No abstract available.
Chelating Agents* ; Lead Poisoning*

PURPOSE: To elucidate the inter-connection between lens nuclear opacity and its proposed two main factors, which are oxidative stress and glycation reaction initiated with sugars and proteins. METHODS: We have collected clinical samples after cataract surgery from 57 patients during 3 month period. We also classified these samples into three groups as initial, intermediate and advanced stages, and performed the biochemical assays for measurements of glutathione(GSH) and advanced glycation end products(AGEs). RESULTS: It showed that the concentrations of GSH in lens soluble proteins were 0.022+/-0.019, 0.017+/-0.011, and 0.011+/-0.010 nmoles/mg lens protein in initial stage, intermediate stage and advanced stage, respectively. Fluorophore formation(Ex370/Em440), which has been reported to represent general AGEs formation, was positively correlated with nuclear opacity showing that 108.8+/-48.3, 174.7+/-116.9, and 188.2+/-130.6 Fluorescence Unit(F.U.) in initial stage, intermediate stage and advanced stage, respectively. Likewise, a marker for AGEs, pentosidine-related fluorophore(Ex335/Em385) was increased with nuclear opacity(67.0+/-30.8, 75.5+/-36.4, and 80.4+/-41.7 F.U. in initial stage, intermediate stage and advanced stage, respectively), although significant differences existed between groups. CONCLUSION: Our results showed that there are clear inter-connection between lens nuclear opacity, oxidative stress and the formation of general AGEs compared with pentosidine, and suggested that therapy using antioxidants, chelating agents, or glycation inhibitors could be beneficial in delaying nuclear cataractogenesis.
Antioxidants ; Carbohydrates ; Cataract* ; Chelating Agents ; Fluorescence ; Humans ; Oxidative Stress*

PURPOSE: The present paper reports a systematic study on the effect of bifunctional chelators (BFC) namely, NOTA, DOTA, and DTPA, on the radiochemical formulation, in vitro stability, and in vivo biological properties of ⁶⁸Ga-labeled RGD peptide derivatives.METHODS: The three RGD conjugates namely, NOTA-Bn-E-[c(RGDfk)]₂, DOTA-Bn-E-[c(RGDfk)]₂, and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled with ⁶⁸Ga and the radiolabeling was optimized with respect to the ligand amount, radiolabeling time, and temperature. Further, the ⁶⁸Ga complexes were assessed for their in vitro and in vivo stabilities. The biodistribution studies of the three radiolabeled conjugates were carried out in C57BL/6 mice bearing melanoma tumor at 30 min and 1 h post-adimistration.RESULTS: NOTA-Bn-E-[c(RGDfk)]₂ could be radiolabeled with ⁶⁸Ga at room temperature while DOTA-Bn-E-[c(RGDfk)]₂ and DTPA-Bn-E-[c(RGDfk)]₂ were radiolabeled at high temperature. ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was found to be the most kinetically rigid in in vitro stability assay. The uptake of the three radiolabeled peptide conjugates in melanoma tumor was comparable at 1 h post-administration (NOTA; DOTA; DTPA (% I.D./g):: 2.78 ± 0.38; 3.08 ± 1.1; 3.36 ± 0.49). However, the tumor/background ratio of ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ was the best amongst the three radiotracers. ⁶⁸Ga-complexes of NOTA-Bn-E-[c(RGDfk)]₂ and DOTABn-E-[c(RGDfk)]₂ showed excellent in vivo stability while ⁶⁸Ga-DTPA-Bn-E-[c(RGDfk)]₂ showed significant metabolic degradation.CONCLUSION: These studies show that ⁶⁸Ga-NOTA-Bn-E-[c(RGDfk)]₂ would be the most appropriate ⁶⁸Ga-labeled radiotracer and the most amenable for kit formulation.
Animals ; Chelating Agents ; In Vitro Techniques ; Melanoma ; Mice ; Pentetic Acid ; Peptides

Background and Objectives: Iron is an essential element that plays a vital role in a wide variety of cellular processes. But when present in excess concentration in organs, it may increase the risk for liver disease, heart failure, and diabetes. Recently, siderophores, which are iron-chelating agents produced by microorganisms, have attracted tremendous attention because of their strong binding and high selectivity to the ferric form of iron. Thus, the use of siderophore in sequestering excess iron in the body as a form of therapy is very attractive. This study determined the effects of commercially available siderophore in sequestering excess iron in organs such as liver, heart, and pancreas under excess iron conditions. Methodology: First, iron-overload was induced by injecting iron dextran (20 mg) into male ICR mice for three consecutive days. The effects of iron to the liver, heart, and pancreas and the possible sequestration by siderophore were determined by scoring histological sections. The liver iron concentration was also assessed by atomic absorption spectroscopy (AAS). Results and Conclusion The study showed that iron-overloaded mice exhibited skin hyperpigmentation and hemosiderosis in liver, heart, and pancreas. Significant changes in the liver include hepatomegaly and development of tumor. Iron-overloaded mice had 2,935% increase in liver iron content compared to the salinetreated mice. However, when iron-overloaded mice were treated with either 100 µg or 200 µg siderophore, there was a 77% and 84% decrease in liver iron content, respectively. Moreover, the treatment of ironoverloaded mice with siderophore prevented the development of hemosiderosis, tumor, and structural changes in the tissues studied. The results showed that siderophore can effectively reduce excess iron and organ damage in iron-overloaded mice and can be potentially employed in chelation therapy of iron-overload diseases. Further studies on the possible mechanisms of siderophore aside from decreasing iron excess and lowering organ dysfunction are recommended.
Siderophores ; Iron Overload ; Iron Chelating Agents ; Hemosiderosis ; Hepatomegaly

