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Biomedical subjects

K L Nuttall

Publications and source records attributed to K L Nuttall.

7 recordsLinked to original sources

Oral dimercaptosuccinic acid and ongoing exposure to lead: effects on heme synthesis and lead distribution in a rat model.

Lead (Pb) exposure and subsequent toxicity continues to be a significant problem in the United States. Treatment with meso-2,3-dimercaptosuccinic acid (DMSA) has been reported to be effective in reducing the body's Pb burden, with fewer adverse side effects than other chelating agents. The oral availability and relative safety of DMSA presents the controversial option of treating patients with Pb poisoning on an outpatient basis. Despite recommendations that children be removed from the Pb contaminated environment, some children will inevitably be exposed to environmental Pb while receiving oral DMSA therapy. The study hypothesized that oral DMSA chelation therapy is beneficial even when faced with continued dietary Pb. Sprague-Dawley rats were exposed to Pb in water for 35 days and then placed in various treatment groups, including groups administered oral DMSA with and without concurrent Pb exposure. The concentration of Pb in blood and critical organs and Pb diuresis were measured. The effect of Pb on heme synthesis was determined by assaying the urinary delta-aminolevulinic acid (delta-ALA), and blood zinc protoporphyrin (ZPP). DMSA reversed the hematological effects of Pb, decreased the blood, brain, bone, kidney, and liver Pb concentration, and produced a marked Pb diuresis, even when challenged with ongoing Pb exposure. In conclusion, even though DMSA treatment without exposure to Pb is optimal, oral DMSA could be beneficial even when challenged with ongoing Pb exposure.

Administration, Oral

A model for metal selenide formation under biological conditions.

The essential trace element selenium is known to be capable of reducing the toxicity of heavy metals like cadmium(II), mercury(II) and silver(I). One mechanism by which this occurs is through the formation of an inert metal selenide like silver selenide. It is not clear why selenide should react in the body preferentially with silver(I) over other metals such as zinc(II), an ion which is capable of forming zinc selenide, and which is present at relatively high levels. A reaction is discussed which can account for the ability of mercury(II) and silver(I) to lead to metal selenide formation in preference to zinc(II). Metal ions which have a sufficiently large formation constant for the metal selenide can induce the disproportionation of elemental selenium to produce the metal selenide; both mercury(II) and silver(I) can induce such reactions, whereas zinc(II) cannot. If this model is accurate, it should provide a basis to predict which metal ions can produce metal selenides in the body, and which ions are unlikely to result in metal selenide formation.

Animals

Elemental selenium and glutathione reductase.

Selenium is an essential trace element important to several metabolic processes, although selenium in the chemical form of elemental selenium (Se degree) is commonly believed to be biologically inert. Recent data shows that colloidal suspensions of red amorphous elemental selenium are more easily reduced than previously thought, and that such reductions can potentially take place under biological conditions. The enzyme glutathione reductase, already known to be involved in selenium metabolism, is a good candidate to mediate the reduction of colloidal selenium to hydrogen selenide (H2Se), a compound of established biological activity. The implications of this hypothesis include the possibility that elemental selenium may be biologically active at least under some conditions, and that glutathione reductase may function in selenium metabolism primarily by maintaining the glutathione concentration in a reduced state.

Colloids

Inductively coupled plasma mass spectrometry for trace element analysis in the clinical laboratory.

Inductively coupled plasma mass spectrometry (ICP-MS) is a relatively new technique for trace element analysis. The basic operating principles of ICP-MS are described and our experience with this technique in a clinical setting is discussed for the analysis of serum, whole blood, and urine. Advantages to ICP-MS include the favorable detection limits (0.01 to 0.1 micrograms/L for many elements), simple specimen preparation, high throughput (about 40 specimens per hour), and the ability to measure more than one element simultaneously. A major disadvantage is the high capital cost of the instrumentation. Heavier elements, such as lead, are well-suited for ICP-MS analysis, whereas lighter elements are prone to more interferences. Lighter elements which are not amenable to assay by ICP-MS include chromium and iron. The ability to measure isotopes is a major advantage for mass spectrometry methods and has the potential to expand the usefulness of trace element analysis.

Female