Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235.

The effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.

Histological features of nerve fibers and endoneural vessels in a case of Wegener's granulomatosis.

A sural nerve biopsy obtained from a patient with Wegener's granulomatosis and overt clinical signs of polyneuropathy showed degenerative changes of both myelinated and unmyelinated fibers. The pathological aspects were those of an axonopathy. Endoneural vessels were also involved, showing changes either in the endothelial cells, which were thickened and enriched with organelles, or in the basal membrane, which was reduplicated and thicker than in the controls. There were no cellular infiltrates nor was there clear evidence of fibrosis in the vascular wall. We suggest that peripheral neuropathy in Wegener's granulomatosis could be secondary to endoneural vessel changes on the basis of a possible immune complex action.

[Age-related changes in peripheral nerves]. / Zur Problematik von Alternsveränderungen an peripheren Nerven.

Semi-thin sections of the sural nerve from 200 autopsy specimens taken from individuals of both sexes, ages 10 to 91 were morphologically examined. Thickness of the endoneurial capillary walls, and of the perineurium, number of endoneurial capillaries, myelinated fiber density and distribution of myelinated fibers were determined. An additional ultrastructural examination of selected nerves with characteristic values was performed. The analysis revealed a statistically significant age dependence for the investigated features. Increasing age was associated with decreased myelinated fiber density and decreased number of endoneurial capillaries. There was an age dependent increase in the thickness of capillary walls and the perineurium as well as increasing loss of large myelinated fibers. The findings were discussed and compared with similar results from the literature. Age related changes in peripheral nerves have to be interpreted as the result of the cumulative, life-long effect of various pathogenic factors, modified by genetic determinants and by a gradual decrease in regenerative capacity.

Microsphere embolization of nerve capillaries and fiber degeneration.

Polystyrene microspheres, the size chosen to plug capillaries and precapillaries, were injected into the arterial supply of rat sciatic nerves. They produced widespread segmental occlusion of capillaries in lower limb nerves. The clinical and pathologic effect was dose-related. One million microspheres produced selective capillary occlusion but no nerve fiber degeneration; approximately 6 million microspheres also produced selective capillary occlusion and associated foot and leg weakness, sensory loss, and fiber degeneration, beginning in a central core of the distal sciatic nerve; 30 million microspheres caused both capillary and arterial occlusion and a greater neuropathologic deficit. From these observations it is inferred that 1) occlusion of isolated precapillaries and capillaries does not produce ischemic fiber degeneration; 2) occlusion of many microvessels results in central fascicular fiber degeneration, indicating that these cores are watershed regions of poor perfusion; and 3) stereotyped pathologic alterations of nerve fibers and Schwann cells are related to dose, anatomic site, and time elapsed since injection.