Selection of the optimal scanning agent for thyroid cancer

Current views on the pathogenesis of Parkinson's disease are presented. Studies, particularly those carried out during the last decade, highlight the significance of endogenic processes responsible for a cumulative production of neurotoxic substances, especially free oxygen radicals which exert chronic effect on neurons. In Parkinson's disease, overproduction of free radicals and concomitant failure of protective mechanisms are most likely. An excess of free radicals is cytotoxic because of their very high chemical activity and uncontrolled chain reactions with numerous organic compounds, especially those which are mostly responsible for vital functions of cells. Oxidative stress disturbs metabolism of the cell what finally leads to its death most probably due to damage of cell membrane. That results in increased plasma membrane permeability for calcium ions which activate several subcellular mechanisms and initiate the final phase of cell death. Nonprotein-bound "free" iron ions are the strongest and most dangerous generators of free oxygen radicals. It is thought that ferric (Fe-3+" iron bound to neuromelanin may play a profound role in the overproduction of especially cytotoxic hydroxyl radicals, derivatives of molecular oxygen. Both, oxygen stress inducing factor and the sequence of related biochemical disorders remain still unknown. However, the synergy of the excess of reactive oxygen metabolites (mainly free radicals), nitric oxide, "free" iron ions and neuromelanin may contribute considerably to the generation of oxygen stress.     

Effects of Lanthanum Chloride on Activity of Redox System in Plasma Membrane of Rice Seedling Roots

ａｒｅｅａｒｔｈｓｈａｖｅａｂｅｎｅｆｉｃｉａｌｅｆｆｅｃｔｓｏｎｐｒｏｍｏｔｉｎｇｔｈｅｃｒｏｐｇｒｏｗｔｈａｎｄｉｎｃｒｅａｓｉｎｇｉｔｓｙｉｅｌｄ .Ｓｏｍｅｒｅｓｅａｒｃｈｅｒｓｈａｖｅｄｅｍｏｎｓｔｒａｔｅｄｔｈａｔｔｈｅｒａｒｅｅａｒｔｈｓｃａｎｎｏｔｅｎｔｅｒｔｈｅｐｒｏｔｏｐｌａｓｔａｎｄｏｎｌｙｓｔａｙｏｕｔｓｉｄｅｔｈｅｐｌａｓｍａｍｅｍｂｒａｎｅ[1] .Ｔｈｅｒｅｉｓａｎｏｘｉｄａｔｉｏｎ ｒｅｄｕｃｔｉｏｎ (ｒｅｄｏｘ)ｓｙｓｔｅｍｏｎｔｈｅｐｌａｓｍａｍｅｍｂｒａｎｅｏｆｐｌ…     

Effects of Lanthanum on Redox Systems in Plasma Membranes of Casuarina equisetifolia Seedlings Under Acid Rain Stress

Theplasmamembraneisapenetrablebarrier ,whichcancontroltheexchangeofsubstancesacrossmembranesincells ,andalsoistheintermediumandreceptorofenergyorinformationtransferencebetweencellsandenvironment.Theplasmamembraneredoxsystem(PMRS)meanstheelectrontransferchainsonplasmamembrane .Owingtohavethepossibilityofejectingprotons ,energizingplasmamembraneandhavingthefunctionofacceleratingtransportationofsoluteacrossmembrane ,theplasmamembraneredoxsystemswerepaidmuchattentionto[1] .Acidrainisoneofthemost…     