In central neurons, an excessive or sustained rise in the concentration of free cytoplasmic Ca2+ ions([Ca2+]i) after hypoxia may promote rapid neurodegeneration both in vitro and in vivo. Treating cells with Ca2+ chelating agents may prevent or delay a loss of cellular Ca2+ homeostasis after hypoxic injury and thus constitute an effective strategy for minimizing neuronal damage. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-aminophenoxy) ethrane -N,N,N',N' -tetraacetic acid acetoxymethyl ester(BAPTA-AM) have shown evidence of neuroprotective effect against hypoxic neuronal injury. This study was designed to examine dose response and to estimate therapeutic window of BAPTA-AM for the recovery from hypoxia in vitro. Electrophysiological studies were made in CA1 neurons in rat hippocampal slices which were superfused with artificial cerebrospinal fluid(ASCF) in tissue chamber. Hypoxia was induced by replacement of 95% N2+5% CO2 from 95% O2+5% CO2 for 20min. Recovery from hypoxic injury was evaluated by using a percentage recovery of population spike. BAPTA-AM in concentration of 1, 10 and 50micrometer were administered to the artificial cerebrospinal fluid(ASCF) for 2 hours prior to hypoxia, simultaneous with hypoxia and after hypoxia. The experimental specimens were divided to seven groups and each group was compared to control ASCF group. Recovery of population spike after hypoxia was about 70% in control ASCF group, which was mild type hypoxic injury. BAPTA-AM in 10 micrometer concentration, when given just prior to hypoxia, enhanced recovery of poppulation spikes at 15 and 30min following reoxygenation(p<0.05), in comparison with control ASCF. BAPTA-AM had no neuroprotective acitvity when given after the onset of hypoxia. Also, BAPTA-AM in 1 and 50 micrometer concentration did not accentuate recovery of population spike after hypoxia. Dose response curve was inverted U-shape and the response was maximun in 10 micrometer concentration of BAPTA-AM.
Animals ; Anoxia ; Chelating Agents ; Cytoplasm ; Enflurane ; Homeostasis ; Neurons ; Neuroprotective Agents* ; Rats

Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.
Animals ; Chelating Agents ; pharmacology ; Humans ; Inactivation, Metabolic ; Radiation-Protective Agents ; pharmacology ; Uranium ; metabolism ; toxicity

OBJECTIVES: Chitosan has been widely investigated and used. However, the literature does not refer to the shelf life of this solution. This study evaluated, through the colorimetric titration technique and an analysis of dentin micro-hardness, the shelf life of 0.2% chitosan solution. MATERIALS AND METHODS: Thirty human canines were sectioned, and specimens were obtained from the second and third slices, from cemento-enamel junction to the apex. A 0.2% chitosan solution was prepared and distributed in 3 identical glass bottles (v1, v2, and v3) and 3 plastic bottles (p1, p2, and p3). At 0, 7, 15, 30, 45, 60, 90, 120, 150, and 180 days, the specimens were immersed in each solution for 5 minutes (n = 3 each). The chelating effect of the solution was assessed by micro-hardness and colorimetric analysis of the dentin specimens. 17% EDTA and distilled water were used as controls. Data were analyzed statistically by two-way and Tukey-Kramer multiple comparison (α = 0.05). RESULTS: There was no statistically significant difference among the solutions with respect to the study time (p = 0.113) and micro-hardness/time interaction (p = 0.329). Chitosan solutions and EDTA reduced the micro-hardness in a similar manner and differed significantly from the control group (p < 0.001). Chitosan solutions chelated calcium ions throughout the entire experiment. CONCLUSIONS: Regardless of the storage form, chitosan demonstrates a chelating property for a minimum period of 6 months.
Calcium ; Chelating Agents ; Chitosan* ; Colorimetry* ; Dentin* ; Edetic Acid ; Glass ; Humans ; Ions ; Plastics ; Product Packaging* ; Water

