Robert A. Bulman

The present status of chelating agents in medicine.

Publisher Summary This chapter describes methods of treating heavy metal intoxication. The chapter discusses the common ground between different approaches to chelation therapy rather than to be over-concerned with the details of individual metal toxicity and its treatment. The chapter also discusses some other medical applications of chelating agents that have become prominent in the past few years. Present treatment of acute iron and lead poisoning is usually gratifyingly successful and a few new agents have been found which appear to have considerable potential. Special attention must be devoted to this interrelationship if metal complexation in areas of medicine other than chelation therapy is to be effectively exploited. The therapeutic potential of chelating agents as a class of compounds is thus, probably, unparalleled. However, all depends on the future design of agents with sufficient chemical and physical selectivity to achieve very specific biochemical objectives.

Molecular mapping of chromosome 2 deletions in murine radiation-induced AML localizes a putative tumor suppressor gene to a 1.0 cM region homologous to human chromosome segment 11p11-12.

Radiation‐induced acute myeloid leukemias (AMLs) in the mouse are characterized by chromosome 2 deletions. Previous studies showed that a minimal deleted region (mdr) of ∼6.5 cM is lost from one homologue in chromosome 2–deleted AMLs. An AML tumor suppressor gene is proposed to map within this mdr. In this study, we refine the mdr to a 1 cM interval between markers D2Mit126 and D2Mit185 by microsatellite analysis of 21 primary radiation‐induced F1 AMLs. The construction of a partial yeast artificial chromosome (YAC) contig spanning the mdr and the location of six known genes indicated that the 1 cM mdr is homologous to human 11p11–12, a region implicated in some human AMLs. Screening of five cell lines derived from primary radiation‐induced AMLs for homozygous loss of microsatellites and genes mapping within the mdr revealed loss of both copies of the hemopoietic tissue‐specific transcription factor Sfpi1 (PU.1/Spi1) in one cell line. Studies of primary and F1 AMLs failed to implicate Sfpi1 as the AML tumor suppressor gene. YAC contig construction, together with data suggesting that the critical gene flanks Sfpi1, represents significant progress toward identifying an AML tumor suppressor gene. Genes Chromosomes Cancer 24:95–104, 1999.

Neutral gadolinium(III) complexes of bulky octadentate dtpa derivatives as potential contrast agents for magnetic resonance imaging

A series of bulky and neutral gadolinium complexes of [bis(R-amide)dtpaH3] (where R = Pri,, Bui,, Bz and phenylethyl, L1--L4)) with potential application as contrast agents for magnetic resonance imaging has been prepared and characterized ; the relaxivity of these complexes is comparable to the contrast agent [Gd(dtpa)(H2OO)]; which is which is currently used in clinics; the X-ray structure analysis of the gadolinium(III) complex of L3 reveals a neutral nine-coordinate complex featuring a water molecule in the tricapped trigonal prismatic metal coordination sphere.

Prediction of the adsorption coefficient (Koc) for soil by a chemically immobilized humic acid column using RP-HPLC.

By determination of HPLC capacity factors (k′) for a series of aromatics it has been possible to determine the soil adsorption coefficients (Koc). The effect of column type and mobile phase composition on the correlation between log Koc and log k′ has also been studied. We have prepared a new HPLC packing material which bears immobilized humic acid and from the values for Koc it appears this new HPLC phase is superior to other procedures - partition into n-octanol and retention on HPLC silica-based phases - which have been used to model the sorption of aromatic substances on soil or sediment.

Determination of the adsorption coefficient (Koc) of some aromatics for soil by RP-HPLC on two immobilized humic acid phases.

Abstract By determination of High Performance Liquid Chromatography (HPLC) capacity factors (k′), a comparison has been made of two new HPLC phases - physically and chemically immobilized humic acid - of their potential for determining soil adsorption coefficients (KOC) for organic pollutants. Log KOC values were estimated from log KOC versus log k′ calibration curves and were determined by using k′ and the humic acid content of the HPLC phases. These calculated log KOC values were compared with log KOC values taken from the literature.

Evaluation of silica-humate and alumina-humate HPLC stationary phases for estimation of the adsorption coefficient, Koc, of soil for some aromatics☆

Abstract Two novel stationary phases have been prepared by immobilizing humic acid on aminopropylsilica and alumina and used to study, by reverse-phased high performance liquid chromatography (RP-HPLC), the contribution of the mineral phase upon the sorptive properties of soil humates for organic pollutants. By determination of K oc , the adsorption coefficient for the organic carbon of soil, for a series of aromatic hydrocarbons it has been shown that the mineral phase has little influence upon their sorption by humic acid, the principal organic component of soil.

