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Nitrite plasma levels in normolipemic and hypercholesterolemic patients with peripheral occlusive arteriopathy.

BACKGROUND: The authors studied the nitrite plasma levels in a group of patients with peripheral obstructive arteriopathy. METHODS: The series consisted of 63 subjects (43 males, 20 females, mean age 64 +/- 9 years) suffering from peripheral arterial occlusive disease of the lower limbs, at II (55 cases) and III (8 cases) Fontaine stage; 21 subjects with total cholesterol (TC) lower than 200 mg/dl were considered as normolipemics, 24 subjects with TC values between 200 and 240 as mild hypercholesterolemics, 18 subjects with TC above 240 mg/dl as severe hypercholesterolemics. For each subject the determination of nitrite plasma levels was carried out, by the Gutman and Hollywood colorimetric method. RESULTS: In the normolipemic arteriopathics the basal value of nitrites was sharply reduced (p < 0.05) compared to the controls; in the mild hypercholesterolemics the mean basal value of nitrites was markedly higher compared to the controls; in the severe hypercholesterolemics the mean basal value of nitrites was statistically (p < 0.05) higher than that of the controls. In the arteriopathic patients, globally considered, the mean basal value of nitrites was superimposable on that of the normal control subjects. CONCLUSIONS: This study, carried out on the nitrite plasma levels in a group of arteriopathic patients allowed us to show the enhanced levels of nitric oxide due to the increase of LDL; this effect, previously observed in hypercholesterolemic diabetic and coronaropathic patients, leads us to the hypothesis of a stimulating effect of LDL upon NO endothelial synthesis; this would be a compensatory response to the damaging and vasoconstricting action of LDL.

Aged↗

Pharmacokinetics of a model organic nitrite inhalant and its alcohol metabolite in rats.

Volatile organic nitrites were originally used to relieve the chest pain that is associated with angina pectoris. Today, these inhalants are predominantly used as drugs of abuse. Little is known regarding the bioavailability and disposition of volatile nitrites. In this study, the pharmacokinetics of a major organic nitrite inhalant, isobutyl nitrite (ISBN), and its primary metabolite, isobutyl alcohol (ISBA), were investigated after inhalation and i.v. administration. ISBN blood concentrations in the rat declined mono-exponentially with a half-life of 1.4 min and a blood clearance of 2.9 l/min/kg that vastly exceeded cardiac output (0.3 l/min/kg). Approximately 98% of ISBN was metabolized to ISBA, which declined monoexponentially with a half-life of 5.3 min when the infusion of ISBN was terminated. The bioavailability of inhaled ISBN, over a range of 300 to 900 ppm, was estimated to be 43%. After inhaled ISBN, the half-life of ISBA decreased approximately 4-fold (t(1/2) inh = 1.5 min versus t(1/2) i.v. = 5.3 min; P <.001), whereas no pharmacokinetic difference was observed for ISBN. Inhalation of another nitrite, isoamyl nitrite, accelerated the apparent clearance of ISBA, suggesting that nitrite inhalation could change the disposition of another compound. A pharmacokinetic model was developed to describe the concentration-time profile of ISBA and ISBN after inhalation and i.v. administration.

Administration, Inhalation↗

Nitrite plasma levels in type 1 and 2 diabetics with and without complications.

