Urinary excretion of orally administered oxalic acid in xylitol fed mice.
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Biomedical subjects
Publications and source records attributed to V Marks.
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A solid phase radioimmunoassay kit method for total conjugated bile acids has been compared to an enzymatic fluorimetric method for total serum bile acids. The methods were compared with respect to: precision, cross-reactivity (molar equivalence) of different bile salts, recovery of different bile salts from serum, the reference range for a healthy population, linearity, coefficient of correlation, diagnostic effectiveness, cost and ease of assay. Both assays seemed equally capable of predicting the presence or absence of liver disease. Radioimmunoassay had little advantage over the enzymatic-fluorimetric method. Its relative ease was far outweighed by its greater cost and poorer analytical performance.
Thyroid microsomes for use in assay systems for anti-thyroid-microsomal antibodies are normally prepared by ultracentrifugation. By means of gel filtration studies we show that preparations made in this way are invariably contaminated with thyroglobulin. A further purification by gel filtration is described which enables the preparation of thyroid microsomes of sufficient purity for use in a micro-ELISA method for the measurement of anti-thyroid-microsomal antibodies. Microsomes prepared in this way would also be suitable for haemagglutination and radioassays, which are also affected by thyroglobulin contamination.
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A radioimmunoassay for the semi-synthetic podophyllotoxin VP16-213 has been developed which is suitable for pharmacokinetic studies of the drug. A high titre antiserum was produced in a sheep in response to a VP16-213-BSA conjugate prepared using sodium periodate. Podophyllotoxin does not cross-react with the antiserum and VM26 cross-reacts to only a small extent (less than 0.6%). In the absence of a high specific activity tritium label, a radioiodinated histamine ligand was produced which was only partially displaced from antibody by native drug. VP16-213 can be measured in plasma without prior drug extraction with a theoretical limit of detection of 5-10 micrograms/l. VP16-213 cis (picro) hydroxy acid is recognised by the antiserum to a greater extent than the drug itself. Thus, in order to eliminate any interference from the trans hydroxy acid metabolite chloroform extraction of plasma samples was carried out.
The possibility of a circadian rhythm in the toxicity of methotrexate was investigated in rats after a single intravenous bolus. Indices of haematological, renal and hepatic toxicity were studied, as were the pharmacokinetics of the drug. All the parameters showed a circadian variation, with maximum toxicity occurring after dosage of 06.00 h and minimum toxicity after dosage at midnight. Administration at the other two time points, 12.00 h and 18.00 h, gave intermediate results.
Xylitol given by gavage to unadapted rats produced profound diarrhoea and no rise in plasma gastric inhibitory polypeptide (GIP) concentration. In xylitol adapted rats it did not cause diarrhoea but still had no effect upon GIP release in contrast to glucose, which did. In healthy human subjects xylitol taken by mouth in solution as a single 30 g dose produced only a minimal rise in blood glucose and no rise in plasma GIP or insulin concentration. Glucose in similar doses, on the other hand, caused a large rise in all three.
Twenty seven patients with acute rheumatoid disease who had not previously received systemic corticosteroid therapy were given a pulse(s) of high dose methylprednisolone sodium succinate (MPS) intravenously. Of the 27 patients 22 received 1 g MPS once and 5 were given the drug on three consecutive days. Plasma "MP" (total MPS plus hydrolysed methylprednisolone) and cortisol levels were measured at various intervals post infusion. Clinical assessments were made before and at 2 week intervals after each infusion for 12 weeks. Patients showed objective improvement for up to 12 weeks post infusion. Maximum "MP" levels ranging between 16 and 72 mumol/l were obtained after single infusions. In a majority of the patients "MP" concentrations in plasma were reduced to values between 0.12-3.4 mumol/l in 24 h, 0.06 to 0.13 mumol/l in 48 h. Plasma cortisol levels were incompletely suppressed for a few days in all patients, but the drug was removed from plasma and normal adrenal function restored within a fortnight after steroid infusion at the latest.
