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F A de Wolff

Publications and source records attributed to F A de Wolff.

At least 55 records · Page 3Linked to original sources
PubMed1992

Increased metallothionein in the liver and kidney of patients with amyotrophic lateral sclerosis.

To evaluate the putative role of metals and trace elements in the pathogenesis of classic amyotrophic lateral sclerosis, we studied the metallothionein levels in liver and kidney samples obtained at autopsy from 24 patients with amyotrophic lateral sclerosis and 18 controls. To assay metallothioneins and copper, cadmium, and zinc bound to metallothioneins, we used high-performance liquid chromatography directly coupled to flame atomic absorption spectrometry. Total cadmium, zinc, and copper concentrations were determined separately with the use of graphite furnace atomic absorption spectrometry with Zeeman background correction. The median liver metallothionein level was 60.3 mg/kg (range, 9 to 318 mg/kg) in the patients with amyotrophic lateral sclerosis and 12.6 mg/kg (range, 0 to 104.5 mg/kg) in the controls. In the kidney, median metallothionein levels were 126.9 mg/kg (range, 44 to 387 mg/kg) in the patients with amyotrophic lateral sclerosis and 64 mg/kg (range, 13.1 to 187 mg/kg) in the controls. Total zinc, cadmium, and copper concentrations, as measured by atomic absorption spectrometry, were not significantly different in patients vs controls. Our finding of elevated metallothionein levels in organs from patients with amyotrophic lateral sclerosis may indicate an increased exposure to metals.

Adolescent↗
PubMed1992

Increased neurotoxicity of arsenic in methylenetetrahydrofolate reductase deficiency.

A 16-year-old girl from Surinam presented with mental deterioration and severe paraparesis with areflexia and bilateral Babinski signs. Laboratory examination showed a hyperhomocysteinemia that was caused by 5,10-methylene-tetrahydrofolate reductase (MTHFR) deficiency. In addition, urine samples contained large amounts of arsenic. An open bag with the pesticide copper acetate arsenite was found to be the source of exposure. In remethylation defects such as MTHFR deficiency, the concentration of methyldonors is severely reduced. As arsenic is detoxified by methylation, we suggest that the MTHFR deficiency in this girl might explain the fact that of all family members exposed to arsenic, only she developed severe clinical signs and symptoms of arsenic poisoning.

Adolescent↗
PubMed1992

Accumulation of aluminium in rat liver: association with constituents of the cytosol.

Aluminium (Al) accumulation occurs in the liver of renal patients and in patients on parenteral nutrition. Human hepatotoxicity is not proven. The role of the liver in storage and biotransformation of Al and in development of osteo- and neurotoxicity is not clarified as yet. The aim of the present investigation was to study the storage of Al in total liver and in subcellular liver fractions, and its association with soluble cytosolic molecular species. Therefore, rats were loaded with Al prior to liver fractionation by ultracentrifugation, and equilibrium gel filtration chromatography of the cytosol, using a previously described method for Al speciation in serum. Al accumulated dose-dependently in liver and subcellular liver fractions, the lowest levels occurring in the cytosol. A dose-dependent elevation of Al in the blood was also observed. Gelfiltration of the cytosol indicated that Al was associated with a low molecular weight form which was not a citrate complex, and a high molecular weight form, which was larger than transferrin. No induction of and association with metallothionein occurred.

Aluminum↗
PubMed1992

Development of a therapeutic procedure for bismuth intoxication with chelating agents.

Although bismuth poisoning is still a rare phenomenon, the increasing use of bismuth-containing drugs warrants a systematic approach to the treatment of bismuth overdose. An effective method of enhancing the elimination of toxic amounts of bismuth from the body has not been reported. Therefore we performed a study to select the best chelator to treat bismuth poisoning. Dimercaprol (BAL), meso-2,3-dimercaptosuccinic acid (DMSA), D,L-2,3-dimercapto-propane-I-sulfonic acid (DMPS), D-penicillamine (D-PEN), N-acetyl-D,L-penicillamine (Ac-PEN), thiopronine (TP), sodium-calcium edetate (EDTA) and deferoxamine (DFO) were tested with an in vitro model of equilibrium dialysis and an in vivo model of rats poisoned with bismuth. The rats (n = 6 per substance tested) were treated with the chelators in intraperitoneal doses of 250 mumol/kg.day for 3 consecutive days. Afterward, tissue and blood samples were collected. Bismuth concentrations were determined with electrothermal atomic absorption spectrometry in serum, buffer, urine, blood, brain, kidney, liver, spleen, and bone. Using in vitro results, we constructed a ranking of chelating agents; it appeared not to predict the in vivo results. The dithiol compounds (DMPS, DMSA and BAL) were effective in most organs (especially in kidney and liver) resulting in a higher elimination of bismuth in urine by DMPS and BAL. BAL was the only chelator effective in lowering brain bismuth concentrations, whereas treatment with EDTA resulted in increased brain bismuth levels. For D-PEN and DFO, no effects could be demonstrated. For clinical practice, DMSA and DMPS may well be the chelators of choice; the application of BAL should be reserved for very severe cases of poisoning because of its own toxicity.