BACKGROUND: The authors thought it interesting to examine the interrelationship between nitric oxide and diabetes mellitus by the determination of the nitrite plasma levels, stable end-products of nitric oxide, in various clinical patterns of diabetes mellitus. METHODS: Our series consisted of 161 female subjects (mean age 54 +/- 7 years, disease duration 5 +/- 3 months) subdivided into: a) 13 patients suffering from insulin-dependent diabetes (IDDM) without clinical and instrumental signs of micro- and macroangiopathy; b) 148 suffering from non insulin-dependent diabetes mellitus (NIDDM) of whom: 1) 52 without vascular complications (28 normal weight, BMI < 25, and 24 obese, BMI > 30); 2) 40 with clinical and instrumental signs of non hypertensive coronary heart disease (CHD); 3) 25 with CHD and hypertension (arterial blood pressure over 160/95 mmHg); 4) 31 with hypercholesterolemia (values over 250 mg/dl). All patients were examined in good glycometabolic conditions reached by oral hypoglycemiant (12 cases) or insulin (149 cases) treatment. As normal control 37 female subjects (mean age 48 +/- 7) without internistic diseases were considered. For each sample we determined the plasma levels of nitrites by the Gutman and Hollywood method. RESULTS: Almost similar nitrite plasma levels in IDDM (17 +/- 0.5 mumol/L) and normal controls (17 +/- 0.2 mumol/L) were found; in non complicated non obese NIDDM a not significantly elevated value (21 +/- 0.8 mumol/L) as compared with the IDDM and control group was found; the obese NIDDM patients showed a value (18 +/- 0.4 mumol/L) not significantly different in comparison with the non obese NIDDM group. In the NIDDM group with non hypertensive CHD) the nitrite value was almost similar (20 +/- 0.5 mumol/L) to the corresponding group without vascular complications. In the patients with CHD and hypertension the nitrite level was superimposable (20 +/- 0.7 mumol/L) on the one recorded in NIDDM patients without vascular complications and in those with CHD without hypertension. In NIDDM patients with hypercholesterolemia the mean nitrite value was sharply elevated (24 +/- 0.8 mumol/L); the difference between this group and those of non hypercholesterolemic, non obese, obese and CHD (with or without hypertension) patients was significant (p < 0.05). CONCLUSIONS: It is conceivable that diabetes mellitus per se causes a tendential not significant increase of NO production in comparison with normal controls; some factors such as blood pressure, overweight, disease duration, therapeutic treatment and coronary complications appear not to influence NO production. In hypercholesterolemic diabetic patients the nitrite enhanced level in plasma might mean a compensatory response to a continuous inactivation of NO involved in a protective competition towards damaging factors and chiefly against oxidised LDL.

Diabetes Mellitus, Type 1↗

Nitrifying microbial community analysis of nitrite accumulating biofilm reactor by fluorescence in situ hybridization.

Biological nitrogen removal via nitrite pathway in wastewater treatment is very important especially in the cost of aeration and as an electron donor for denitrification. Wastewater nitrification and nitrite accumulations were carried out in a biofllm reactor. The biofilm reactor showed almost complete nitrification and most of the oxidized ammonium was present as nitrite at the ammonium load of 1.2 kg N/m3/d. Nitrite accumulation was achieved by the selective inhibition of nitrite oxidizers by free ammonia and oxygen limitation. Nitrite oxidation activity was recovered as soon as the inhibition factor was removed. Fluorescence in situ hybridization studies of the nitrite accumulating biofilm system have shown that genus Nitrosomonas which is specifically hybridized with probe NSM156 was the dominant nitrifying bacteria while Nitrospira was less abundant than those of normal nitrification systems. Further FISH analysis showed that the combinations of Nitrosomonas and Nitrospira cells were identified as important populations of nitrifying bacteria in an autotrophic nitrifying biofilm system.

Biofilms↗

[The nitrite accumulation in a biological aerobic filter (BAF) and the influences factors].

The nitrite accumulation in a bench-scale biological aerobic filter (BAF) for nitrogen removal was reported in this paper. The influences of operational variables on filter performance and nitrite accumulation were also investigated. The influent loading of NH4+(-)N and TN were 0.26-0.62 kg/(m3.d) and 0.28-0.63 kg/(m3.d) respectively, the hydraulic loading, gas/water ratio and temperature were 1-2 m/h, 3:1 and 20.5 degrees C-26.5 degrees C respectively, the nitrogen removal loading of NH4+(-)N, TN were among 0.15-0.52 kg/(m3.d) and 0.18-0.42 kg/(m3.d) respectively. The nitrite concentrations in the bulk and effluent, the profiles of inorganic nitrogen-compounds, the microbial populations in the reactor and their activity were investigated, suggesting that the nitrite accumulation and shortcut nitrification-denitrification took place in the bioreactor. The mechanism of nitrite accumulation and the influences of operational variables were analyzed. The backwash process was considered as the key influential factor of nitrite accumulation. It was believed that the structure feature and operational pattern were the principal factors that may result in the nitrite accumulation and shortcut nitrification-denitrification occurring in the BAF reactor.