In order to study the change of laboratory parameters of lead poisoning, 8 persons who had not been treated previously for lead poisoning (Group 1) and 6 persons who had been inadequately treated for few months for chronic lead poisoning at local clinic (Group 2) were examined. They had occupational exposure to lead for 3 to 18 years (mean, 7.6). In group 1 blood lead, urine lead, urine coproporphyrin and delta-aminolevulinic acid levels before our treatment exceeded the critical levels of lead poisoning. In group 2 urine lead level exceeded but blood lead, urine coproporphyrin and delta-aminolevulinic acid levels were within normal limits. All of them were treated with D-penicillamine for 4 months as inpatients at Industiral Accident Hospital. The dose of D-penicillamine was the same in all patients; 600 mg per day p.o. and the chelating agent was administer every other week. For laboratory analysis, 24 hour urine and 10 gm of whole blood were collected every 1 month on last day of non-administration period. The results were as follows: 1. It was found that urine lead level was decreased below the critical level of lead poisoning after 4 month's treatment with D-penicillamine and blood lead level was decreased more progressively below the critical level after 1 month treatment. 2. Urine coproporphyrin and delta-aminolevulinic acid levels were decreased progressively to normal range after 1 month treatment. 3. Two months after treatment, blood lead, urine lead, urine coproporphyrin and delta-adminolevulinic acid levels showed some increasing trends. 4. Urine lead level should be checked in a person who had been inadequately treated with chelating agents because blood lead, coproporphyrin and delta-adminolevulinic acid might be in normal range.
Aminolevulinic Acid ; Chelating Agents ; Humans ; Inpatients ; Lead Poisoning* ; Occupational Exposure ; Penicillamine ; Reference Values

Trace mineral studies involving metal ion chelators have been conducted in investigating the response of gene and protein expressions of certain cell lines but a few had really focused on how these metal ion chelators could affect the availability of important trace minerals such as Zn, Mn, Fe and Cu. The aim of the present study was to investigate the availability of Zn for the treatment of MC3T3-E1 osteoblast-like cells and the availability of some trace minerals in the cell culture media components after using chelexing resin in the FBS and the addition of N,N,N',N'-tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN, membrane-permeable chelator) and diethylenetriaminepentaacetic acid (DTPA, membrane-impermeable chelator) in the treatment medium. Components for the preparation of cell culture medium and Zn-treated medium have been tested for Zn, Mn, Fe and Cu contents by atomic absorption spectrophotometer or inductively coupled plasma spectrophotometer. Also, the expression of bone-related genes (ALP, Runx2, PTH-R, ProCOL I, OPN and OC) was measured on the cellular Zn depletion such as chelexing or TPEN treatment. Results have shown that using the chelexing resin in FBS would significantly decrease the available Zn (p<0.05) (39.4 +/- 1.5 micrometer vs 0.61 +/- 10.15 micrometer) and Mn (p<0.05) (0.74 +/- 0.01 micrometer vs 0.12 +/- 0.04 micrometer). However, levels of Fe and Cu in FBS were not changed by chelexing FBS. The use of TPEN and DTPA as Zn-chelators did not show significant difference on the final concentration of Zn in the treatment medium (0, 3, 6, 9, 12 micrometer) except for in the addition of higher 15 micrometer ZnCl2 which showed a significant increase of Zn level in DTPA-chelated treatment medium. Results have shown that both chelators gave the same pattern for the expression of the five bone-related genes between Zn- and Zn+, and TPEN-treated experiments, compared to chelex-treated experiment, showed lower bone-related gene expression, which may imply that TPEN would be a stronger chelator than chelex resin. This study showed that TPEN would be a stronger chelator compared to DTPA or chelex resin and TPEN and chelex resin exerted cellular zinc depletion to be enough for cell study for Zn depletion.
Absorption ; Cell Culture Techniques ; Cell Line ; Chelating Agents* ; Gene Expression ; Minerals ; Osteoblasts* ; Pentetic Acid* ; Plasma ; Zinc

PURPOSE: Chitin and chitosan are nontoxic natural chelators that chelate radiostrontium effectively. The purpose of this study was to compare radiostrontium chelation of chitin and chitosan with that of well known chemical chelators, namely EDTA and DTPA. MATERIALS AND METHODS: The chelaton rates of chitin, chitosan, EDTA and DTPA were compared using a column chromatography method (Sephadex G-25M, Sweden). Three kinds of chitins and four kinds of chitosans were used. All of them were water soloble. RESULTS: Phosphated chitosan showed the highest chelation yield of more than 97% at pH 7. All of chitins, chitosans, EDTA and DTPA showed chelation yield of more than 90% independent of varing pH level. CONCLUSION: Chitin and chitosan have similar chelation rate as compared with EDTA and DTPA.
Chelating Agents ; Chitin* ; Chitosan* ; Chromatography ; Edetic Acid* ; Hydrogen-Ion Concentration ; Pentetic Acid*