Calcium Diethylenetriaminepentaacetic Acid Research Articles

Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia

Desensitization treatment for anaphylactoid reactions to desferrioxamine in a pediatric patient with thalassemia

Effects of macromolecular chelating agents on the release of 239Pu and 59Fe from rat alveolar macrophages after phagocytic uptake of 239Pu-59Fe-iron hydroxide colloid.

The chelation-mediated mobilization of 239Pu and 59Fe from rat alveolar macrophages which had engulfed 239Pu-59Fe-hydroxide colloids was studied by exposing the macrophages to diethylenetriaminepentaacetic acid and macromolecular weight forms of diethylenetriaminepentaacetic acid. The release of 239Pu and 59Fe by these macromolecular weight chelating agents and diethylenetriaminepentaacetic acid was assessed in monolayer culture and shown to be dependent upon the nature of the engulfed colloids. Whereas calcium-diethylenetriaminepentaacetic acid, aminoethylcellulose-diethylenetriaminepentaacetic acid, and aminoethylcellulose-diethylenetriaminepentaacetic acid oxidized with periodic acid (aminoethylcellulose-diethylenetriaminepentaacetic acid(I2) exhibited some effectiveness at releasing 239Pu and 59Fe from macrophages which had engulfed the low aggregative colloid, they were less effective in the release of these radionuclides from the high aggregative colloid. The efficacy of these chelating agents on the removal of radionuclides from alveolar macrophages differed between iron and plutonium, suggesting the significant difference in the dissolution and subsequent metabolism of these radionuclides in alveolar macrophages. From the similarities of the percentage increases in 239Pu mobilized from the low aggregate colloid by aminoethylcellulose-diethylenetriaminepentaacetic acid (I2) and diethylenetriaminepentaacetic acid, it would appear that both forms of diethylenetriaminepentaacetic acid could be accessing the same deposits of 239Pu; however, for 59Fe the percentage increases are quite different for the two forms of diethylenetriaminepentaacetic acid. SiO2-diethylenetriaminepentaacetic acid, an insoluble macromolecular weight chelating agent, was ineffective at releases 239Pu but was slightly effective at releasing radioiron.

塩化マンガンおよびＣａ‐ＤＴＰＡの体内マンガン‐５４除去効果

Efficacies of manganese chloride and Ca-DTPA (calcium diethylenetriaminepentaacetic acid) for the elimination of incorporated 54Mn were investigated in mice. Each mouse was given an intraperitoneal injection of 54Mn and initial whole-body radioactivity was measured immediately. Manganese chloride (10mg-Mn/kg) or Ca-DTPA (10 or 100mg/kg) was injected intraperitoneally once or repeatedly at various times after 54Mn injection. Efficacies for elimination were estimated by measuring the whole-body retention of 54Mn for 14 or 21 days.A single injection of manganese chloride eliminated more than 80% of the incorporated 54Mn when it was injected within 24h after the injection of 54Mn. Although the efficacy was decreased with the passage of time after the injection of 54Mn, about 50% was still eliminated after 14 days. Repeated injection of this agent raised the efficacy, but the second or later injection was less effective than the first injection. Ca-DTPA eliminated the incorporated 54Mn by 57% for 100mg/kg and by 19% for 10mg/kg when it was injected after 3h. But after 6h or later, Ca-DTPA had little efficacy.These results indicate that manganese chloride is very effective to eliminate the 54Mn from accidentally contaminated persons and the efficacy of Ca-DTPA is less than that of manganese chloride.

Toxicological Study of DTPA as a Drug(VI). Effects of Intravenously Injected Ca-DTPA, Ca-EDTA, CBMIDA and Orally Administered Zn-DTPA to Bone Metabolism in Beagle Dogs.