Animals↗
PubMed1991

Analysis of bismuth in serum and blood by electrothermal atomic absorption spectrometry using platinum as matrix modifier.

Bismuth-containing medicines have been used for years, but there is a lack of clinically applicable methods for measuring bismuth in body fluids. We describe a sensitive, accurate and precise method for analysis of bismuth in blood and serum, which is suitable both for monitoring purposes and for further investigations into the biokinetics and safety of bismuth. Bismuth was quantitated with electrothermal atomic absorption spectrometry with Zeeman background correction. In the furnace programme a cool-down step was introduced and platinum was used as a matrix modifier. Recovery for 40 micrograms/l is 93.7 +/- 4.6% (mean +/- SD) from serum and 92.8 +/- 5.4% from blood; within-day precision (n = 10) at 40 micrograms/l is 3.2% for serum and 4.2% for blood. Day-to-day precision at 40 micrograms/l (n = 10) was 4.5% for serum and 4.0% for blood. The detection limit is 0.7 microgram/l for serum and 1.0 microgram/l for blood. Blood samples have to be collected in glass tubes and stored at -20 degrees C.

Animals↗
PubMed1991

Renal damage in mice after sequential cisplatin and irradiation: the influence of prior irradiation on platinum elimination.

Doses of 4-6 mg kg-1 c-DDP given 6 months before renal irradiation caused only a modest increase in functional radiation damage (DEF 1.1). These effects could be explained by additive toxicities and the damage was much less than when c-DDP was given 3-6 months after irradiation. Pharmacokinetic studies did not demonstrate any decrease in the rate of platinum elimination after previous low-dose renal irradiation.

Animals↗
PubMed1991

Biological effect monitoring of occupational exposure to 1,3-dichloropropene: effects on liver and renal function and on glutathione conjugation.

A prospective study was performed in the Dutch flower bulb culture to investigate the possible effects of subchronic exposure to the soil fumigant 1,3-dichloropropene (DCP) on liver and kidney function and on glutathione conjugation capacity in blood. Urine spot samples and venous blood samples from 14 workers applying DCP (applicators) were taken at the start of the season in July, and after the season in October. The parameters of liver function measured were: alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and total bilirubin (conjugated and unconjugated). Total bilirubin was significantly decreased from 9.5 before to 7.0 mumol/l after the season. In combination with an increase in serum gamma-glutamyltranspeptidase activity from 12.5 to 19.5 U/l this indicates moderate hepatic enzyme induction. To study renal function, creatinine and beta 2-microglobulin in serum, and beta 2-microglobulin, albumin, alanine aminopeptidase, beta-galactosidase, and retinol binding protein in urine were measured. The glomerular function parameters albumin in urine and creatinine in serum changed significantly during the season: albumin concentration increased from 5.2 to 7.6 mg/l, whereas creatinine concentration [corrected] decreased from 93.0 to 87.5 mumol/l. The tubular function parameter retinol binding protein also increased in concentration from 20.0 to 26.9 micrograms/l. Therefore, a subclinical nephrotoxic effect of subchronic exposure to DCP cannot be excluded. Effects on glutathione conjugation capacity were studied by measuring erythrocyte glutathione S-transferase activity and blood glutathione concentrations. The activity of glutathione S-transferase in erythrocytes was significantly decreased from 4.7 before to 3.3 U/g haemoglobin after the season. The same was true for the blood glutathione concentrations, which decreased from 0.93 to 0.82 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Thioether excretion in urine of applicators exposed to 1,3-dichloropropene: a comparison with urinary mercapturic acid excretion.

The excretion of thioethers in urine of applicators occupationally exposed to the soil fumigant 1,3-dichloropropene (DCP) was determined by the thioether assay. The mercapturic acid metabolite of E-1,3-dichloropropene, N-acetyl-S-(E-3-chloropropenyl-2-)-L-cysteine (E-DCP-MA), was the reference compound in the thioether assay. The mean recovery of E-DCP-MA was 58.5% (coefficient of variation (CV) 9%, n = 4). In non-exposed men mean background of urinary thioethers was 6.05 mmol SH/mol creatinine (n = 56). In applicators exposed to soil fumigants containing DCP, urinary excretion of thioethers followed first order elimination kinetics. Urinary half lives of elimination of thioethers were 8.0 (SD 2.5) hours based on excretion rates and 9.5 (SD 3.1) hours based on creatinine excretion. The urinary half life of elimination of thioethers was almost twofold higher compared with half lives of elimination of the mercapturic acids of Z- and E-1,3-dichloropropene. The post- minus pre-shift thioether concentrations in urine and the cumulative urinary thioether excretions correlated well with exposure to DCP. In urine samples the mean thioether concentration was 1.38 higher than mean DCP mercapturic acid concentration. This suggests the presence of unidentified thioether metabolite(s) due to exposure to soil fumigants containing DCP. According to the present data, an eight hour time weighted average exposure to the Dutch occupational exposure limit of 5 mg/m(3) DCP results in a post- minus pre-shift thioether concentration of 9.6 mmol SH/mol creatinine (95% confidence interval (95%CI) 7.4-11.8 mmol SH/mon creatinine) and in a cumulative thioether excretion of 139 micromol SH (95% CI 120-157 micromol SH). It is concluded that the thioether assay can be used to assess comparatively high levels of exposure to DCP.

