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Clinical and laboratory studies in iron metabolism with particular reference to ferritin
Başlık:
Clinical and laboratory studies in iron metabolism with particular reference to ferritin
Yazar:
Cumming, Robert L. C., author.
ISBN:
9780438052703
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (121 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: A. Goldberg.
Özet:
A review of iron metabolism, with the emphasis on the storage compounds and on the conditions associated with iron overload in the body, is presented. The initial part of the work of this thesis deals with the chelating agent desferrioxamine B (DFA) which has a specific affinity for trivalent iron. The first reports on the use of this compound suggested that it was capable of bringing about the excretion of approximately 80 mg of iron in the urine per day. Subsequent reports however showed that a figure of 20 mg per day was a more usual one. This compares unfavourably with the 230 - 250 mg of iron removed by the venesection of one pint of blood. It had been noted that in patients with a haemolytic anaemia the urinary excretion of iron after DFA was somewhat greater than in control subjects. In view of these observations it was decided to study the effect of a mild phenylhydrazine-induced haemolysis on the urinary excretion of iron in guineapigs and in patients with iron-storage disease. Work with guineapigs showed an eight-fold excretion of iron in the urine and a four-fold excretion in the faeces when combined DFA and phenylhydrazine treatment was given compared to the excretion when DFA was given alone. There was a significant increase in urinary iron excretion in patients with untreated iron-storage disease who were given DFA and phenylhydrazine, compared with the urinary iron excretion when they were given DFA alone. Most of the published literature on the iron chelating agent desferrioxamine (DFA) relates to urinary excretion of iron following its administration. In the present study, patients suffering from various iron storage diseases were maintained on a fixed dietary intake of iron and a basal value for faecal iron excretion was obtained. In all cases the faecal iron content rose significantly after treatment with desferrioxamine. The mean increase in faecal iron after DFA was 40 per cent of the total increase in both urinary and faecal iron excretion. This finding has a relevance to the interpretation of tests using DFA for the assessment of body iron stores. The serum ferritin levels of another group of patients suffering from various iron storage diseases were measured before and after DFA administration. In all cases the serum ferritin level increased significantly 2 hours after administration of DFA. Quantitative studies on the ferritin protein and ferritin iron content of liver, spleen, kidney and intestinal mucosa in rats showed that DFA causes significant reductions in both these substances in liver and spleen. It was calculated that over 70 per cent of the iron removed by DFA emanated from liver and that the amount of ferritin protein released from rat liver after DFA was sufficient to bind all the iron removed. Thus the major source of the iron excreted after DFA therapy is probably liver ferritin iron. In the course of the work on the mechanism of action of DFA an immunological technique for the small scale isolation of ferritin was developed. Since recent work has suggested that ferritin has an important role in the regulation of intestinal iron absorption, particularly with regard to an excretory function, a study was carried out on the ferritin content and ferritin turnover in rat liver and intestinal mucosa in iron deficient, normal and iron loaded animals. Radio-leucine incorporation into ferritin was used as a measure of its synthesis and turnover in rat liver and intestinal mucosa. A significantly greater ferritin accumulation was found in the intestinal mucosa of the group of iron loaded animals compared with normal or iron deficient rats. In the liver the ferritin protein, ferritin iron and labelled ferritin content was significantly different in all three groups, the amounts being higher in the iron loaded animals and lower in the iron deficient animals when compared with the normal group. These results may explain how the absorption of iron in the small intestine is controlled by body iron stores. Iron is known to increase ferritin synthesis but the mechanism of this stimulation has been the subject of controversy. The various hypotheses proposed have been that iron (1) stabilises pre-formed apoferritin molecules, (2) activates or derepresses the gene responsible for apoferritin synthesis, or (3) acts by induction at the level of translation. Actinomycin D, which blocks DNA dependent synthesis of RNA, was used to test for genetic involvement in ferritin synthesis, and cycloheximide, which inhibits protein synthesis in rat liver by inhibiting the assembly of amino-acid on the polysomes, was used to distinguish between induction and stabilisation of ferritin. Actinomycin D was found to have no inhibitory effect on iron induced radio-leucine incorporation into ferritin but appeared to augment its effect. Cycloheximide on the other hand completely abolished the stimulation by iron of ferritin synthesis and was subsequently utilised to show that iron acts in vivo by translational induction of apoferritin synthesis, rather than by stabilisation of apoferritin or its precursors. This conclusion was confirmed by showing that 2 days after acute bleeding, when iron was being removed from hepatic stores, ferritin synthesis was decreased whereas breakdown rates were unchanged.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684416.1) | 684416-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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