Differential uptake and metabolism of nitrite in normoxic and hypoxic goldfish

Nitrite is a physiologically important nitric oxide donor at low concentrations but becomes toxic at high concentrations, as develops in freshwater fish exposed to environmental nitrite. We hypothesized that nitrite uptake across the gills differs between normoxic and hypoxic fish and that nitrite accumulation causes excess nitric oxide formation and nitrosative stress. Nitrite and its metabolites were measured via chemiluminescence in normoxic and hypoxic goldfish in control conditions and after 1 day of nitrite exposure. Exposure to nitrite produced much higher nitrite levels in plasma, red blood cells (RBCs) and muscle tissue of normoxic than hypoxic goldfish, suggesting that nitrite uptake was augmented by normoxia in spite of a predictable lower gill surface area. Elevation of nitrite was associated with increased concentrations of S-nitroso, N-nitroso and Fe-nitrosyl compounds in both extracellular and intracellular compartments, revealing nitrosative stress with extensive nitros(yl)ation of thiols, amines and heme groups. The degree of nitrosative stress correlated with nitrite load. Nitrate levels increased in all compartments, reflecting that a significant fraction of the nitrite taken up was converted to non-toxic nitrate. The generation of methemoglobin and nitrosylhemoglobin (assessed by spectral deconvolution) was more pronounced during normoxic nitrite exposure than during hypoxic nitrite exposure, in agreement with the higher nitrite load in normoxic fish. However, at any given nitrite load inside RBCs, the formation of S-nitroso compounds was augmented by hypoxia. We conclude that ambient oxygen conditions have profound influence on branchial nitrite uptake and that nitrosative stress is an integral part of nitrite toxicity at high nitrite concentrations.     

Validation of Microdialysis Probes for Studying Nitrosative Chemistry Within Localized Regions of the Human Upper Gastrointestinal Tract

Background: We have examined the suitability of microdialysis probes for examining nitrosative chemistry within localized regions of the lumen of the gastrointestinal tract. Chemical nitrosation occurs maximally at pH 2.5 in the presence of nitrite and thiocyanate and absence of ascorbic acid. Nitrite and thiocyanate are delivered into the stomach in saliva and ascorbic acid is secreted in gastric juice. Methods: We used a benchtop model to reproduce the nitrosative chemistry occurring in the human upper GI tract and assessed the ability of the microdialysis probes to measure it. Results: The microdialysis probes were reliable at measuring nitrite ascorbic acid, total vitamin C and thiocyanate in both aqueous solutions and human gastric juice over the full range of intragastric pH, i.e. 1.5, 2.5, 3.5, 5.0 and 7.0. The probes were also reliable at measuring these chemicals under conditions simulating the active interaction between nitrite and ascorbic acid. Under such conditions with ascorbic acid in excess the probes gave a more accurate assessment of the nitrite level than that obtained by directly sampling the gastric juice. This was due to the probes not being subject to artefactual measurement of nitric oxide as nitrite. This was prevented by the rapid diffusion of nitric oxide through the probe collecting tube. Conclusion: Microdialysis probes provide a reliable means of examining nitrosative chemistry within the lumen of the upper GI tract. In addition, they have the advantage of measuring this chemistry in very local regions and of simultaneously comparing the chemistry in different regions of the upper GI tract.     

水中亚硝酸盐测定不确定度评定分析

目的依据国家标准检验方法规定的检测步骤,计算出该方法能够造成分析不确定度的分量,按照统计加权法求得验证实验的扩展不确定度。方法以重氮偶合分光光度法测定亚硝酸盐氮为例,从检测的精密度、准确度、校准工作曲线、分析过程中量器具使用等方面计算各分量的不确定度值,通过统计加权计算出验证实验的标准合成不确定度。结果验证实验标准合成不确定度为0.0014mg/L,包含因子k=2,对应的置信概率为95.45%,扩展不确定度为0.0028mg/L。结论按照分析方法步骤确定样品的不确定度,分别求出检测样品的精密度、准确度、校准工作曲线,分析过程中量器具使用等方面的不确定度值,通过统计加权方法计算出验证实验的标准合成不确定度。     

