Peripheral choriovitreal neovascularization in proliferative diabetic retinopathy: histopathologic and ultrastructural study

We describe the histopathologic and ultrastructural evidence of choriovitreal neovascularization in the peripheral fundus of a non-vitrectomized eye with proliferative diabetic retinopathy (PDR). One eye with PDR was surgically enucleated because of neovascular glaucoma and studied with light and electron microscopy. The eye had neovascular membranes at the ora serrata of the peripheral fundus. The newly formed vessels originated from the choroid, passed through Bruch's membrane and the retina, and extended into the vitreous. These vessels had either developing or mature characteristics. The endothelial cells of the developing vessels contained a bulky cytoplasm with many intracytoplasmic filaments, ribosomes and rough endoplasmic reticulum. Budding endothelial cells were frequently found in the developing vessels. The endothelial cells of the mature vessels had attenuated cytoplasm and fenestrations with diaphragms. These observations suggest that choriovitreal neovascularization in the peripheral fundus is one of the features of PDR.     

E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide.

1. The major pathological responses to Gram-negative bacterial sepsis are triggered by endotoxin or lipopolysaccharide. As endotoxin is shed from the bacterial outer membrane, it induces immunological responses that lead to release of a variety of cytokines and other cellular mediators. As part of a program aimed at developing a therapeutic agent for septic shock, we have developed E5531, a novel synthetic lipopolysaccharide antagonist. 2. As measured by release by tumour necrosis factor-alpha, human monocytes or whole blood can be activated by lipopolysaccharide, lipid A, and lipoteichoic acid (from Gram-positive bacteria). E5531 potently antagonizes activation by all these agents while itself being devoid of agonistic activity. 3. The inhibitory activity of E5531 was dependent on time of addition. When 10 nM E5531 was added simultaneously with lipopolysaccharide or 1 - 3 h before addition of lipopolysaccharide, production of tumour necrosis factor-alpha was inhibited by more than 98%. The addition of E5531 1 h after lipopolysaccharide reduced the efficacy of E5531 by 47%. 4. Antagonistic activity of E5531 was specific for lipopolysaccharide as it was ineffective at inhibiting interferon-gamma mediated NO release of RAW 264.7 cells, phorbor 12-myristate 13-acetate stimulated superoxide anion production in human neutrophils, concanavalin A stimulated mitogenic activity in murine thymocytes and tumor necrosis factor-alpha induced E-selectin expression in human umbilical vein endothelial cells. 5. E5531 as well as MY4, an anti-CD14 antibody, inhibited radiolabelled lipopolysaccharide binding in human monocytes. 6. These results support our contention that E5531 is a potent antagonist of lipopolysaccharide-induced release of tumour necrosis factor-alpha and other cellular mediators and may be an effective therapeutic agent for human septic shock due to Gram-negative bacteria.     

The effect of motivation on preschool children's sharing judgment and behavior]

The purpose of this study was to examine the effect of motivation on preschool children's sharing judgment and behavior. In Experiment 1, 45 4-year-olds and 41 5-year-olds were asked whether they wanted to share seals in a fictional situation, and were observed whether they shared their seals in an actual situation. The main results indicated that the number of children who shared seals in the latter situation was smaller than those who judged to share seals in the former one. Especially there was a great difference regarding this point in 4-year-olds children. "Empathic orientation" motivated preschool children's sharing behavior, while "self-focused orientation" did not. In Experiment 2, 52 4-year-olds and 60 5-year-olds were divided into two empathic levels (middle, high) and two motivational cost levels (low, high) to examine the effects of "empathic orientation" and "self-focused orientation." The main results indicated that high motivational cost restrained children from sharing in an actual situation.     

Chronic inhibitory effect of insulin on plasma lipid concentrations in rats with transplanted pancreas

BACKGROUND: Hyperinsulinemia, which is usually related to insulin resistance, is considered to be an important risk factor for coronary artery disease. Our study examines the influence of portal delivery of endogenous insulin after pancreas transplantation on plasma lipid metabolism, as compared with systemic delivery of insulin. METHOD: Pancreas was transplanted heterotopically in normal rats by anastomosis of the donor portal vein to the recipient portal vein (PPTx) or inferior vena cava (CPTx) as an in vivo model of endogenous hyperinsulinemia. RESULTS: The mean value of plasma insulin concentration of CPTx and PPTx rats was 149 and 165% that of control rats, whereas the plasma glucose concentration of CPTx and PPTx rats did not differ significantly from that of control rats. Plasma triglyceride (TG) concentrations were significantly lower in both PPTx and CPTx rats than control rats. During the intravenous glucose tolerance test, the area under the insulin concentration curves of CPTx and PPTx rats was 204 and 215% that of control rats, and they were correlated negatively with plasma TG concentrations. Plasma cholesterol and TG concentrations were significantly lower in PPTx rats than in control and CPTx rats. CONCLUSIONS: Chronic hyperinsulinemia has a dose-dependent inhibitory effect on the regulation of plasma TG concentrations in rats with a transplanted pancreas. Significant lower lipid levels in PPTx rats than in CPTx rats suggest that portal delivery of insulin from the transplanted pancreas is relatively preventive for the atherosclerotic process as compared with systemic delivery of insulin.     

Metabolism of 2 alpha-propoxy-1 alpha,25-dihydroxyvitamin D3 and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1.

Recently, we demonstrated that some A-ring-modified vitamin D3 analogs had unique biological activity. Of these analogs, 2alpha-propoxy-1alpha,25(OH)2D3 (C3O1) and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the Km and kcat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1alpha,25(OH)2D3. Thus, the catalytic efficiency, kcat/Km, of human CYP24A1 for O2C3 is only 2% of 1alpha,25(OH)2D3. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis.     

A case of aconitine poisoning saved with cardiopulmonary bypass

"Torikabuto" is a kind of plant which contains deadly poison. Its ingredient is aconitine alkaloids. We report a case of aconitine poisoning with fatal arrhythmia and acute pulmonary edema who was saved with cardio pulmonary bypass. A 41-year-old male ate to mistake "Torikabuto" for wild plant. He developed symptoms of dysarthria and admitted to our hospital. He developed ventricular tachycardia and fibrillation soon after his admission. Then he developed cardiogenic shock. He was resuscitated and supported with a percutaneous cardio pulmonary bypass. Ventricular tachycardia disappeared 24 hours after admittion. About 1 week later, cardio pulmonary bypass was terminated and about 3 months later, he discharged from our hospital.