The effects of dietary Korean pine (Pinus koraiensis)-seed oil containing a peculiar trienoic acid (cis-5, cis+9,cis-1218:3, pinolenic acid, approximately 18%) on various lipid variables were compared in rats with those of flaxseed (Linum usitatissimum L.) oil, safflower (Curthamus rinctorius L.) oil and evening primrose (Oenotkra biemis L.) oil under experimental conditions where the effects of different polyunsaturated fatty acids could be estimated. In Sprague-Dawley rats fed on diets containing 100 g fat and 5 g cholesterol/kg, the hypocholesterolaemic activity of pinolenic acid was intermediate between a-linolenic and linoleic acids. Analysis of the fatty acid composition of liver phosphatidylcholine indicated that, in contrast to a-linolenic acid, pinolenic acid does not interfere with the desaturation of linoleic acid to arachidonic acid. However, the effects on ADP-induced platelet aggregation and aortic prostacyclin production were comparable. When spontaneously hypertensive rats were fed on diets containing 100 g fat/kg but free of cholesterol, y-liwlenic and pinolenic acids, as compared with liwleic acid, increased prostacyclin production and tended to reduce platelet aggregation. In addition, pinolenic acid attenuated the elevation of blood pressure after 5 weeks of feeding. Thus, the results of the present studies indicate the beneficial effects of pinolenic acid on various lipid variables.

A bioartificial pancreas, that is, transplantation of islets of Langerhans (islets) which are enclosed in a semipermeable membrane, has been proposed as a treatment for type I diabetes. The islets are immuno-isolated from the host by the semipermeable membrane preventing rejection while maintaining control of glucose metabolism for an extended period. The purpose of the current research is to evaluate the feasibility of preparing agarose microbeads with xenogeneic hamster islets as a bioartificial pancreas in streptozotocin induced diabetic mice. In the recipients with a low level of anti-hamster antibodies, the combination of encapsulation of hamster islets in 5% agarose microbeads and in vitro culture of them prolonged xenograft survivals. Four of 6 recipients were still normoglycemic at 100 days after implantation. However, the same procedure was not effective in the recipients which were sensitized in advance by transplantation of free hamster islets and thus had high levels of anti-hamster antibodies. The average normoglycemic period was 32 days. Antibodies permeated through the microbeads and activated complement on the cell surfaces. The network of agarose microbeads was rendered dense by increasing the concentration of agarose to restrict the diffusion of antibodies. Graft survivals were prolonged with increasing concentrations of agarose. As an analysis using diffusion equations predicted, the survivals were inversely proportional to the diffusion coefficient of IgG in each agarose gel. Islet xenotransplantation was enabled by the combination of the microbeads with a concentration of agarose higher than 7.5% and in vitro culture even in recipients having a high level of preformed antibodies.

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The purpose of this study was to determine if calpain-induced proteolysis was associated with retinal degeneration or dysfunction in the rat acute ocular hypertensive model. Acute glaucoma was produced by elevation of IOP to 120 mm Hg for 1 hr. Retinal degeneration was evaluated by H&E staining and apoptosis was determined by TUNEL staining in histologic sections of retina. Electroretinogram (ERG) was carried out to evaluate changes in functionality. Activation of calpains was determined by casein zymography and immunoblotting. Total calcium in retina was measured by atomic absorption spectrophotometry. Proteolysis of alpha-spectrin, tau, cdk5, and p35 (a regulator of cdk5) were evaluated by immunoblotting. The thickness of inner plexiform layer (IPL) and inner nuclear layer (INL), and the number of cells in the ganglion cell layer (GCL) decreased after ocular hypertension. Numerous cells in the INL stained positive for TUNEL and some cells in the outer nuclear layer (ONL) showed TUNEL staining. The a-wave in ERG was temporarily decreased after ocular hypertension and then recovered to normal. In contrast, the b-wave was completely lost. Calpains were activated after ocular hypertension. Activation of calpains was associated with increased calcium in retina. Calpain-dependent proteolysis of alpha-spectrin, tau, and p35 were observed in retina after ocular hypertension. The results suggested that increased calcium and subsequent proteolysis by activated calpains was associated with the death of inner retinal cells due to acute ocular hypertension in the rat model. Calpain inhibitors may be candidate drugs for treatment of retinal degeneration and dysfunction resulting from glaucoma.

The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation. The inhibitor relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow. Our results suggest that the ROCK inhibitor is a promising treatment for glaucoma therapy in the next generation.