Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone. We have examined the role of superoxide anion (O-2) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O-2 contributes significantly to the instability of EDRF.     

Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodilators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO from endothelial cells in culture. No was determined as the chemiluminescent product of its reaction with ozone. The biological activity of EDRF and of NO was measured by bioassay. The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO. Both substances were equally unstable. Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Thus NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator. We suggest that EDRF and NO are identical.     

Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain

In the vascular system, endothelium-derived relaxing factor (EDRF) is the name of the local hormone released from endothelial cells in response to vasodilators such as acetylcholine, bradykinin and histamine. It diffuses into underlying smooth muscle where it causes relaxation by activating guanylate cyclase, so producing a rise in cyclic GMP levels. It has been known for many years that in the central nervous system (CNS) the excitatory neurotransmitter glutamate can elicit large increases in cGMP levels, particularly in the cerebellum where the turnover rate of cGMP is low. Recent evidence indicates that cell-cell interactions are involved in this response. We report here that by acting on NMDA (N-methyl-D-aspartate) receptors on cerebellar cells, glutamate induces the release of a diffusible messenger with strikingly similar properties to EDRF. This messenger is released in a Ca2+-dependent manner and its activity accounts for the cGMP responses that take place following NMDA receptor activation. In the CNS, EDRF may link activation of postsynaptic NMDA receptors to functional modifications in neighbouring presynaptic terminals and glial cells.     

Ultrastructural localization of choline acetyltransferase in vascular endothelial cells in rat brain

Furchgott and Zawadski have shown that acetylcholine (ACh) does not act directly on the smooth muscle of blood vessel walls, but rather via receptors on the endothelial cells lining the lumen, to release an endothelium-derived relaxing factor (EDRF). As it is very unlikely that neurotransmitter released from the periarterial nerves, which are confined to the adventitial-medial border, diffuses all the way through the medial muscle coat before acting on endothelial cells to release EDRF to produce vasodilatation, this discovery has been regarded as an indication of a pathophysiological mechanism, rather than a physiological one (see refs 2, 3). ACh is rapidly degraded in the blood by acetylcholinesterase, so that ACh must be released locally to be effective on endothelial cells. Here we demonstrate the immunocytochemical localization of choline acetyltransferase in endothelial cells of small brain vessels, which is consistent with the view that the ACh originates from endothelial cells that can synthesize and store it. We suggest that release of ACh following damage to endothelial cells during ischaemia contributes to a pathophysiological mechanism of vasodilation which protects that segment of vessel from further damage as well as brain cells from hypoxia.     

Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.     

新型的聚合物改性剂──2,3-二甲基-2,3-二苯基丁烷及其衍生物

2,3－二甲基－2,3－二苯基丁烷,由于其结构上的特殊性,在一定条件下易形成稳定性较高的自由基,可作为一种自由基引发剂用于聚合物的交联共聚,达到改善聚合物性能的目的。对于烯烃类聚合物可用作阻燃剂的增效剂,降低卤素类阻燃剂的用量及对聚合物性能的影响,提高聚合物的防火阻燃效果。与常见自由基引发剂相比较,使用安全是它的又一特性。     

Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta

The vascular endothelium, in response to pulsatile flow and vasoactive agents including acetylcholine, secretes the endothelium-derived relaxing factor (EDRF), a substance which regulates vascular tone. Recent interest in EDRF has focused on its possible dysfunction in atherosclerosis. In animal models of the disease, endothelium-dependent relaxation is markedly reduced. The continuous exposure of the endothelium in hyperlipidaemia to high concentrations of low-density lipoprotein (LDL), a known atherogenic risk factor, may explain this dysfunction. Here, we demonstrate that pathophysiological concentrations of LDL directly inhibit endothelium-dependent relaxation. Chemically modified LDL, in contrast, is inactive, implying that the inhibition is through a receptor-dependent mechanism.     

