This study was carried out to determine whether polymorphisms of organic anion-transporting polypeptide 1B1 (OATP1B1) have an effect on rosuvastatin pharmacokinetics in Koreans. Among 200 subjects genotyped for OATP1B1 c.388A>G, and c.521T>C, 30 subjects were selected for the rosuvastatin pharmacokinetic study. The area under the concentration-time curve for 0 to infinity (AUC(0-infinity)) of rosuvastatin for group 1 (*1a/*1a, *1a/*1b, *1b/*1b), group 2 (*1a/*15, *1b/*15), and group 3 (*15/*15) were 111+/-49.3, 126+/-45.2, and 191+/-31.0 ng h/ml, respectively, with significant differences among the three groups (P=0.0429) and between *15/*15 and the other groups (P=0.0181). The maximum plasma concentration (Cmax) also showed a significant difference between *15/*15 and the other groups (P=0.0181). There were no significant differences in rosuvastatin-lactone pharmacokinetics among the three groups. The pharmacokinetic exposure of rosuvastatin was higher in the OATP1B1*15/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations.
A keratinolytic proteinase (KPase) which is regarded as an important factor in the pathogenesis of dermatophytosis was isolated and purified from Microsporum (M.) canis culture filtrates. Enzyme-linked immunosorbent assay (ELISA) was used to determine the occurrence of circulating antibodies to this enzyme in sera samples from guinea pigs with superficial fungal infections caused by M. canis. Of sera samples from guinea pigs infected with M. canis, 75% were reactive within 10 weeks, however, those ELISA values were relatively low compared with those from guinea pigs immunized with KPase. The presence of circulating antibodies was first detected 2 weeks post inoculation with M. canis, corresponding to the period when the lesions were most severe. The titers of the ELISA antibodies reached a peak at 4 weeks; at that time the lesions had disappeared completely.
Aims: Anions have an important role in the regulation of airway surface liquid (ASL) volume, viscosity and pH. However, functional localization and regulation of anion exchangers (AEs) have not been clearly described. The aim of this study was to investigate the regulation of AE mRNA expression level in accordance with mucociliary differentiation and the functional expression of AEs cultured normal human nasal epithelial (NHNE) cells. Methods: Nasal mucosal specimens from three patients are obtained and serially cultured cells are subjected to morphological examinations, RT-PCR, Western blot analysis and immunocytochemistry. AE activity is assessed by pHi measurements. Results: Expression of ciliated cells on the apical membrane and expression of MUC5AC, a marker of mucous differentiation, increased with time. AE2 and SLC26A4 mRNA expression decreased as mucociliary differentiation progressed, and AE4, SLC26A7 and SLC26A8 mRNA expression increased on the 14th and 28th day after confluence. Accordingly, AE4 protein expression also progressively increased. AE activity in 100 mm K + buffer solutions was nearly twofold higher than that in 5 mm K + buffer solutions. Moreover, only luminal AE activity increased about fourfold over the control in the presence of 5 lm forskolin. In the presence of 100 lm adenosine-5¢-triphosphate (ATP) which evokes intracellular calcium signalling through activation of purinergic receptors, only luminal AE activity was again significantly increased. On the other hand, 500 lm 4,4¢-diisothiocyanostilbene-2,2¢-disulfonic acid (DIDS), an inhibitor of most SLC4 and SLC26AE isoforms, nearly abolished AE activity in both luminal and basolateral membranes. We found that AE activity was affected by intracellular cAMP and calcium signalling in the luminal membrane and was DIDS-sensitive in both membranes of cultured NHNE cells. Conclusion: Our findings through molecular and functional studies using cultured NHNE cells suggest that AEs may have an important role in the regulation of ASL.
An 16-year-old Korean girl presented with a 3-year history of extrafacial atrophic lesions on her arms, forearms, thighs and legs, which had gradually developed since she was 13 years old, slowly increasing in size and number over time. The patient was otherwise healthy, and had not experienced any preceding trauma or inflammation. There was no familial history of a similar disorder.Physical examination revealed bilateral distribution of a number of lenticular and punctate depressed lesions on the patient's limbs (Fig. 1). The depressed sites were varioliform, nonscaly lesions, 1-3 mm wide, of normal skin colour with no pigmentary change, and had sharply defined margins. There was no herniation on palpation.
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