Bacteria↗

[The evaluation of nitrate, nitrite and antioxidant vitamin intake in daily food ration of children aged 1-6 year of age].

The aim of this study was evaluation of nitrates, nitrites and antioxidant vitamins intake in daily food rations of children aged 1-6 years. The levels of nitrites and nitrates in daily food rations were calculated using menu data and literature nitrites and nitrates content data in food products and compared with the acceptable daily intake (ADI). The percentage contribution of selected groups of products in nitrates and nitrites supply was calculated. Antioxidant vitamins level was calculated with using menu data and Food composition tables and compared to the recommendations. Nitrates content exceeded acceptable daily intake (ADI) for children aged 1-6 twice, but level of nitrites was below (88% ADI). The main food source of nitrates were vegetables supplied 90% of one. The main sources of nitrite were meat products supplied 27.6% of one, vegetables and their products--26.2% and cereals supplied 24.6% of nitrites. All calculated vitamins (A, E, C) exceeded recommendations what protected children from high level of nitrates.

Antioxidants↗

Use of Griess reagent containing vanadium(III) for post-column derivatization and simultaneous determination of nitrite and nitrate in baby food.

An ion chromatographic method with post-column derivatization and spectrophotometric detection is presented for the determination of nitrate and nitrite (NOx) in baby food. NOx residues found naturally or added as preservatives were extracted from baby foods and determined by using ion chromatography with post-column derivatization and spectrophotometric detection. Nitrate was reduced to nitrite online by post-column reduction using vanadium(lll) chloride and heat. Nitrite reacted with Griess reagent to produce a dye that was detected at 525 nm. The use of V(III) and heat to promote the reduction of nitrate to nitrite online is a novel feature of this detection system. The determination of incurred NOx residues in samples by using AOAC Method 993.03 yielded results comparable to those obtained by ion chromatography with spectrophotometric detection. The toxic and carcinogenic metal cadmium used in the AOAC Method to reduce the nitrate to nitrite was avoided. The proposed method provides simultaneous determination of nitrate and nitrite. Average recoveries of nitrate and nitrite residues ranged from 82 to 107% for fortification levels of 25-400 ppm.

Chromatography, High Pressure Liquid↗

Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite.

A variety of foodstuffs including soy sauce, vegetables and smoked foods showed direct-acting mutagenicity in bacteria upon nitrite treatment. From these foodstuffs, several nitrosatable mutagen precursors were isolated and their structures were found to be aromatic compounds such as phenol and indole derivatives, but not alkylamides. Many phenol and indole derivatives present in our environment were also demonstrated to form mutagenic nitrosated compounds. The direct-acting mutagenic products of phenolic compounds with nitrite were all diazo derivatives, and those from indole compounds with nitrite were N-1 and/or C-3 nitrosated products. Relatively high amounts of nitrite were necessary for the formation of diazo compounds from phenolic compounds. By contrast, indole reacted very rapidly with nitrite, even at low, physiologically feasible concentrations such as are found in the human stomach. Piperine, aminoimidazoquinoline and butylated hydroxyanisole also reacted with nitrite and produced compounds showing mutagenicity in bacteria without metabolic activation. Besides having activity in bacteria, two nitrosated products, diazo and nitrosoindole compounds, were demonstrated to be mutagenic in cultured mammalian cells. They also formed DNA adducts and induced ornithine decarboxylase and replicative DNA synthesis in rat stomach. Furthermore, the diazo compound formed from tyramine with nitrite was proved to be carcinogenic in rats.

