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- Esbjörner, Elisabeth, 1947-
(författare)
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Studies on albumin binding properties in pregnancy and early infancy : with special reference to maternal sulphasalazine treatment
- 1990
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sulphasalazine (SASP) has been avoided during the later part of pregnancy and during breast-feeding as some sulphonamides possess the ability to displace bilirubin from albumin and thus increase the risk of bilirubin-induced brain damage in jaundiced neonates. However, withdrawal of SASP in a woman with ulcerative colitis would mean a cqnsiderable risk of relapse of her disease.In this study, SASP and its metabolite sulphapyridine (SP) was shown to pass the placenta. Sulphapyridine but not SASP appeared in breast-milk, although concentrations in breast-fed infants were low. The substances were eliminated slower in newborns than in adults.The possible bilirubin-displacing effect of SASP and SP was evaluated by using the MADDS (monoacetyldiaminodiphenyl sulphone) method to determine the binding 'properties of serum albumin.MADDS is used as a deputy ligand for bilirubin. In vivo and in vitro studies, using the MADDS and the peroxidase methods, showed that SASP and SP in pharmacological concentrations did not displace bilirubin from albumin.During that study it was noted that the reserve albumin concentration for MADDS was far lower in women at delivery than in non-pregnant women. In a longitudinally followed group of pregnant women, the reserve albumin concentration was gradually lowered during pregnancy, reaching 530/o of the concentration in non-pregnant women at term. This can have pharmacokinetic effects on those drugs that share the binding function on albumin with MADDS and bilirubin. The reduction of the reserve albumin concentration was due to a reduced albumin concentration during pregnancy but also to a reduced binding ability of the albumin molecule.
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| 2. |
- Zdolsek, Johann, 1960-
(författare)
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Effects of reactive oxygen species on the cellular vacuolar apparatus
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Reactive and potentially harmful oxygen species occur, and are continuously formed, in all cells of a living organism. Increased production of these metabolites are seen in a number of pathological states, for instance in inflammatory foci or during reoxygenation of ischemic tissue. Reactive oxygen species are considered to be associated with aging, the development of cancer and atherosclerosis.The main aim of this study was to investigate the effects of reactive oxygen species on the cellular vacuolar apparatus, in particlar lysosomes.It was found that neither superoxide radicals nor hydrogen peroxide alone had any damaging effect on lysosomes. With the presence of iron and, when hydrogen peroxide is concerned, a reducing agent damage to lysosomes was detected in the form of impaired proton gradient, leakage of lysosomal enzyme and lipid peroxidation, suggesting involvement of hydroxyl radicals.By refining and modifying an existing cytochemical method it was also possible to detect iron at both light- and electron microscopicallevel with preserved ultrastructure. Iron was mainly found in secondary lysosomes.It was also found that hydrogen peroxide-toxicity to cultured cells is iron dependent and could be much reduced by deferoxamine, an iron-chelator. This drug also prevented the hydrogen peroxide-mediated loss of the lysosomal proton gradient, suggesting intralysosomal Fentonreactions with generation of hydroxyl radicals.Acridine orange is an acidotropic photosensitizer which mainly accumulates in lysosomes. By exposing acridine orange-loaded cultured cells to blue light reactive oxygen, found to be singlet oxygen, was generated intralysosomally. This lead to loss of the proton gradient over the lysosomal membrane and a decrease in lysosomal cathepsin activity. Inhibition of lysosomal proteases lead to a reduction in acridine orange-mediated cell death suggesting a role for these enzymes in cell death. Electron microscopy revealed bleb-formation and increased autophagocytosis in photosensitized cells.
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