Size distribution of radionuclides in nuclear fuel reprocessing liquids after mixing with seawater

Discharges from the Sellafield nuclear site are a major source of artificially produced radionuclides detected in the North Sea. The transport, distribution, and biological uptake of radionuclides in the marine environment depends, however, on the physico-chemical forms of radionuclides in the discharged effluent and on the transformation processes which occur after entry into the coastal waters. Information on these processes is needed to understand the transport and long-term distribution of the radionuclides. In the present work, waters from two separate waste tanks at the nuclear fuel reprocessing site at Sellafield were mixed with coastal waters. The diluted radioactive material was fractionated with respect to particle size by using cross flow ultrafiltration. The size distribution patterns of α-emitters, (Pu-isotopes), β-emitters, (90Sr, 99Tc), and γ-emitters, (137Cs, 95Nb, 95Zr, 125Sb), were determined over 48 h. Except for 137Cs, the radionuclides from the two sources exhibit different size distribution patterns. The association of 90Sr and 239,240Pu with colloids is particularly evident. 137Cs is present in a presumably colloidal form, with a mol. wt. < 10 kDa. The distribution patterns do not appear to be significantly influenced by transformation processes taking place in the mixing zone during 48 h.

Investigations of the uptake of transuranic radionuclides by humic and fulvic acids chemically immobilized on silica gel and their competitive release by complexing agents

The chemistry of the interactions of transuranic elements (TUs) with humic substances needs to be understood so that humate-mediated movement of transuranic radionuclides through the environment can be predicted. This paper reports the chemical immobilization on silica gel of humic and fulvic acids and evaluates the potential of these new materials for the retention of Pu and Am. In addition to the preparation of the foregoing immobilized humic substances, other low molecular weight metal-binding ligands have also been immobilized on silica gel to investigate the binding sites for transuranic elements (TUs) in humic substances. The X-ray photoelectron spectra (XPS) of Th(IV) complexed by humic acid and the immobilized humic acid are similar thus it appears that immobilization of humic acid does not generate any configurational changes in the Th(IV)-binding sites of the macromolecule. A variety of chelating agents partly mobilize these TUs sorbed on the solid phases. A batch method was used to determine the distribution coefficients (Rd) of Pu and Am between the silica gels and aqueous solutions of phosphate and citrate. The effects of the immobilized ligands, the anions and pH in the solution on sorption were assessed. Distribution coefficients (Rd) for the uptake of Pu and Am by these prepared solid phases are, in some cases, of a similar order of magnitude as those determined for soil and particles suspended in terrestrial surface waters.

Investigations of the potential bioavailability of 210Po in some foodstuffs

Extraction of 210Po from lambs liver, pigs kidneys, mussel flesh and brown crabmeat with a series of solvent systems has been used to gain some insight into the uncertainty about the gastrointestinal absorption factor for Po incorporated into foodstuffs. By extracting the tissues with diethyldithiocarbamate dissolved in chloroform, and also in methanol, it has been shown that 210Po is more effectively extracted from lambs liver and crabmeat than it is from each of the other tissues. A similar pattern of extractability is also evident for aqueous solutions of citric acid on crabmeat and mussel flesh. Of particular note is the low extractability by dimethylsulphoxide (3%) of 210Po in mussel flesh as opposed to 24% extractability of 210Po from crabmeat. 210Po-binding macromolecules of about 10 kDa have been released from crabmeat and mussel flesh by digestion with pepsin.

An examination of new procedures for fractionation of plutonium- and americium-bearing sediments

Abstract Sediment from the Ravenglass estuary has been fractionated by procedures which might be expected to bring about no change in the chemical forms of the bound plutonium and americium. The action of molten N -methylmorpholine- N -oxide (NMMNO) on the sediment extracts 20% of the 239 Pu and 241 Am, possibly in forms associated with humic-like materials. On dialysis, these extracts appear to lose 40% of the 239 Pu and 20% of the 241 Am. However, on pretreatment with base there is no significant loss of radioactivity on subsequent dialysis and this may indicate the existence of cationic forms of these elements. High gradient magnetic separation (HMGS) has fractionated the clay constituents ( μ m and 0.2–2.0 μ m) into three subfractions. From an analysis of the 239 Pu/ 241 Am ratio it would appear that there is no conservation of isotopic ratios; this might indicate that the environmental forms of 239 Pu and 241 Am exhibit markedly different affinities for the organo-mineral phases of the sediment.