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Biomedical subjects

D C Wigfield

Publications and source records attributed to D C Wigfield.

At least 19 recordsLinked to original sources
PubMed1990

Dose-response relationships in hexachlorobenzene-induced porphyria.

The rate of development of hexachlorobenzene (HCB)-induced porphyria in female Wistar rats was determined using HCB dosage and porphyrin analysis protocols designed to determine factors which contribute to the delay commonly observed between initial exposure to HCB and the detection of porphyria. Measurements were made of HCB and porphyrin concentrations in the livers, kidneys, and spleens of female Wistar rats exposed continuously (up to 56 days) or for 1 day to HCB (at dietary concentrations of 1000 ppm and 100 ppm). The experiments showed that when a corn oil solution of HCB was added to the diet at a concentration of 1000 ppm, HCB accumulated rapidly in all organs, and the delay in appearance of elevated liver highly carboxylated porphyrins (HCPs) was at most 4 days (approximately 8-fold elevation of HCPs on day 4). One day of exposure to this diet was sufficient to cause elevated liver HCPs, thus showing that continuous exposure to HCB was not required to cause porphyria in this species. Solid HCB added directly to the diet (1000 ppm) resulted in less rapid HCB accumulation and less rapid development of porphyria. The experiments demonstrated that the appearance of a delay in HCB-induced porphyria in the Wistar rat is caused by the rate at which HCB is absorbed, and by using total hepatic porphyrins (rather than HCPs) as the indicator of the disorder. The experiments also showed that HCB-induced liver enlargement and neurotoxicity are not necessarily associated with the severity of porphyria.

Administration, Oral↗
PubMed1990

The effect of metals on the activity of L-phenylalanine hydroxylase.

The effects of 12 metals other than iron on the native (iron-containing) L-phenylalanine Hydroxylase from rat liver have been measured. The metals were tested in vivo at 10X and 100X molar excess. The effects generally are moderate deactivation of the enzyme; mercury and copper are particularly deactivating while rubidium is slightly activating. Complete restoration of the activity to the apoenzyme can only be achieved by iron(II). However, partial restoration is achieved by aluminium, thallium and cadmium. While restoration of activity under anaerobic conditions can also be achieved by iron(III), the increase in restoration ability of other transition metals under anaerobic conditions is not great. The restoration ability of rubidium increases, surprisingly, under anaerobic conditions.

Aerobiosis↗
PubMed1987

Interaction of divalent metal ions with normal and lead-inhibited human erythrocytic porphobilinogen synthase in vitro.

The effects of Zn2+, Hg2+, Cd2+, and Cu2+ on normal and lead-inhibited erythrocytic porphobilinogen synthase (PBG-S) were studied in vitro using human whole blood hemolysate. The results demonstrate that each of the divalent ions tested has a characteristic effect on the pH-activity relationship of PBG-S. The effects for a given ion are concentration- and pH-dependent. For Zn2+ these effects are also time-dependent. The results obtained provide an explanation for the contradictory reports of the action of some of the metals in vitro and indicate that future investigations of the effects of metals on an enzyme such as PBG-S are best performed over a judiciously selected pH range rather than at a single pH value. It is also shown that the metals studied will only have a significant effect on the proposed PBG-S activity ratio test for lead intoxication in instances of gross contamination of blood collection devices. The activation and/or inhibition of PBG-S and associate pH-activity profile changes resulting from interaction with the four metal ions tested were attributed to their respective affinity for the thiol and other groups at the active sites. The occurrence of a relatively specific pH optimum for PBG-S after interaction with each ion investigated remains unexplained.

Cadmium↗
PubMed1986

Tissue porphyrin pattern determination by high-speed high-performance liquid chromatography.

A rapid and sensitive method for the determination of porphyrin carboxylic acids in liver, kidney, and spleen by high-speed high-performance liquid chromatography is described. Porphyrins were extracted with recoveries greater than or equal to 98%, concentrated on disposable octadecylsilyl cartridges, and analyzed with a liquid chromatograph equipped with a 3 microns X 3 cm octadecylsilyl column and a fluorescence detector. Separation of di-, tetra-, penta-, hexa-, hepta-, and octacarboxylic acids was achieved within 5 min. The detection limits for uro, copro, and protoporphyrin were 20, 10, and 20 fmol, respectively.

Animals↗
PubMed1986

The mechanism of biooxidation of mercury.

The mechanism of oxidation of mercury by peroxidase is reported. The reaction is first order both in mercury and in peroxidase Compound I, and involves a one-step two-electron oxidation. The enzyme acts as a recycling chemical oxidant.

Hydrogen Peroxide↗
PubMed1986

Evaluation of the relationship between chemical and biological monitoring of low-level lead poisoning.

Blood lead levels, together with delta-aminolevulinic acid dehydratase activity determinations have been measured on rats dosed with up to 1000 ppm lead acetate in their drinking water for periods up to 5 weeks. Despite evidence of a compensation mechanism developing in the enzyme determinations, enzyme activity ratios, if properly chosen, still correlate reasonably well (r = 0.87) with blood lead levels. Activity ratios using data on the shoulders of pH-activity profiles (e.g. activity ratios of 6.4 and 7.2), however, give much less satisfactory correlations. These data provide a more stringent test of the chemical monitor-biological monitor correlation than has previously been possible.

Animals↗
PubMed1986

Chemical and biological monitoring of chronic lead poisoning in the rat. Implications to the assessment of hazard of low-level lead.