Anxiety and alcohol abuse in patients in treatment for depression

Oxygen transport in thylakoid membranes of spinach chloroplasts (Spinacia oleracea) has been studied by observing the collisions of molecular oxygen with spin labels, using line broadening electron paramagnetic resonance (EPR) spectroscopy. Stearic acid spin labels were used to probe the local oxygen diffusion-concentration product. The free radical moiety was located at various distances from the membrane surface, and collision rates were estimated from linewidths of the EPR spectra measured in the presence and absence of molecular oxygen. The profile of the local oxygen diffusion-concentration product across the membrane determined at 20 degrees C demonstrates that this product, at all membrane locations, is higher than the value measured in water. From the profile of the oxygen diffusion-concentration product, the membrane oxygen permeability coefficient has been estimated using the procedure developed earlier (W.K. Subczynski, J.S. Hyde, A. Kusumi, Proc. Natl. Acad. Sci. USA 86 (1989) 4474-4478). At 20 degrees C, the oxygen permeability coefficient for the lipid portion of the thylakoid membrane was found to be 39.5 cm s-1. This value is 20% higher than the oxygen permeability coefficient of a water layer of the same thickness as the thylakoid membrane. The high permeability coefficient implies that the oxygen concentration difference across the thylakoid membrane generated under the illumination of the leaf by saturating actinic light is negligible, smaller than 1 microM.     

Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR

The brain is susceptible to oxidative stress. This is due to the high content of polyunsaturated fatty acids, high rate of oxygen consumption, regional high concentrations of iron, and relatively low antioxidant capacity. These factors may predispose the premature infant to brain damage. Brain damage may be due to: 1. Brief anoxia followed by hyperoxia (mimics parturition oxidative stress); or 2. Prolonged exposure to hyperoxia (mimics oxidative stress from postpartum maintenance in a hyperoxic environment). We have developed two animal models to examine these forms of oxidative stress on the brains of rats. In Model I rats were exposed to brief anoxic anoxia (100% N2) followed by hyperoxia (100% O2). Using T2-weighted Magnetic Resonance Imaging (MRI) brain intensity decreased following the treatment suggesting water loss or free radical production. In vivo 1H-NMR showed brain water content appeared to increase, however variability rendered this result insignificant. Electron spin resonance (ESR) spin trapping, using a-phenyl-N-tert-butylnitrone (PBN) produced a free radical signal from the anoxic-anoxia hyperoxia treated animals which suggests the decrease in MRI T2-weighted image signal intensity was due to free radicals. In Model II, we examined the effects of prolonged normobaric hyperoxia (85% O2) on blood-brain barrier (BBB) integrity and brain phosphorous metabolism. BBB permeability increased following 1 week of hyperoxia. In addition, measurement of high energy phosphates, using in vivo 31P-NMR, showed the PCr/ATP ratio significantly decreased, the ATP/Pi ratio increased and the (ATP+PCr)/Pi ratio increased. Because the BBB is sensitive to oxidative stress its loss of integrity may be due to free radicals. The level of oxidative stress may result in brain elevation of ATP as an adaptation mechanism. In conclusion, anoxic-anoxia and prolonged hyperoxia exposure produce MRI visible changes in the brain. These two mechanisms may be important in the etiology of brain damage observed in many premature infants.     

Reactive oxygen species produced in metal-catalyzed oxidation of bis(trifluoromethyl)disulfide and protection by ZE

Bis(trifluoromethyl)disulfide (TFD), used as an industrial fumigant, was found to generate a thiyl free radical as seen by EPR/spin trapping. Oxygen appears to be an absolute requirement for radical production. The results obtained in this investigation implicate the production of thiyl and reactive oxygen species (ROS), superoxide radical anion and hydroxyl radicals, during TFD autoxidation. The rate of production of these free radical intermediates was found to increase in the presence of iron(III) and copper(II). In addition, the metal ion chelator DETAPAC and ROS scavengers ethanol, mannitol, and PEG-SOD/catalase were found to inhibit free radical production. Reactive oxygen species were not formed when a high-potency zinc plus antioxidant, ZE caps, was present. These results provide support for the pro-oxidation of TFD and a protective role for zinc.     

