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F A De Wolff

Publications and source records attributed to F A De Wolff.

16 recordsLinked to original sources
PubMed2001

Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity.

1. The interindividual variation and enantioselectivity of the in vitro styrene oxidation by cytochrome P450 have been investigated in 20 human microsomal liver samples. Liver samples were genotyped for the CYP2E1*6 and CYP2E1*5B alleles. 2. Kinetic analysis indicated the presence of at least two forms of styrene-metabolizing cytochrome P450. The enzyme constants for the high-affinity component were subject to appreciable interindividual variation, i.e. Vmax1 ranged from 0.39 to 3.20 nmol mg protein(-1) min(-1) (0.96+/-0.63) and Km1 ranged from 0.005 to 0.03 mM (0.011+/-0.006). Inhibition studies with chemical inhibitors of CYP2E1, CYP1A2, CYP2C8/9 and CYP3A4 demonstrated that CYP2E1 was the primary enzyme involved in the high-affinity component of styrene oxidation. No relationship between the interindividual variation in Vmax1 and Km1 and the genetic polymorphisms of the CYP2E1 gene was found. 3. Cytochrome P450-mediated oxidation of styrene demonstrated a moderate enantioselectivity, with an enantiomeric excess (ee) of (S)-styrene oxide of 15% (range 4-27%) at low styrene concentration and an ee of (R)-styrene oxide of 7% (range -11 to +22%) at high styrene concentration. This points towards the involvement of at least two cytochrome P450, with different enantioselectivities. 4. The data indicate that cytochrome P450-mediated styrene oxidation is subject to considerable interindividual variation, but only to a moderate product enantioselectivity.

Adult↗
PubMed1999

Comparative in vivo study of iodine-123-labeled beta-CIT and nor-beta-CIT binding to serotonin transporters in rat brain.

Both iodine-123-labeled beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) and nor-beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) have shown to be suitable radioligands for imaging serotonin (5-HT) transporters. [(123)I]nor-beta-CIT has the highest in vitro affinity for 5-HT transporters among beta-CIT analogs reported so far. However, no direct comparison-studies of these two radiotracers as to their in vivo binding to 5-HT transporters have been reported so far. Therefore, it is still unclear which of the two radiotracers is more suitable for single photon emission computed tomography (SPECT) imaging of 5-HT transporters. The purpose of this study was to compare directly in a controlled design the in vivo [(123)I]beta-CIT and [(123)I]nor-beta-CIT binding to 5-HT transporters under the same conditions in rats with the focus on brain kinetic characteristics by means of a two-compartment analysis. We observed that [(123)I]beta-CIT has a higher binding potential and faster kinetics for 5-HT transporters than [(123)I]nor-beta-CIT, suggesting that [(123)I]beta-CIT may be a more suitable radioligand than [(123)I]nor-beta-CIT for imaging 5-HT transporters with SPECT.

Animals↗
PubMed1998

Comparison of enhanced elimination of bismuth in humans after treatment with meso-2,3-dimercaptosuccinic acid and D,L-2,3-dimercaptopropane-1-sulfonic acid.

Two groups of 12 human volunteers, who had been treated with colloidal bismuth subcitrate, because of Helicobacter pylori-associated gastritis, participated in the study. The patients received a single dose of meso-2,3-dimercaptosuccinic acid (DMSA) or D,L-2,3-dimercaptopropane-1-sulfonic acid (DMPS) at a dose of 30 mg kg-1 in a randomized single blind study. In contrast to DMPS, increasing concentrations of bismuth in blood were observed during the first 4 h after intake of DMSA. In urine, both chelators induced a 50-fold increase in urinary bismuth excretion compared with the control urines. The treatment was well tolerated. The results indicate that both DMSA and DMPS effectively increase the elimination of bismuth in human urine. Consequently, both chelators may be of benefit in the treatment of patients with bismuth intoxication.

Adult↗
PubMed1988

Serum copper and zinc and the risk of death from cancer and cardiovascular disease.

