processes. This article reviews the latest evidence for the effects of melatonin on NO/NOS regulation in different organs and disease conditions, the potential cellular mechanisms by which melatonin is involved in organ protection are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Nitric oxide production from macrophages is regulated by arachidonic acid metabolites.

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Imai, Y; Kolb, H; Burkart, V

1993-11-30

In activated macrophages the inducible form of the enzyme nitric oxide (NO) synthase generates high amounts of the toxic mediator NO. After 20 h of treatment with LPS rat peritoneal macrophages release 12-16 nmol NO2-/10(5) cells which is detectable in the culture supernatant by the Griess reaction as a measure of NO formation. The addition of aminoguanidine (1 mM), a preferential inhibitor of the inducible NO-synthase, completely abolished NO2-accumulation. Incubation with indomethacin or acetyl-salicylic acid, preferential inhibitors of the cyclooxygenase pathway of the arachidonic acid metabolism, did not influence NO2- levels. Nordihydro-guaiaretic acid (50 microM), a preferential inhibitor of the lipoxygenase pathway, caused strong reduction of NO2- accumulation to 1.9 +/- 0.3 nmol/200 microliter. Simultaneous inhibition of cyclo- and lipoxygenase by BW755c resulted in an intermediate effect (7.3 +/- 1.1 nmol/200 microliter NO2-). These results show that the induction of NO production in activated macrophages is regulated by products of the lipoxygenase-pathway of the arachidonic acid metabolism.

Geomagnetic control of mesospheric nitric oxide concentration from simultaneous D and F region ionization measurements

International Nuclear Information System (INIS)

Pradhan, S.N.; Shirke, J.S.

1978-01-01

Investigations are made of D-region electron density profiles derived from 'partial reflection' measurements over a low latitude station (Ahmedabad) during a year of low solar activity. The index relating the electron density with the solar zenith angle is found to increase towards lower zenith angles suggesting both diurnal and seasonal variations in the Nitric oxide concentration. A close correlation is also found between the electron density at 80 km and the maximum ionization density in the F region above. This is interpreted as due to concomitant variation of a sizeable fraction of the Nitric oxide concentration in the mesosphere and lower thermosphere with the overhead F region ionization. A simplified global model is presented for the mesospheric Nitric oxide concentration based on the morphological features of F region and the relationship existing between the ionization levels in F and D regions. Many observed features of the D region ionization including the solar zenith angle dependence, latitudinal and geomagnetic anomaly and long term variability are explained on the basis of this model

Role of nitric oxide in the radiation-induced bystander effect.

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Yakovlev, Vasily A

2015-12-01

Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Investigations on the oxidation of nitric acid plutonium solutions with ozone

International Nuclear Information System (INIS)

Boehm, M.

1983-01-01

The reaction of ozone with nitric acid Pu solutions was studied as a function of reaction time, acid concentration and Pu concentration. Strong nitric acid Pu solutions are important in nuclear fuel element production and reprocessing. The Pu must be converted into hexavalent Pu before precipitation from the homogeneous solution together with uranium-IV, ammonia and CO 2 in the form of ammonium uranyl/plutonyl carbonate (AUPuC). Formation of a solid phase during ozonation was observed for the first time. The proneness to solidification increases with incrasing plutonium concentrations and with decreasing acid concentrations. If the formation of a solid phase during ozonation of nitric acid Pu solutions cannot be prevented, the PU-IV oxidation process described is unsuitable for industrial purposes as Pu solutions in industrial processes have much higher concentrations than the solutions used in the present investigation. (orig./EF) [de

Nitric oxide in plants: an assessment of the current state of knowledge

DEFF Research Database (Denmark)

Mur, Luis A J; Mandon, Julien; Persijn, Stefan

2013-01-01

Background and aims After a series of seminal works during the last decade of the 20th century nitric oxide (NO) is now firmly placed in the pantheon of plant signals. NO acts in plant-microbe interactions, responses to abiotic stress, stomatal regulation and a range of developmental processes...... of NO production from DEANO (diethylamine nitric oxide), S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP) following infiltration of tobacco leaves which could aid workers in their experiments. Further, based on current data it is difficult to define a bespoke plant NO signalling pathway, but rather....... By considering the recent advances in plant NO biology, this review will highlight certain key aspects that require further attention. Scope and conclusions The following questions will be considered. Whilst cytosolic nitrate reductase is an important source of NO, the contributions of other mechanisms...

Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture

DEFF Research Database (Denmark)

Jansen-Olesen, Inger; Zhou, MingFang; Zinck, Tina Jovanovic

2005-01-01

RNA and protein could be detected. The data suggest that iNOS expression may be a molecular mechanism mediating the adaptive response of trigeminal ganglia cells to the serum free stressful stimulus the culture environment provides. It may act as a cellular signalling molecule that is expressed after cell......Nitric oxide (NO) is an important signalling molecule that has been suggested to be a key molecule for induction and maintenance of migraine attacks based on clinical studies, animal experimental studies and the expression of nitric oxide synthase (NOS) immunoreactivity within the trigeminovascular......, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In trigeminal ganglia cells not subjected to culture, endothelial (e) and neuronal (n) but not inducible (i) NOS mRNA and protein were detected. Culture of rat neurones resulted in a rapid axonal outgrowth of NOS positive...

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

Science.gov (United States)

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.

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Ning, Shoucheng; Bednarski, Mark; Oronsky, Bryan; Scicinski, Jan; Knox, Susan J

2014-05-09

Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa

Science.gov (United States)

Song, Hao; Lavoie, Michel; Fan, Xiaoji; Tan, Hana; Liu, Guangfu; Xu, Pengfei; Fu, Zhengwei; Paerl, Hans W; Qian, Haifeng

2017-01-01

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors. PMID:28398349

Exhaled nitric oxide in stable chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Beg Mohammed F S; Alzoghaibi, Mohammad A; Habib, Syed S; Abba, Abdullah A

2009-01-01

The objective of the study was to test the hypothesis that fraction of exhaled nitric oxide (FENO) is elevated in nonsmoking subjects with stable chronic obstructive pulmonary disease (COPD) and compare it with the results in patients with asthma and a control population. Pulmonology Clinic at a University Hospital. Twenty five control subjects, 25 steroid naive asthmatics and 14 COPD patients were studied. All the patients were nonsmokers and stable at the time of the study. All subjects completed a questionnaire and underwent spirometry. Exhaled nitric oxide was measured online by chemiluminescence, using single-breath technique. All the study subjects were males. Subjects with stable COPD had significantly higher values of FENO than controls (56.54+ - 28.01 vs 22.00 + -6.69; P =0.0001) but lower than the subjects with asthma (56.54+ - 28.01 vs 84.78+ - 39.32 P 0.0285). The FENO values in COPD subjects were inversely related to the FEV 1 /FVC ratio. There was a significant overlap between the FENO values in COPD and the control subjects. There is a significant elevation in FENO in patients with stable COPD, but the elevation is less than in asthmatic subjects. Its value in clinical practice may be limited by the significant overlap with control subjects. (author)

Lower thermospheric nitric oxide concentrations derived from WINDII observations of the green nightglow continuum at 553.1 nm

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C. H. A. von Savigny

1999-11-01

Full Text Available Vertical profiles of nitric oxide in the altitude range 90 to 105 km are derived from 553 nm nightglow continuum measurements made with the Wind Imaging Interferometer (WINDII on the Upper Atmosphere Research Satellite (UARS. The profiles are derived under the assumption that the continuum emission is due entirely to the NO+O air afterglow reaction. Vertical profiles of the atomic oxygen density, which are required to determine the nitric oxide concentrations, are derived from coordinated WINDII measurements of the atomic oxygen OI 557.7 nm nightglow emission. Data coverage for local solar times ranging from 20 h to 04 h, and latitudes ranging from 42°S to 42°N, is achieved by zonally averaging and binning data obtained on 18 nights during a two-month period extending from mid-November 1992 until mid-January 1993. The derived nitric oxide concentrations are significantly smaller than those obtained from rocket measurements of the airglow continuum but they do compare well with model expectations and nitric oxide densities measured using the resonance fluorescence technique on the Solar Mesosphere Explorer satellite. The near-global coverage of the WINDII observations and the similarities to the nitric oxide global morphology established from other satellite measurements strongly suggests that the NO+O reaction is the major source of the continuum near 553 nm and that there is no compelling reason to invoke additional sources of continuum emission in this immediate spectral region.Key words. Atmospheric composition and structure (airglow and aurora; thermosphere – composition and chemistry; instruments and techniques

