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Chelation
Kinds of Chelation Terms modified by Chelation Selected AbstractsANTI-OXIDANT MECHANISMS OF KOLAVIRON: STUDIES ON SERUM LIPOPROTEIN OXIDATION, METAL CHELATION AND OXIDATIVE MEMBRANE DAMAGE IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005EO Farombi SUMMARY 1.,In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2.,Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3.,In vitro, kolaviron (10,60 µmol/L) inhibited the Cu2+ -induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 µmol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 µmol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 µmol/L) elicited a 53% increase in lag time, whereas 40 and 60 µmol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4.,Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 µmol/L) had a significant chelating effect on Fe2+ (78%). 5.,In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis. [source] Electrophysiological and morphological characterization of dentate astrocytes in the hippocampusDEVELOPMENTAL NEUROBIOLOGY, Issue 2 2005Masako Isokawa Abstract We studied electrophysiological and morphological properties of astrocytes in the dentate gyrus of the rat hippocampus in slices. Intracellular application of Lucifer yellow revealed two types of morphology: one with a long process extruding from the cell body, and the other with numerous short processes surrounding the cell body. Their electrophysiological properties were either passive, that is, no detectable voltage-dependent conductance, or complex, with Na+/K+ currents similar to those reported in the Ammon's horn astrocytes. We did not find any morphological correlate to the types of electrophysiological profile or dye coupling. Chelation of cytoplasmic calcium ([Ca2+]i) by BAPTA increased the incidence of detecting a low Na+ conductance and transient outward K+ currents. However, an inwardly rectifying K+ current (Kir), a hallmark of differentiated CA1/3 astrocytes, was not a representative K+ -current in the complex dentate astrocytes, suggesting that these astrocytes could retain an immature form of K-currents. Dentate astrocytes may possess a distinct current profile that is different from those in CA1/3 Ammon's horn. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005 [source] Kinetics and Mechanism of Ni(II) Chelation in Model and Real Solutions of Xylem Sap of Quercus ilexELECTROANALYSIS, Issue 22 2007Margarida, Maria Correia, Santos Abstract The kinetics of formation and dissociation of Ni(II) complexes with oxalic and citric acids was studied by cyclic voltammetry in model solutions of xylem sap of Q. ilex (the dominant tree growing on serpentine soils of Northeast Portugal) using representative concentrations, pH and ionic strength. The role of magnesium on complex formation was analyzed from solutions where Mg is present at concentration levels found in the xylem sap of Q. ilex growing on both nonserpentine and serpentine soils. Kinetics studies were also done in diluted solutions of real xylem sap samples, spiked with increasing amounts of magnesium. The values obtained for the apparent rate constants were those anticipated by the proposed model. To test the validity of the methodology and mechanisms, formation rate constants, kf (M,1 s,1) of Ni(II) complexes with citrate and oxalate were evaluated that compare with the values from Eigen mechanism. [source] Iron(III) Chelation: Tuning of the pH Dependence by Mixed LigandsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 14 2003Anne-Marie Albrecht-Gary Abstract The iron(III) chelating properties of two heteropodands with 8-hydroxyquinoline and catechol binding groups were examined and compared to those of the corresponding homopodal analogues, O-TRENSOX and TRENCAMS. Like the parent homopodands, the two heteropodands are based on the TREN scaffold and the chelating units are connected by amide groups, TRENSOX2CAMS having two 8-hydroxyquinoline and one catechol arms and TRENSOXCAMS2 one 8-hydroxyquinoline and two catechol moieties. The aqueous coordination chemistry of these ligands was examined by potentiometric and spectrophotometric methods in combination with 1H NMR spectroscopy. The respective pFeIII values showed a cooperative effect of the mixed chelating units. Moreover, the pFeIII dependence on pH showed that the mixed ligands exhibit a higher complexing ability than the parent ligands over the pH range 5,9 which is of biological relevance. This result could be of great interest for medical applications. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Synthesis of Some New Substituted Photochromic N,N, -Bis(spiro[1-benzopyran-2,2,-indolyl])diazacrown Systems with Substituent Control over Ion ChelationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2006Craig J. Roxburgh Abstract The reversible photochemical ion chelation of the newly synthesised substituted N,N, -bis(spiro[1-benzopyran-2,2,-indolyl])diazacrown systems 15a,c and the subsequent molecular electronic control of this process using appropriately placed substituent groups on the spiro-benzopyran skeleton is reported. The principle of molecular electronic control of ion chelation is demonstrated by comparing the behaviour of the newly synthesised nitro-substituted and pyrido-annulated spiro-benzopyran system 9b with that of the unsubstituted compound 9a. Electronic substituent control over ion chelation is then exemplified for the new N,N, -bis(5,-nitrospiro[1-benzopyran-2,2,-indolyl])diazacrown system 15c and further exemplified for the corresponding 5,-trifluoromethyl derivative 15b, which contains the photochemically more robust trifluoromethyl group. The crown system 15a, unsubstituted in the spiro-indole moiety, is also reported. