Concept: Nitric acid
Inositol-stabilized arginine silicate (ASI; Nitrosigine(®)) has been validated to increase levels of arginine, silicon and nitric oxide production. To evaluate potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail Making Test (TMT, Parts A and B). In the two studies, healthy males took ASI for 14 and 3 days, respectively. In the first study, after 14 days of dosing, TMT B time decreased significantly from baseline (28% improvement, p = 0.045). In the second study evaluating shorter-term effects, TMT B time decreased significantly compared to placebo (33% improvement, p = 0.024) in a 10-min period. After 3 days of dosing, TMT B time significantly decreased from baseline scores (35% improvement, p < 0.001). These findings show that ASI significantly improved the ability to perform complex cognitive tests requiring mental flexibility, processing speed and executive functioning.
The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-l-arginine concentrations in plasma of MS patients during interferon-β1b therapy.
Although nitric oxide (NO) is a bactericidal component of the macrophage’s innate response to intracellular infections such as tuberculosis (TB), prolonged inhalation of NO gas has little benefit in chemotherapy of TB. The impact of controlled release of NO through intracellular delivery of NO donors to macrophages infected in vitro with Mycobacterium tuberculosis (Mtb) was investigated. Inhalable microparticles (MP) were prepared by spray-drying. Isosorbide mononitrate (ISMN), sodium nitroprusside (SNP), and diethylenetriamine nitric oxide adduct (DETA/NO) were incorporated in poly(lactic-co-glycolic acid) (PLGA) with encapsulation efficiencies of >90% to obtain MP yields of ∼70%. The mass median aerodynamic diameter (MMAD) of the MP was 2.2-2.4 μm within geometric standard deviations (GSD) of ≤0.1 μm. MP were phagocytosed by THP-1 derived macrophages in culture and significantly (P < 0.05) sustained NO secretion into culture supernatant from 6 to 72 h in comparison to equivalent amounts of drugs in solution. Significantly (P < 0.05) higher dose-dependent killing of intracellular Mtb by MP compared to equivalent amounts of drugs in solution was observed on estimation of colony forming units (CFU) surviving 24 h after exposure to drugs or MP. The cytotoxicity of MP toward macrophages was lower than that of dissolved drugs. It was concluded that inhalable MP can target NO donors to the macrophage, control NO release in the macrophage cytosol, and reduce Mtb CFU by up to 3-log in 24 h, at doses that are much lower than those required for cardiovascular effects.
- Progrès en urologie : journal de l'Association française d'urologie et de la Société française d'urologie
- Published almost 6 years ago
The aim was to review the literature on nitric oxide and female lower urinary tract.
Despite the wide current use of praziquantel (PZQ) in treatment of schistosomiasis, low cure rates have been recorded in many studies. The aim of this study was directed to evaluate the curative effect of propolis (Pps) alone or in combination with PZQ on biochemical, immunological, parasitological, and histological changes associated with experimental schistosomiasis in mice. Schistosoma mansoni-infected mice were divided into two experimental sets, each with four subgroups: (i) untreated, (ii) treated with Pps/day p.o for 4 weeks, (iii) treated with PZQ p.o 2 × 500 mg/kg bd wt, and (iv) treated with Pps + PZQ as in group ii and iii; all treatments started on the 8th week postinfection, in addition to uninfected group as control for the previous groups. Treatment of infected mice with Pps, although failed to eradicate the worm, significantly reduced the hepatic granuloma number, their lymphocytic infiltration and aggregation, hepatic and splenic myeloperoxidase (MPO) activity and plasma, and liver and thymus nitric oxide (NOx) levels together with normalization of plasma proteins and alleviation of oxidative stress in the examined tissues as evidenced by reduction of malondialdehyde (MDA) and normalization of glutathione (GSH). Promising results were obtained when Pps was given in combination with PZQ, where the anti-schistosomal activity of PZQ was markedly potentiated with complete alleviation and amelioration of the histological and biochemical alteration associated with schistosomiasis. This study highlights the potential usefulness of Pps as an adjunct to PZQ in schistosomiasis.
