The immunosuppressive effects of synthetic sulfo-glycolipids in the class of sulfoquinovosyl-diacylglycerols (SQDG), including stereoisomers, were interesting in development of a promising clinical ...drug. Especially, 1,2-di-
O-stearoyl-3-
O-(6-deoxy-6-sulfo-β-
d-glucopyranosyl)-
sn-glycerol (β-SQDG-C
18) was thought to be a valuable candidate because of the preliminary observations of its high inhibitory activities in spite of low toxicities. The problem of using this material is to find an applicable way avoiding its low solubility in water. The vesicle formation of β-SQDG-C
18 is advantageous to i.v. administration in its chemico-structural character. With preparation in water, β-SQDG-C
18 was hard to form vesicles, because its hydrophilicity was strong. We examined the suitable parameter of the vesicle forming condition. It was possible to take a balance between the hydrophilicity and the hydrophobicity of the β-SQDG-C
18 molecule to be optimized to form vesicles in 150
mM PBS. In addition, we demonstrated the strong immunosuppressive activity of β-SQDG-C
18 vesicles. This is the first report of the preparation method of β-SQDG-C
18 vesicles, which should facilitate in vitro and in vivo application.
The conversion of the larval to adult epidermis during metamorphosis of tadpoles of bullfrog,
Rana catesbeiana, was investigated utilizing newly cloned
Rana keratin cDNAs as probes.
Rana larval ...keratin (RLK) cDNA (
rlk) was cloned using highly specific antisera against
Xenopus larval keratin (XLK). Tail skin proteins of bullfrog tadpoles were separated by 2-dimensional gel electrophoresis and subjected to Western blot analysis with anti-XLK antisera. The
Rana antigen detected by this method was sequenced and identified as a type II keratin. We cloned
rlk from tadpole skin by PCR utilizing primers designed from these peptide sequences of RLK. RLK predicted by nucleotide sequences of
rlk was a 549 amino acid -long type II keratin. Subtractive cloning between the body and the tail skin of bullfrog tadpole yielded a cDNA (
rak) of
Rana adult keratin (RAK). RAK was a 433 amino acid-long type I keratin. We also cloned a
Rana keratin 8 (RK8) cDNA (
rk8) from bullfrog tadpole epidermis. RK8 was 502 amino acid-long and homologous to cytokeratin 8. Northern blot analyses and
in situ hybridization experiments showed that
rlk was actively expressed through prometamorphosis in larva-specific epidermal cells called skein cells and became completely inactive at the climax stage of metamorphosis and in the adult skin. RAK mRNA was expressed in basal cells of the tadpole epidermis and germinative cells in the adult epidermis. The expression of
rlk and
rak was down- and up-regulated by thyroid hormone (TH), respectively. In contrast, there was no change in the expression of RK8 during spontaneous and TH-induced metamorphosis. RK8 mRNA was exclusively expressed in apical cells of the larval epidermis. These patterns of keratin gene expression indicated that the expression of keratin genes is differently regulated by TH depending on the type of larval epidermal cells. The present study demonstrated the usefulness of these genes for the study of molecular mechanism of postembryonic epidermal development and differentiation.
Study Objective. To compare the absorption profile of cyclosporine after preprandial administration with that after postprandial administration, and to determine which administration time resulted in ...a more stable absorption profile and the timing of the drug concentration that was the most reliable marker for monitoring drug absorption.
Design. Prospective analysis.
Setting. University teaching hospital in Japan.
Patients. Sixteen patients with refractory nephrotic syndrome.
Intervention. Thirteen patients received cyclosporine after breakfast (postprandial group) and eight received the drug 30 minutes before breakfast (preprandial group).
Measurements and Main Results. Blood cyclosporine concentration was measured 5 times serially: before administration (C0) and at 1‐hour intervals until 4 hours after administration of cyclosporine (C1‐C4). Also, area under the concentration‐time curve from 0–4 hours (AUC0–4) was calculated. Of the 13 patients in the postprandial group, six (46%) showed fair absorption and exhibited a peak concentration at C1 or C2 (high‐absorption pattern); seven (54%) showed poor absorption and did not reach the peak concentration within the 4‐hour period (low‐absorption pattern). Five of the seven patients with the low‐absorption pattern were switched from postprandial to preprandial administration. All patients in the preprandial administration group showed a high‐absorption pattern and reached the peak cyclosporine concentration at C1. The C2 value showed the best correlation with AUC0–4 in both groups, and the C0 parameter did not correlate with AUC0–4 in either group.
Conclusion. Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC0–4, we concluded that C2, and not C0, is a reliable marker for monitoring cyclosporine exposure.
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