Role of the decreased nitric oxide bioavailability in the vascular complications of diabetes mellitus.

Science.gov (United States)

Masha, Andi; Dinatale, Stefano; Allasia, Stefano; Martina, Valentino

2011-09-01

This mini-review takes into consideration the physiology, synthesis and mechanisms of action of the nitric oxide (NO) and, subsequently, the causes and effects of the NO bioavailability impairment. In diabetes mellitus the reduced NO bioavailability is caused by the increased free radicals production, secondary to hyperglycemia. The reactive oxygen species oxidize the cofactors of the nitric oxide synthase, diminishing their active forms and consequently leading to a decreased NO production. Furthermore the decreased concentration of reduced glutathione results in a diminished production of nitrosoglutathione. These molecules are important intermediates of the NO pathway and physiologically activate the soluble guanylate cyclase. Their decrease in oxidative states of the cell, therefore, leads to a reduced cGMP production which represents the principal molecule that carries out NO's major effects. Finally we considered the eventual therapeutic strategies to improve NO bioavailability by acting on the causes of its decrease. Therefore the treatments proposed are based on the possibility to counteract the oxidation and, in this context, the physiopathological mechanisms strongly support the treatment with thiols.

Nitric oxide production by necrotrophic pathogen Macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions.

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Tuhin Subhra Sarkar

Full Text Available M. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. With the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. This is the first report on M. phaseolina infection in Corchorus capsularis (jute plants which resulted in elevated nitric oxide, reactive nitrogen species and S nitrosothiols production in infected tissues. Time dependent nitric oxide production was also assessed with 4-Amino-5-Methylamino-2',7'-Difluorofluorescein Diacetate using single leaf experiment both in presence of M. phaseolina and xylanases obtained from fungal secretome. Cellular redox status and redox active enzymes were also assessed during plant fungal interaction. Interestingly, M. phaseolina was found to produce nitric oxide which was detected in vitro inside the mycelium and in the surrounding medium. Addition of mammalian nitric oxide synthase inhibitor could block the nitric oxide production in M. phaseolina. Bioinformatics analysis revealed nitric oxide synthase like sequence with conserved amino acid sequences in M. phaseolina genome sequence. In conclusion, the production of nitric oxide and reactive nitrogen species may have important physiological significance in necrotrophic host pathogen interaction.

Nitric oxide in a diesel engine : laser-based detection and interpretation

NARCIS (Netherlands)

Stoffels, G.G.M.

1999-01-01

Nitric oxide (NO) is one of the most polluting components in the exhaust gases of a diesel engines. Therefore, knowledge of the time and place where it is produced during the combustion process is of interest to find a way to reduce diesel engine emissions. Non-intrusive optical diagnostics, based

The Antibiofilm efficacy of nitric oxide on soft contact lenses.

