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Biomedical subjects

A Van Langenhove

Publications and source records attributed to A Van Langenhove.

13 recordsLinked to original sources
PubMed1996

The LAURA multichannel cochlear implant in a true Mondini dysplasia.

A congenitally deaf child with bilateral Mondini dysplasias of the inner ear was successfully implanted with a LAURA multichannel cochlear prosthesis. This is the first report of a patient with a Mondini dysplasia in whom a LAURA multichannel cochlear prosthesis was successfully implanted. The cerebrospinal fluid leakage typically occurring after cochleostomy in similar patients was readily controlled, indicating that the deformity present was not a contra-indication for cochlear surgery. The audiological results obtained are described in detail. Since the internal unit of the LAURA prosthesis is very flexible, various speech processing strategies, such as continuous interleaved and phase-locked continuous interleaved strategies, can be tried and evaluated.

Child↗
PubMed1989

High-performance liquid chromatographic/mass spectrometric and high-performance liquid chromatographic/tandem mass spectrometric analysis of carbamate pesticides.

The thermospray ionization mass spectra of selected carbamate pesticides were obtained using both single-stage and triple-stage quadrupole mass spectrometry in conjunction with high-performance liquid chromatography. With the use of the single-quadrupole mass spectrometer and ammonium acetate as the mobile phase, enhanced sensitivity for the analytes of interest was obtained by monitoring the relatively intact [M + 1]+ or [M + 18]+ adduct ions. Further structural characterization of the carbamates was not readily obtainable owing to the lack of diagnostic bond cleavages. The single-stage quadrupole analyses were therefore complemented by triple-stage quadrupole analyses. Here, collisionally activated daughter ion spectra exhibited structure-specific fragmentations. In addition, the enhanced selectivity and specificity provided by tandem mass spectrometry allowed use of the technique as a rapid screening tool for carbamates without the need for the chromatographic separation step.

Carbamates↗
PubMed1987

5-Aminosalicylate: oxidation by activated leukocytes and protection of cultured cells from oxidative damage.

It has been postulated that oxygen radicals may play a role in the pathogenesis of inflammatory bowel disease. If so, then a drug like 5-aminosalicylate (5-ASA), which is used to treat such diseases, might work by interacting with oxygen-derived species. We found that activated mononuclear cells and activated granulocytes, as well as the products of the Fenton reaction, transformed [14C]5-ASA to a number of metabolites, among which we have characterized salicylate and gentisate. We also found that the lethal effect on cultured Chinese hamster ovary cells of adding either superoxide radical or hydrogen peroxide, components of the respiratory burst of activated white blood cells, was diminished by the addition of 100 micrograms/ml (0.65 mM) of 5-ASA. Thus, we have demonstrated that 5-ASA was oxidized by the oxidative burst of white blood cells and that 5-ASA protected cells from damage by oxygen-derived species, two findings which may offer an explanation for the role of 5-ASA in the treatment of inflammatory bowel disease.

Aminosalicylic Acids↗
PubMed1986

Characterization of O-glycosidically linked oligosaccharides of rat erythrocyte membrane sialoglycoproteins.

The carbohydrate units of the rat erythrocyte membrane sialoglycoprotein rSGP-4 [Edge, A. S. B., & Weber, P. (1981) Arch. Biochem. Biophys. 209, 697-705] have been characterized. All of the carbohydrate of this Mr 19,000 glycoprotein occurs in O-glycosidic linkage to the peptide; following alkaline borohydride treatment and chromatography on Bio-Gel P-2, sialic acid containing oligosaccharides terminating in N-acetylgalactosaminitol were obtained. Their structures were determined by compositional analysis, exoglycosidase digestions, alkaline sulfite degradation, and periodate oxidation. The oligosaccharides were characterized for molecular weight and linkage by direct chemical ionization and gas-liquid chromatography/mass spectrometry, respectively. The structures are proposed to be NeuAc alpha 2----3Gal beta 1----3GalNAc-ol, Gal beta 1----3(NeuAc alpha 2----6)GalNAc-ol, NeuAc alpha 2----3Gal beta 1----3(NeuAc alpha 2----6)GalNAc-ol, and NeuAc alpha 2----3Gal beta 1----3(NeuAc alpha 2----3Gal beta 1----4GlcNAc beta 1----6)GalNAc-ol. Two of the N-acetylglucosamine-containing hexasaccharides were present per molecule of rSGP-4 along with two trisaccharides and seven tetrasaccharides.

Animals↗
PubMed1985

Determination of polysaccharide linkage and branching by reductive depolymerization. Gas-liquid chromatography and gas-liquid chromatography-mass spectrometry reference data.

A series of partially methylated anhydro-D-alditol acetates has been prepared and analyzed by g.l.c. and g.l.c.-m.s. The reference compounds were obtained by reductive cleavage of permethylated and partially methylated standard methyl glycosides, and standard di-, tri-, and tetra-saccharides of known composition and linkage. Structural characterization included retention times on g.l.c. using DB-225 capillary columns and mass spectrometry in both the chemical- and electronionization modes. This compiled library allows further evaluation of the applicability of the reductive cleavage procedure for determining linkage or branching (or both) of new and more complex oligosaccharides. The technique has been applied to microgram amounts of a bacterial-membrane oligosaccharide and to a saccharide obtained from the urine of a mannosidosis patient. The procedures are simple, reliable, and applicable to small amounts of isolated biological materials.

