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Biomedical subjects

K D Setchell

Publications and source records attributed to K D Setchell.

At least 127 records · Page 7Linked to original sources
PubMed1982

A rapid method for the quantitative extraction of bile acids and their conjugates from serum using commercially available reverse-phase octadecylsilane bonded silica cartridges.

Described is a rapid semi-automated technique for the quantitative extraction of bile acids and their conjugates from serum samples using commercially available reverse-phase octadecylsilane bonded silica cartridges. Serum is diluted with 4 volumes of 0.1 mol/l sodium hydroxide and the sample heated to 64 degrees C before application to the cartridge. Bile acids and their conjugates are adsorbed to the octadecylsilane bonded silica particles and reproducibly recovered by elution with a small volume of methanol. The technique is superior to extraction procedures using either Amberlite XAD resins or liquid-liquid partitioning, and gives a quantitative recovery of polar bile acid sulphates. The method is convenient and rapid and by using a specially designed apparatus it is possible to extract up to 60 samples/hour.

Bile Acids and Salts↗
PubMed1982

Capillary gas chromatographic method for the analysis of lignans in human urine.

We describe a capillary column gas chromatographic (GC) method for the analysis of lignans in urine. Lignans are excreted as mono-glucuronides which are first extracted on a small reversed-phase cartridge of octadecylsilane bonded silica (Sep-Pak C18) and thereafter isolated by anion exchange chromatography on DEAE-Sephadex A-25, prepared in the acetate form. Lignan mono-glucuronides are enzymatically hydrolysed and re-extracted on a Sep-Pak C18 cartridge. Quantification is carried out by capillary column GC of the trimethylsilyl ether derivatives. The specificity of the method was checked by GC/MS and the intra-assay coefficient of variation (CV) for the two lignans, enterolactone (trans-2,3-bis(3-hydroxybenzyl)butyrolactone) and enterodiol (2.3-bis(3-hydroxybenzyl)butane-1,4-diol) varied between 5 and 8%. Some values for the excretion of these lignans by normal men and women are presented.

4-Butyrolactone↗
PubMed1982

Bile acid profiles of human serum and skin interstitial fluid and their relationship to pruritus studied by gas chromatography-mass spectrometry.

1. Pruritus was assessed in 19 patients by measurement of nocturnal limb movement. 2. Serum (nine pruritic, ten non-pruritic) and interstitial fluid (five pruritic, three non-pruritic) bile acids were fractionated according to their mode of conjugation by using DEAP-Sephadex LH-20 and measured by gas chromatography-mass spectrometry. 3. No correlation was found between serum or interstitial fluid total bile acid or individual bile acid concentrations and pruritus. Bile acid profiles in the two groups of patients were similar and there was no correlation between pruritus and the conjugation pattern. 4. Te bile acid profile of interstitial fluid reflected that of serum and a linear relationship was found between serum and interstitial fluid bile acid concentrations (r ;.95, P less than 0.001). 5. The proportion of bile acid sulphate in interstitial fluid was significantly smaller than that in serum (P less than 0.025), where sulphates accounted for up to 46% of the total bile acids. 6. In three patients, a decrease in serum bile acid concentrations achieved by percutaneous transhepatic biliary drainage had little or no effect on pruritus. 7. These findings suggest that bile acids do not have a causative role in the pruritus of cholestatic liver disease.

Adult↗
PubMed1982

Diurnal changes in serum unconjugated bile acids in normal man.

Unconjugated bile acids were measured using gas chromatography-mass spectrometry in the serum of two subjects throughout a 24 hour period and in two other subjects over a six hour period after breakfast. Unconjugated bile acids were found in all samples of serum and included cholic, chenodeoxycholic, deoxycholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanic (iso-chenodeoxycholic), ursodeoxycholic, 3 beta, 7 beta-dihydroxy-5 beta-cholanic (iso-ursodeoxycholic), 3 beta-hydroxy-5-cholenoic, and lithocholic acids. The maximum concentration of each bile acid generally occurred between breakfast and dinner and total unconjugated bile acid concentrations attained levels of between 2-3 mumol/l. Concentrations increased after breakfast and were often as high as 30-40% of the conjugated bile acid glycocholate, but returned to fasting levels in the absence of lunch. The intestinal absorption of unconjugated bile acids is therefore of greater quantitative importance than was previously thought.

Adult↗
PubMed1981

The definitive identification of the lignans trans-2,3-bis(3-hydroxybenzyl)-gamma-butyrolactone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol in human and animal urine.

The definitive identification of the first lignans to be found in humans and animals is described. Gas chromatography--mass spectrometry, n.m.r. spectroscopy, i.r. spectroscopy and chemical techniques were employed to establish the structures of two lignans as trans-2,3-bis(3-hydroxybenzyl)-gamma-butyrolactone and 2,3-bis(3-hydroxybenzyl)butane-1,4-diol. Both compounds are essetially racemic. Evidence was also found for several methoxy analogues of these lignans in the vervet monkey.

4-Butyrolactone↗
PubMed1981

Diet and urinary excretion of lignans in female subjects.

Lignans, a class of compounds having a 2,3-dibenzylbutane skeleton, have recently been identified for the first time in humans and animals and evidence indicating their formation by intestinal microflora has previously been established in rats and humans. In the present report the influence of diet on the biosynthesis of this new group of compounds was investigated by comparing the urinary excretion of the principal lignan, trans-2,3-bis-(3-hydroxybenzyl) -butyrolactone (enterolactone, HBBL), in 12 omnivoric and 14 vegetarian women. Young vegetarian women were found to excrete significantly greater amounts of enterolactone than omnivores, while old vegetarians excreted comparable amounts to the omnivore group. A statistically significant (P less than 0.01-0.001) correlation was found between the amount of fibre in the diet and the urinary enterolactone excretion.

Adult↗
PubMed1980

Lignans in man and in animal species.

In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.

Adult↗
PubMed1979

A study of the disposition of alpha-methyldopa in newborn infants following its administration to the mother for the treatment of hypertension during pregnancy.

1 The nine infants participating in this study were born to mothers who received continuous therapy with alpha-methyldopa (0.75-2.0 g/day) for several weeks extending to the time of delivery. 2 The concentration of free and total (free plus conjugated) alpha-methyldopa was determined by gas chromatography-mass spectrometry in amniotic fluid, umbilical cord plasma and maternal plasma at delivery; also in urine collected over time intervals from neonates during the first days after birth. 3 The results indicate that alpha-methyldopa administered to the mother is present in the infant at birth at a level comparable to the maternal level and persists for some days. The ratio of conjugated to free drug increases with time after birth. 4 The excretion of free and conjugated alpha-methyldopa in the urine indicated that the drug is slowly eliminated in the neonate by excretion in the urine and apparently by metabolism, mainly to the sulphate conjugate. 5 The concentration of free and conjugated alpha-methyldopa in amniotic fluid tended to be higher than in umbilical cord plasma but lower than in neonatal urine, conjugated drug predominated.

Amniotic Fluid↗