Animals↗

Nitrite inhalants: historical perspective.

There are important reasons for considering nitrite inhalation as a factor in the development of AIDS-related KS in young male homosexuals. These are (1) the pharmacologic properties of amyl, butyl, and isobutyl nitrites, which are toxic; (2) the mutagenic, teratogenic, and carcinogenic products resulting from metabolism of N-nitroso compounds; (3) the potent carcinogenicity of N-nitroso compounds in 39 different animal species; and (4) the deleterious effects of volatile nitrites on human lymphocytes both in vitro and in vivo. Specifically related to this epidemic, there are additional reasons for pursuing the connection between nitrite inhalation and development of KS. These include: (1) the timing of the production and sales of volatile nitrites for use as recreational drugs and the subsequent outbreak of the AIDS epidemic (7 to 10 years); (2) the extensive use of nitrites among male homosexuals; (3) the virtual universal history of nitrite use by young male homosexuals in whom KS has developed during the past 3 years; and (4) the age group in which KS is developing is consistent with a cohort initially exposed 7 to 10 years ago.

Acquired Immunodeficiency Syndrome↗

Esophageal spasm: clinical and manometric response to nitroglycerine and long acting nitrites.

The effect of nitroglycerine and long acting nitrites was studied in a group of 8 normal control subjects and 12 patients with esophageal spasm. The objective response of the esophagus to these drugs was recorded by obtaining esophageal manometric studies and was correlated with response in clinical symptoms. In 7 patients who had significant gastroesophageal reflux associated with spasm, the response to nitroglycerine was unpredictable. But in the group of 5 patients with diffuse esophageal spasm without gastroesophageal reflux, the response was uniformly good. All of the patients who responded to nitroglycerine also responded to long acting nitrites. These 5 patients, who were placed on long term management with long acting nitrites, remained symptom-free from 6 months to 4 years. None of them had recurrence of symptoms while they were on long acting nitrite therapy. The study suggests that if esophageal spasm is associated with reflux, the use of nitrites is less effective in controlling spasm than it is in those who do not show this association, and that diffuse esophageal spasm can be effectively managed with long acting nitrites on a long term basis in the absence of reflux. If there is esophageal spasm associated with reflux esophagitis, nitrites may be beneficial as an adjunct to antireflux therapy.

Adult↗

Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids and tyramine as precursors of mutagens in soya sauce after nitrite treatment.

Soya sauce showed marked direct-acting mutagenicity toward Salmonella typhimurium TA 100 after nitrite treatment. Three precursors showing mutagenicity after nitrite treatment were isolated from soya sauce. Their structures were determined to be (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid [(-)-(1S,3S)-MTCA], its stereoisomer (-)-(1R,3S)-MTCA and tyramine. The numbers of revertants of TA 100 induced by 1 mg each of (-)-(1S,3S)-MTCA, (-)-(1R,3S)-MTCA and tyramine, after nitrite treatment, were 17 400, 13 000 and 3 900, respectively, without S9 mix. The amounts of MTCA isomers and tyramine in various Japanese soya sauces showing mutagenicity after nitrite treatment were 82-678 and 17-2 250 micrograms/mL, respectively. Most soya sauces produced in the USA showed weaker mutagenicity than those produced in Japan and contained lower, if not undetectable, amounts of the three precursors of mutagens. The mutagenicity of MTCA isomers and tyramine accounted for 16-61 and 1-35%, respectively, of the mutagenicity of the soya sauces after nitrite treatment. The mutagen(s) produced from (-)-(1S,3S)-MTCA with nitrite was a minor product(s), the major product being the non-mutagen, (-)-(1S,3S)-1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carbo xylic acid [(-)-(1S,3S)-MNTCA], but the mutagen 4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone, produced from tyramine with nitrite, was one of the major products.