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] The triakontatetraneuropeptide TTN increases [Ca2+]i in rat astrocytes through activation of peripheral-type benzodiazepine receptorsGLIA, Issue 2 2001Pierrick Gandolfo Abstract Astrocytes synthesize a series of regulatory peptides called endozepines, which act as endogenous ligands of benzodiazepine receptors. We have recently shown that one of these endozepines, the triakontatetraneuropeptide TTN, stimulates DNA synthesis in astroglial cells. The purpose of the present study was to determine the mechanism of action of TTN on cultured rat astrocytes. Binding of the peripheral-type benzodiazepine receptor ligand [3H]Ro5-4864 to intact astrocytes was displaced by TTN, whereas its C-terminal fragment (TTN[17,34], the octadecaneuropeptide ODN) did not compete for [3H]Ro5-4864 binding. Microfluorimetric measurement of cytosolic calcium concentrations ([Ca2+]i) with the fluorescent probe indo-1 showed that TTN (10,10 to 10,6 M) provokes a concentration-dependent increase in [Ca2+]i in cultured astrocytes. Simultaneous administration of TTN (10,8 M) and Ro5-4864 (10,5 M) induced an increase in [Ca2+]i similar to that obtained with Ro5-4864 alone. In contrast, the effects of TTN (10,8 M) and ODN (10,8 M) on [Ca2+]i were strictly additive. Chelation of extracellular Ca2+ by EGTA (6 mM) or blockage of Ca2+ channels with Ni2+ (2 mM) abrogated the stimulatory effect of TTN. The calcium influx evoked by TTN (10,7 M) or by Ro5-4864 (10,5 M) was not affected by the N- and T-type calcium channel blockers ,-conotoxin (10,6 M) and mibefradil (10,6 M), but was significantly reduced by the L-type calcium channel blocker nifedipine (10,7 M). Patch-clamp studies showed that, at negative potentials, TTN (10,7 M) induced a sustained depolarization. Reduction of the chloride concentration in the extracellular solution shifted the reversal potential from 0 mV to a positive potential. These data show that TTN, acting through peripheral-type benzodiazepine receptors, provokes chloride efflux, which in turn induces calcium influx via L-type calcium channels in rat astrocytes. GLIA 35:90,100, 2001. © 2001 Wiley-Liss, Inc. [source] Ethanol Enhances Taurine-Activated Glycine Receptor FunctionALCOHOLISM, Issue 9 2010Brian T. Welsh Background:, Emerging evidence suggests that taurine acts as a partial agonist on glycine receptors (GlyR) in vitro and in vivo. Ethanol acts as an allosteric modulator on the GlyR producing a leftward shift of the glycine concentration,response curve, with no enhancing effects observed at saturating glycine concentrations. However, to date, no electrophysiological studies have been performed on ethanol modulation of taurine-activated GlyR. Methods:, Wild-type ,1 GlyR, or those bearing a serine-267 to isoleucine replacement (S267I), were homomerically expressed in Xenopus oocytes and voltage clamped at ,70 mV. Ethanol was co-applied with varying concentrations of glycine or taurine and the enhancing effects of ethanol compared. Results:, Ethanol potentiated glycine- and taurine-activated GlyR responses in a concentration-dependent manner. It shifted taurine and glycine concentration,response curves to the left, having no effects at saturating agonist concentrations. Chelation of zinc by tricine decreased ethanol enhancement of taurine-gated GlyR function. The S267I mutation prevented ethanol enhancement of taurine-mediated responses as previously also reported for glycine. Conclusion:, Ethanol modulates taurine activation of GlyR function by a mechanism similar to that of the full agonist glycine. The lack of effect of ethanol at saturating taurine concentrations provides mechanistic information on alcohol actions at the GlyR. [source] Design, synthesis and properties of novel iron(III)-specific fluorescent probesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2004Wei Luo ABSTRACT Bidentate chelators such as hydroxypyridinones and hydroxypyranones are highly iron selective. The synthesis of two novel fluorescent probes N -[2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl]-2-(7-methoxy-2-oxo-2H -chromen-4-yl)acetamide (CP600) and N -[(3-hydroxy-6-methyl-4-oxo-4H -pyran-2-yl)methyl]-2-(7-methoxy-2-oxo-2H -chromen-4-yl)acetamide (CP610) is reported. The method involves coupling the bidentate ligands, 3-hydroxypyridin-4-one and 3-hydroxypyran-4-one, with the well-characterised fluorescent probe methoxycoumarin. Fluorescence emission of both probes at 380 nm is readily quenched by Fe3+. The fluorescence was quenched to a greater extent by Fe3+ than by Mn2+, Co2+, Zn2+, Ca2+, Mg2+, Na+ and K+ and to approximately the same extent as Cu2+. Comparison of the fluorescence-quenching