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Biomedical subjects

I D Wilson

Publications and source records attributed to I D Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Solid phase extraction chromatography and NMR spectroscopy (SPEC-NMR) for the rapid identification of drug metabolites in urine.

The use of solid phase extraction onto disposable columns containing a C18 bonded silica gel provides a rapid and simple procedure for the removal of interfering endogenous components from urine samples containing drug metabolites prior to detection and identification by (1)H NMR spectroscopy. In addition, these columns can be used to retain and concentrate the compounds of interest, thus improving the effective sensitivity of the NMR detection method. Using simple step gradients chromatographic separations can be performed, and metabolites may be rapidly fractionated. This approach (solid phase extraction chromatography with NMR or SPEC-NMR) utilises the multiparametric metabolite detection facility of a Fourier transform NMR spectrometer to monitor a chromatographic separation, as such it has some of the beneficial properties of a directly linked liquid chromatography-NMR system without any of the disadvantages. Applications of the SPEC-NMR method in the investigation of drug metabolism are illustrated here by reference to excretion studies on the drugs ibuprofen, paracetamol, aspirin, oxpentifylline and naproxen.

Journal Article↗
PubMed1988

Application of high resolution 1H-NMR spectroscopy to the detection of penicillamine and its metabolites in human urine.

Preliminary studies on the use of high resolution 1H-NMR spectroscopy for the detection of the thiol drug penicillamine and its metabolites in human urine are described. The technique is rapid, simple and requires minimal sample pretreatment. Application of NMR to the qualitative analysis of penicillamine in urine is illustrated by penicillamine disulphide formation from penicillamine following spiking into human urine and the detection of penicillamine, penicillamine disulphide and penicillamine-cysteine disulphide (following oral administration of the drug to patients).

Cysteine↗
PubMed1987

The metabolism of [14C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in man.

[14C]-N-Ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvaton) was administered orally at a dose of 2 mg per subject to eight healthy male volunteers. Maximal plasma concentrations of total radioactivity of 32.4 +/- 6.4 ng equiv./ml (mean +/- S.D.) were detected compared with maximum plasma concentrations of 14.1 +/- 5.9 ng/ml (mean +/- S.D.) of molsidomine. In both cases these were attained at 0.5 h after dosing. From the peak, concentrations of parent drug fell rapidly with a half-life of 1.25 +/- 0.38 h (mean +/- S.D.). In contrast, total radioactivity declined more slowly with a terminal half-life of 138 +/- 42.7 h (mean +/- S.D.). The bulk of the radiolabel was rapidly excreted as metabolites in the urine, with over 85% of the dose recovered in the first 24 h. The main urinary radiolabelled metabolites appeared, from chromatographic evidence, to be similar to those previously identified in animals, namely N-morpholinosydnonimine, N-cyanomethylamino-N-(2'-hydroxyethyl)glycine and (N-cyanomethylenamino-2-aminoethoxy)-acetic acid.

Administration, Oral↗
PubMed1986

Component quantitation of rat ileum.

Precise and accurate light microscopic morphometric analyses of biological tissue can be achieved utilizing component quantitative techniques. Component quantitation refers to measurements of the relative volumes of components in tissue sections. Such an assessment is predicated upon the mathematically verifiable assumption that direct quantitative relationships exist between an aggregate of profiles of a component contained per unit area in multiple sections and an aggregate of profiles contained per unit volume. A linear scanning device (micrometer component quantitator) was initially employed for quantitative analyses of pancreas. This quantitative technique has subsequently been applied to normal rat ileum conventionally processed for light microscopy, and the requisite sampling parameters have been defined. An identical technique was then applied to physiologically manipulated rat ileum--a gnotobiotic group, a group with ileal self-filling blind loops, and a group with ileal Thiry-Vella loops. The results observed support the following conclusions. The volume percentage of the various components of the rat ileal wall of control animals was defined utilizing the micrometer component quantitator. Hypertrophy of the ileal muscularis externa within the ileal self-filling blind loops was observed, probably secondary to mechanical obstruction. Atrophy of the ileal epithelium within the gnotobiotic group and within the Thiry-Vella loops was observed, possibly secondary to an altered endogenous microbial flora. Recognition of quantitative variations among the histological components of the intestinal wall in association with physiological manipulations or pathologic states was (is) feasible by utilization of this component quantitative technique.

Animals↗
PubMed1986

The metabolism of [14C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in laboratory animals.