Carbolines↗

Purification and characterization of a dissimilatory nitrite reductase from the phototrophic bacterium Rhodopseudomonas palustris.

A dissimilatory nitrite reductase from the facultatively phototrophic bacterium, Rhodopseudomonas palustris strain 1a1 was studied. A basic level of the enzyme (10-50 mU/mg protein) was measured in dark, aerated and anaerobic, photosynthetic cultures. A marked derepression of enzyme synthesis occurred under conditions of oxygen limitation (200-300 mU/mg protein). The addition of nitrite (or nitrate) to the culture medium had only a slight effect on the maximal nitrite reductase titer of cells. The enzyme was purified from photosynthetically grown cells by precipitation with ammonium sulfate, gel filtration through Sepharose 6B and repeated chromatography on DE 52-cellulose. As estimated by gel filtration, the nitrite reductase had a molecular weight of about 120 000 +/- 12 000 and yielded only one band (mol. wt. of about 68 000 +/- 7000) in SDS-gel electrophoresis. The isoelectric point of the enzyme was at pH 5.1. Nitric oxide (NO) was identified as the reaction product of nitrite reduction. The enzyme also exhibited cytochrome c-oxidase activity and was active with chemically reduced viologen dyes, FMN and cytochrome c as electron donors. Highly purified nitrite reductase preparations contained 10 mol% of a c-type cytochrome. Trace metal analyses indicated the presence of Cu in the enzyme. Consistent with the detection of Cu was the finding that the Cu-chelator, diethyldithiocarbamate, strongly inhibited the nitrite reductase.

Catalysis↗

Structural effects in alkyl nitrite oxidation of human hemoglobin.

Oxidations of hemoglobin in oxygen-saturated and deoxygenated media by 10 structurally variant alkyl nitrites have been examined in kinetic detail. Pronounced structural influences on rate constants, whose values span a range of 80 in oxidations of both oxy- and deoxyhemoglobin, have been observed. tert-Butyl nitrite provides the slowest oxidation rate that for deoxyhemoglobin terminates after only half of the available iron(II) heme units have been oxidized. Activation parameters have been determined for oxidations of oxyhemoglobin and deoxyhemoglobin by ethyl, isopropyl, and neopentyl nitrites from kinetic evaluation of these reactions as a function of temperature. The differences in free energies of activation (delta G) between hemoglobin R and T states range from 1.8 to 2.9 kcal/mol for the three alkyl nitrites examined. The composite data portray alkyl nitrite oxidations as inner sphere electron transfer processes whose kinetic characteristics reflect the ligand binding properties of hemoglobin. A sulfhydryl-induced alkyl nitrite oxidation of oxyhemoglobin that is most pronounced in oxygen-saturated media has been observed, and its cause has been traced to nitrosyl exchange of alkyl nitrites with the beta-93 cysteine sulfhydryl group of hemoglobin.

Hemoglobin A↗

Mutagenicity of various Japanese foodstuffs treated with nitrite.

Mutagenic activities of various Japanese foodstuffs treated with nitrite at pH 4.2 for 10 min (37 degrees C) were tested using Salmonella typhimurium TA 100, TA 1535 and also a streptomycin(SM)-dependent strain of Salmonella typhimurium TA 100. Among 46 common food samples tested, smoked ham, red wines, black teas, soybean pastes and instant coffee powder gave greatly increased numbers of His+ revertants or SM-independent colonies when treated with nitrite. Vegetables, soybean-seasonings and a variety of broths developed no significant mutagenic potential when treated with nitrite. Broiled fish, such as broiled mackerel pike, jack mackerel, tuna and sardine, gave a very slight increase, or often a decrease, in numbers of mutant colonies when treated with nitrite. In order to explore the substances responsible for the development of mutagenic activities in nitrite-treated foodstuffs, several nitrosatable compounds, including polyamines, were investigated. Polyamines are known to react with nitrite to produce several direct-acting mutagens in a short incubation time. Food samples were hydrolyzed with 6 mol/l hydrochloric acid, followed by purification using Amberlite CG-120, and were then submitted to GC analysis, after ethyloxycarbonylation. The high concentration of polyamines which was found in soybean paste could, to some extent, be correlated to the large increase of the mutagenic activities in the foodstuffs treated with nitrite.

