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Diabetic polyneuropathy is a major complication of diabetes and the most common cause of peripheral neuropathy. Sensory-dominant neuropathy is the most common type. We previously used streptozotocin (STZ)-induced diabetic ddY mice with sensory neuropathy to evaluate the therapeutic effects of vascular endothelial growth factor and placental growth factor isoforms. In this study, to characterize the development of diabetic sensory neuropathy, electrophysiological, behavioral, and histopathological studies were performed in these diabetic mice. A significant difference in sensory conduction velocity in the tail nerve was observed between healthy and diabetic mice at 1 week after STZ injection. Diabetic mice developed hypoalgesia at 5 weeks after STZ injection. Axon area and myelin thickness of the myelinated fibers were increased in 17-week-old healthy mice compared with those in 8-week-old healthy mice. However, these increases were retarded in 17-week-old diabetic mice. In unmyelinated fibers, axon area was significantly reduced in 17-week-old diabetic mice compared with 8- and 17-week-old healthy mice. These findings suggest that both impaired maturation of myelinated fibers and atrophy of unmyelinated fibers simultaneously occur in the early stage of diabetes in these mice. Our mouse model may be useful for studying the pathogenesis of and therapies for diabetic sensory neuropathy.

The use of curdlan, a natural beta-1,3-glucan, in the preparation of sustained release suppositories was studied in vitro. To prepare the suppositories, indomethacin, prednisolone or salbutamol sulfate was mixed with curdlan gel. Preparation conditions, including heating time and curdlan concentrations of 5 and 10%, had little effect on the drug release. The tonicity (hypotonic or isotonic) of the media for the suppository preparation and for in vitro drug release study also had little effect on drug release. However, the heating temperature during gel preparation, the drug amount in the suppository and the type of release media did affect drug release. It was found that drug release was sustained and diffusion-controlled in the three drugs. And finally, curdlan can be applicable for use in a sustained release suppository.

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We prepared a new liquid preparation for eradication of Helicobacter pylori (HP), and examined drug release in vitro and in vivo. The liquid preparation mainly consisted of a sodium alginate (AG) aqueous solution containing ampicillin (ABPC), an antibiotic drug, or methylene blue, a dye. Drug release was retarded by Ca pre-treatment (0.10 M, 20 s) of the AG preparation in in vitro drug release studies due to gel-formation at the liquid surface. In in vivo experiments, the AG preparations were administered orally to rats. The rats were divided into two groups, with or without pre-administration of ranitidine hydrochloride (RH, an H2-blocker). The total remaining % of ABPC in the stomach was high in the rats administered the AG preparation compared to the ABPC solution. The AG preparation might float in the stomach without adhering to the gastric wall in the rats without pre-administration of RH. The total remaining % of ABPC at 30 min was almost 100% in the RH pre-administration rats administered the AG preparation, and about 80% of the drug existed in fraction 2 (implying adhesion of the preparation on the gastric mucus). At 60 min, the total remaining % in the AG preparation plus Ca (mean 87%) increased about 2-fold compared to that in the AG preparation alone (mean 44%). In this case, a large portion of the remaining ABPC also existed in fraction 2. This preparation may be useful for eradication of HP.