[Conservative therapy of diabetic eye disease].
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Biomedical subjects
Publications and source records attributed to N Hotta.
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In addition to the results of our clinical trial of epalrestat in diabetic retinopathy (the open study), the current progress in the clinical trials of aldose reductase inhibitors for the 'triopathy' of complications (neuropathy, retinopathy and nephropathy) in Japan is reported. No data from the placebo-controlled double-blind studies in Japan are shown because a detailed analysis of the effects of epalrestat on diabetic neuropathy and retinopathy is now under way. However, it must be stressed that in the phase III placebo-controlled double-blind studies in neuropathy and retinopathy, epalrestat was effective.
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Nitrides used in this experiment are hBN, A1N and Si3N4. We studied feasibility of nitrides as wax pattern coating materials for Co-Cr alloy in an atmosphere of argon. Wax patterns were painted with coating material of nitrides (first investing), then a mixture of phosphate bonded investment and water was used in outer investing (second investing). The temperature of mold was 800 degrees C, and an argon arc vacuum-pressure casting machine was used. We cast the thin specimens in Co-Cr alloy (composition Co: 63 wt%, Cr: 27 wt%, Mo: 5 wt%, Bal.: 5 wt%; melting point: 1,380 degrees C). Surfaces of cast specimens were investigated using the unaided eye, a scanning electron microscope and a surface roughness analyzer. Furthermore, the thick specimens (globular form: phi 6.5 mm) using coating material of hBN were investigated using the unaided eye. Results were summarized as follows; 1. The nitrides controlled remarkably the reaction between cast specimen and investment. 2. The nitrides had the good effect of separation. 3. The cast surface coated the nitrides had less clinging than uncoated one, and this indicated that its cleansability was improved. 4. The nitrides decreased the surface roughness (Rz) of the cast to about 1/3. 5. hBN had the best effect in nitrides. 6. hBN also had the effect in a thick globular specimen.
Isolated adipocytes from severely diabetic rats exhibited hypersensitivity to epinephrine at low concentrations (0.05-0.1 microM) on lipolysis, compared with isolated adipocytes from normal and mildly diabetic rats. Hypersensitivity to dibutyryl cyclic AMP and theophylline at concentrations from 0.05 to 0.50 mM was not observed in adipocytes of severely diabetic rats. Insulin could not exert an inhibitory effect on epinephrine-induced lipolysis in adipocytes of severely diabetic rats. In isolated adipocytes from normal rats, hyperosmolarity due to the combination of 50 mM glucose and 100 mM sodium chloride only had an inhibitory effect on 0.25 microM epinephrine-induced lipolysis. Ten mM beta-hydroxybutyrate did not inhibit lipolysis caused by epinephrine although any lipolysis stimulated by epinephrine, dibutyryl cyclic AMP and theophylline was inhibited by insulin. Our present findings may partly explain insulin resistance in the severely diabetic state and the pathogenesis of the absence of ketosis in hyperglycemic hyperosmolar conditions.
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The present study investigated whether or not, in addition to the oral glucose tolerance test, oral alanine loading was a useful diagnostic tool for hormonal and metabolic diseases. Fifty g of L-alanine was administered orally in 14 normal, 12 diabetic, and 8 liver cirrhotic subjects. The influence of oral alanine loading on hormones and metabolites was compared with the results of 100 g oral glucose loading. The results obtained were as follows: 1) In the normal subjects and cirrhotics, lactate and pyruvate concentrations gradually increased with time and reached their peak levels at 60 min, whereas they remained unchanged throughout the course in the diabetic group at glucose loading. 2) Alanine administration accelerated ureogenesis but did not affect blood glucose levels. 3) In both glucose and L-alanine administration, free fatty acid, glycerol and ketone body levels declined nonspecifically in all groups. 4) Serum glucagon levels during L-alanine loading increased in all groups, especially in liver cirrhotics. 5) L-alanine was a potent stimulus for insulin secretion in diabetics, while no insulin release during glucose loading was observed. 6) The molar ratio of insulin levels (during glucose loading)/glucagon levels (during L-alanine loading) was a good indicator of systemic glucose homeostasis from the hormonal aspect. It is suggested that, in addition to the oral glucose tolerance test, the oral administration of L-alanine can be a useful tool for the diagnosis of the status in diabetes mellitus and cirrhosis.
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Myo-inositol uptake by erythrocytes from humans, rabbits and rats was studied with an isotope technique. In human erythrocytes, the inhibitory effect on myo-inositol uptake was stronger with glucose than with ouabain. However, an aldose reductase inhibitor (ONO-2235, 100 microM) or insulin (200 microU/ml) failed to correct the decrease in myo-inositol uptake in packed RBC, produced by either 10 mM glucose or 2mM ouabain. Ten mM ouabain had an inhibitory effect on myo-inositol uptake in all species, but an inhibitory effect was not observed with 20 mM glucose in rabbit erythrocytes. The results suggest that myo-inositol uptake by erythrocytes may be dependent on the active transport system via sodium-ATPase and that erythrocytes may not be a suitable model to monitor the possible effect of an aldose reductase inhibitor on myo-inositol concentrations in other tissues concerned with diabetic complications.