Budesonide is a highly potent non-halogenated glucocorticoid with local anti-inflammatory properties. A sensitive radioimmunoassay for the measurement of the drug in unextracted plasma has been developed. Budesonide 21-hemisuccinate and budesonide 3-(O-carboxymethyl)oxime were conjugated to ovalbumin using the mixed anhydride method and antibodies to the haptens produced in sheep. The specificity of the antisera towards cortisol, and possible budesonide metabolites reflected the different sites of the attachment of the haptens to the carrier protein. An antiserum raised against the 3-(O-carboxy methyl)oxime conjugate was more specific (0.001% cross reaction) with respect to cortisol than the antiserum raised against the 21-hemisuccinate conjugate (0.344% cross reaction). Endogenous steroids at concentrations normally encountered in clinical samples, would not interfere with the measurement of budesonide. The radioimmunoassay was developed using the budesonide 3-(O-carboxy methyl)oxime antiserum, [3H]-budesonide and dextran coated charcoal phase separation. The theoretical limit of detection of the assay was 50 pg/ml. Budesonide was quantitatively recovered from normal human drug/free plasma at concentrations above 1 ng/ml (2.32 nmol/l) with a between batch variation of 12-15%. Budesonide was measured in the unextracted plasma of volunteers who had inhaled the drug from a pressurised aerosol spray.
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Melatonin, free and total cortisol, insulin, C-peptide and glucose-dependent insulin-releasing peptide (GIP) were measured in the plasma of twelve normal volunteers (eight women and four men), at hourly intervals for 24 h following a meal and subsequent fasting. One volunteer was excluded from calculations due to a possible effect of stress on melatonin secretion. Melatonin and cortisol showed the normal 24-h variation with peak values at 0200-0500 h, and 0900 h respectively. Following post-prandial stimulation, gut hormones remained basal throughout the sampling period. No significant relationship was found between 24-h melatonin secretion and basal, or stimulated gut hormone secretion. Melatonin secretion did relate significantly to body weight, suggesting that data concerning pineal effects in endocrine physiology and pathology, and affective disease, should be reviewed in the light of these observations.
The bioequivalence of two different tablets and a solution, each containing 10 mg propranolol hydrochloride was studied in twelve healthy volunteers. Single oral doses of each preparation were administered at intervals of one week. Samples of blood for propranolol radioimmunoassay were taken up to 8 h after dosing. The plasma propranolol concentration at 0.5 h was significantly higher for the solution than for the two tablet formulations which did not differ significantly from each other at any sampling point. The area under the curve was similar for all three preparations. The study demonstrated that the three different preparations of propranolol were bioequivalent.
Maximum plasma levels in six acute colitics were about three times greater after an intravenous bolus of 20 mg prednisolone than the mean level achieved during infusion of the same dose (p<0.001) over eight hours; the level during infusion was about twice as great as the maximum recorded previously after a single 40 mg oral dose of prednisolone. These findings favour the use of intravenous administration in severe acute colitis. No difference was found between plasma levels of patients and six normal subjects after the intravenous bolus.
A rapid sensitive radioimmunoassay for pepleomycin (PM) has been developed using an antiserum produced in a sheep in response to a bovine serum albumin-drug conjugate. Radioiodinated PM was prepared using Iodogen. The assay was reproducible with a limit of detection in plasma of 200 ng/liter. The antiserum does not cross-react with bleomycin or with a number of unrelated drugs. Pharmacokinetic studies using the assay were carried out in three patients who received a short iv infusion of 5 mg/m2 of PM. The drug disappeared from the plasma with an elimination half-life of approximately 3 hours.
Five healthy male volunteers were subjected to accelerations of up to +6 Gz for 1 min in order to investigate the effect of acceleration stress upon the concentration of various hormones in peripheral blood. No significant changes were seen in the levels of GH, PRL, TSH, LH, and FSH compared to control values obtained at +1 Gz (normal gravity). Changes in serum cortisol levels were significant (p less than 0.001) with peak values occurring 20 min after acceleration stress. A significant effect (p less than 0.001) of acceleration was also observed on plasma volume with maximum reductions occurring at the end of acceleration. The unusual specificity of the hormone responses is discussed.