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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 325 records · Page 18Linked to original sources

Unstirred water layer and age-dependent changes in rabbit jejunal D-glucose transport.

The unidirectional flux of solutes into the intestinal mucosal cell is determined by passage through the microvillus membrane and the overlying unstirred water layer, UWL. An in vitro technique was employed to determine the effect of the UWL on glucose transport into the jejunum of suckling, mature, and old rabbits. When the resistance of UWL was high, the uptake from high concentrations of glucose increased as the animals grew older; this change with aging was not seen from low concentrations of glucose. When UWL resistance was minimized by stirring the bulk phase, similar amounts of glucose were absorbed from high doses, but uptake from low doses was greater in young than in old animals. Studies undertaken to determine the kinetic basis of these age-related changes showed that with increasing age i) the apparent passive permeability coefficient P of glucose fell, ii) the maximum transport rate Jdmax rose, and iii) the apparent affinity constant Km increased. These differences were not observed when the resistance of the UWL was high: P and Km were similar in suckling, mature, and old animals, and the increase in glucose uptake with age was due to the greater Jdmax. Thus the potential benefit of the high affinity, high permeability transport system of young animals may be obscured by high resistance of the UWL.

Aging↗

In vitro testing of immunoresponsiveness in patients with inflammatory bowel disease: prevalence and relationship to disease activity immunoresponsiveness in IBD.

Abnormalities in the numbers and function of thymus and function of thymus-derived and bone marrow-derived lymphocytes (T and B cells) and K cells were determined in sixty-nine consecutive patients with Crohn's disease or ulcerative colitis. Rosetting techniques to identify subpopulations of lymphocytes showed a significant decrease in E-rosettes (T cells) and significant increase in EA- and EAC-rosettes (B cells) in patients with inflammatory bowel disease when compared to normals. In vitro lymphocyte transformation responses to mitogens and antigens were depressed to a variable degree. Mean levels of K cell activity were not significantly different from normal controls. A considerable degree of individual variation was noted in all groups. When the results of each groups were considered, none of the laboratory variables correlated with the site, duration or activity of disease, therapy, presence of iron deficiency anemia, weight loss or hypoalbuminaemia. Thus, in vitro evidence of abnormal immune responses in patients with inflammatory bowel disease cannot be directly related to clinical or laboratory variables and probably reflects a multi-factorial aetiology.

Adolescent↗

Quantitative sacroiliac scintigraphy in patients with Crohn's disease.

Sixty patients with Crohn's disease have been assessed radiologically and by quantitative sacroiliac scintigraphy for evidence of sacroilitis and/or ankylosing spondylitis. The incidence of radiologic sacroiliitis (11%) and ankylosing spondylitis (5%) was no greater in our series than previously reported. However, the incidence of increased uptake of radiotracer at the sacroiliac joints was 52%. There was no correlation in the group as a whole between radiologic and/or scintigraphic evidence of sacroiliitis and the tissue antigen HLA-B27.

Adolescent↗

Serum ferritin levels in anemia of rheumatoid arthritis.

Thirty-five anemic patients with rheumatoid arthritis were studied to determine the relationship between serum ferritin levels and body iron status, as assessed by the grading of bone marrow iron stores. The incidence of greatly reduced or absent marrow iron stores was 60%. Peripheral blood smear, RBC indices, serum iron, and iron binding capacity correlated poorly with stainable marrow iron. Serum ferritin levels only correlated approximately with iron stores, and in iron deficient rheumatoid patients the levels were higher than would be expected in patients with uncomplicated iron deficiency. The study shows that reduced marrow iron stores is common in patients with rheumatoid arthritis, and that the serum ferritin concentration may provide a useful indication of reduced body iron stores in these subjects, but only if a range of normal values can be established for this disease.

Adult↗

Kinetics of the subcellular distribution of iron and cobalt in the intestinal mucosa of the rat.

A differential centrifugation technique was used to compare the subcellular distribution of labeled iron (Fe) and cobalt (Co) in iron-deficient animals (FeD), in which transport was active, with iron-loaded animals (FeL), in which transport was by diffusion. In FeL the amount of Fe and Co in each subcellular fraction was dependent upon dose; there was a linear relation between the amount of Fe or Co in each fraction and metal absorption. In FeD a curvilinear relation was noted between both Fe dose and absorption, and the amount of Fe in the particulate fractions I and II. In contrast, a linear relation was noted between both dose and absorption, and the smaller amounts of Fe in the other fractions. Most of the Co was in V ("soluble"), and the relation between Co in all the fractions and absorption was linear. The addition of Co to the Fe test dose was associated with a decrease in Fe in I and II. The results suggest that a constituent(s) in the particulate fractions I and II is involved in the enhanced absorption of Fe in FeD. The subcellular fraction responsible for the increased Co absorption in FeD was not identified.