口服甲氰咪胍对胃内环境的影响及口服维生素C的作用

本文报导34例溃疡病人服用甲氰咪胍后胃内环境的变化以及甲氰咪胍和维生素C同服对胃内环境、特别是对亚硝酸盐含量的影响。结果显示:服甲氰咪胍后,胃液pH值、亚硝酸盐及细菌总数明显增加(P<0.01);而甲氰咪胍和维生素C同时服用,亚硝酸盐无明显增加(P>0.05),且两个治疗组的BAO、PAO和MAO无明显差异。说明在服用甲氰咪胍时,同时服用维生素C可以防止由于甲氰咪胍引起的亚硝酸盐含量增高的现象,而对甲氰咪胍的抑酸作用无明显影响,这对甲氰咪胍及其它强抑酸剂可能具有重要的意义。     

催化光度法测定痕量亚硝酸盐的研究

本文研究了测定亚硝酸盐的一种新的催化光度法。该方法基于—氯乙酸缓冲溶液中溴酸钾氧化灿烂绿受亚硝酸盐催化的褪色反应。在室温下进行,操作简便、选择性好,测定灵敏度为7. 44×10~(10)g/mL的亚硝酸盐。该方法应用于测定几种水样中亚硝酸盐含量,结果满意。相对标准偏差小于5.6％,加标平均回收率102.1％。     

Nitrosamine,nitrate and nitrite in relation to gastric cancer: A case-control study in Marseille,France

A case-control study on gastric cancer and diet was conducted in Marseille (France). Ninety-two patients with histologically confirmed adenocarcinoma and 128 controls undergoing functional reeducation for injuries or trauma were interviewed by a trained dietician using a dietary history questionnaire on their usual diet during the year preceding the first symptoms for cases, or preceding interview for controls. Intake of nitrite, nitrate and pre-formed N-nitrosodimethylamine (NDMA) from food was estimated using a food composition table compiled ad hoc. Odds ratios (ORs) were calculated after adjustment for age, sex, occupation and calorie intake. The results indicated that high intake of NDMA was associated with increased risk for gastric cancer. The ORs for the second and third tertile of NDMA intake were: OR₂=4.13 (95% CI=0.93 to 18.27) and OR₃=7.00 (95% CI=1.85 to 26.46). Intake of nitrate and nitrite was not associated with increased risk of stomach cancer. Consumption of vegetables was protective in general and independent of their estimated nitrate content.     

对二甲氨基酚、依地酸二钴和亚硝酸钠对氢氰酸严重中毒狗血流动力学的影响

在麻醉和人工呼吸下,研究了iv HCN中毒及中毒后2min分别用对二甲氨基酸(DMAP)、依地酸二钴(Co_2EDTA)或亚硝酸钠(NaNO_2)治疗对狗血流动力学的影响。结果表明iv HCN 3 mg/kg很快使HR、SI、CI、MAP、LVP及其±dp/dt_(max)进行性下降,TPVR和MPAP持续增高,4～9.5min后相继死于心功能衰竭。iv DMAP 3.2mg/kg后2～8min CI、MAP、LVP及其±dp/dt_(max)明显增加,TPVR和MPAP恢复稍晚。iv NaNO_2 20mg/kg后4～6min使±dp/dt_(max)明显增加,CI、MAP、LVP、TPVR和MPAP恢复。ivCO_2EDTA 15mg/kg后6min MAP明显升高,LVP及其±dp/dt_(max)恢复,CI、TPVR和MPAP恢复较慢。治后观察约1h,NaNO_2和Co_2EDTA降压明显,DMAP较轻。提示(1)DMAP使HCN中毒后循环功能的恢复比Co_2EDTA和NaNO_2快而强,(2)对恢复后的循环功能DMAP比NaNO_2和Co_2EDTA较能维持平稳,(3)DMAP和NaNO_2快速逆转HCN中毒心血管功能改变的药理特性.可能是它们的另一抗氰作用机制。     