ability by a range of metal ions on CP600 and CP610 and the hexadentate chelator, calcein, under in-vitro conditions, demonstrated advantages of the two novel fluorescent probes with respect to both iron(III) sensitivity and selectivity. Chelation of iron(III) by CP600 and CP610 leads to the formation of a complex with a metal-to-ligand ratio of 1:3. Fluorescence is quenched on formation of such complexes. These probes possess a molecular weight less than 400 and thus they are predicted to permeate biological membranes by passive diffusion, and have potential for reporting intracellular organelle labile iron levels. [source] Single-Molecule Kinetics of Two-Step Divalent Cation Chelation,ANGEWANDTE CHEMIE, Issue 30 2010Eine doppelte Umarmung: Zwei halbchelatisierende Liganden wurden kovalent im Lumen einer Proteinnanopore angebunden (siehe Bild). Durch Aufzeichnung elektrischer Ströme wurde die Bildung vollständig chelatisierter Zn2+ -Ionen auf dem Einzelmolekülniveau verfolgt, was die Geschwindigkeitskonstanten für die acht Hauptschritte des Prozesses ergab. [source] The Na-K-ATPase is a target for an EDHF displaying characteristics similar to potassium ions in the porcine renal interlobar arteryBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2002Eckhart Büssemaker The present study was performed to determine the characteristics of the endothelium-derived hyperpolarizing factor (EDHF) that mediates the nitric oxide (NO)- and prostacyclin (PGI2)-independent hyperpolarization and relaxation of porcine renal interlobar arteries. Bradykinin-induced changes in isometric force or smooth muscle membrane potential were assessed in rings of porcine renal interlobar artery preconstricted with the thromboxane analogue U46619 in the continuous presence of N, -nitro- L -arginine and diclofenac to inhibit NO synthases and cyclo-oxygenases. Inhibition of NO- and PGI2 -production induced a rightward shift in the concentration-relaxation curve to bradykinin without affecting maximal relaxation. EDHF-mediated relaxation was abolished by a depolarizing concentration of KCl (40 mM) as well as by a combination of charybdotoxin and apamin (each 100 nM), two inhibitors of calcium-dependent K+ (K+Ca) channels. Charybdotoxin and apamin also reduced the bradykinin-induced, EDHF-mediated hyperpolarization of smooth muscle cells from 13.7±1.3 mV to 5.7±1.2 mV. In addition to the ubiquitous ,1 subunit of the Na-K-ATPase, the interlobar artery expressed the , subunit as well as the ouabain-sensitive ,2, ,3 subunits. A low concentration of ouabain (100 nM) abolished the EDHF-mediated relaxation and reduced the bradykinin-induced hyperpolarization of smooth muscle cells (13.6±2.8 mV versus 5.20±1.39 mV in the absence and presence of ouabain). Chelation of K+, using cryptate 2.2.2., inhibited EDHF-mediated relaxation, without affecting NO-mediated responses. Elevating extracellular KCl (from 4 to 14 mM) elicited a transient, ouabain-sensitive hyperpolarization and relaxation that was endothelium-independent and insensitive to charybdotoxin and apamin. These results indicate that in the renal interlobar artery, EDHF-mediated responses display the pharmacological characteristics of K+ ions released from endothelial K+Ca channels. Smooth muscle cell hyperpolarization and relaxation appear to be dependent on the activation of highly ouabain-sensitive subunits of the Na-K-ATPase. British Journal of Pharmacology (2002) 137, 647,654. doi:10.1038/sj.bjp.0704919 [source] Analysis of Platinum Adducts with DNA Nucleotides and Nucleosides by Capillary Electrophoresis Coupled to ESI-MS: Indications of Guanosine 5,-Monophosphate O6,N7 ChelationCHEMBIOCHEM, Issue 11 2004Ulrich Warnke Dr. Abstract DNA is the ultimate target of platinum-based anticancer therapy. Since the N7 of guanine is known to be the major binding site of cisplatin and its analogues, adduct formation with model nucleotides, especially 2,-deoxyguanosine 5,-monophosphate (dGMP), has been studied in detail. During the last few years a coupled capillary eletrophoresis/electrospray-ionization mass spectrometry (CE/ESI-MS) method has been advantageously used in order to separate and identify platinum adducts with nucleotides in submillimolar concentrations in aqueous solutions. Beside the bisadduct, [Pt(NH3)2(dNMP)2]2,(NMP=2,-deoxynucleoside 5,-monophosphate), and the well-known monochloro and monohydroxo adducts, [Pt(NH3)2Cl(dNMP)],and [Pt(NH3)2(dNMP)OH],, respectively, a third kind of monoadduct species with a composition of [Pt(NH3)2(dNMP)],can be separated by CE and detected through the m/z values measured with ESI-MS. Different experimental setups indicate the existence of an O6,N7 chelate, whereas the formation of N7,,PO4macrochelates or dinuclear species is unlikely. Additionally, offline MS experiments with 2,-deoxyguanosine (dG) and stabilization of the controversially discussed O6,N7 chelate by oxidation with hydrogen peroxide support the assumption of the existence of O6,N7 chelation. [source] Rhodium-Catalyzed Intermolecular Chelation Controlled Alkene and Alkyne Hydroacylation: Synthetic Scope of ,-S-Substituted Aldehyde Substrates.CHEMINFORM, Issue 47 2006Michael C. Willis Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] The