Science.gov (United States)

Kim, Dong Ju; Park, Joo-Hee; Kim, Marth; Park, Choul Yong

2017-11-21

To investigate the antibiofilm efficacy of nitric oxide (NO) on soft contact lenses. Nitrite (NO precursor) release from various concentrations (0-1000 μM) of sodium nitrite (NaNO 2, NO donor) was measured by Griess Assay. Cell viability assay was performed using human corneal epithelial cell under various concentration (0-1000 μM) of NaNO 2 . Biofilm formation on soft contact lenses was achieved by adding Staphylococcus aureus or Pseudomonas aeruginosa to the culture media. Various concentrations of NaNO 2 (0-1000 μM) were added to the culture media, each containing soft contact lens. After incubation in NaNO 2 containing culture media for 1, 3, or 7 days, each contact lens was transferred to a fresh, bacteria-free media without NaNO 2 . The bacteria in the biofilm were dispersed in the culture media for planktonic growth. After reculturing the lenses in the fresh media for 24 h, optical density (OD) of media was measured at 600 nm and colony forming unit (CFU) was counted by spreading media on tryptic soy agar plate for additional 18 h. Nitrite release from NaNO 2 showed dose-dependent suppressive effect on biofilm formation. Most nitrite release from NaNO 2 tended to occur within 30 min. The viability of human corneal epithelial cells was well maintained at tested NaNO 2 concentrations. The bacterial CFU and OD showed dose-dependent decrease in the NaNO 2 treated samples on days 1, 3 and 7 for both Staphylococcus aureus and Pseudomonas aeruginosa. NO successfully inhibited the biofilm formation by Staphylococcus aureus or Pseudomonas aeruginosa on soft contact lenses in dose-dependent manner.

Role of nitric oxide in cellular iron metabolism.

Science.gov (United States)

Kim, Sangwon; Ponka, Prem

2003-03-01

Iron regulatory proteins (IRP1 and IRP2) control the synthesis of transferrin receptors (TfR) and ferritin by binding to iron-responsive elements (IREs) which are located in the 3' untranslated region (UTR) and the 5' UTR of their respective mRNAs. Cellular iron levels affect binding of IRPs to IREs and consequently expression of TfR and ferritin. Moreover, NO*, a redox species of nitric oxide that interacts primarily with iron, can activate IRP1 RNA-binding activity resulting in an increase in TfR mRNA levels. We have shown that treatment of RAW 264.7 cells (a murine macrophage cell line) with NO+ (nitrosonium ion, which causes S-nitrosylation of thiol groups) resulted in a rapid decrease in RNA-binding of IRP2, followed by IRP2 degradation, and these changes were associated with a decrease in TfR mRNA levels. Moreover, we demonstrated that stimulation of RAW 264.7 cells with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) increased IRP1 binding activity, whereas RNA-binding of IRP2 decreased and was followed by a degradation of this protein. Furthermore, the decrease of IRP2 binding/protein levels was associated with a decrease in TfR mRNA levels in LPS/IFN-gamma-treated cells, and these changes were prevented by inhibitors of inducible nitric oxide synthase. These results suggest that NO+-mediated degradation of IRP2 plays a major role in iron metabolism during inflammation.

Simulation of nitrous oxide and nitric oxide emissions from tropical primary forests in the Costa Rican Atlantic Zone

Science.gov (United States)

Shuguanga Liu; William A. Reiners; Michael Keller; Davis S. Schimel

2000-01-01

Nitrous oxide (N2O) and nitric oxide (NO) are important atmospheric trace gases participating in the regulation of global climate and environment. Predictive models on the emissions of N2O and NO emissions from soil into the atmosphere are required. We modified the CENTURY model (Soil Sci. Soc. Am. J., 51 (1987) 1173) to simulate the emissions of N2O and NO from...

[Techniques and complementary techniques. Complementary treatments: nitric oxide, prone positioning and surfactant].

Science.gov (United States)

Martos Sánchez, I; Vázquez Martínez, J L; Otheo de Tejada, E; Ros, P

2003-11-01

The management of hypoxic respiratory failure is based on oxygen delivery and ventilatory support with lung-protective ventilation strategies. Better understanding of acute lung injury have led to new therapeutic approaches that can modify the outcome of these patients. These adjunctive oxygenation strategies include inhaled nitric oxide and surfactant delivery, and the use of prone positioning. Nitric oxide is a selective pulmonary vasodilator that when inhaled, improves oxygenation in clinical situations such as persistent pulmonary hypertension of the newborn, pulmonary hypertension associated with congenital heart disease, and acute respiratory distress syndrome (ARDS). When applied early in ARDS, prone positioning improves distribution of ventilation and reduces the intrapulmonary shunt. The surfactant has dramatically decreased mortality caused by hyaline membrane disease in premature newborns, although the results have been less successful in ARDS. Greater experience is required to determine whether the combination of these treatments will improve the prognosis of these patients.