Relevance of arteriovenous concentration differences in pharmacokinetic-pharmacodynamic modeling of midazolam

In macrophages, NF-kappaB can be activated by H2O2 generated by the respiratory burst or added exogenously. The mechanism of H2O2 signaling may involve changes in the cellular redox state or a redox reaction at the plasma membrane; however, the site of H2O2 action cannot be readily ascertained because of its membrane permeability. Ferricyanide, a nonpermeable redox active anion, activated NF-kappaB in the macrophage cell line, J774A.1. In contrast with exogenous H2O2, activation by ferricyanide did not correlate with net oxidation of NAD(P)H or glutathione, suggesting that a transplasma membrane redox reaction itself was the first signaling process in NF-kappaB activation.     

不同体系中黄河沉积物对La3+的吸附特性

对比实验研究揭示,不同体系中La3 的吸附等温线类型差别较大,单离子体系中La3 的吸附属于典型的一级吸附模式,多离子体系中,La3 的吸附等温线呈不规则变化,用现有的等温吸附方程均不能较好拟合其等温吸附过程;不同体系中La3 的pH突跃区域无显著性差异;随温度的升高,单离子体系中,表层沉积物对La3 的吸附量增加,多离子体系中则降低;随着泥沙浓度、离子强度的增加和有机质的去除,表层沉积物对La3 的吸附量均降低,而且悬浮物对La3 的吸附量大于表层沉积物。     

Nitric oxide prevents oxidative damage produced by tert-butyl hydroperoxide in erythroleukemia cells via nitrosylation of heme and non-heme iron. Electron paramagnetic resonance evidence

We studied protective effects of NO against tert-butylhydroperoxide (t-BuOOH)-induced oxidations in a subline of human erythroleukemia K562 cells with different intracellular hemoglobin (Hb) concentrations. t-BuOOH-induced formation of oxoferryl-Hb-derived free radical species in cells was demonstrated by low temperature EPR spectroscopy. Intensity of the signals was proportional to Hb concentrations and was correlated with cell viability. Peroxidation of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin metabolically labeled with oxidation-sensitive cis-parinaric acid was induced by t-BuOOH. An NO donor, (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]-diazen-1-iu m-1, 2-diolate], produced non-heme iron dinitrosyl complexes and hexa- and pentacoordinated Hb-nitrosyl complexes in the cells. Nitrosylation of non-heme iron centers and Hb-heme protected against t-BuOOH-induced: (a) formation of oxoferryl-Hb-derived free radical species, (b) peroxidation of cis-parinaric acid-labeled phospholipids, and (c) cytotoxicity. Since NO did not inhibit peroxidation induced by an azo-initiator of peroxyl radicals, 2, 2'-azobis(2,4-dimethylvaleronitrile), protective effects of NO were due to formation of iron-nitrosyl complexes whose redox interactions with t-BuOOH prevented generation of oxoferryl-Hb-derived free radical species.     

Effects of La~(3+)on H~+ Transmembrane Gradient and Membrane Potential in Rice Seedling Roots

Ｔｈｅｒｅａｒｅｌｏｔｓｏｆｓｔｕｄｉｅｓｉｎｔｈｅｆｉｅｌｄｓｏｆａ ｇｒｉｃｕｌｔｕｒａｌａｎｄｍｅｄｉｃａｌａｐｐｌｉｃａｔｉｏｎｓｏｆｒａｒｅｅａｒｔｈｓ[1,2 ] .ＴｈｅｒｅｓｕｌｔｓｆｒｏｍＣｈｉｎａｓｕｇｇｅｓｔｅｄｔｈａｔｓｕｐｐｌｙｉｎｇｒａｒｅｅａｒｔｈｓｍｉｇｈｔｈａｖｅｂｅｎｅｆｉｃｉａｌｅｆｆｅｃｔｓｏｎｐｌａｎｔｇｒｏｗｔｈａｎｄｃｒｏｐｐｒｏｄｕｃｔｓｑｕａｌ ｉｔｙ[3 ] .Ｓｏｍｅｒｅｓｅａｒｃｈｅｒｓｄｅｍｏｎｓｔｒａｔｅｄｔｈａｔｒａｒｅｅａｒｔｈｓｃａｎｎｏｔｅｎｔ…     

