Recently, we established a collagen-binding growth factor consisting of epidermal growth factor and the fibronectin collagen-binding domain (FNCBD-EGF). FNCBD-EGF is a biologically active fusion protein that could stably bind to collagen materials, and exert its growth factor activity even after collagen binding. In this study, we investigated the concept that FNCBD moiety with high collagen affinity may enhance the effective local concentration of EGF at the site of administration in the following tissues: skin wounds, catheter-injured arteries, and hind limb muscles. In an animal model of impaired wound healing, application of FNCBD-EGF in combination with collagen gel induced granulation tissue formation in the wounds due to its sustained retention. In the injured artery, infused FNCBD-EGF remained bound to collagen exposed on the injured tissues even after blood circulation was restored. Injection of the fusion protein into the hind limbs revealed that our delivery system was effective for direct administration to muscular tissue.
All these findings suggest that the increased content and total activity of tubulovesicular H+,K(+)-ATPase after ranitidine treatment may contribute to the mechanism for acid rebound after H2-blocker therapy.
The direct addition of levamisole to murine splenic lymphocytes had no effect on the mitogenic activity of lipopolysaccharide. However, the addition of serum of mice orally treated with levamisole increased the mitogenic activity, and this increased activity using serum was similar to the result obtained in an in vivo experiment. These results suggest that the new in vitro experimental method using serum may be able to reproduce the in vivo effect of drugs.
We have very recently demonstrated the low acidity of gastric juice and the high susceptibility to the development of gastric ulceration in Otsuka Long-Evans Tokushima Fatty (OLETF) rats not expressing CCK-A receptors. In the present study, gastric emptying in this strain was examined and compared with control Long-Evans Tokushima Otsuka (LETO) rats. Gastric emptying was evaluated by the phenol red method. Gastric emptying 30 and 60 min after a liquid meal in OLETF rats was significantly delayed compared to that in control LETO rats. Intraperitoneal injection of CCK-8 at a dose of 5 microg/kg significantly inhibited gastric emptying in control LETO rats, whereas the same dose of CCK-8 failed to inhibit gastric emptying in OLETF rats. These results suggest for the first time that gastric emptying was suppressed in OLETF rats. We also confirmed with this mutant that CCK delays gastric emptying through the CCK-A receptors.
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