Nitrite or sildenafil, but not BAY 41-2272, blunt acute pulmonary embolism-induced increases in circulating matrix metalloproteinase-9 and oxidative stress

IntroductionInhibition of matrix metalloproteinases (MMPs) improves the hemodynamics during acute pulmonary embolism (APE) and oxidative stress upregulates MMPs. We compared the effects of different NO-cGMP pathway activators on APE-induced increases in MMPs.Materials and MethodsHemodynamic and biochemical evaluations were performed in non-embolized dogs treated with saline (N = 5), and in microspheres embolized dogs receiving saline (n = 9), or nitrite (6.75 µmol/kg i.v. over 15 min followed by 0.28 µmol/kg/min; n = 5), or sildenafil (0.25 mg/kg; n = 5), or BAY 41-2272 (0.03, 0.1, 0.3, and 1 mg/kg/h; n = 5). Plasma thiobarbituric acid reactive substances (TBARS) concentrations were determined. Zymograms of plasma samples were performed, and in vitro antioxidant effects or inhibition of MMPs by these drugs were examined.ResultsAPE increased mean pulmonary artery pressure by ~ 25 mmHg. Nitrite, BAY 41-2272, or sildenafil reversed this increase by ~ 40% (P < 0.05). Similar effects were seen on the pulmonary vascular resistance. While both nitrite and sildenafil produced no systemic effects, the highest dose of BAY 41-2272 produced systemic hypotension (P < 0.05). While nitrite and sildenafil blunted the increases in plasma pro-MMP-9 levels and TBARS (all P < 0.05), BAY 41-2272 produced no such effects. Nitrite and sildenafil produced in vitro antioxidant effects and inhibited MMPs only at high concentrations. BAY 41-2272 produced no such effects.ConclusionsActivation of the NO-cGMP pathway with nitrite or sildenafil, but not with BAY 41-2272, attenuates APE-induced oxidative stress and increased MMP-9 levels. These findings are consistent with the idea that NO-cGMP pathway activators with antioxidant effects prevent the release of MMP-9 during APE.     

孕期亚硝酸盐暴露对仔鼠海马损伤的影响

目的 探讨孕期亚硝酸盐暴露对海马损伤的作用。 方法 利用C57BL/6J小鼠建立孕期亚硝酸盐暴露模型,分为对照组（生理盐水）、低剂量亚硝酸盐组（60mg/kg）和高剂量亚硝酸盐组(120mg/kg)。收集出生当日（P0）、P7、P14及P30各年龄点仔鼠大脑,用于免疫荧光染色、彗星实验、Western blotting蛋白半定量分析,对海马损伤进行研究。 结果 不论是亚硝酸盐暴露组还是对照组,仔鼠齿状回增殖的神经干细胞数目均随着年龄的增长逐渐减少;在P0、P7、P14和P30年龄点,暴露组仔鼠增殖的神经干细胞的数量明显比对照组少,且具有剂量依赖性（P<0.05,n=96）。为了鉴别这种抑制作用是否具有选择性,我们对P0仔鼠室管膜下区神经干细胞的增殖情况进行了观察。结果发现,亚硝酸盐暴露组室管膜下区的神经干细胞增殖较对照组也减少,同样具有剂量依赖性（P<0.05）;亚硝酸盐暴露组仔鼠门区炎症损伤细胞和凋亡细胞的数目比对照组多,具有剂量依赖性（P<0.05）;彗星实验结果显示,亚硝酸盐暴露组P0仔鼠海马细胞的彗尾比对照组长,具有剂量依赖性(P<0.01);与对照组P0仔鼠相比,亚硝酸盐暴露组仔鼠海马组织内Caspase-8和核因子κB（NF-κB）蛋白的表达量较高（P<0.05）。
结论 孕期亚硝酸盐暴露可通过抑制神经干细胞增殖,促进细胞损伤和凋亡而对仔鼠海马造成损伤。     

The role of surface receptor stimulation on the cytotoxicity of resveratrol to macrophages

