Yu-Ichiro Satoh

Potentiation of enteral absorption of human interferon alpha and selective transfer into lymphatics in rats

Enhancement of human leucocyte interferon (HuIFN-α) absorption from rat large intestine was studied with the aid of lipid, surfactant and lipid-surfactant mixed micelles. Neither the emulsified lipid (linoleic acid) nor the surfactant (HCO60, polyoxyethylated [60 moles] hydrogenated castor oil) alone were able to enhance the absorption of HuIFN-α. However, linoleic acid-HCO60 mixed micelles enhanced the absorption of HuIFN-α from the large intestine. Highly selective delivery of HuIFN-α into the lymphatics compared to the blood was also observed.

Development of Interferon Suppositories. I. Enhanced Rectal Absorption of Human Fibroblast Interferon by Fusogenic Lipid via Lymphotropic Delivery in Rats

We attempted to enhance the rectal absorption of human fibroblast interferon (HuIFN-β) in rats by the administration of suppositories containing fusogenic lipid and a nontoxic surfactant. Suppositories containing either the lipid (linoleic acid) or the surfactant [HCO60; polyoxyethylated (60 mol) hydrogenated castor oil] alone failed to enhance the absorption of HuIFN-β. However, suppositories containing both linoleic acid and HCO60 facilitated the rectal absorption of HuIFN-β. The absorbed HuIFN-β was selectively delivered via the lymph.

Carbohydrate-Dependent Biological Activities of Glycosylated Human Interferon-β on Human Hepatoblastoma Cells In Vitro

To evaluate the relationship between the sugar chain structure and biological activity, fibroblast‐derived glycosylated human interferon‐β, Chinese hamster ovary cell‐derived glycosylated recombinant human interferon‐β and Escherichia coli‐derived unglycosylated recombinant human interferon‐β were evaluated using human hepatoblastoma cells in vitro. Native fibroblast interferon‐β expressed more cell‐growth inhibitory action, 2′5′‐oligoadenylate synthetase induction, and the inhibition of hepatitis B virus DNA replication than its asialoform and two recombinant interferon‐βs. These results showed that the sugar chain structure of human interferon‐β affects its biological activity on human hepatoblastoma cells.

Effects of natural human interleukin-6 on thrombopoiesis and tumor progression in tumor-bearing mice

The growth of inoculated colon 26 adenocarcinoma (colon 26) in mice gradually increased the platelet count owing to murine IL-6 secreted from the tumor, while Lewis lung carcinoma (LLC) decreased the platelet count in the hosts, depending on the tumor growth. Natural human IL-6 injections (hIL-6), 280 micrograms/kg/day, stimulated the platelet production in both types of carcinoma-bearing mice. When the administration of mitomycin C or cisplatin decreased the platelet number as a side reaction with a concomitant of suppressing the growth of colon 26 and LLC, respectively, hIL-6 could also increase the platelet count without the augmentation of tumor growth. However, loss of carcass weight was observed in colon 26-bearing mice treated with hIL-6, suggesting the development of cachexia is associated with hIL-6 administration. Despite the possibility of inducing cachexia in some types of tumors, our results suggest that IL-6 could be a useful means of restoring the decreased platelet number in cancer patients after intensive chemotherapy.

Effect of Salicylate on the Uptake of Cefmetazole into Brain of Mice

Cefmetazole distribution into mice cerebral cortex was minimal when the drug was administered alone. However, the co-administration of salicylate or diethyl maleate enhanced cefmetazole uptake into the cerebral cortex, while it decreased the level of reduced nonprotein sulfhydryls in cerebral cortex. The enhanced cerebral uptake of cefmetazole was suppressed by the simultaneous administration of cysteamine with a concomitant recovery of the reduced nonprotein sulfhydryl concentration in cerebral cortex.