Ischemic brain injury is acute local inflammation, leading to accumulation of pro-inflammatory cytokines. Cytokines influence the recruitment of leucocytes and play a key role in the inflammatory injury processes. Recently, a number of studies have demonstrated a close relationship between brain ischemia and cytokines. Interleukin-17 (IL-17) is a newly identified T-cell-specific cytokine. In this study, we evaluated the source and the action of IL-17 over the course of cerebral ischemia in rats (Sprague-Dawley) and humans. The levels of IL-17 in the ischemic hemisphere of the human brain, which was removed at necropsy, were assayed immunohistochemically. In rats, permanent middle cerebral artery occlusion (pMCAO) was obtained by inserting nylon monofilament into the right external carotid artery, occluding the right middle cerebral artery. The expression of IL-17 mRNA in rat was assayed using oligoprobe in situ hybridization. IL-17 production by neuroglial cells was assayed by double-staining using antibody glial fibrillary acidic protein (GFAP) and antibody IL-17. Levels of IL-17 were elevated in the ischemic hemispheres of human brain compared with the opposite normal hemispheres and peaked at days 3-5 after brain ischemia. The IL-17-positive cells were found in the ischemic lesion region. IL-17 mRNA was also elevated in ischemic hemispheres of pMCAO-operated rats, which were slightly elevated after 1 h and peaked at 6 days. IL-17 and GFAP double-stained were extensive in rat ischemic hemisphere. The ischemia-induced IL-17 expression in human brain reported here for the first time was very similar to that in rat model except that the peak was slightly earlier. We found for the first time that IL-17 was involved in an intense inflammatory reaction of brain ischemic injury in human. In pMCAO-operated rats, our findings suggest that IL-17 is produced by the neuroglial cells in the brain region undergoing ischemic insult. We suggest that in additional to T cells the neuroglial cell may be another cellular origin of IL-17 in later progression of brain ischemia.

Succinyl and 3'-substituted glutaryl betulin derivatives showed stronger anti-HIV activity and higher therapeutic index (TI) values than their dihydrobetulin counterparts, with ratios of 1.2:1 to 15:1 (cf. 7 and 15, 9 and 17, 10 and 18, 11 and 19, and 12 and 20). For various 3'-substituted glutaryl compounds, the order of anti-HIV effects, from strong to weak inhibition, was 3',3'-dimethyl, 3'-methyl, 3'-ethyl-3'-methyl, followed by 3',3'-tetramethylene glutaryl derivatives (10 > 9 > 11 > 12, 18 > 17 > 19 > 20). The most potent compound, 10, has two 3',3'-dimethylglutaryl groups and displays significant anti-HIV potency with an EC50 value of 0.000 66 microM and a TI of 21 515. Results for compounds (22 and 23) without a C-3 acyl group confirmed the importance of the C-3 acyl group to the anti-HIV effect. With 3',3'-tetramethylene glutaryl derivatives, triacyl 29 showed stronger inhibition than diacyl 12; in contrast, 3',3'-dimethylglutaryl compounds displayed opposite results. 3-Keto compounds (35 and 36) and 2,3-dihydro compounds (39 and 40) had EC50 values in the range of 4.3-10.0 microM, suggesting that A ring modification led to decreased potency. The reduced activity of amide (33 and 34), ester (41), and oxime (42) analogues suggested that the orientation and linkage of the C-3 acyl side chain play crucial roles in the potent anti-HIV activity. Finally, replacing the C-28 acyl group with a bulky non-carboxylic group produced a less potent compound (44). In the study of mechanism of action, our results indicated that fusion is not the primary target for the anti-HIV activity of 10. It appears to inhibit HIV replication at a late stage of the viral life cycle, i.e., after viral protein synthesis.

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Abstract:Objective: To study the effects of end-to-side anastomosis of initially-denatured nerves at different times. Method: 60 male Wistar albino rats were used to fabricate animal models for the experiment on end-to-side anastomosis of peripheral nerves and 50 female Wistar albino rats were used to fabricate animal models for the experiment on the effect of FK506 on end-to-side anastomosis. Bilateral common peroneal nerve, tibialis anterior muscle electrophysiological and histological examinations, tibialis anterior muscle wet muscle weight determination, and motor end plate examination were performed 3 months after operation.Results: All recovery rates of action potential, single muscle contraction force and tetanic contraction force of the FK506 experimental group are signifi cantly higher than those of the control group and the sectional area of muscle fi ber is also higher than that of the control group of normal saline. Conclusion:The best time for end-to-side anastomosis of nerves should be controlled within 2 weeks and the effect of end-to-side anastomosis of nerves will gradually become unsatisfactory. FK506 plays a role in promoting functional rehabilitation following nerve end-to-side anastomosis (Tab. 7, Fig. 4, Ref. 31). Text in PDF www.elis.sk.