糖尿病性ニューロパチーの表皮神経の評価
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Summary: In an attempt to evaluate the morphological abnormalities of dermal non-myelinated nerve fibers of diabetic monkeys and elucidate the pathogenesis of diabetic peripheral neuropathy, the terminal part of peripheral nerve in the upper dermis was observed on electron microscopy using skin samples biopsied in 10 diabetic monkeys with symptomatic neuropathy and 10 control monkeys. In diabetic monkeys, the density of nerve fibers was significantly lower than in controls. In addition, swelling, lytic change and vacuolization in the axon, multiplication of basement membrane of the Schwann cell and Schwann cell cluster devoid of axon were more frequently observed in diabetic monkeys. The Schwann cell did not show significant structural alterations. These findings suggest that the axon is primarily involved, at least in the terminal region of nerve fiber, in diabetic peripheral neuropathy. It is also concluded that the skin biopsy technique is unharmful, cosmetically not troublesome and might be beneficial for studying peripheral neuropathies including diabetic neuropathy.Animals: The subjects were 10 diabetic monkeys (male 5, female 5) aged 3 to 12 years with neurological symptoms such as pain, parenthesis, and hyperesthesia and 10 controls aged 5 to 15 years without any neurological symptoms. All the diabetic monkeys had the decreased vibration sense and the Achilles tendon jerk. The duration of diabetic state ranged from 3 to 5 years. They were controlled with insulin therapy.Skin biopsy: A piece of skin, approximately 3x3x0.5 mm in size, was biopsied from the right calf under local anesthesia by 0.5% procaine chloride. Tissue preparation and electron microscopical observation:Blocks of the specimens were fixed in Karnovsky's fixative solution (2.5 % glutaraldehyde, 2 % paraformaldehyde in 0.1 M sodium cacodylate, pH 7.4). After overnight fixation, the specimens were rinse in 0.1 M sodium cacodylate, followed by post-fixation in 1 % osmium tetroxide, dehydration in graded concentration of ethanol, treatment with propylene oxide and embedding in Epon 812. Three blocks per subject capable of being cut tangential to the skin surface were used for electron microscopical observation. After trimming those blocks into about 400μm in depth from the basal layer of the epidermis, both semithin section of 1 μm and ultrathin ones of 1000A in thickness were cut on an LKB Ultrotome 8800. The former sections, after being stained with toluidine-blue, were served for measurement of the area of the dermis. The latter sections stained with uranyl acetate and lead citrate were observed under JEM 100 CX electron microscopy (JEOL Ltd., Tokyo Japan).Conclusion: In conclusion, skin biopsy is thought to be a very useful and harmless procedure for the morphological evaluation of diabetic peripheral neuropathy.
- 日本毒性学会の論文
日本毒性学会 | 論文
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