Oxidative stress and the brain

Although the cause of Parkinson's disease is unknown, oxidative stress has been implicated in its pathogenesis. This theory postulates that normal metabolic processes in the nigrostriatal dopaminergic system may lead to loss of neurons, and that iron-dependent membrane lipid peroxidation may play an important role in the neuronal death. Recent research concerning iron-dependent lipid peroxidation is presented. First, catechols (including dopa and dopamine) and iron form strong oxidizing complexes and induce lipid peroxidation (LPO) in phospholipid liposomes. Active oxygen species including superoxide, hydrogen peroxide, hydroxyl radical and singlet oxygen, do not participate in this LPO, which is inhibited by an excess of dopa (dopamine). Cultured neurons and the substantia nigra are vulnerable to LPO. Second, synthetic melanin prepared by the autooxidation of catechols promotes LPO in the presence of iron. The effects of scavenging agents indicate that this LPO is mediated by superoxide, but not by other oxygen free radicals. Neuronal cell cultures are destroyed by this LPO. Third, catechols and superoxide produced by microglia cause the release of iron from ferritin. Microglia stimulated by phorbol myristate acetate produce superoxide and cause the release of iron from ferritin. Catechols also induce mobilization of ferritin iron. The released iron (i.e. loosely-bound iron) is available to iron-dependent LPO. These data suggest that the biochemical and morphological characteristics of the substantia nigra, which are concomitant with its functional role, provoke iron-dependent lipid peroxidation. It is essential to elucidate how iron bound loosely to low molecules comes into contact with catechols, neuromelanin and superoxide. Drugs that chelate iron site-specifically or modulate the microglial function may bring about some favorable changes in the disease process.     

Direct measurement of oxygen free radicals during in utero hypoxia in the fetal guinea pig brain

The present study tested the hypothesis that maternal hypoxia induces oxygen free radical generation in the fetal guinea pig brain utilizing techniques of electron spin resonance spectroscopy and alpha-phenyl-tert-butyl nitrone (PBN) spin trapping. Pregnant guinea pigs of 60 days gestation were divided into normoxic and hypoxic groups and exposed to 21% or 7% oxygen for 60 min. Free radical generation was documented by measuring the signal of PBN spin adducts. Fluorescent compounds were determined as an index of lipid peroxidation and the activity of Na+,K+-ATPase was determined as an index of brain cell membrane function. Hypoxic fetal cerebral cortical tissue showed a significant increase in spin adducts (normoxic: 33.8+/-9.3 units/g tissue vs. hypoxic: 57.9+/-9.2 units/g tissue, p<0.01) and fluorescent compounds (normoxic: 0.639+/-0.054 microg quinine sulfate/g brain vs. 0.810+/-0.102 microg quinine sulfate/g brain, p<0.01) and a decrease in Na+,K+-ATPase activity (normoxic: 43.04+/-2.50 micromol Pi/mg protein/h vs. hypoxic: 33. 80+/-3.51 micromol Pi/mg protein/h, p<0.001). These results demonstrate an increased free radical generation during hypoxia in the fetal guinea pig brain. The spectral characteristics of the radicals were consistent with those of alkoxyl radicals. The increased level of fluorescent compounds and decreased activity of Na+,K+-ATPase indicated hypoxia induced brain cell membrane lipid peroxidation and dysfunction, respectively. These results directly demonstrate an increased oxygen free radical generation during hypoxia and suggest that hypoxia-induced increase in lipid peroxidation and decrease in membrane function, as indicated by a decrease in Na+,K+-ATPase activity, are consequences of increased free radicals. The nature of predominantly present alkoxyl radical indicates ongoing lipid peroxidation during hypoxia. The direct demonstration of oxygen free radical generation during hypoxia is the critical missing link in the mechanism of hypoxia-induced brain cell membrane dysfunction and damage.     