Vitamin E modulates the lipoxygenation of arachidonic acid in leukocytes

The arachidonic acid released from cellular phospholipids of specifically stimulated platelets and leukocytes is oxygenated enzymatically by two major pathways. A complex cycloxygenase converts some of the free arachidonic acid to labile endoperoxides that are transformed to prostaglandins, thromboxanes and prostacyclin (PGI2). Lipoxygenases convert part of the arachidonic acid to unstable hydroperoxy-eicosatetraenoic acids (OOHETEs) that are transformed to monohydroxyeicosatetraenoic acids (HETEs), oligohydroxy-eicosatetraenoic or -eicostatrienoic acids such as di-HETEs and tri-HETEs, and, in some instances, more complex humoral mediators, including slow-reacting substances. Both the nature of the HETEs and the ratio of the HETEs to the cyclo-oxygenase products are specific characteristics of each type of cell. In human neutrophils, the sum of the lipoxygenase products 5-HETE, 11-HETE and 5,12-di-HETE substantially exceeds the total amount of PGE2 and other cyclo-oxygenase metabolites that are generated concurrently, and the endogenous lipoxygenase products regulate neutrophil function. The present data indicate that vitamin E (alpha-tocopherol) bidirectionally modulates the activity of the lipoxygenase pathway of human neutrophils in vitro. Normal plasma concentrations of alpha-tocopherol enhance the lipoxygenation of arachidonic acid, whereas higher concentrations of alpha-tocopherol exert a suppressive effect that is consistent with its role as a hydroperoxide scavenger.     

乙二醛/尿素树脂的合成及在造纸上的应用

尿醛树脂是一种传统的纸张施胶剂,由于其廉价,而且施强效果明显,因此一直被广泛的应用。但它在生产和使用过程中容易释放出游离甲醛,带来极大的健康危害。该文研究了以乙二醛部分或全部替代甲醛合成脲醛树脂的合成条件以及产物对纸张产生的湿增强效果,并通过光谱分析初步探讨了乙二醛、甲醛、尿素合成脲醛树脂的反应机理及作为纸张湿强剂的湿增强机理     

EDRF coordinates the behaviour of vascular resistance vessels

Constriction of vascular smooth muscle in response to the stimulus of raised intravascular pressure--the myogenic response--represents a positive feedback mechanism which, if unopposed, could theoretically lead to instability in the intact circulation. Dilation in response to increased intraluminal flow would provide an opposing feedback mechanism which could confer overall stability. Flow-dependent dilation in conduit vessels is mediated by endothelium-derived relaxing factor (EDRF), but the relationship between flow and EDRF activity has not been studied in resistance vessels in situ. We here demonstrate that EDRF can coordinate the aggregate hydrodynamic properties of an intact network. Under control conditions, EDRF maintains a fourth-power relationship between diameter and flow so that the pressure gradient in each vessel asymptotically approaches a constant value at high flow rates. Basal EDRF release may also maintain a similar spatial distribution of flow at different flow rates, even under conditions of moderate pharmacological constriction.     

不同物质对大豆幼苗化学发光的影响

大豆的子叶，幼茎和幼根者都能产生超弱的光，组织受到伤害，发光增强。脂肪酸，脂氧合酶，曙红以及过氧反氢，促进发光，煮沸使发光大为减弱。种子浸出液中也有发光物质存在，煮沸也使发光减弱。种子萌发过程中，有大量的过氧化作用产物丙醛生成，指氧合酶的作用也很活跃，暗示强烈的过氧化作用在进行。     

三取代烷氧基均三嗪衍生物的合成研究

三嗪类衍生物是一类应用十分广泛的化合物．主要应用领域有染料工业、农用化学品工业、医药工业和石化助制工业等，主要被用作除草剂、杀菌剂、杀虫剂、新型阻燃绝缘高聚物材料的主要原料，荧光增白剂、活性染料、医药以及新型多功能润滑油添加制等．采用打钠砂的方法，将三聚氯氰与长碳链的脂肪醇进行反应，制备了两种三取代的烷氧基均三嗪衍生物，制备方法简单，反应条件温和，效果好．     