Acetylation↗
PubMed1983

Synthesis of a cyclic fibrin-like peptide and its analysis by fast atom bombardment mass spectrometry.

For immunochemical purposes, a cyclic 12-peptide was synthesized to model the gamma-gamma-chain cross-link site in human fibrin. The model was based upon the structure proposed by Chen & Doolittle (Biochemistry (1971) 10, 4486-4491) which is characterized by two reciprocating epsilon-(gamma-Glu)Lys bonds between adjacent fibrin gamma-chains oriented in an antiparallel manner. To achieve the antiparallel orientation of the peptide backbone, Pro and Gly were inserted at positions 6 and 7 of the linear 12-peptide: acetyl-Gly-Glu-Gln-His-His-Pro-Gly-Gly-Gly-Ala-Lys-Gly-amide. The insertions were made to facilitate a reverse turn of the peptide during the last synthetic step, which was formation of the epsilon-(gamma-Glu)Lys bond between Glu at position 2 and Lys at position 11 with diphenylphosphorylazide. The resulting cyclic peptide represented half of the symmetrical cross-linked region in clotted fibrin. Following purification by HPLC, both linear and cyclic 12-peptides were analyzed by fast atom bombardment mass spectrometry. Abundant molecular protonated ions were observed for both peptides. In addition, the amino acid sequence of the linear peptide and the location of the epsilon-(gamma-Glu)Lys bond in the cyclized peptide could be verified.

Amino Acid Sequence↗
PubMed1982

Simultaneous determination of phenobarbital and p-hydroxyphenobarbital and their stable isotope labeled analogs by gas chromatography mass spectrometry.

A method suitable for pulse dosing studies is described for the quantitation by gas chromatography mass spectrometry of phenobarbital (5-ethyl-5-phenylbarbituric acid), p-hydroxyphenobarbital (5-ethyl-5(4-hydroxyphenyl)barbituric acid) and, simultaneously, their (13C15N2)-labeled analogs in serum and urine. Differently labeled analogs are used as internal standards (5-ethyl-5(2,3,4,5-tetradeuterophenyl)-2-(13C)barbituric acid for quantitation of phenobarbital, and 5-ethyl-5(4-hydroxy-3,5-dideuterophenyl)2-(13C)-1,3-(15N2)barbituric acid for p-hydroxyphenobarbital). In the procedure, the chemical work-up of the samples (1.0 ml for serum, 0.5 ml for urine) is based on an extractive methylation technique for the generation of the permethylated derivatives. The mass spectrometric measurement technique consists of repetitive scanning over a preselected mass region of the permethylated derivatives of the analytes as they elute from the gas chromatograph. The method is evaluated for serum concentrations ranging from 0.1-30.0 micrograms ml-1 for phenobarbital and 0.1-10.0 micrograms ml-1 for p-hydroxyphenobarbital, and for urine concentrations of both phenobarbital and p-hydroxyphenobarbital of 1.0-50.0 micrograms ml-1. Application of the method to determination of the pharmacological equivalence of phenobarbital and (13C15N2)-labeled phenobarbital in man is also demonstrated.

Carbon Isotopes↗
PubMed1982

Pharmacokinetic equivalence of stable-isotope-labeled and unlabeled drugs. Phenobarbital in man.

Stable isotope labeling of drugs has been used in human metabolism studies because it eliminates the risk of radiation exposure accompanying use of radioactive tracers. The labeled drug can be measured by gas-chromatographic mass spectrometry (GCMS). However, if reliable pharmacokinetic data are to be obtained, one has to be certain the rate of metabolism of labeled and unlabeled drug is the same, i.e., there is no kinetic isotope effect. To evaluate this for phenobarbital (PB), three humans were infused with a 1:1 mixture of phenobarbital and 1,3-15N2-2-13C-PB. Serum was collected at regular intervals. Concentrations of labeled and unlabeled phenobarbital were determined by GCMS. Within each subject, there was no trend for concentrations of labeled phenobarbital to be higher or lower than concentrations of unlabeled phenobarbital (P greater than 0.90 for all three subjects). There was no difference in the zero time intercepts, distribution and elimination time constants and half-lives, volumes of distribution and central compartment, or clearance of the two forms of phenobarbital. Thus, no isotope effect was found. Published data on other labeled drugs and the likelihood of encountering an isotope effect based on type of isotope and its location in the molecule are discussed.

Adult↗
PubMed1981

A gas chromatographic/mass spectrometric method for the simultaneous quantitation of 5,5-diphenylhydantoin (phenytoin), its para-hydroxylated metabolite and their stable isotope labelled analogs.