Effects of four kinds of chelating agents, Ca-DTPA (calcium diethylenetriaminepentaacetic acid), Ca-EDTA (calcium ethylenediaminetetraacetic acid), CBMIDA [catechol-3, 6-bis(methyleiminodiacetic acid)] and Zn-DTPA (zinc DTPA), on bone metabolism were examined in beagle dogs by bone histomorphometry and measurement of serum biochemical constituents related to bone metabolism. Ca-DTP, Ca-EDTA or CBMIDA (150μmol/kg) was injected intravenously to dogs for 1 month, respectively. Three doses (30, 150 and 300μmol/kg) of Zn-DTPA were administered orally to dogs for 1 month respectively. All dogs received twice tetracycline hydrochloride infections at an interval of 7 days before the beginning of administration of chelating agents and also twice calcein injections at the same time schedule prior to sacrifices for analyzing bone dynamics. Bone samples were obtained from ilium and undecalcified bone sections were made. Bone histomorphometry of cancellous bone area of ilium was performed using an image analyzer.Bone volume and mean trabecular thickness did not change in any of the groups. Osteoid volume in the CBMIDA group increased (p<0.05). Osteoid volume and mean osteoid thickness in the 150μmol/kg of Zn-DTPA group decreased (p<0.05 and p<0.01). Mineral apposition rate and bone formation rate did not change in any groups except the CBMIDA and 150μmol/kg of Zn-DTPA groups, in which fluorescent bone labeling was absent or obscure, revealing inhibition of bone mineralization.Serum total calcium levels did not change in any of the groups. Serum phosphorus level decreased significantly in the 30μmol/kg dose of Zn-DTPA group (p<0.05). Parathyroid hormone level increased in the 30μmol/kg dose of Zn-DTPA (p<0.05), while it decreased in the 150μmol/kg dose of Zn-DTPA group (p<0.05).The results suggest that the protracted therapy using the above four kinds of chelating agents may incur damages of bone such as decrease of bone volume and inhibition of mineralization.

Toxicological study of DTPA as a drug (V). Toxicities of Ca-DTPA, Ca-EDTA and CBMIDA after intravenous injection in beagle dogs.

The toxicity of Ca-DTPA (calcium diethylenetriaminepentaacetic acid), Ca-EDTA (calcium ethylenediaminetetraacetic acid) and CBMIDA [Catechol-3, 6-bis (methyleiminodiacetic acid)] after intravenous injection were examined in beagle dogs. In the test (1), the change of serum total and ionic calcium levels following intravenous injection of each chelating agent was examined. The results showed that both total and ionic calium levels did not change at all by any of these chelating agents. In the test (2), each of these chelating agents (150μmol/kg) were intravenously injected to dogs daily for 1 month. No clinical untoward signs were observed in all groups. However, the significant decrease of mean body weights in Ca-DTPA groups was seen at 4 weeks after the beginning of injection. In a serum biochemical examination, the increases of GOT and GPT values in one dog, and BUN and creatinine values in another one were seen in Ca-DTPA group. No changes in all measured items were seen in Ca-EDTA group. The increases of GPT, ALP and creatinine values in one dog and GPT value in another one were observed in CBMIDA group. The slight congestion of mucosa in small intestine, the increase of lymphocytes in the lamina propria of small intestine and in the proximal tubles of kidney, and the degeneration of liver were observed in all groups. There were almost no differences in the degree of these histological changes in each group.

5 Results of long-term subcutaneous desferrioxamine therapy

Regular subcutaneous desferrioxamine therapy has prolonged the life and reduced the incidence of cardiac, endocrine and liver complications of iron overload in patients with thalassaemia major and other refractory transfusion-dependent anaemias. Its full impact will be apparent only when patients who began this treatment as children 10 years ago reach adult life. The major problems with s.c. DF therapy are its cost and the difficulty of patient compliance with a painful and cumbersome method of administration. Attempts to maintain normal iron stores in these patients has resulted in significant toxicity caused by the excessive use of DF. Although recent studies have shown that long-term subcutaneous calcium diethylene triamine penta-acetic acid (Ca-DTPA) can be used as an effective alternative to s.c. DF (Wonke et al, 1988), this treatment presents additional potential problems of zinc depletion which can be prevented only by careful management. The prospects of an inexpensive, orally active iron chelator are now real (Kontoghiorghes and Hoffbrand, 1988) and it is to be hoped that long-term results at least as good as those with s.c. DF will be achievable. Such oral chelators may be available to a far wider group of patients, than s.c. DF, and the problems of cost and compliance may be diminished.

Chelating-agent suppression of cadmium-induced hepatotoxicity.

The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action.

Chelate antidotes for sodium vanadate and vanadyl sulfate intoxication in mice.

Eighteen different chelating agents, including all of those previously shown to have a protective action in vanadium intoxication, have been compared as antidotes for acute vanadium intoxication using mice. Of these compounds, those found to be effective antidotes for both vanadate (VO3(-3)) and vanadyl (VO2+) include ascorbic acid, deferoxamine, D-penicillamine, sodium calcium diethylenetriaminepentaacetic acid (Na3CaDTPA), Na2CaEDTA, glutathione, Tiron, and ethylenediaminetetra(methylene phosphonate). Of the compounds examined, ascorbic acid appeared to be the most promising for human use. When administered at the levels used in this study, it is an effective antidote for intoxication due to either the vanadate or the vanadyl ion. Certain compounds are able to act as antidotes for vanadate solely by virtue of their action as a reducing agent; when these compounds are unable to form complexes with the reduction product (vanadyl ion), they are effective antidotes for the higher oxidation state only when the concentration of vanadyl produced is less than the level that results in toxic effects.