两种含锌化合物对慢性染铅大鼠海马NADPH-d阳性神经元影响的比较

为探讨硫酸锌(ZnSO4)和牛磺酸锌(TZC)拮抗铅对学习记忆的损害的不同，采用NADPH-黄递酶(NADPH-d)组化，观察了饮用含0.2g／L醋酸铅(PbAc)饮水和含不同剂量(5．0，15．0g／kg)ZnSO4、(5．9、17．7g／kg)TZC饲料喂养的大鼠海马一氧化氮合酶(NOS)活性的变化。结果表明，各补锌组均不同程度地缓解铅致NOS活力减低，铅 低TZC组、铅 高ZnSO4组和铅 低ZnSO4组大鼠海马神经元的NOS活性明显高于染铅组，其中铅 低TZC组的保护作用最显著，而铅 高TZC组的NOS活性明显低于对照组，而接近染铅组水平。结论是锌对抗铅的毒性作用与锌的化学结合形式、锌的剂量密切相关。     

低硒对大鼠血管一氧化氮合酶和微循环的影响

采用低硒饲料饲养大鼠造成体内贫硒。１４周时测定血浆中脂质过氧化物（ＬＰＯ）、前列环素（ＰＧＩ２）和血栓素（ＴＸＡ２）的水平以及部分血液流变学指标。实验第３９周,测定血管组织一氧化氮合酶（ＮＯＳ）活性及一氧化氮（ＮＯ）水平。结果显示,低硒饲料组的血管ＮＯＳ活性、ＮＯ水平显著低于常规饲料的对照组;而在实验第１４周时,当低硒饲料组的血硒、血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性显著下降、血浆ＬＰＯ水平明显上升的同时,其对应的血浆６－酮－ＰＧＦ１α水平也显著降低,但其ＴＸＢ２与对照组无显著差异。此外,随着大鼠体内的贫硒,其红细胞变形能力下降,但红细胞聚集指数和血沉方程Ｋ值提高。因此,硒不足可能会通过影响ＮＯＳ活性和ＰＧＩ２的合成以及红细胞特性而损害微循环功能。     

氯化镧对烧伤大鼠胸腺iNOS表达及细胞凋亡的影响

用原位末端标记术、免疫组织化学术和体视学形态记量法观察稀土化合物氯化镧（LaCl3）对严重烧伤大鼠胸腺诱导性一氧化氮合酶（iN-OS）表达及胸腺细胞凋亡的影响。结果显示,LaCl3能减轻烧伤后大鼠胸腺应激性萎缩的程度,降低病理性胸腺细胞凋亡率,其行为主要是通过部分抑制iNOS在烧伤后大鼠胸腺组织中的表达,表明LaCl3对严重烧伤后机体免疫功能具有一定的保护作用,可作为一种有效的烧伤后免疫功能调节和保护剂。     

模拟微重力效应引起大鼠脑氧化应激与Na~+,K~+-ATP酶表达下调

采用地基模拟微重力效应的大鼠吊尾模型重现了微重力环境导致的氧化应激现象。对脑组织中OH自由基及丙二醛含量测定结果表明,吊尾组大鼠脑纹状体及海马均较其对照组显著性升高,反映了脑中发生了明显的氧化应激。通过比较蛋白质组学方法测定了纹状体突触蛋白的差异表达情况,发现鉴定到的所有ATP酶的表达均发生下调。这些结果表明,微重力效应的影响与氧化应激增强、Na+,K+-ATP酶表达或活性下降密切相关,为进一步探究微重力环境的作用机制及其对于生理系统造成的其它损伤研究提供了依据。     

高硒情况下维生素E对老龄大鼠血清中抗氧化作用的影响

研究了高Se或高维生素E下，老龄大鼠体内抗氧化活性的变化以及高Se下维生素E对其体内抗氧化水平的影响。将十二月龄Wistar大鼠32只随机分成4组：（1）正常饲料组；（2）高Se饲料组；（3）高维生素E饲料组；（4）高Se高维生素E饲料组。饲至十周末，处死大鼠，按试剂盒要求取其血液制成血清测GSH－Px,SOD活性，MDA含量。结果表明，高Se或高维生素E下饲养下的大鼠与对照组比较，血清中GSH－Px活性升高（P＜0．05）。SOD活性未见改变，MDA含量分别减少50％和56％，有显著差异（P＜0．01）；维生素E与高Se合用与高Se组比较能进一步同GSH－Px,SOD活性（P＜0．01）。结论：高Se会升高老龄大鼠的抗氧化活性，而与维生素E合用更加升高老龄大鼠血液中抗氧化活性。     

新显色剂二溴对甲基偶氮磺光度测定铅的研究与应用

在０．２４ｍｏｌ．Ｌ＾－１Ｈ３ＰＯ４介质中，铅与二溴对甲基偶氮磺形成１：２的蓝色配合物，最大吸收波长在６３０ｎｍ表现摩尔吸光系数为７．９９×１０＾４Ｌ．ｍｏｌ＾－１．ｃｍ＾－１铅量在０－２０μｇ／２５ｍＬ，内符合比耳定律，方法应用于铜合金中微量铅的测定，结果满意。     

