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- Evengård, B, et al.
(författare)
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Low incidence of toxoplasma infection during pregnancy and in newborn in Sweden
- 2001
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Ingår i: Epidemiology and Infection. - 0950-2688. ; 127:1, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identi®ed based on: 1, detection of speci®c IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months; 2, detection of speci®c IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0±73}10000 (95% CI 0±15±2±14) (3}40978). The incidence of primary infection during pregnancy was 5±1}10000 (95% CI 2±6±8±9) susceptible pregnant women. The seroprevalence in the southern part was 25±7% and in the Stockholm area 14±0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility.
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- Engman, Helena, 1968-
(författare)
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Intestinal barriers to oral drug absorption: Cytochrome P450 3A and ABC-transport proteins
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The subject of this thesis was to study two intestinal barriers to oral drug bioavailability, drug efflux proteins of the ABC-transporter family, and in particular ABCB1/P-glycoprotein (Pgp), and the drug metabolizing enzyme cytochrome P450 (CYP) 3A4. At the onset of this thesis, similarities between CYP3A4 and Pgp in terms of their tissue distribution and gene regulation, along with overlapping substrate specificities, had generated the hypothesis that CYP3A4 and Pgp may have a complementary function and thus form a coordinated intestinal barrier to drug absorption and gut wall metabolism.In the first part of this thesis, a cell culture model of the intestinal epithelium that expressed both functional Pgp and CYP3A4 was developed. This model was then used to investigate the steroselective drug efflux and metabolism of R/S-verapamil. In summary, the results indicated that the two barriers in the cell culture model were in agreement with those in the human intestine.Both ABC-transporters and CYPs are regulated by drugs that interact with nuclear receptors. However, while the regulation of CYPs is quite well understood, less is known about how repeated drug administration regulates the most abundantly expressed ABC-transporters. Therefore, in the second part of this thesis, the effects of repeated drug administration on the gene regulation of four ABC-transporters and CYP3A4 were studied in intestinal epithelial cell lines in vitro and in the perfused human jejunum in vivo. The in vitro studies revealed that the ABC-transporters are induced by drugs that interact with slightly different sets of nuclear receptors. The in vivo study showed that repeated oral administration of St John’s wort decreased the bioavailability of verapamil, predominantly by induction of intestinal CYP3A4. This part of the thesis provides new information about the regulation of ABC-transporters, shows that the intestinal metabolism is the most significant barrier to oral bioavailability of verapamil and provides evidence for a clinically significant interaction between verapamil and St John’s wort in vivo.
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