A new neo-clerodane diterpene, named ajugacumbin J (1), together with 13 known compounds (2-14) was isolated from Ajuga decumbens. The structure of ajugacumbin J (1) was elucidated by 1D and 2D NMR spectra and MS. Ajugacumbin J (1) and ajugacumbin D (5) exhibited inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with an IC50 value of 46.2 and 35.9 μM, respectively.
It has been reported that nitrate supplementation can improve exercise performance. Most of the studies have used either beetroot juice or sodium nitrate as a supplement; there is lack of data on the potential ergogenic benefits of an increased dietary nitrate intake from a diet based on fruits and vegetables. Our aim was to assess whether a high-nitrate diet increases nitric oxide bioavailability and to evaluate the effects of this nutritional intervention on exercise performance. Seven healthy male subjects participated in a randomized cross-over study. They were tested before and after 6 days of a high (HND) or control (CD) nitrate diet (~8.2 mmol∙day(-1) or ~2.9 mmol∙day(-1), respectively). Plasma nitrate and nitrite concentrations were significantly higher in HND (127 ± 64 µM and 350 ± 120 nM, respectively) compared to CD (23 ± 10 µM and 240 ± 100 nM, respectively). In HND (vs. CD) were observed: (a) a significant reduction of oxygen consumption during moderate-intensity constant work-rate cycling exercise (1.178 ± 0.141 vs. 1.269 ± 0.136 L·min(-1)); (b) a significantly higher total muscle work during fatiguing, intermittent sub-maximal isometric knee extension (357.3 ± 176.1 vs. 253.6 ± 149.0 Nm·s·kg(-1)); © an improved performance in Repeated Sprint Ability test. These findings suggest that a high-nitrate diet could be a feasible and effective strategy to improve exercise performance.
A single laboratory validation (SLV) has been performed for a method that simultaneously determines choline and car-nitine in nutritional products by ulta high performance liquid chromatography-tandem mass spectrometry UHPLC-MS/MS. All eleven SPIFAN matrices (from the AOAC Stakeholder Panel on Infant Formulas and Adult Nutritionals) were tested. Depending on the sample preparation, either the added (free, with a water dilution and filtering) or total (after microwave digestion at 120° in nitric acid and subsequent neutralization with ammonia) species can be detected. For non-milk containing products, the total carnitine is almost always equal to the free carnitine. A substantial difference was noted between free and total choline in all products. All Standard Method Performance Requirements (SMPRs) for carnitine and choline have been met. This report summarizes the material sent to the SPIFAN ERP (Expert Review Panel) for the review of this method as well as some additional data from an internal validation. This method was granted First Action status for carnitine in 2014 (2014.04), but the choline data is also being presented. A comparison of choline results to those from other AOAC methods is given.
Hydrogen sulfide (H2S) and nitric oxide (NO) are important signaling molecules that regulate several physiological functions. Understanding the chemistry behind their interplay is important for explaining these functions. The reaction of H2S with S-nitrosothiols to form the smallest S-nitrosothiol, thionitrous acid (HSNO), is one example of physiologically relevant cross-talk between H2S and nitrogen species. Perthionitrite (SSNO(-)) has recently been considered as an important biological source of NO that is far more stable and longer living than HSNO. In order to experimentally address this issue here, we prepared SSNO(-) by two different approaches, which lead to two distinct species: SSNO(-) and dithionitric acid [HON(S)S/HSN(O)S]. (H)S2NO species and their reactivity were studied by (15)N NMR, IR, electron paramagnetic resonance and high-resolution electrospray ionization time-of-flight mass spectrometry, as well as by X-ray structure analysis and cyclic voltammetry. The obtained results pointed toward the inherent instability of SSNO(-) in water solutions. SSNO(-) decomposed readily in the presence of light, water, or acid, with concomitant formation of elemental sulfur and HNO. Furthermore, SSNO(-) reacted with H2S to generate HSNO. Computational studies on (H)SSNO provided additional explanations for its instability. Thus, on the basis of our data, it seems to be less probable that SSNO(-) can serve as a signaling molecule and biological source of NO. SSNO(-) salts could, however, be used as fast generators of HNO in water solutions.