微量元素、抗氧化剂与湿热证的相关性的研究

建立了温病湿热证动物模型，研究了清香散对大鼠微旦元素锌（Zn）、硒（Se)、铜（Cu)和维生素E代谢水平，一氧化氮（NO）含量以及谷胱甘肽过氧化物酶（GSH－Px)活力变化的影响，并将正常对照组、湿热模型组、清香散治疗组进行两两比较。结果表明，湿热证模型大鼠血清Zn、Se、维生素E、NO含量显著下降，Cu含量显著升高，GSH－Px活力明显降低，经清热祛湿的经验方清香散治疗后，大鼠血清Zn、Se、维生素E、NO含量及GSH－Px活力明显升高，Cu含量明显下降。抗氧化能力下降是湿热证的本质之一，微量元素锌（Zn)、硒（Se)、铜（Cu)在机体内的含量反映了抗氧化酶活性的高低，清香散能显著提高大鼠血液Zn、Ee、维生素E、NO含量及GSH－Px活力，降低Cu含量，恢复其抗氧化能力。     

1－芳氧乙酰氧基－1－（1H－1，2，4－三唑－1－基）－3，3－二甲基－2－丁酮衍生物的研究

以三乙胺为缚酸剂，用芳氧乙酸同ω－溴代－ω－（１Ｈ－１，２，４－三唑－１－基）频哪酮反应，合成了一系列三唑类新化合物，探讨了化合物的合成方法。通过ＩＲ￣１ＨＮＭＲ、ＭＳ分析及元素分析确定了化合物的结构，生物活性测定结果表明，部分化合物具有良好的除草活性，同时表现出一定程度的植物生长调节活性及杀菌活性．     

维生素E与铅

维生素E参与血红素或血红素蛋白质的合成 ,并能同时影响ALS和ALAD活性。在实验中观察到 ,维生素E缺乏的大鼠发生铅中毒时 ,可出现贫血、脾大和红细胞脆性增加 ,通过饲料补充维生素E则可预防由铅引起的红细胞变形 (LevanderOA ,1 975 ,1 979)。Dhawan也发出 ,在接触铅的同时 ,补充维生素E可预防血ALAD活性下降、尿中ALA升高及铅在血和肝中的蓄积。维生素E对铅的这种预防作用可能与其抗氧化特性和影响药物代谢酶系有关。Trivedi ( 1 998)最近观察到 ,用维生素E预处理可降低肝、心LPO含量 ,增加肝、肾过氧化氢酶(CAT)活性。维生素…     

酶-配体复合物亲和性的计算

描述了一种新的计算酶－配体复合物亲和性的方法．它考虑了酶－配体结合过程中自由能变化的各主要因素，并利用经验公式加以计算、从蛋白质结构数据库中选取了66个酶－配体复合物作为训练集，利用回归分析得出最后的模型．此模型通用于各种类型的酶－配体复合物，计算结果比技准确，预测算合物解离常数的平均偏差小于一个数量级．此方法还可以定量评价配体分子中每个部分对结合过程的贡献大小，可以为先导他合物的优化提供非常直接的信息     

Imaging of nitric oxide generation in the rat brain

Nitric oxide radicals produced in the rat brain subjected to ischemia-hypoxia were trapped by the systemically administered diethyldithiocarbamate and iron. The right hemisphere of the brain was then removed and frozen with liquid nitrogen. Three-dimensional spatial distribution of the nitric oxide radicals in this hemisphere was performed using electron paramagnetic resonance imaging techniques. The results suggest that nitric oxide radicals were produced and trapped in the areas which are known to have high nitric oxide synthase activity, such as piriform cortex, hippocampus, hypothalamus, amygdala, and substantia nigra. In this model, which did not interrupt the posterior circulation, the production and trapping of nitric oxide in the cerebellum was relatively weak.     

Possible mechanism for nitric oxide and oxidative stress induced pathophysiological variance in acute myocardial infarction development: A study by a flow injection-chemiluminescence method

The acute myocardial infarction (AMI) model was established through rabbits, and this kind of model was used to investigate the possible mechanism for the AMI mediated damage, induced by NO release and oxidative stress. The biomedical parameters nitric oxide (NO), total antioxidant capacity (TAC) variation in vivo and the enzymatic activity of nitric oxide synthase (NOS) and superoxide dismutase (SOD), which are considered as the major markers for pathophysiological variation, were detected. The results obtained gave evidence that AMI can lead to the NO excess release and compensation by excess cellular respiration, and both of them can result in oxidative stress and further generation of reactive oxygen species (ROS). The latter can bring a series of damages to the organism, including decrease of the TAC value, and NOS and SOD activity.     