The present work has evaluated the role of lipopolysaccharide (LPS) stimulation and of TLR4 receptors on the cytotoxicity of resveratrol (RES), a polyphenolic stilbene component of red wine, in TLR4-bearing (i.e., RAW 264.7) and TLR4-deficient (i.e., 10ScNCr/23) macrophages. Based on the results of the MTT assay, DNA fragmentation analysis, and scanning electron microscopic examination, cell stimulation with LPS was found to maintain the viability of, attenuate DNA fragmentation in, and preserve normal morphology of TLR4-proficient macrophages exposed to RES. In contrast, LPS failed to spare TLR4-deficient macrophages from the deleterious effects of RES. Moreover, while LPS treatment conferred protection from RES toxicity in TLR4-bearing macrophages, this stilbene inhibited the production of nitric oxide by stimulated cells in a concentration-dependent fashion. It is therefore likely that the cytotoxic effects of RES towards non-stimulated macrophages and the propensity of RES to inhibit nitric oxide production by activated macrophages are both contributing, at least in part, to the anti-inflammatory activity of this natural product.     

Electroreduction of nitrate ion to nitrite and ammonia on a gold electrode in acidic and basic sodium and cesium nitrate solutions

The electroreduction of NO₃^? to NO₂^? and NH₃ has been investigated using a polycrystalline Au electrode in 0.5 M NaNO₃ and CsNO₃ solutions with pH in the ranges 1.1–3.0 and 9.85–12.8. The reduction of NO₃^? does not occur significantly in the strongly acidic solutions with pH lower than 1.4 to 1.6: the current efficiency for the NO₃^? reduction is less than 5%. A further increase in pH significantly facilitates the NO₃^? reduction. In basic solutions the reduction of NO₃^? occurs predominantly: the current efficiency reaches the range 80 to 99%. In the case of NaNO₃ solutions the ratio of the current efficiencies for NH₃ and NO₂^? production, CE_NH3/CE_NO2^? is nearly unity in the acidic solutions and 2 to 3 in basic solutions. On the other hand, in CsNO₃ solutions, the current efficiency of NO₂^? production becomes much higher and the CE_NH3/CE_NO2^? is 1 to 0.5 at pH in the range 2.0–3.0 and 0.2 to 0.5 at pH in the range 10.0–12.7. Partially positively-charged Na or Cs adatoms underpotentially deposited (upd) on the Au electrode surface are believed to facilitate the adsorption of NO₃^? ions, resulting in the preferential reduction of NO₃^?.     

湘江衡阳段水体中氮含量的动态变化及成因分析

对1991年－2000年湘江衡阳段干流水体中氨氮、亚硝酸盐氮和硝酸盐氮在不同江段、不同年际的时空变化规律进行了分析。结果表明,亚硝酸盐氮和硝酸盐氮含量有逐年升高的趋势,氨氮含量年际变化幅度较大,是湘江衡阳段水体超标指标之一。对水体中氮的来源作了分析,并提出了保护水资源的措施。     

英蓝渗析-离子色谱法分析奶粉中的硝酸盐、亚硝酸盐

目的:建立一种快速检测奶粉中硝酸盐和亚硝酸盐的离子色谱分析方法。方法:称取一定量的奶粉试样用超纯水溶解定容后,通过英蓝渗析技术对试样溶液进行在线的前处理并直接进样进行离子分析。结果:该方法线性范围较宽,在方法研究的范围内,相关系数均优于0.9990,回收率在94.9%~104.2%之间,NO3-和NO2-的最小检出限分别为1.74μg/L和0.96μg/L。结论:本方法有效的去除了奶粉试样溶液中的蛋白质、脂肪以及其它复杂的有机物,较好的净化了试样溶液,具有操作简便、自动化程度高、结果准确可靠的优点。     

Tierexperimentelle Untersuchungen zur Carcinomgefährdung des Magens nach Vagotomie

Zusammenfassung Der Einfluß einer trunculären Vagotomie in Kombination mit verschiedenen Drainageoperationen (Pyloroplastik, Gastroenterostomie ohne Enteroanastomose, Y-Roux-Gastroenterostomie) wurde im Hinblick auf eine Carcinomgefährdung des vagotomierten Magens tierexperimentell an männlichen Wistarratten untersucht. Es wurde überprüft, inwieweit hiernach im Vergleich zu einer nicht-vagotomierten Kontrollgruppe Schleimhautveränderungen auftreten, die unter Exposition mit dem Carcinogen MNNG zeitlich früher und häufiger zur Carcinomentstehung prädisponieren. Als mögliche wichtige cocarcinogene Faktoren wurden zusätzlich die intragastrale Bakterienflora und Nitrit-Konzentration der einzelnen Versuchsgruppen untereinander verglichen. Es zeigte sich, daß der Schweregrad gefundener Magenschleimhautveränderungen, sowie das Ausmaß der bakteriellen Besiedlung und die Nitrit-Konzentration im Magensaft neben der durch Vagotomie angestrebten Säurereduktion vor allem durch Störung der Magenmotilität oder einen enterogastrischen Reflux verstärkt wird. Die Ergebnisse der Untersuchungen sprechen dafür, daß nach Vagotomie, soweit eine ausreichende Magenentleerung gesichert und diese nicht durch einen enterogastrischen Reflux (Gastroenterostomie) erkauft wird, das Risiko für ein Operationsfolgecarcinom gering anzusehen ist.