Nitric oxide donors prevent while the nitric oxide synthase inhibitor L-NAME increases arachidonic acid plus CYP2E1-dependent toxicity

International Nuclear Information System (INIS)

Wu Defeng; Cederbaum, Arthur

2006-01-01

Polyunsaturated fatty acids such as arachidonic acid (AA) play an important role in alcohol-induced liver injury. AA promotes toxicity in rat hepatocytes with high levels of cytochrome P4502E1 and in HepG2 E47 cells which express CYP2E1. Nitric oxide (NO) participates in the regulation of various cell activities as well as in cytotoxic events. NO may act as a protectant against cytotoxic stress or may enhance cytotoxicity when produced at elevated concentrations. The goal of the current study was to evaluate the effect of endogenously or exogenously produced NO on AA toxicity in liver cells with high expression of CYP2E1 and assess possible mechanisms for its actions. Pyrazole-induced rat hepatocytes or HepG2 cells expressing CYP2E1 were treated with AA in the presence or absence of an inhibitor of nitric oxide synthase L-N G -Nitroarginine Methylester (L-NAME) or the NO donors S-nitroso-N-acetylpenicillamine (SNAP), and (Z)-1-[-(2-aminoethyl)-N-(2-aminoethyl)]diazen-1-ium-1,2-diolate (DETA-NONO). AA decreased cell viability from 100% to 48 ± 6% after treatment for 48 h. In the presence of L-NAME, viability was further lowered to 23 ± 5%, while, SNAP or DETA-NONO increased viability to 66 ± 8 or 71 ± 6%. The L-NAME potentiated toxicity was primarily necrotic in nature. L-NAME did not affect CYP2E1 activity or CYP2E1 content. SNAP significantly lowered CYP2E1 activity but not protein. AA treatment increased lipid peroxidation and lowered GSH levels. L-NAME potentiated while SNAP prevented these changes. Thus, L-NAME increased, while NO donors decreased AA-induced oxidative stress. Antioxidants prevented the L-NAME potentiation of AA toxicity. Damage to mitochondria by AA was shown by a decline in the mitochondrial membrane potential (MMP). L-NAME potentiated this decline in MMP in association with its increase in AA-induced oxidative stress and toxicity. NO donors decreased this decline in MMP in association with their decrease in AA-induced oxidative stress and

NITRIC OXIDE ACTIVITY OF NEUTROPHIL IN BLOOD AND CEREBROSPINAL FLUID OF THE CHILDREN WITH BACTERIAL AND VIRAL MENINGITIS

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V. P. Molochniy

2014-01-01

Full Text Available The article presents the results of study of nitric oxide activity of neutrophil leucocytic and freeradical processes in blood and cerebrospinal fluid of the children with bacterial and viral meningitison the acute period diseases. The peculiarities or activity of freeradical processes and nitric oxide of cerebrospinal fluid with bacterial meningitis in acute period diseases and activities of studies of ferments with the health children. 

Exhaled nitric oxide in diagnosis and management of respiratory diseases

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Abba Abdullah

2009-01-01

Full Text Available The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.

Effects of Curcumin on the Proliferation and Mineralization of Human Osteoblast-Like Cells: Implications of Nitric Oxide