Food Additives↗

[Nitrites block the Ca-dependent habituation of neurons at the level of an electroexcitable membrane: a possible role for nitric oxide].

Penetration of Ca2+ into neuron have been shown earlier to be mainly responsible for the cell habituation to repeated intracellular stimulation by impulse depolarizing current. Considering the key role of nitric oxide (NO) in regulation of intracellular Ca2+ turnover, effects of exogenous nitrite NaNO2, used as a source of NO, on plasticity properties of the electrostimulated membrane were studied in the identified habituating and non-habituating neurones of snail (Gastropoda) brain. The sodium nitrite 10(-6)-10(-4) M was found to inhibit, with a latent period 10-30 min, the ability of the habituating neurones to get accustomed to stimulation; this phenomenon was oscillatory. The concentration of nitrite 10(-3) M affected irreversibly the habituation. Serotonin potentiated the inhibitory effect of nitrite on habituation and vice versa nitrite augmented the serotonin effect on habituation of the same neurones. The exogenous nitrite sensitized the non-habituating neurones to intracellular stimulation. These data suggest that nitrite affects the plasticity properties of the electrostimulated neurone membrane. Besides, these results and well-known properties of NO allowed one to assume that NO-dependent regulation of intracellular Ca2+ was responsible for the phenomenon observed as well as that NO- and serotoninergic systems appear to interact in the snail brain.

Animals↗

[Nitrates and nitrites in gastric juice in chronic gastritis].

Atrophic gastritis is precancerous condition of the intestinal type of gastric carcinoma. This process supposes a genotoxic effect of N-nitroso-compounds which are formed in the stomach by nitrosation of nitrites and organic nitrogen compounds. The authors examined 41 patients with chronic superficial and atrophic gastritis. They examined the pH and concentration of nitrates and nitrites in gastric juice taken in the morning before meal. They discovered that in severe atrophic gastritis the amount of nitrates is significantly increased and the amount of nitrites is decreased, all in comparison with superficial gastritis. An exponential relation of the concentration of nitrites towards the pH of gastric juice was found to be NO2- = epH-6.5, CC = 0.935. A significant elevation of nitrite concentration was observed in cases of pH being higher than 5.5. Nitrate concentration altered in dependence of the value of gastric pH. Oral administration of 300 mg of vitamin C or 250 mg of vitamin E did not significantly affect the amount of gastric nitrites. The work discusses the mutual relation of nitrites, ascorbic acid and alpha-tocopherol towards the formation of N-nitroso-compounds in the stomach inflicted by atrophic gastritis. (Tab. 3, Fig. 2, Ref. 25.)

Adult↗

Kinetic studies of nitrite uptake by Aspergillus nidulans.

1. In the filamentous mold Aspergillus nidulans, net nitrite uptake is inducible by nitrate and nitrite, is probably different from the nitrate uptake system and is partially repressed by ammonium. 2. The concentration dependence of net nitrite uptake by the biA1 facA303 strain of A. nidulans shows a saturation kinetics with an apparent Km value of 0.64 mM. 3. Strains of A. nidulans carrying the nihA1 and nihA1 chlA14 mutations considerably reduced the affinity of the nitrite uptake system for the substrate when nitrite concentrations ranging from 2.5 mM to 10.0 mM were tested (apparent Km values of 5.9 mM and 23.6 mM, respectively). 4. These results suggest that the toxic effect of nitrite on A. nidulans is due to enhanced nitrite uptake by nihA strains when high concentrations are present in the medium.

Ammonia↗

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Adult↗