General and renal toxicity of phenacetin,paracetamol and some anti-mitotic agents in the rat

The general and the renal toxicity of large doses of phenacetin, paracetamol, some antimitotic drugs and other constituents of analgesic mixtures was investigated in medium term toxicity tests in a large number of rats. Phenacetin and paracetamol depressed food intake and retarded growth. 800–1200 mg/kg · day paracetamol induced a larger mortality than 1500–3000 mg/kg · day phenacetin. Both analgesics and isophthalanilide, an antimitotic agent, induced hyperchromic anemia. Phenacetin induced methemoglobinemia more readily than paracetamol. Neither the analgesics, nor caffeine, sodium nitrite, isophthalanilide or mercaptopurine depressed GFR, maximal urinary concentration after dehydration plus vasopressin, urinary dilution after hypotonic expansion, or urinary acidification. Phenacetin, paracetamol and isophthalanilide depressed the fractional excretion of urea by the kidney. Very large doses of paracetamol slightly increased the proteinuria and the urinary excretion of tubular cells. Phenacetin and paracetamol induced degenerative histological alterations in cortical proximal and distal tubules, detected and quantitated under blind conditions. There were no inflammatory changes, nor any medullary or papillary lesions. The degenerative lesions could not be explained by the presence of methemoglobinemia or hemolysis. Isophthalanilide actually improved the histological appearance of the kidneys. The urinary excretion of tubular cells was not significantly correlated with the severity of the histological changes. It was concluded that neither phenacetin nor paracetamol exert major nephrotoxic effects in rats.Supported by grants-in-aid of Office intercantonal pour le contrôle des médicaments, Bern, and Centre d'études sur les lymphômes malins, Lausanne as well as by research grants of Fonds National Suisse de la Recherche Scientifique.     

Emerging role of nitrite in human biology

Nitric oxide (NO) plays a fundamental role in maintaining normal vascular function. NO is produced by endothelial cells and diffuses both into smooth muscle causing vasodilation and into the vessel lumen where the majority of this highly potent gas is rapidly inactivated by dioxygenation reaction with oxyhemoglobin to form nitrate. Diffusional barriers for NO around the erythrocyte and along the endothelium in laminar flowing blood reduce the inactivation reaction of NO by hemoglobin, allowing sufficient NO to escape for vasodilation and also to react in plasma and tissues to form nitrite anions (NO(2)(-)) and NO-modified peptides and proteins (RX-NO). Several recent studies have highlighted the importance of the nitrite anion in human biology. These studies have shown that measurement of plasma nitrite is a sensitive index of constitutive NO synthesis, suggesting that it may be useful as a marker of endothelial function. Additionally, recent evidence suggests that nitrite represents a circulating storage pool of NO and may selectively donate NO to hypoxic vascular beds. The conversion of nitrite to NO requires a reaction with a deoxygenated heme protein, suggesting a novel function of hemoglobin as a deoxygenation-dependent nitrite reductase. This review focuses on the role of nitrite as a circulating NO donor, its potential as an index of NO synthase (NOS) activity and endothelial function, and discusses potential diagnostic and therapeutic applications.     

离子色谱法测定生活饮用水中亚硝酸盐氮

目的:建立离子色谱法测定水中亚硝酸盐氮的检测方法。方法:通过对淋洗液的选择,以Na2CO3-NaHCO3混合液为淋洗液,使亚硝酸盐氮与C l-、NO3--N、SO42-同时测定。结果:方法最低检出限为5.0μg/L,标准曲线线性范围0.05~5.00 mg/L,相关系数0.9997,相对标准偏差RSD<4.2%,回收率92.5%~104.7%。结论:本方法操作简单,适于基层单位日常检测中需要。