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Animal experiments to assess the risk of cancer in the stomach after vagotomy

Summary To assess the possible risk of cancer in the operated stomach, the influence of truncal vagotomy combined with different operative drainage procedures (pyloroplasty, gastro-enterostomy without entero-anastomosis, Roux-en-Y gastro-enterostomy) was studied in animal experiments. The aim of the study was to determine whether, compared to controls an earlier and higher incidence of precancerous epithelial lesions or cancers in the stomach occurs in vagotomized animals after oral administration of carcinogens (MNNG). To consider conditions, that may predispose to in vivo formation of carcinogenicN-nitroso compounds, bacterial flora and intragastric nitrite concentration were measured and compared in the various operative groups. The severity of induced epithelial lesions and the quantity of bacterial growth and nitrite concentration in the gastric juice were influenced, apart from the reduction of acid output after vagotomy, mainly by prolonged gastric stasis or the degree of enterogastric reflux. The results suggest that there is probably no increased risk of cancer following vagotomy, if sufficient gastric clearance is guaranted and enterogastric reflux is largely excluded.

     

籍溴酸钾氧化吖啶黄新催化褪色光度法测定痕量亚硝酸根的研究

研究了在 0 .10mol·dm-3 的盐酸介质中 ,亚硝酸根催化溴酸钾氧化伯胺基结构碱性染料吖啶黄褪色反应的适宜条件与影响因素 ,建立了催化动力学褪色光度法测定痕量亚硝酸盐的新方法。亚硝酸根浓度在 0 .2 5～ 2 0 .0 0 μg/ 2 5ml范围内符合比耳定律 ,其λmax=4 5 5nm ,Sandell灵敏度为 36 .2 0ng·cm-2 ,RSD %为 1.95 %～ 5 .97% ,CV为 97.6 0 %～ 10 5 .0 0 %。该法用于环境样品、生物材料、食品等实际样品中亚硝酸根的测定 ,试剂简单 ,方法快速 ,选择性好 ,结果满意可靠。     

血清和尿中亚硝酸盐含量的离子色谱测定法

目的建立离子色谱法测定食物中毒样品如血清和尿液中NO2-含量的方法。方法样品通过系统预处理,选用Dionix Ionpac AS19—2mm型分析柱,RFIC淋洗液在线发生器在线生成KOH淋洗液进行梯度淋洗,抑制型电导检测器,进样体积为150ul。结果该方法NO2-最低检出限为7．0ug/L,回收率在91．9％-109．6％之间。结论该方法操作简单,灵敏度高,重现性好。     

The stress caused by nitrite with titanium dioxide nanoparticles under UVA irradiation in human keratinocyte cell

Our previous work found that in the presence of nitrite, titanium dioxide nanoparticles can cause protein tyrosine nitration under UVA irradiation in vivo. In this paper, the human keratinocyte cells was used as a skin cell model to further study the photo-toxicity of titanium dioxide nanoparticles when nitrite was present. The results showed that nitrite increased the photo-toxicity of titanium dioxide in a dose-dependant manner, and generated protein tyrosine nitration in keratinocyte cells. Morphological study of keratinocyte cells suggested a specific apoptosis mediated by apoptosis inducing factor. It was also found the main target nitrated in cells was cystatin-A, which expressed abundantly in cytoplasm and functioned as a cysteine protease inhibitor. The stress induced by titanium dioxide with nitrite under UVA irradiation in human keratinocyte cells appeared to trigger the apoptosis inducing factor mediated cell death and lose the inhibition of active caspase by cystatin-A. We conclude that nitrite can bring new damage and stress to human keratinocyte cells with titanium dioxide nanoparticles under UVA irradiation.