To investigate the association of serum copper and zinc with mortality from cancer and cardiovascular disease, the authors performed a case-control analysis of data obtained in a Dutch prospective follow-up study. Cancer (n = 64) and cardiovascular disease (n = 62) deaths and their matched controls were taken from a cohort of 10,532 persons examined in 1975-1978. Trace elements were measured in baseline serum samples, which had been stored during the six to nine years of follow-up. The adjusted risk of death from cancer and cardiovascular disease was about four times higher for subjects in the highest serum copper quintile (greater than 1.43 mg/liter) compared with those with normal levels. The excess mortality observed in subjects with low copper status suggests a U-shaped relation. No significant change in the risk of death from cancer and cardiovascular disease was found for subjects with low or high baseline levels of serum zinc. However, a protective effect of a high zinc status on the risk of cancer and cardiovascular disease is compatible with the data. For definitive conclusions, analysis of larger prospective data sets is recommended.

Aged↗
PubMed1987

The effect of di- and trivalent iron on the intestinal absorption of aluminum in rats.

The effect of iron (Fe) on the intestinal absorption of aluminum (A1) was studied in an in situ perfusion system of rat small intestine in combination with systemic and portal blood sampling. The gut was perfused with media containing 0.0, 10.0, 15.0, 20.0, and 25.0 mmol/liter Al chloride and 5 mmol/liter Fe(II) or Fe(III) chloride at pH 3.0. Neither luminal disappearance nor intestinal absorption of A1 were affected by Fe(III). Fe(II), however, enhanced luminal disappearance and reduced absorption of Al.

Aluminum↗
PubMed1984

Determination by flameless atomic absorption of aluminium in serum and hair for toxicological monitoring of patients on chronic intermittent haemodialysis.

Determination of aluminium in serum of patients on chronic intermittent haemodialysis is of paramount importance in the prevention or early diagnosis of aluminium intoxication. We present a new method based on flameless atomic absorption spectroscopy, in which the serum matrix is destroyed by oxygen. A comparison has been made between the described method and another procedure which is used in the Laboratory of Toxicology in Ghent, with favourable results. In addition, a method is presented for the determination of aluminium in hair, in which special attention has been paid to the cleaning of the hair samples prior to destruction. As yet it cannot be concluded whether aluminium concentrations in hair give a better representation of the body burden than serum levels do.

Aluminum↗
PubMed1983

Intraindividual and interindividual variability in 8-methoxypsoralen kinetics and effect in psoriatic patients.

Our purpose was to investigate the origin of intraindividual variation in comparison with interindividual variation of 8-methoxypsoralen (8-MOP) kinetics in different body fluids. The clinical test in therapy with psoralens and ultraviolet A (PUVA), expressed as the minimal phototoxic dose (MPD), was performed to establish a possible connection between biologic effect and kinetics of 8-MOP. The MPD and 8-MOP kinetics in serum and suction blister fluid (sbf) were determined in 18 psoriatic patients on PUVA therapy in 4 test days spread over a 7-mo period. Evidence showed that interindividual fluctuations are caused by differences in intrinsic clearance (Cl). Interindividual variations are large in comparison with intraindividual variations. A correlation was found among maximal serum concentrations, Cls, MPDs, and concentrations in sbf. In clinical practice the maximal serum concentration, determined in blood samples taken at 1, 2, and 3 hr after 8-MOP ingestion, is indicative of the rate of 8-MOP metabolism and thus of the biologic effect in the patient.

Dose-Response Relationship, Radiation↗
PubMed1982

Influenced of food on the kinetics of 8-methoxypsoralen in serum and suction blister fluid in psoriatic patients.

The influence of food on the kinetics of 8-methoxypsoralen (8-MOP) in serum and suction blister fluid was evaluated in a cross-over study in 19 psoriatic patients under PUVA treatment. The peak serum concentration of 8-MOP was reached 1.5 h after ingestion on an empty stomach, and in suction blister fluid the maximum concentration was already present in the first sample taken after 2 h, the time when UVA radiation was given. The postprandial kinetics of 8-MOP in serum and suction blister fluid differed, the highest levels being reached, respectively, at 2.4 and 3 h after intake, i.e. in both body fluids after irradiation had started. The side effects of 8-MOP, such as nausea and dizziness, in the two groups were similar. The present results indicate that to optimize the therapeutic effect of PUVA in individual patients, 8-MOP should be given on an empty stomach.

Blister↗
PubMed1982

Difference in bioavailability between two brands of 8-methoxypsoralen and its impact on the clinical response in psoriatic patients.