Acetylcysteine↗
PubMed1990

Analysis of phenprocoumon and its hydroxylated and conjugated metabolites in human urine by high-performance liquid chromatography after solid-phase extraction.

The anticoagulant phenprocoumon is mainly metabolized in humans to hydroxylated metabolites and their glucuronides. A method is described for the determination of phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon, 7-hydroxyphenprocoumon, and their glucuronide and sulphate conjugates in human urine. Reversed-phase high-performance liquid chromatography is performed after selective extraction with disposable quaternary amine columns of untreated, and beta-glucuronidase- or sulphatase-treated urine samples. Urinary excretion data are presented for total, glucuronidated, sulphated and free phenprocoumon, 4'-hydroxyphenprocoumon, 6-hydroxyphenprocoumon and 7-hydroxyphenprocoumon in twelve patients after an average daily dosage of 1.3-4.2 mg phenprocoumon.

Adult↗
PubMed1990

Cytochrome P450 and Parkinson's disease. Poor parahydroxylation of phenytoin.

Phenytoin-parahydroxylation capacity was determined in 24 patients with Parkinson's disease (PD) and 17 controls. Different function of the phenytoin-metabolizing cytochrome P450 subsystem was found in 6 patients, but in none of the controls. These results add to previous studies suggesting a relation between the pathogenesis of PD and the function of cytochrome P450 subsystems.

Aged↗
PubMed1990

Aluminium binding to serum constituents: a role for transferrin and for citrate.

The binding of aluminium in rat serum was studied. Rats were loaded intraperitoneally with different doses of aluminium(III)chloride 4 times during one week, before being killed by cardiac puncture. One ml of serum was applied to a Sephacryl S-200 SF column and 70 fractions were collected. In the collected fractions, the distribution of aluminium was measured and compared with the concentrations of total protein, transferrin, and citrate. The presence of a high molecular weight aluminium-complex in serum is confirmed. Although a possible role for albumin cannot be excluded, it is most likely that transferrin plays a role as a carrier for biological transport of aluminium in plasma. In addition to transferrin, aluminium was shown to be associated with citrate in serum, resulting in a low-molecular weight complex. It is postulated that citrate acts as a chelator for aluminium, and that the Al/citrate complex in serum may play an important role in intracellular accumulation, and hence the toxicity, of aluminium.

Aluminum↗
PubMed1990

Improved method of analysis for aluminum in brain tissue.

To improve the accuracy and precision of the assay of aluminum in brain tissue, we modified for application to brain samples from rats and humans the wet-digestion method of Trapp et al. (Biol Psychiatry 1978; 13:709-18), established the contribution of contamination, and examined the effect of precipitation of nonoxidizable fatty residues on the analysis. Specifications of the modified assay are a detection limit of 5 ng of aluminum per gram wet weight of brain tissue, a within-day CV of 4.8% (24.3 microgram/L; n = 10), and a day-to-day CV of 5.5% (27.8 micrograms/L; n = 5). Contamination, a systematic error in the analysis of aluminum, was established to be 13 ng (SD = 7.9 ng; n = 8) per tube. The presence of indestructible fatty residues did not affect the accuracy of the method. Application of the method to brain hemispheres of nonexposed rats revealed an aluminum content of 0.041 mg/kg wet weight of tissue (SD = 0.032 mg/kg; n = 8). The aluminum content in human cortex samples, consisting of gray and white matter, ranged from 0.14 to 0.22 mg/kg. Modification of the wet-digestion method resulted in a reliable, simple sample pretreatment before analysis for aluminum in brain tissue. The extent of the aluminum contamination must be controlled by including appropriate blanks.

Adult↗
PubMed1989

Intestinal absorption of aluminum in rats: stimulation by citric acid and inhibition by dinitrophenol.

The effects of citric acid and dinitrophenol on the mucosal uptake of aluminum (Al) and its appearance in the portal and systemic blood were investigated to establish the energy dependence of these processes. Therefore, the rat small intestine was perfused in situ with media containing 20 mmol Al/liter, with or without 5 mmol citric acid/liter, and with or without 0.1 mmol/liter of the metabolic inhibitor DNP. It is concluded that (1) the appearance of Al in systemic blood depends on the mucosal Al uptake after perfusion and the systemic blood level before perfusion and (2) citric acid stimulates and DNP inhibits both mucosal uptake and Al absorption in situ.

Aluminum↗