Effects of photoinhibition on the QA-Fe2+ complex of photosystem II studied by EPR and M?ssbauer spectroscopy

Effects of photoinhibition on the iron-quinone electron acceptor complex of oxygen-evolving photosystem II have been studied using low-temperature EPR and M?ssbauer spectroscopy. Photoinhibition of spinach photosystem II membrane particles at 4 degrees C decreases the EPR signal arising from the interaction of QA- with Fe2+ to 30% in 90 min under our conditions. The free radical EPR signal from QA- induced by cyanide treatment of the iron [Sanakis, Y., et al. (1994) Biochemistry 33, 9922-9928] declines with the same kinetics as the QA-Fe2+ EPR signal. In contrast, Fe2+ is present in about 70% of the centers after 90 min of photoinhibition, as shown by its EPR-detected interaction with NO and by its M?ssbauer absorption. Complete oxidation of this Fe2+ population to Fe3+ by ferricyanide is possible only in the presence of glycolate, which lowers the redox potential of the Fe3+/Fe2+ couple. In a fraction of PSII centers, which reach 30% after 90 min of photoinhibition, the iron cannot be detected. It is concluded that photoinhibition of oxygen-evolving photosystem II affects both QA and Fe2+. However, the photoinhibitory impairment of the QA redox functioning precedes the modification of the non-heme iron. In a considerable portion of the photoinhibited centers, which do not have functional QA, the non-heme iron is still present and redox active, but its redox potential is increased relative to that in the normal centers. This is probably due to a minor modification of the bicarbonate ligation site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular modelling study of the netropsin complexation with a nucleic acid triple helix

The relationship between lipid peroxidation and uptake of transferrin- free iron, Fe(II), by reticulocytes in an experimental system for studying membrane transport of Fe(II) was investigated by using free radical scavengers: BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), superoxide dismutase, alpha-tocopherol, propyl gallate and DPPD (N,N-diphenyl-1,4-phenylenediamine), and producers: t-butyl hydroperoxide, cumene hydroperoxide, H2O2 and aluminium carbonate. Measurements were made of MDA (malondialdehyde) and the rate of Fe(II) uptake from a sucrose solution buffered at pH 6.5 by Pipes. Most scavengers and producers used could increase or decrease only slightly the rate of Fe(II) uptake and some of them had no effect on Fe(II) uptake and MDA could not be detected at iron concentration of lower than 10 microM and incubation time of 20 min. At iron concentration of higher than 100 microM and incubation time of 4 h, there was the production of MDA which increased with the increment of iron concentration of incubation medium and BHT could inhibit the production of MDA. In addition, no difference was found in the rates of Fe(II) uptake in three experimental groups whose incubation medium was buffered by Pipes, Mops and Mes respectively. The results suggested that iron could induce free radical reaction under experimental conditions, especially at high concentration of iron and longer incubation time; however, at low concentration of iron (<10 microM) and the usual incubation time (20 min) free radical reaction was very slight and the extent of the reaction was not enough to damage the integrity and function of the membrane of reticulocytes, and that Fe(II) uptake by reticulocytes was not the result of free radical reaction and lipid peroxidation. It was therefore concluded that iron could not initiate its own membrane transport in rabbit reticulocytes by free radical reaction and lipid peroxidation and that the experimental system we used for studying membrane transport of Fe(II) is valid.     

Papaverine-induced changes in physiological characters of Ehrlich ascites tumor cell membranes

Physiological characters of Ehrlich ascites tumor cell membranes were altered by papaverine. The agent induced changes in membrane potential as monitored by cyanine dye (diS-C3-(5)) technique. Papaverine also strongly inhibited increase in membrane permeability to K+ ion induced by lysolecithin. In addition, papaverine inhibited oxygen uptake of the tumor cells and oxidative phosphorylation of their mitochondria, and slightly increased membrane fluidity. The results suggest that papaverine maintains compartmentation of K+ ion, energy metabolism, and membrane fluidity by regulating intracellular mitochondrial metabolism of Ehrlich ascites tumor cells.     