1 Several 8-methoxypsoralen (8-MOP) preparations are now available for photochemotherapy of psoriasis. To assess differences in clinical response two preparations marketed in The Netherlands, Oxsoralen capsules (Elder) and Meladinine tablets (Basotherm), were given to eight psoriatic patients. Serum concentrations and the minimal phototoxic dose (MPD) as a measure for clinical response were determined. 2 Bioavailability and serum peak concentrations were significantly higher for Maladinine in all patients and the MPD value favoured Maladinine in 5 of the 8 patients. The mean time of the serum peak concentrations was 1 h earlier for Maladinine than for Oxsoralen. 3 These findings are relevant not only for the choice of drug in individual patients but also for comparison of the results of multicentre trials performed in different parts of the world.

Biological Availability↗
PubMed1978

Improved micromethod for determination of underivatized clonazepam in serum by gas chromatography.

We describe a gas-chromatographic micromethod, with use of a solid injection system and an electron capture detector, for determination of underivatized clonazepam in serum. Vigorous mixing of 100 microliter of serum with 20 microliter of borate buffer (pH 9.0) and 100 microliter of a cyclohexane/dichloromethane mixture (4/6 by vol) containing methyl nitrazepam as internal standard suffices to extract 86% of the clonazepam into the organic layer. We obtained a linear response curve for clonazepam in serum in the concentration range 5 to 150 microgram/liter. The lowest detectable concentration by our method is about 1 microgram/liter of serum. Interference by several anticonvulsant drugs, metabolites, and related compounds was investigated. The assay is simple, rapid, and suitable for clinical routine determination of clonazepam in serum in therapeutic concentrations. We illustrate the steady-state concentration of clonazepam in serum during chronic oral administration to 28 patients.

Benzodiazepinones↗
PubMed1976

Determination of quinidine in human serum in the presence of diuretics.

A new method for the determination of quinidine in human serum by fluorometry is described. The interference of triamterene encountered with other methods is greatly reduced, whereas a number of other diuretics do not interfere at all. The specificity is based on quenching of the fluorescence of cinchona alkaloids by chloride ions. The method has good reproducibility and linearity, and gives a recovery of 98%. A serum sample of 0.1 ml is sufficient for the assay. Comparison with two other methods showed that this procedure yields the total amount of cinchona alkaloids present in serum, which makes it extremely useful for routine clinical analysis.

Chlorides↗
PubMed1975

Stimulation of vitamin D-dependent Ca-ATPase and of intestinal caldium absorption by diphenylhydantoin.

The effects of diphenylhydantoin (DPH) and ouabain were studied in vitro on Mg-ATPase, Ca-ATPase and alkaline phosphatase (AlPase) in isolated brush borders from rat jejunum, and in vivo on intestinal calcium absorption. Vitamin D-deficient, -repleted and normal rats were used in this study. Repletion of deficient animals with vitamin D restored Ca-ATPase activity and AlPase activity partly. Ca-absorption was normalized by repletion with the vitamin. DPH greatly stimulated Ca-ATPase activity in vitro and Ca-absorption in vivo, but it inhibited AlPase activity. Mg-ATPase was not affected by vitamin D, nor by DPH. Ouabain had no consistent effect on any of the parameters studied. It was concluded that Ca-ATPase, and not AlPase, is involved in the transport of calcium through the jejunal microvillous membrane, and that DPH enhances Ca-absorption by activation of Ca-ATPase.

Adenosine Triphosphatases↗
PubMedDate not supplied

Environmental lead and renal effects in children.

The effect of lead on five renal-effect parameters was studied in 151 children (i.e., 3-6-y-olds) who resided at different distances from a lead smelter in Baia Mare, Romania. A relationship was found between concentration of lead in blood (mean +/- standard deviation: 342 +/- 224 microgram/l) and the activity of N-acetyl-beta-D-glucosaminidase in urine, as demonstrated by a 14% increase of N-acetyl-beta-D-glucosaminidase per 100 micrograms/l blood lead that was indicative of renal tubular damage. No relationship was found between blood lead level and the renal-effect parameters albumin, alpha-1-microglobulin, retinol binding protein, or alanine aminopeptidase in urine. Cadmium in blood was not elevated. It is well known that N-acetyl-beta-D-glucosaminidase is a sensitive parameter for renal effects, resulting from lead exposure in adults and from diabetes and nephrotoxic medicines in children. This study is the first to demonstrate an effect of environmental lead exposure on renal integrity in children.

Acetylglucosaminidase↗