Role of Organic Fluorine in Directing Alkylation Reactions via Lithium Chelation.CHEMINFORM, Issue 19 2005Kenny Tenza Abstract For Abstract see ChemInform Abstract in Full Text. [source] Metal Chelation in Asymmetric Diels,Alder Reaction (II).CHEMINFORM, Issue 35 2004Kyoo-Hyun Chung Abstract For Abstract see ChemInform Abstract in Full Text. [source] Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanismsCONTACT DERMATITIS, Issue 2 2008Itai Chipinda Background:, Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD), are rubber accelerators and contact allergens that cross-react in some individuals. Objective:, This study explored potential protein haptenation mechanisms of ZDEC and its oxidation products. Methods:, ZDEC oxidation/reduction products and sites of protein binding were assessed using high-performance liquid chromatography and mass spectrometry. The murine local lymph node assay (LLNA) was employed to probe haptenation mechanisms of ZDEC by examining its allergenicity along with its oxidation products and through elimination of oxidation and chelation mechanisms by substituting cobalt for zinc [cobalt (II) dithiocarbamate, CoDEC]. Results:, Oxidation of ZDEC by hypochlorous acid (bleach, HOCl), iodine, or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide, and tetraethyldicarbamoyl disulfide (TEDCD). Albumin thiols reduced TETD with subsequent mixed disulfide formation/haptenation. ZDEC directly chelated the copper ion on the active site of the superoxide dismutase, whereas CoDEC did not bind to Cu proteins or form mixed disulfides with free thiols. ZDEC, sodium diethyldithiocarbamate, TEDCD, and TETD were all positive in the LLNA except CoDEC, which was non-allergenic. Conclusion:, The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides. [source] Remodeling of the actin cytoskeleton of target hepatocytes and NK cells during induction of apoptosisCYTOSKELETON, Issue 2 2001W. Marty Blom Abstract Natural Killer cells are immune cells that recognize and eliminate altered and non-self cells from the circulation. To study the interaction between NK cells and target cells, we set up an experimental system consisting of rat Interleukin-2 activated Natural Killer cells (A-NK cells) and rat hepatocytes with a masked Major Histocompatibility Complex (MHC). The masking of the MHC induces recognition of the hepatocytes by the NK cells as non-self. We showed that in vitro apoptosis is rapidly induced in the hepatocytes [Blom et al., 1999] after co-incubation with A-NK cells. Now we describe the morphological changes that occur during and after interaction of A-NK cells with hepatocytes. Confocal laser scanning microscopy showed that the actin cytoskeleton of the NK cells was remodeled during attack of hepatocytes. Some NK cells were in close contact with the hepatocytes while others had formed actin-containing dendrites of varying length that made contact with the hepatocytes. However, dendrite formation is not obligatory for induction of apoptosis because cells that were unable to form these did induce FAS-dependent apoptosis in hepatocytes. Apparently both direct as well as distant contact resulted in apoptosis. Formation of the dendrites was calcium-dependent as EGTA largely prevented it. Importantly, chelation of the calcium also suppressed killing of the hepatocytes. Within 1 h after addition of the A-NK cells, morphological changes in hepatocytes that are characteristic of apoptosis, such as the formation of apoptotic bodies and fragmented nuclei, became apparent. Specifically, the actin cytoskeleton of the hepatocytes was remodeled resulting in the formation of the apoptotic bodies. Inhibition of caspase activity by z-Val-Ala-DL-Asp-fluoromethylketone (100 ,M) partly protected against the rearrangement of the actin filaments in the hepatocytes. Cell Motil. Cytoskeleton 49:78,92, 2001. © 2001 Wiley-Liss, Inc. [source] Citrate-mediated increase in the uptake of weathered 2,2-bis(p -chlorophenyl)1,1-dichloroethylene residues by plantsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002Jason C. White Abstract Experiments were conducted to determine the ability of citrate to enhance the plant uptake of weathered 2,2-bis(p -chlorophenyl) 1,1-dichloroethylene (p,p,-DDE) from soil. Plots containing three rows of clover, mustard, hairy vetch, or rye grass were constructed in soils containing p,p,-DDE. On 11 occasions, the rows of each crop received water or sodium citrate (0.005 or 0.05 M). For each crop, there were significant reductions in p,p,-DDE concentration in the soil fractions (near root and rhizosphere) closely associated with the plant versus bulk soil. The roots of each crop accumulated 2 to 5 times more of the weathered contaminant (dry wt) than present in the bulk soil. Citrate (0.05 M) increased the concentration of p,p,-DDE in the roots of clover, mustard, and hairy vetch by 39% compared with vegetation that received water. In batch desorption studies, the release of weathered p,p,-DDE was significantly greater in the presence of 0.05 M citrate than in water. Citrate increased the extracted aqueous concentrations of five metal ions (Al, Fe, Ca, K, Mn) from soil by five- to 23-fold over distilled water. We hypothesize that