A study on rats of the effects of lead on delta-aminolevulinate dehydratase (ALA-D) activity, and its pH-dependent maximal enzyme activity is reported. Over a 5-week period, the lead burden and ALA-D activity in kidney, liver and brain are documented. Lead concentrations in the organs, expressed as micrograms/g protein are in the sequence kidney greater than liver greater than brain and reach essentially a constant level after 3 days of exposure. This is consistent with the existence of an efficient mechanism removing lead from these organs. Lead affects the ALA-D in all three organs by reducing the activity and shifting the pH of maximum enzyme activity to more acidic values. In common with the lead levels, the ALA-D activity does not deteriorate beyond the levels reached after 3 days of exposure. The existence of a mechanism removing lead from the organs is further supported in a recovery study on blood and kidney, in which both lead level and ALA-D activity return essentially to normal values after 7 days of no exposure to lead.

Animals↗
PubMed1986

The delay in polyhalogenated aromatic hydrocarbon-induced porphyria: the effect of diet preparation.

Porphyria development in female Wistar rats has been followed by dosing the animals with hexachlorobenzene (HCB) either dissolved in corn oil or as a solid mixed with the diet. It was found that the corn oil preparation resulted in much faster uptake of HCB into the liver, and much faster accumulation of liver porphyrins. Diet preparation is thus shown to be a major factor in determining whether the development of porphyria is associated with the delay phenomenon. Evidence is also presented suggesting that the neurological symptoms of porphyria are not caused by high porphyrin levels.

Administration, Oral↗
PubMed1986

The delay in polyhalogenated aromatic hydrocarbon-induced porphyria: mechanistic reality or methodological artefact?

Hepatic porphyria was induced in female Wistar rats exposed to dietary hexachlorobenzene (HCB) for 56 days. The well-documented several-week delay before liver total porphyrins became elevated was observed using conventional methods. However, a newly developed high-performance liquid chromatography (HPLC) technique revealed a much earlier response. Highly carboxylated porphyrins were found to increase soon after exposure to the toxicant. The long delay observed by total porphyrin analysis is shown to be due to the relatively small contribution of highly carboxylated porphyrins to the total porphyrin pool. It is concluded that the concept of a latent period is largely a methodological artefact which has confused the search for a fundamental understanding of chemically induced porphyria.

Administration, Oral↗
PubMed1985

Oxidation state analysis of mercury: evidence of the formation of mercurous ion in the oxidation of mercury by peracetic acid.

Both elemental mercury and the mercurous ion give rise to a signal in Cold-Vapor Atomic Absorption Analysis under non-reducing conditions. Distinction between these species based on the greater solubility of the mercurous ion in water is possible, and the potential of this analytical distinction is illustrated with the finding that oxidation of mercury by peracetic acid involves the mercurous state.

Acetates↗
PubMed1984

Comparison of the in vivo and in vitro effects of lead on the pH-activity relationship of human erythrocytic delta-aminolaevulinic acid dehydratase.

The effect of lead in vitro on the pH-activity relationship of human erythrocytic delta-aminolaevulinic acid dehydratase (delta-ALAD) and on the assessment of lead exposure with ratios of delta-ALAD activity measured at specific pH values was investigated. The addition of lead nitrate to whole blood at concentrations ranging from 0.40 to 8.1 mumole Pb2+/1, for periods of contact ranging from 16 h to 20 days at 4 degrees C, resulted in a time and dose dependent shift of the enzyme's pH optimum to a more acid value. The pH optimum shift obtained at raised lead concentrations or after long periods of contact at 4 degrees C, in both, closely approximated that observed in vivo. The loss of enzyme activity, however, was significantly less in vitro than that in vivo for similar whole blood lead concentrations. These findings indicate that the presence of trace amounts of lead in blood collection devices can seriously affect results obtained with the pH activity ratio method of assessing lead exposure.

Dose-Response Relationship, Drug↗
PubMed1983

Oxidation of mercury by catalase and peroxidase in homogeneous solution.

Experiments in homogeneous solution confirm previous findings that catalase is an effective oxidant for Hg0 leads to Hg2+. Peroxidase also effects the oxidation, and in both oxidations the co-substrate hydrogen peroxide is not essential for mercury oxidation, although the oxidation is enhanced by the presence of hydrogen peroxide.

Animals↗
PubMed1982

Biomonitoring lead exposure with delta-aminolevulinate dehydratase (ALA-D) activity ratios.

The occupational or environmental exposure of selected populations to lead, either alone or in combination with other metals, was monitored using ratios of the activity of the erythrocytic enzyme delta-aminolevulinate dehydratase. The results obtained have reaffirmed earlier findings that this test affords several significant advantages over the use of the enzyme's activity value measured at a set pH value and other types of activity ratios to assess lead exposure. Furthermore, the activity ratios' proven sensitivity, reliability, reproducibility, specificity and stability warrant that they be considered as viable alternatives to the more widely accepted diagnostic criteria of lead intoxication namely zinc protoporphyrin and lead levels in blood.

Adult↗
PubMed1981

Assay of delta-aminolaevulinate dehydratase in 10 microL of blood.

A method is presented for the assay of delta-aminolaevulinate dehydratase (EC 4.2.1.24) to be performed on 10 microL of whole blood. Results compare favorably with those obtained with an accepted method (J. Clin. Chem. Clin. Bio-chem. 12: 389-390, 1974) that involves use of 200 microL of blood.

Blood Chemical Analysis↗