UV自由基固化和阳离子固化涂层的比较研究

对 U V自由基固化和阳离子固化两种机理进行了对照试验 .考察了温度和 O2 对固化速度的影响 ,涂层性能及它们作为 UV固化涂料、油墨的优缺点 ,并从理论上进行了分析 .U V自由基固化和阳离子固化的固化速度随温度的升高而加快 ,并且自由基的固化速度大于阳离子固化速度 .自由基固化体积收缩大 ,附着力差 ;阳离子固化体积收缩小 ,附着力优异 .氧对自由基固化有显著的阻聚作用 ,而对阳离子固化没有阻聚效应 .此外 ,阳离子固化存在“暗反应”,当移走 UV光源后 ,仍会发生固化反应     

Sequence-specific artificial photo-induced endonucleases based on triple helix-forming oligonucleotides

Homopyrimidine oligonucleotides bind to homopurine-homopyrimidine sequences of duplex DNA forming a local triple helix. This binding can be demonstrated either directly by a footprinting technique, gel assays, or indirectly by inducing irreversible reactions in the target sequence, such as photocrosslinking or cleavage. Binding occurs in the major groove with the homopyrimidine oligonucleotide orientated parallel to the homopurine strand. Thymine and protonated cytosine in the oligonucleotide form Hoogsteen-type hydrogen bonds with A.T and G.C Watson-Crick base pairs, respectively. Here we report that an 11-residue homopyrimidine oligonucleotide covalently attached to an ellipticine derivative by its 3' phosphate photo-induces cleavage of the two strands of a target homopurine--homopyrimidine sequence. To our knowledge, this is the first reported case of a sequence-specific artificial photoendonuclease. In addition we show that a strong binding site for a free ellipticine derivative is induced at the junction between the triplex and duplex structures on the 5' side of the bound oligonucleotide. On irradiation, cleavage is observed on both strands of DNA. This opens new possibilities for inducing irreversible reactions on DNA at specific sites by the synergistic action of a triple helix-forming oligonucleotide and an intercalating agent.     

5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue

The release of cerebral acetylcholine from terminals in the cerebral cortex has been shown to be regulated by 5-hydroxytryptamine (5-HT) but it is not known which subtype of the 5-HT receptor is involved. 5-HT receptor agonists increase acetylcholine levels in vivo, indicating a reduced turnover, and reduce release of acetylcholine from striatal slices in vitro. Depleting 5-HT by inhibiting synthesis or by destroying the neurons containing 5-HT potentiates acetylcholine release, and increases acetylcholine turnover in the cerebral cortex and hippocampus. Selective antagonists for the 5-HT3 receptor subtypes which seem to have effects on mood and activity may exert their effect through the regulation of acetylcholine release in the cortex and limbic system. Radioligand binding studies show a high density of 5-HT3 receptors in the cholinergic-rich entorhinal cortex and we provide evidence that a reduction in cortical cholinergic function can be effected in vitro by 5-HT3 receptors.     

Phosphorylation of the nicotinic acetylcholine receptor regulates its rate of desensitization

Recent studies have provided evidence for a role of protein phosphorylation in the regulation of the function of various potassium and calcium channels (for reviews, see refs 1, 2). As these ion channels have not yet been isolated and characterized, it has not been possible to determine whether phosphorylation of the ion channels themselves alters their properties or whether some indirect mechanism is involved. In contrast, the nicotinic acetylcholine receptor, a neurotransmitter-dependent ion channel, has been extensively characterized biochemically and has been shown to be directly phosphorylated. The phosphorylation of this receptor is catalysed by at least three different protein kinases (cyclic AMP-dependent protein kinase, protein kinase C and a tyrosine-specific protein kinase) on seven different phosphorylation sites. However, the functional significance of phosphorylation of the receptor has been unclear. We have now examined the functional effects of phosphorylation of the nicotinic acetylcholine receptor by cAMP-dependent protein kinase. We investigated the ion transport properties of the purified and reconstituted acetylcholine receptor before and after phosphorylation. We report here that phosphorylation of the nicotinic acetylcholine receptor on the gamma- and delta-subunits by cAMP-dependent protein kinase increases the rate of the rapid desensitization of the receptor, a process by which the receptor is inactivated in the presence of acetylcholine (ACh). These results provide the first direct evidence that phosphorylation of an ion channel protein modulates its function and suggest that phosphorylation of postsynaptic receptors in general may play an important role in synaptic plasticity.     