A stable isotope dilution method for the quantitation by GC-MS of 5,5-diphenylhydantoin, its major metabolite (5-(4-hydroxyphenyl)-5-phenylhydantoin), and, simultaneously, their stable isotope labelled analogs (5,5-diphenyl-2-(13)C-1,3-(15)N2-hydantoin and 5-(4-hydroxyphenyl)-5-phenyl-2-(13)C-1,3-(15)N2-hydantoin) is discussed and evaluated. 5,5-di-(pentadeuterophenyl)hydantoin and 5-(4-hydroxy-3,5-dideuterophenyl)-5-phenyl-2-(13)C-1,3(15)N2-hydantoin are used as internal standards. The chemical work-up procedure of serum (1.0 ml) and urine (0.5 ml) involves acid hydrolysis, extraction at pH 7.4 and permethylation of drug and metabolite analogs by extractive methylation. The mass spectrometric technique consists of repetitive scanning over the molecular ion region of the permethylated derivatives of the phenytoin and para-hydroxy metabolite analogs as they elute from the gas chromatograph. Molecular ion abundances are measured. Reproducibility, selectivity and linearity of the method are discussed in the light of the planned applications.

Carbon Radioisotopes↗
PubMed1981

Kinetic equivalence of stable-isotope-labeled and unlabeled phenytoin.

Stable isotope labeling (SIL) of a drug results in a higher molecular weight than that of the unlabeled drug. SIL tracer doses can be quantitated separately from unlabeled drug by gas chromatography-mass spectrometry (GC-MS) without exposing the patient to radiation. The higher molecular weight of SIL drug could cause a higher energy of activation for (and slowing of) metabolic reactions ("isotope effect"). To evaluate possible isotope effect, three dogs and three men were infused with a mixture containing equal amounts of SIL (2-13C-1,3-15N2) and unlabeled phenytoin (PHT). Plasma and urine were collected at regular intervals. Concentrations of SIL and unlabeled PHT and HPPH (the major metabolite of PHT) were determined by GC-MS. Within each subject there was no trend for concentrations of SIL PHT or HPPH to be higher or lower than concentrations of their unlabeled analogs (greater than 0.20 to 0.90). There was no difference in the distribution and elimination half-lifes (t 1/2s), volume of distribution, volume of central compartment, or clearance of the two forms of PHT. Thus, no isotope effect was found.

Animals↗
PubMed1980

A mass spectrometric method for the determination of stable isotope labeled phenytoin suitable for pulse dosing studies.

A gas chromatographic mass spectrometric method has been developed for the determination in biological fluids of phenytoin (5,5-diphenylhydantoin), 5-(4-hydroxyphenyl)-5-phenylhydantoin (the major metabolite of phenytoin), and simultaneously, their stable isotope labeled analogs [5,5-diphenyl-2-13C-1,3-15N2-hydantoin and 5-(4-hydroxyphenyl)-5-phenyl-2-13C-1,3-15N2-hydantoin]. Quantification was achieved by an isotopic dilution technique: 5,5-di(pentadeuterophenyl)-hydantoin and 5-(4-hydroxy-3,5-dideuterophenyl)-5-phenyl-2-13C-1,3-15N2-hydantoin were used as internal standards. Molecular ion abundances of the permethylated derivatives were measured using a limited mass range repetitive scanning technique. The method is accurate, selective, reproducible and linear for analysis of 1.0 ml of serum and 0.5 ml of urine samples at the expected concentrations of drug (serum: 0.1-30.0 micrograms ml-1) and metabolite (serum: 0.1-10.0 micrograms ml-1; urine: 5.0-200.0 micrograms ml-1). The pharmacological equivalence of labeled and unlabeled phenytoin is demonstrated for a human volunteer. The results are discussed in the light of the further applications of the method, i.e. determination of the pharmacokinetics of a pulse dose of the labeled drug administered to patients who are taking a steady state dose of the unlabeled drug.

Animals↗
PubMedDate not supplied

Isotope effects: definitions and consequences for pharmacologic studies.

The use of stable isotope-labeled compounds for pharmacologic studies requires careful consideration of the nature of the stable isotope label (2H, 13C, 15N, 18O) and its position of incorporation in the molecule. When deuterium is used, improper positioning can lead to significant primary isotope effects. Primary isotope effects occur when the breaking of the bond to the heavy isotope is the rate-limiting step in a reaction (or metabolic transformation). A reaction will proceed slower for the molecule with the heavy isotope label because of the mass difference between the light and the heavy isotope. In addition to these primary isotope effects, smaller but nevertheless important secondary isotope effects, physicochemical isotope effects, active hydrogen/deuterium exchange, or isotope effects associated with either the enzyme-catalyzed biotransformation or the mass spectrometric ionization and fragmentation can be operative. In mechanistic studies, isotope effects are used to their advantage; however, in pharmacokinetic studies, the occurrence of isotope effects can lead to grossly misleading biologic and analytic results: the metabolism of the drug will differ when 'in vivo' isotope effects are operative, and isotope effects occurring during the analysis procedure will obscure the true metabolic profile of the drug.

Animals↗