[14C]N-Ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvaton) was found to be extensively metabolized following oral dosing to rat and dog and intravenous dosing to rabbit. The majority of the radiolabel was rapidly excreted in the urine with the main radiolabelled components being characterized as acidic metabolites resulting from oxidative metabolism of the morpholine ring. A new metabolite, (N-cyanomethylenamino-2-aminoethoxy)-acetic acid, was identified and shown to be a major component of the 14C-labelled urinary metabolites in all three species. However, the previously identified metabolite, N-cyanomethylenaminomorpholine-2-one (compound D) was not detected and may therefore have been formed artefactually in the earlier studies. The long terminal half-life for plasma radioactivity observed in previous studies was shown to be the result of the production of small amounts of 14C-thiocyanate from the nitrile-containing metabolites of molsidomine.

Administration, Oral↗
PubMed1985

Blood acetyl- and butyrylcholinesterases in senile dementia of Alzheimer type.

The major neurochemical abnormality described to date in senile dementia of the Alzheimer type (SDAT) is a central cholinergic deficit. To determine whether this central deficit is reflected by changes in the levels of blood cholinesterases, plasma and erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), were measured in SDAT and other psychiatric disorders. Plasma AChE, which has only recently been described in human blood, was significantly elevated (P less than 0.01) in the SDAT group compared with the control and other clinical groups investigated. In contrast there were no significant differences in the activities of either erythrocyte AChE or plasma BChE between any of the clinical groups. Although the source of plasma AChE is unknown the possibility that some portion originates from the central nervous system and that the elevated AChE levels in SDAT reflect increased release from degenerating cholinergic neurons is discussed.

Acetylcholinesterase↗
PubMed1985

Contemporary developments in thin-layer chromatography.

Qualitative and quantitative applications of thin-layer chromatography (TLC) in the biomedical and pharmaceutical fields are briefly surveyed. Some recent developments, including high-performance TLC (HPTLC) and reversed-phase TLC (RPTLC), together with techniques such as multiple development and continuous development, are considered. Instrumentation for HPTLC, and new developments in the detection and spectroscopic characterization of substances on TLC plates, are briefly described.

Journal Article↗
PubMed1984

Occurrence of specific secretory immunoglobulin A in bile after inoculation of Giardia lamblia trophozoites into rat duodenum.

We studied the appearance of specific secretory immunoglobulin A (IgA) antibody in bile after inoculation of live Giardia lamblia trophozoites into rat intestine. Serial bile specimens collected before and after inoculation of trophozoites were assayed for IgA antibodies by indirect immunofluorescence. Secretory IgA antibodies to Giardia lamblia were first detected in bile at 3 days after inoculation, remained elevated through 12 days, and then returned to control levels. Positive immunofluorescence of trophozoites for IgA was observed at bile titers of 1:80 to 1:160, whereas control biles were usually negative at dilutions of 1:10 or less. Scanning electron microscopic examination of Giardia in conjunction with immunocytochemistry revealed IgA antibodies bound to the flagella and surfaces of the trophozoites including the adhesive disk. These data demonstrate the occurrence of a secretory IgA immune response directed against surface antigens of Giardia lamblia trophozoites in the rat.

Animals↗
PubMed1983

Light microscopic morphometric analysis of rat ileal mucosa. I. Component quantitation of IgA-containing immunocytes.

A light microscopic morphometric analysis of IgA-containing immunocytes within samples of ileal mucosa was performed. The following groups of rats were studied: (1) animals raised in a gnotobiotic environment (microbial reduction); (2) animals with iatrogenic self-filling intestinal blind loops (microbial proliferation); and (3) control animals (sham operation). The unlabeled antibody enzyme immunohistochemical localization technique was employed for the identification of intracellular IgA. Component quantitation involved use of a micrometer component quantitator. Numerical density of the immunocyte population was determined by component quantitation of individual and total immunocyte volumes and by application of the Floderus equation. The methodology employed provided a precise quantitative analysis of all mucosal components of normal and manipulated rat ileum. A statistically significant reduction in the volume percentage of IgA-containing immunocytes in association with both microbial reduction and microbial proliferation was observed. The volume percentage reduction of the IgA-containing immunocyte population associated with gnotobiosis may reflect decreased microbial antigenic stimulation, whereas that associated with microbial proliferation may reflect the presence of an increased population of immunocytes producing non-IgA immunoglobulins.

Animals↗