citrate physically disrupts the soil through chelation of structural metal ions and release of bound humic material, facilitating p,p,-DDE availability and uptake by plants. [source] Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2006A. E. R. Kartikasari Abstract Background, Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. Materials and methods, Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. Results, An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. Conclusions, Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis. [source] Reversal of cardiac complications in thalassemia major by long-term intermittent daily intensive iron chelationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003H. Miskin Abstract: Objectives: In patients with thalassemia major (TM) who are non-compliant with long-term deferoxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional siderosis. It was recently shown in a small group of TM patients with established cardiac damage that continuous 24-h DFO infusion via an indwelling intravenous (i.v.) catheter is effective in reversing cardiac toxicity. The aim of the present study was to evaluate the results with intermittent daily (8,10 h) i.v. DFO. Patients: Eight TM patients with cardiac complications treated with intensive intermittent DFO were retrospectively evaluated by the mean annual serum ferritin, radionucleated ventriculography and 24-h electrocardiography recordings. Results: The median age at diagnosis of cardiac disease was 17.5 yr (range 14,21), and the median follow-up time was 84 months (range, 36,120). In the majority of patients (seven of eight) high-dose DFO (mean 95 ± 18.3 mg/kg/d) was administered via a central venous line. During follow-up, there was a significant decrease in the mean ferritin levels (5828 ± 2016 ng/mL to 1585 ± 1849 ng/mL, P < 0.001). Both cardiac failure (mean ejection fraction 32 ± 5) and cardiac arrhythmias were resolved in four of five patients. One non-compliant patient died during the follow-up. Following discontinuation of the i.v. therapy, compliance with conventional DFO therapy improved. The complications of this regimen, mainly catheter-related infections and catheter-related thrombosis, were similar to those described earlier. Conclusions: These results with the longest follow-up period in the literature suggest that i.v. high-dose DFO for 8,10 h daily may be as effective as continuous 24-h infusion for the reversal of established cardiac disease in TM. [source] Control of Intramolecular Ether-Oxygen Coordination in the Crystal Structure of Copper(II) Complexes With Dipicolylamine-Based LigandsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 8 2007Yuji Mikata Abstract Thirteen crystal structures of copper(II) complexes with a series of dipicolylamine (DPA)-derived ligands, N -(2-methoxyethyl)- N,N -bis(2-pyridylmethyl)amine (L1), N -[2-(2-hydroxyethyloxy)ethyl]- N,N -bis(2-pyridylmethyl)amine (L2) and N -(3-methoxypropyl)- N,N -bis(2-pyridylmethyl)amine (L3), have been determined and the factors that control the coordination of the ether-oxygen atom of these ligands to the copper centre are discussed. Complexes that have +1 or +2 charges exhibit coordination of the ether-oxygen atom, whereas neutral complexes in which two anions are bound to the copper(II) centre tend to lose the oxygen coordination. Upon chelation of the oxygen atom, L3 forms a six-membered chelate ring with respect to the 3-aminopropyl ether moiety whereas L1 and L2 form a five-membered chelate. This difference, especially in the nitrate and bromide complexes, determines whether the ether-oxygen atom chelates to the metal centre to give a monocationic complex, or the second anion coordinates to the metal centre to form the ether-free, neutral complex. The terminal anchor hydroxy group of L2 facilitates the ether-oxygen coordination via a hydrogen bond interaction to the donor atom located trans to the aliphatic nitrogen atom in the basal plane. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Oxidation of oleuropein studied by EPR and spectrophotometryEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 2 2008Evaggelia D. Tzika Abstract The autoxidation at alkaline pH and enzymatic oxidation by mushroom tyrosinase of oleuropein, the dominant biophenol present in the fruits and leaves of Olea europea, was followed by both electron paramagnetic resonance (EPR) and absorption spectroscopy. For comparison, the same oxidation processes were applied to 4-methylcatechol, a simple polyphenol present in olive mill wastewaters. EPR spectra of stable o -semiquinone radicals produced during autoxidation at pH,12 and short-lived o -semiquinone free radicals produced during autoxidation at pH,9.0 or tyrosinase action and stabilized by chelation with a diamagnetic metal ion (Mg2+) were recorded for both polyphenols, and the corresponding hyperfine splitting constants were determined. The UV-Vis spectral characteristics of the oxidation of polyphenols were highly dependent on the type of polyphenol, oxidant type and the pH of the reaction. The kinetic behavior of tyrosinase in the presence of oleuropein and 4-methylcatechol was followed by recording spectral changes at 400,nm (absorption maximum) over