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Juan D. Pedrera-Zamorano

2012-11-01

Full Text Available Curcumin (diferuloylmethane is found in the rhizomes of the turmeric plant (Curcuma longa L. and has been used for centuries as a dietary spice and as a traditional Indian medicine used to treat different conditions. At the cellular level, curcumin modulates important molecular targets: transcription factors, enzymes, cell cycle proteins, cytokines, receptors and cell surface adhesion molecules. Because many of the curcumin targets mentioned above participate in the regulation of bone remodeling, curcumin may affect the skeletal system. Nitric oxide (NO is a gaseous molecule generated from L-arginine during the catalization of nitric oxide synthase (NOS, and it plays crucial roles in catalization and in the nervous, cardiovascular and immune systems. Human osteoblasts have been shown to express NOS isoforms, and the exact mechanism(s by which NO regulates bone formation remain unclear. Curcumin has been widely described to inhibit inducible nitric oxide synthase expression and nitric oxide production, at least in part via direct interference in NF-κB activation. In the present study, after exposure of human osteoblast-like cells (MG-63, we have observed that curcumin abrogated inducible NOS expression and decreased NO levels, inhibiting also cell prolifieration. This effect was prevented by the NO donor sodium nitroprusside. Under osteogenic conditions, curcumin also decreased the level of mineralization. Our results indicate that NO plays a role in the osteoblastic profile of MG-63 cells.

Genetic responses against nitric oxide toxicity

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B. Demple

1999-11-01

Full Text Available The threat of free radical damage is opposed by coordinated responses that modulate expression of sets of gene products. In mammalian cells, 12 proteins are induced by exposure to nitric oxide (NO levels that are sub-toxic but exceed the level needed to activate guanylate cyclase. Heme oxygenase 1 (HO-1 synthesis increases substantially, due to a 30- to 70-fold increase in the level of HO-1 mRNA. HO-1 induction is cGMP-independent and occurs mainly through increased mRNA stability, which therefore indicates a new NO-signaling pathway. HO-1 induction contributes to dramatically increased NO resistance and, together with the other inducible functions, constitutes an adaptive resistance pathway that also defends against oxidants such as H2O2. In E. coli, an oxidative stress response, the soxRS regulon, is activated by direct exposure of E. coli to NO, or by NO generated in murine macrophages after phagocytosis of the bacteria. This response is governed by the SoxR protein, a homodimeric transcription factor (17-kDa subunits containing [2Fe-2S] clusters essential for its activity. SoxR responds to superoxide stress through one-electron oxidation of the iron-sulfur centers, but such oxidation is not observed in reactions of NO with SoxR. Instead, NO nitrosylates the iron-sulfur centers of SoxR both in vitro and in intact cells, which yields a form of the protein with maximal transcriptional activity. Although nitrosylated SoxR is very stable in purified form, the spectroscopic signals for the nitrosylated iron-sulfur centers disappear rapidly in vivo, indicating an active process to reverse or eliminate them.

Storm time variation of radiative cooling of thermosphere by nitric oxide emission

Science.gov (United States)

Krishna, M. V. Sunil; Bag, Tikemani; Bharti, Gaurav

2016-07-01

The fundamental vibration-rotation band emission (Δν=1, Δ j=0,± 1) by nitric oxide (NO) at 5.3 µm is one of the most important cooling mechanisms in thermosphere. The collisional vibrational excitation of NO(ν=0) by impact with atomic oxygen is the main source of vibrationally excited nitric oxide. The variation of NO density depends on latitude, longitude and season. The present study aims to understand how the radiative flux gets influenced by the severe geomagnetic storm conditions. The variation of Nitric Oxide (NO) radiative flux exiting thermosphere is studied during the superstorm event of 7-12 November, 2004. The observations of TIMED/SABER suggest a strong anti-correlation with the O/N_2 ratio observed by GUVI during the same period. On a global scale the NO radiative flux showed an enhancement during the main phase on 8 November, 2004, whereas maximum depletion in O/N_2 is observed on 10 November, 2004. Both O/N_2 and NO radiative flux were found to propagate equatorward due to the effect of meridional wind resulting from joule and particle heating in polar region. Larger penetrations is observed in western longitude sectors. These observed variations are effectively connected to the variations in neutral densities. In the equatorial sectors, O/N_2 shows enhancement but almost no variation in radiative flux is observed. The possible reasons for the observed variations in NO radiative emission and O/N_2 ratios are discussed in the light of equator ward increase in the densities and prompt penetration.