Animals↗

Integrity of the iron transport process in mice with X-linked anaemia.

The defect in iron (Fe) absorption in X linked anaemia (sla) remains an enigma; absorption of a tracer dose of Fe is impaired in mice raised on an iron-containing cube diet but not in those raised on an iron-deficient diet. Because cobalt (Co) shares a similar intestinal transport pathway with Fe, a study was made of the effect of iron deficient diet on Co absorption. The duodenum of sla and genetically normal mice was perfused for 30 min with labelled solutions containing Co or Fe. Co uptake and transfer were similar in sla and normals fed cubes whereas Fe uptake and transfer were less in sla than in normals. The iron deficient diet caused an increase in the uptake and transfer of Co and Fe in sla and normals. When Co and Fe were perfused together in sla fed deficient diet, the uptake and transfer of each metal was less than when performed alone. The distribution of Fe and Co in subcellular mucosal fractions was determined by a differential centrifugation technique. Deficient diet resulted in a directionally similar change in the subcellular distribution of Co and Fe in sla and normals. The increase in Co as well as Fe absorption in the sla on an iron deficient diet to the same high level found in genetically normal animals, and the inhibitory effect of each metal on the absorption of the other suggests that the absorption defect in sla is unlikely to be due to a primary defect in the function of the transport carrier.

Anemia, Hypochromic↗

Competitive nature of the intestinal transport mechanism for cobalt and iron in the rat.

Dose- and time-response studies were performed in iron-loaded and iron-deficient rats in order to define, (a) the kinetics of absorption of cobalt and iron, (b) the nature of the inhibitory effect of one metal on the absorption of the other, and (c) the effect of variations in body iron stores on these processes. The duodenum was perfused for 5-90 min with labeled solutions containing 5.0 mM iron or 5.0 mM cobalt. In iron-loaded rats, the rate of cobalt absorption was constant for 90 min whereas the rate of iron absorption fell after 30 min. In comparison to these results, the rate of absorption of both metals was increased in iron deficiency, and was more rapid in the first 30 min than in the 30-90 min period.To determine the response to varying doses of metal, we perfused duodenal loops for 30 min with 0.1-10.0 mM solutions of either iron or cobalt. In both iron-loaded and iron-deficient groups, a greater proportion of the metals was absorbed from smaller than from larger doses. When iron and cobalt were perfused together in iron-deficient animals, cobalt competitively inhibited iron absorption, and conversely, iron reduced cobalt absorption. The apparent maximum transport velocity was similar for both metals, but the affinity for cobalt was greater than iron. The results suggest that the absorption of cobalt and iron is mediated by a transport system in which two processes operate simultaneously; the first is limited largely by the concentration of available metal in the lumen of the intestine, whereas the second process depends upon the activity of a mechanism which displays saturation kinetics and competitive inhibition. The former process prevails when iron stores are replete, whereas the latter predominates when there is a need for iron, such as in iron deficiency.

Animals↗

Steady-state pharmacokinetics of metronidazole in Crohn's disease.

The pharmacokinetics of metronidazole (MTZ) were studied in six Crohn's disease patients after multiple oral daily doses of 250, 500, 750, and 1000 mg day-1. Pharmacokinetic indices were found to be independent of the dose administered. The half-life, volume of distribution and oral clearance of metronidazole were 9.5 +/- 2.1 h, 0.732 +/- 0.094 l kg-1 and 0.921 +/- 0.175 (ml min-1) kg-1 (mean +/- SD), respectively. A strong linear correlation (r = 0.95) was found between the volume of distribution of MTZ and the patients' total body weight. The percentage of dose of metronidazole excreted in urine as the intact drug and metabolites as well as glucuronic acid conjugates ranged from 34.7 +/- 7.4 to 58.9 +/- 5.2. Both plasma and urine data exhibited very large inter-patient variations. However, intra-patient variations were negligible. Strong positive linear correlations were observed between the dose and the areas under the plasma concentration versus time curves, peak plasma concentrations as well as cumulative urinary excretion of the drug and its metabolites. It is concluded that in Crohn's disease, the pharmacokinetics of MTZ and its metabolites are linear and that the drug concentrations are dependent on the total body weight.

Adult↗