钛白表面苯乙烯固相接枝改性

提出了钛白表面苯乙烯固相接枝改性新工艺,并对工艺的各主要影响因素进行了较为详细的研究,得出了最佳的工艺条件.在此基础上,分析研究了力化学法钛白表面苯乙烯固相接枝改性机理,认为钛白苯乙烯改性的作用机理是负离子聚合反应和自由基聚合反应; 钛白和改性剂的性能是该工艺能够实施的内因和热力学因素,搅拌磨中的机械力化学作用、引发剂的化学作用、外加热和自生热以及由此产生的体系温度变化是该工艺能够实施的外因和重要动力学因素,由外因和内因的共同作用使这一工艺得以顺利高效进行.     

自由基研究在生物、药学及动力学中的应用

自由基研究是开展自由基化学、生物学及医学研究的重要途径.由于自由基活性高、半衰期短,其研究方法呈现多样化的特点.在自由基研究方法中,根据检测仪器的差异较常见的研究方法有电子自旋共振与自旋捕获技术、化学发光法、荧光法、比色法、分光光度法、色谱法和脉冲辐解技术等.由于不同的仪器其检测对象、范围及精度都存在差异,导致研究方法具有不同的特点,因此在众多的实验方案中,根据仪器及研究对象的特点选择合适及合理的研究方法是必要的.     

Carcinogenesis of asbestos switched on by inducing cross-linkage between DNA complementary pair bases

Since the beginning of the 1980s, Dai Qianhuan predicted based upon his di-region theory that the carcinogenesis switched on by the so-called physical carcinogenic factors including radiation, asbestos and foreign matter implantation, is just initiated through the cross-linking between DNA complementary pair bases induced by them. In this note, it was evidenced with the DNA filter elution method that the oxygenase activated by asbestos induces the cross-linking between DNA inter-strands and DNA-protein with dosage correlation, in which over 80% of DNA inter-strand cross-link ratio account for the total cross-link ratio. Obviously, both of the cross-linkages are just induced by hydroxyl free radical, HO ·, because the ferrous ion increased the cross-link ratios up to several times through Fenton reaction and vitamin C inhibited the cross-link ratios with factors of 8–9 by destroying the hydroxyl radical. Non-carcinogen but with lower free radical formation energy, pyrene, by culturing with asbestos gave 3–4 times cross-link ratios than the original ratios induced by asbestos only. Estradiol, an endogenous carcinogen, as a bio-electrophilic species but with higher free radical formation energy by culturing with asbestos, gave only 1.2 time cross-link ratios than expected ones. Ferrous ion which can increase HO · concentration through Fenton reaction, increased the ratios to 2–2.5 times in the former case but only 1.2 time in the latter case. Vitamin C, a free radical scavenger, gave a powerful inhibition to the cross-linking with a factor of 8–11 in the former case but a weak inhibition with a factor of 1.2 only in the latter case. So, it is evidenced further that the cross-linkages induced by asbestos are originated from hydroxyl radical. Reasonable structures of the cross-linking products induced by asbestos or hydroxyl radical have been depicted based upon AMI MO theory. These structures have been verified further by a reasonable explanation of the mutational spectrum induced by hydroxyl radical.     

茶多酚对自由基抑制效应

采用循环伏安法测定自制茶多酚及标准儿茶素的氧化峰电位．结果表明,前者高于后者,即后者还原能力较强．经加温强化处理的各种食用油,分别加入同量、不同量的上述两种试样;不同来源的食用油加同量的标准儿茶素,用ＥＳＲ方法测试它们随温度、时间条件的改变引起自由基强度变化的规律．结果说明：茶多酚、儿茶素均有很强的自由基抑制效应,儿茶素更强（和还原能力较强相一致）．该研究对于从茶叶中提取茶多酚并用于食品工业,具有一定的理论意义和应用的参考价值．