time. The tysosinase activity with oleuropein showed a pronounced pH optimum at pH,6.5 and a minor one around pH,8. From the data analysis of the initial rate at pH,6.5, the kinetic parameters Km = 0.34,±,0.03,mM and Vmax = 0.029,±,0.002 ,A400,min,1 were determined for oleuropein. [source] Synthesis of Some New Substituted Photochromic N,N, -Bis(spiro[1-benzopyran-2,2,-indolyl])diazacrown Systems with Substituent Control over Ion ChelationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2006Craig J. Roxburgh Abstract The reversible photochemical ion chelation of the newly synthesised substituted N,N, -bis(spiro[1-benzopyran-2,2,-indolyl])diazacrown systems 15a,c and the subsequent molecular electronic control of this process using appropriately placed substituent groups on the spiro-benzopyran skeleton is reported. The principle of molecular electronic control of ion chelation is demonstrated by comparing the behaviour of the newly synthesised nitro-substituted and pyrido-annulated spiro-benzopyran system 9b with that of the unsubstituted compound 9a. Electronic substituent control over ion chelation is then exemplified for the new N,N, -bis(5,-nitrospiro[1-benzopyran-2,2,-indolyl])diazacrown system 15c and further exemplified for the corresponding 5,-trifluoromethyl derivative 15b, which contains the photochemically more robust trifluoromethyl group. The crown system 15a, unsubstituted in the spiro-indole moiety, is also reported. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Non-enzymatic hydrolysis of fluorescein diacetate (FDA) in a Mediterranean oak (Quercus ilex L.) litterEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 2 2008E. Alarcón-Gutiérrez Summary We show the presence of interfering substances when the total microbial activity in litter samples is measured with fluorescein diacetate (FDA), and we propose some methodological modifications to avoid such interference. Three distinct litter layers (the OhLn, the OhLv and the OhLf) of evergreen oak (Quercus ilex L.) were characterized by 13C CPMAS NMR and the spectra show that the recalcitrant aromatic and phenolic compounds increase with the degree of degradation of litter. A wide range of sources of interference in the hydrolysis of FDA was found. To understand the origin of this interference, sterilized litter materials (i.e. ,-irradiated or autoclaved) and a wide range of organic substances (i.e. amino acids, glucose, sorbitol and organic humic acids) were investigated. Insignificant differences on the FDA hydrolysis activity (FDA activity) were found in the ,-irradiated and non-irradiated OhLn litter, indicating that ,-irradiation does not destroy enzymes. Conversely, after heat-sterilization of litter, samples showed FDA activity corresponding to 60, 34.8 and 30.8% (in the OhLn, the OhLv and the OhLf layers, respectively) of that of control litters. This indicates the presence of non-enzymatic interfering substances in the FDA assays. As the humification and litter depth increased, hydrolysis of FDA due to interferences decreased, indicating degradation and/or chelation of interfering substances. We hypothesize that lysine, arginine, histidine and cysteine are mainly responsible for the hydrolysis of FDA. We suggest that the use of phosphate buffer (50 mm, pH 7.0) with incubation <,30 minutes, in combination with a temperature between 30 and 40°C, produces insignificant interference in the determination of the final FDA activity in litter samples. [source] Stimulation of epidermal calcium gradient loss and increase in TNF-, and IL-1, expressions by glycolic acid in murine epidermisEXPERIMENTAL DERMATOLOGY, Issue 8 2005Se Kyoo Jeong Abstract:, In a previous study, we reported that ,-hydroxy acids (AHA), such as glycolic acid and lactic acid, did not induce any significant changes in transepidermal water loss for normal murine skin. The ultrastructural observations, however, showed that the extent of lamellar body exocytosis significantly increased. Because AHA can theoretically decrease the calcium ion concentration by chelation, topical AHA may induce the loss of epidermal calcium gradient by lowering the calcium ion concentration in the granulocytes and, subsequently, induce lamellar body secretion. The aim of this study is to verify that glycolic acid could modulate the epidermal calcium gradient and increase lamellar body exocytosis. Seventy per cent of glycolic acid aqueous solution was applied to the normal skin of hairless mice and biochemical and morphological studies were performed. The loss of epidermal calcium gradient was observed in glycolic-acid-applied skin of hairless mice and subsequent barrier function recovery processes, such as an increase in lamellar body secretion, were observed. The extracellular glycolic acid was found to inhibit the change in intracellular calcium ion concentration in response to extracellular calcium ion concentration changes in the cultured mouse keratinocyte in vitro. The protein and mRNA expressions of tumour necrosis factor-, and interleukin-1, in the murine epidermis were significantly increased after glycolic acid application. An in vitro study using cultured keratinocytes suggested that glycolic acid could lower the calcium ion concentration, at