Indications for the Occurrence of Nitric Oxide Synthases in Fungi and Plants and the Involvement in Photoconidiation of Neurospora crassa*

Indications for the occurrence of nitric oxide synthases in Dictyostelium, Neurospora, Phycomyces and the leguminous plant Mucuna hassjoo as well as a physiological role of nitric oxide in Neurospora crassa are demonstrated. An exogenous nitric oxide donor, sodium nitroprus-side, inhibited light-stimulated conidiation in N. crassa. Specific inhibitors of nitric oxide synthase, like the arginine derivatives N^G-nitro-L-arginine (L-NA) and N^G-nitro-L-arginine-methyl ester (L-NAME), enhanced conidiation in darkness and in the light, whereas the stereo-isomer D-NAME was inactive. This communication reports to our knowledge the first time the presence of enzymatic activity of nitric oxide synthase in fungi and a higher plant and an effect of nitric oxide in fungal photophysiology.     

Suppression of inducible nitric oxide synthase expression by yakuchinones and their analogues

Analogues of yakuchinones were synthesized as inhibitors of nitric oxide production in lipopolysaccharide-activated macrophage cell line, RAW 264.7 cells. We prepared stronger inhibitors than the original natural molecules, yakuchinones A and B reported from Alpinia oxyphylla. From the limited structural activity relation study of analogues, we concluded that the optimal length of linker between two aryl groups and the presence of enone moiety in the linker were identified as essential for the activity. The IC50 value of the most potent structure was 0.92 microM. The active analogues suppressed the expression of inducible nitric oxide synthase protein and mRNA.     

Angiogenin induces nitric oxide release independently from its RNase activity

Nitric oxide (NO), a biological mediator involved in vascular physiology, was sensed electrochemically using a microelectrode array. Angiogenin was shown to trigger nitric oxide synthase (NOS) activity in human umbilical vein endothelial cells and embryonic stem cell derived endothelial cells independently from its RNase activity.     

Nitric oxide producing artificial enzymes based on metalloporphyrins

Artificial enzymes are synthetic materials or molecules that exhibit enzyme-like activities. Herein, we report artificial enzymes based on metalloporphyrins (MPs) that can mimic nitric oxide synthase (NOS) to produce nitric oxide (NO) from l-arginine (Arg) using hydrogen peroxide (H₂O₂) as an oxidant, and we determine the microenvironmental influence on their activity and stability. An assortment of structurally diverse water-soluble MPs was synthesized, and their NO production was compared. Improved catalytic activity and stability of the lead MP were observed when it was conjugated to the hydrophilic homopolymer poly(2-carboxyethyl acrylate) (PCEA). Micelles assembled from the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-PCEA functionalized with the lead MP, and MP-conjugated PCEA polymer chains immobilized on silica particles resulted in moieties with ～3× higher catalytic activity compared to the monomeric MP. Finally, the PCEA-coated silica particles could use the MPs as motor units to exhibit enhanced diffusion in the presence of the required fuel molecules Arg and H₂O₂. Taken together, the microenvironments of the artificial enzymes have a marked impact on their activity and stability, and these NO-producing MPs offer an interesting synthetic alternative to their natural counterparts.     

Thalidomide as a nitric oxide synthase inhibitor and its structural development

Thalidomide has been found to exhibit weak nitric oxide synthase (NOS)-inhibitory activity. Structural development studies of thalidomide showed that some N-2,6-dimethylphenylhomophthalimide analogs possess NOS-inhibiting activity.     

Mitochondrial targeting of radioprotectants using peptidyl conjugates

Ionizing radiation activates a mitochondrial nitric oxide synthase, leading to inhibition of the respiratory chain, generation of excess superoxide, peroxynitrite production and nitrosative damage. We have measured the radioprotective effects of a nitric oxide synthase antagonist (AMT) versus a free radical scavenger (4-amino-TEMPO) using electrochemical detection of nitric oxide and peroxynitrite. To enhance their efficacy, we have conjugated these compounds to peptides and peptide isosteres--derived from the antibiotic gramicidin S--that target the mitochondria. The targeting ability of these peptidyl conjugates was measured using quantitative mass spectrometry.     

Anti-inflammatory diterpene from Thyrsanthera suborbicularis

Bioactivity-guided isolation on a n-hexane-soluble fraction of Thyrsanthera suborbicularis led to the isolation of a new rosane-type diterpene, 19-hydroxy-1(10), 15-rosadiene (1), along with three known compounds, taraxerol, acetyl aleuritolic acid, and spathulenol. The structures of isolated compounds were determined by interpretation of NMR spectroscopic data and mass spectrometry. Compound 1 demonstrated significantly inhibitory activity on nitric oxide production in RAW264.7 lipopolysaccharide (LPS)-activated mouse macrophages with an IC(50) value of 2.91 μg/ml via the suppression of inducible nitric oxide synthase (iNOS) mRNA expression.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 25. Synthesis of new imidazolyl and pyrazolyl derivatives of thiophene as inhibitors of nitric oxide synthase

Some novel imidazolyl and pyrazolyl thiophene derivatives were synthesized. Different substituted N‐containing heterocycles were chosen with the aim of enhancing the activity or selectivity of the products towards inhibition of one of the three isoforms of nitric oxide synthase. One series of substances was prepared by substitution reactions of 3‐bromo‐2‐nitrothiophene with various heterocycles. In the other series introduction of a second heterocyclic substituent to pyrazolylthiophene compounds was attempted.