White blood cell counts and plasma C3a have synergistic predictive value in patients at risk for acute respiratory distress syndrome

The molecular pathobiology of membrane-associated iron is clearly illustrated by the sickle red blood cell. The cytosolic aspect of the membranes of these cells carries several discrete iron compartments, including denatured hemoglobin and free heme, as well as molecular iron associated with membrane aminophospholipid and denatured globin. Affinity of the membrane for molecular iron is extraordinarily high and predicted to keep cytosolic free iron concentration < 10(-20) M. Membrane iron is bioactive and able to valence cycle, thus serving as a catalyst for generation of highly reactive hydroxyl radical. As a consequence of this oxidative biochemistry at the cytosol/membrane interface, multiple membrane defects arise that are of pathophysiologic importance. Thus, sickle red cells provide a pathobiologic paradigm for the membrane-damaging effect of iron-mediated targeting of oxidative damage at a sub-cellular level. This is relevant to a variety of biologic conditions accompanied by decompartmentalization of iron.     

Gap junctions and particle aggregates in the tegumentary syncytium of a trematode

The tegumentary syncytium of a Trematode is studied by transmission EM and freeze-fracture with the following results. (1) Infoldings of the basal plasma membrane suggest that transport of water and solutes occur through the tegument. (2) Heterocellular gap junctions are found between the tegumentary cell bodies and the parenchymal cells. Gap junctional particles, 8 nm in diameter, are visible on the P face of membrane and form an irregular pattern. (3) Orthogonal arrays of small particles (6 nm in diameter) are abundant on the P face of the tegument basal plasma membrane and on the cell necks connecting tegumentary cell bodies to the tegument. (4) Hemidesmosomal particles are found on the E face of the tegument basal plasma membrane. The significance of these structures with respect to tegumentery permeability and exchanges with parenchyma are discussed.     

Lipid hydroperoxide generation, turnover, and effector action in biological systems

Lipid peroxidation is a well known example of oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures. Peroxidative modification of unsaturated phospholipids, glycolipids, and cholesterol can occur in reactions triggered by i) free radical species such as oxyl radicals, peroxyl radicals, and hydroxyl radicals derived from iron-mediated reduction of hydrogen peroxide or ii) non-radical species such as singlet oxygen, ozone, and peroxynitrite generated by the reaction of superoxide with nitric oxide. Lipid hydroperoxides (LOOHs) are prominent non-radical intermediates of lipid peroxidation whose identification can often provide valuable mechanistic information, e.g., whether a primary reaction is mediated by singlet oxygen or oxyradicals. Certain cholesterol-derived hydroperoxides (ChOOHs) have been used very effectively in this regard, both in model systems and cells. Being more polar than parent lipids, LOOHs perturb membrane structure/function and can be deleterious to cells on this basis alone. However, LOOHs can also participate in redox reactions, the nature and magnitude of which often determines whether peroxidative injury is exacerbated or prevented. Exacerbation may reflect iron-catalyzed one-electron reduction of LOOHs, resulting in free radical-mediated chain peroxidation, whereas prevention may reflect selenoperoxidase-catalyzed two-electron reduction of LOOHs to relatively non-toxic alcohols. LOOH partitioning between these two pathways in an oxidatively stressed cell is still poorly understood, but recent cell studies involving various ChOOHs have begun to shed light on this important question. An aspect of related interest that is under intensive investigation is lipid peroxidation/LOOH-mediated stress signaling, which may evoke a variety of cellular responses, ranging from induction of antioxidant enzymes to apoptotic death. Ongoing exploration of these processes will have important bearing on our understanding of disease states associated with peroxidative stress.