least in part, through the chelating effects of the glycolic acid on the cationic ions. [source] Molecular physiology of SLC4 anion exchangersEXPERIMENTAL PHYSIOLOGY, Issue 1 2006Seth L. Alper Plasmalemmal Cl,,HCO3, exchangers regulate intracellular pH and [Cl,] and cell volume. In polarized epithelial cells, they contribute also to transepithelial secretion and reabsorption of acid,base equivalents and of Cl,. Members of both the SLC4 and SLC26 mammalian gene families encode Na+ -independent Cl,,HCO3, exchangers. Human SLC4A1/AE1 mutations cause either the erythroid disorders spherocytic haemolytic anaemia or ovalocytosis, or distal renal tubular acidosis. SLC4A2/AE2 knockout mice die at weaning. Human SLC4A3/AE3 polymorphisms have been associated with seizure disorder. Although mammalian SLC4/AE polypeptides mediate only electroneutral Cl,,anion exchange, trout erythroid AE1 also promotes osmolyte transport and increased anion conductance. Mouse AE1 is required for DIDS-sensitive erythroid Cl, conductance, but definitive evidence for mediation of Cl, conductance is lacking. However, a single missense mutation allows AE1 to mediate both electrogenic SO42,,Cl, exchange or electroneutral, H+ -independent SO42,,SO42, exchange. In the Xenopus oocyte, the AE1 C-terminal cytoplasmic tail residues reported to bind carbonic anhydrase II are dispensable for Cl,,Cl, exchange, but required for Cl,,HCO3, exchange. AE2 is acutely and independently inhibited by intracellular and extracellular H+, and this regulation requires integrity of the most highly conserved sequence of the AE2 N-terminal cytoplasmic domain. Individual missense mutations within this and adjacent regions identify additional residues which acid-shift pHo sensitivity. These regions together are modelled to form contiguous surface patches on the AE2 cytoplasmic domain. In contrast, the N-terminal variant AE2c polypeptide exhibits an alkaline-shifted pHo sensitivity, as do certain transmembrane domain His mutants. AE2-mediated anion exchange is also stimulated by ammonium and by hypertonicity by a mechanism sensitive to inhibition by chelation of intracellular Ca2+ and by calmidazolium. This growing body of structure,function data, together with increased structural information, will advance mechanistic understanding of SLC4 anion exchangers. [source] Understanding the binding properties of an unusual metal-binding protein , a study of bacterial frataxinFEBS JOURNAL, Issue 16 2007Chiara Pastore Deficiency of the small mitochondrial protein frataxin causes Friedreich's ataxia, a severe neurodegenerative pathology. Frataxin, which has been highly conserved throughout evolution, is thought to be involved in, among other processes, Fe,S cluster formation. Independent evidence shows that it binds iron directly, although with very distinct features and low affinity. Here, we have carried out an extensive study of the binding properties of CyaY, the bacterial ortholog of frataxin, to different divalent and trivalent cations, using NMR and X-ray crystallography. We demonstrate that the protein has low cation specificity and contains multiple binding sites able to chelate divalent and trivalent metals with low affinity. Binding does not involve cavities or pockets, but exposed glutamates and aspartates, which are residues that are unusual for iron chelation when not assisted by histidines and/or cysteines. We have related how such an ability to bind cations on a relatively large area through an electrostatic mechanism could be a valuable asset for protein function. [source] Calcium-independent cytoskeleton disassembly induced by BAPTAFEBS JOURNAL, Issue 15 2004Yasmina Saoudi In living organisms, Ca2+ signalling is central to cell physiology. The Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane- N,N,N,,N,-tetraacetic acid (BAPTA) has been widely used as a probe to test the role of calcium in a large variety of cell functions. Here we show that in most cell types BAPTA has a potent actin and microtubule depolymerizing activity and that this activity is completely independent of Ca2+ chelation. Thus, the depolymerizing effect of BAPTA is shared by a derivative (D-BAPTA) showing a dramatically reduced calcium chelating activity. Because the extraordinary depolymerizing activity of BAPTA could be due to a general depletion of cell fuel molecules such as ATP, we tested the effects of BAPTA on cellular ATP levels and on mitochondrial function. We find that BAPTA depletes ATP pools and affects mitochondrial respiration in vitro as well as mitochondrial shape and distribution in cells. However, these effects are unrelated to the Ca2+ chelating properties of BAPTA and do not account for the depolymerizing effect of BAPTA on the cell cytoskeleton. We propose that D-BAPTA should be systematically introduced in calcium signalling experiments, as controls for the known and unknown calcium independent effects of BAPTA. Additionally, the concomitant depolymerizing effect of BAPTA on both tubulin and actin assemblies is intriguing and may lead to the identification of a new control mechanism for cytoskeleton assembly. [source] Iron-mediated suppression of bloom-forming cyanobacteria by oxine in a eutrophic lakeFRESHWATER BIOLOGY, Issue 5 2010LEWIS A. MOLOT Summary 1. Published studies show that cyanobacteria have higher Fe requirements than eukaryotic algae. To test whether Fe availability can affect formation of a cyanobacterial bloom, a strong Fe chelator, oxine (8-hydroxyquinoline, C9H7NO), was added to enclosures in eutrophic Lake 227 in the Experimental Lakes Area (ELA) (northwestern Ontario). 2. Aphanizomenon schindlerii growth was suppressed, and growth of eukaryotic chlorophytes significantly promoted in enclosures to which oxine had been added. Significant eukaryotic growth did not occur in enclosures treated with ammonium, suggesting that N supplied by degradation of oxine was not responsible for eukaryotic success in the oxine enclosures. 3. In situ Fe2+ measurements were unreliable because of interference from high concentrations of dissolved organic compounds. However, oxine rapidly promoted oxidation of Fe2+ to Fe3+ in deionised water, suggesting that rapid removal of Fe2+ also occurred in the oxine-treated enclosures. 4. In batch cultures, 10 ,m Fe and 10 ,m oxine (a 1 : 1 ratio) completely inhibited the growth of the cyanobacteria Synechococcus sp. and Anabaena flos-aquae and the chlorophytes Pseudokirchneriella subcapitata and Scenedesmus quadricauda. Increasing Fe 10-fold to 100 ,m Fe completely and partially reversed oxine inhibition in the two chlorophytes but could not overcome inhibition of the cyanobacteria, indicating that inhibition was Fe-mediated at least in the eukaryotes. Since oxine binds Fe3+ in a 1 : 3 ratio (Fe : oxine), inhibition at a 1 : 1 ratio indicates that not all of the Fe is bound, and a mechanism involving Fe other than chelation was at least partly responsible for inhibition. 5. Collectively, the enclosure and laboratory results suggest that the outcome of competition between cyanobacteria and eukaryotic algae in the oxine-treated enclosures in Lake 227 was likely a result of decreased availability of Fe, especially Fe2+. 6. The results suggest that remediation methods that dramatically restrict the supply rate of Fe2+ could reduce the relative abundance of cyanobacteria in eutrophic systems. [source] Gq/11-induced intracellular calcium mobilization mediates Per2 acute induction in Rat-1 fibroblastsGENES TO CELLS, Issue 9 2006Naoyuki Takashima Phase resetting is one of the essential properties of circadian clocks that is required for the adjustment to a particular environment and the induction of Per1 and Per2 clock genes is believed to be a primary molecular event during this process. Although the intracellular signal transduction pathway underlying Per1 gene activation has been well characterized, the mechanisms that control Per2 up-regulation have not yet been elucidated. In our present study, we demonstrate that Gq/11 coupled receptors mediate serum-induced immediate rat Per2 (rPer2) transactivation in Rat-1 fibroblasts via intracellular Ca2+ mobilization. Stimulation of these cells with a high concentration of serum was found to rapidly increase the intracellular Ca2+ levels and strongly up-regulated rPer2 gene. rPer2 induction by serum stimulation was abrogated by intracellular Ca2+ chelation and depletion of intracellular Ca2+ store, which suggests that the calcium mobilization is necessary for the up-regulation of rPer2 gene. In addition, suppression of Gq/11 function was observed to inhibit both Ca2+ mobilization and rPer2 induction. Further, we demonstrated that endothelin-induced acute rPer2 transactivation via Gq/11-coupled endothelin receptors is also suppressed by a Gq/11 specific inhibitor. These findings together suggest that serum and endothelin utilize a common Gq/11-PLC mediated pathway for the transactivation of rPer2, which involves the mobilization of calcium from the intracellular calcium store. [source] Rare Earth Element Concentrations in the Natural Water Reference Materials (NRCC) NASS-5, CASS-4 and SLEW-3GEOSTANDARDS & GEOANALYTICAL RESEARCH, Issue 2 2007Michael G. Lawrence terres rares; yttrium; pré-concentration; ICP-MS; matériaux de référence du NRCC The rare earth element and yttrium concentrations of the NRCC reference materials North Atlantic Surface seawater, NASS-5; Coastal Atlantic Surface Seawater, CASS-4; and the estuarine water, SLEW-3 have been precisely determined by ICP-MS after ca. 1:8 preconcentration following a triple chelation using HDEHP (phosphoric acid 2-ethylhexyl ester -mono and di ester mixture) in heptane, and back extraction in nitric acid. We propose reference values with uncertainties for all naturally occurring lanthanides and yttrium. Les concentrations en terres rares et en yttrium des matériaux de référence suivants (du NRCC): l'eau de surface de l'Atlantique Nord NASS-5, l'eau de surface de l'Atlantique Côtier CASS-4 et l'eau d'estuaire SLEW-3 ont été déterminées précisément par ICP-MS après concentration d'un facteur 1 : 8 environ, suivie d'une triple chélation avec de l'HDEHP (mixture d'acide phosphorique 2-ethylhexyl ester - mono et di ester) dans de l'heptane et une extraction inverse en acide nitrique. Nous proposons des valeurs de référence avec leur incertitude pour toutes les terres rares naturelles et l'yttrium. [source] | |||||||||||||||||||||||||||||||||||||||||||