Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

The mammalian suprachiasmatic nucleus (SCN) is a master circadian pacemaker. It is not known which SCN neurons are autonomous pacemakers or how they synchronize their daily firing rhythms to coordinate circadian behavior. Vasoactive intestinal polypeptide (VIP) and the VIP receptor VPAC(2) (encoded by the gene Vipr2) may mediate rhythms in individual SCN neurons, synchrony between neurons, or both. We found that Vip(−/−) and Vipr2(−/−) mice showed two daily bouts of activity in a skeleton photoperiod and multiple circadian periods in constant darkness. Loss of VIP or VPAC(2) also abolished circadian firing rhythms in approximately half of all SCN neurons and disrupted synchrony between rhythmic neurons. Critically, daily application of a VPAC(2) agonist restored rhythmicity and synchrony to VIP(−/−) SCN neurons, but not to Vipr2(−/−) neurons. We conclude that VIP coordinates daily rhythms in the SCN and behavior by synchronizing a small population of pacemaking neurons and maintaining rhythmicity in a larger subset of neurons

Unreamed intramedullary tibial nailing - Fatigue of locking bolts

Between January 1990 and October 1993 toe investigated 72 consecutive patients who had an unreamed tibial nail inserted for fractures of the tibial shaft; 75 per cent (N = 54) were closed fractures and 25 per cent (N = 18) were open fractures. The mean follow up was 15.2 months. Of the patients 91.7 per cent (N = 66) were interlocked, 58 per cent (N = 38) statically and 42 per cent (N = 28) dynamically. Union rate was 98.6 per cent, time to union was 18.5 weeks, 17.3 weeks for closed fractures, 22 weeks for open fractures. Shortening greater than 1 cm occurred in 1.4 per cent (N = 1), varus and valgus deformity in 4.1 per cent each (N = 3). There was no rotational deformity. Of the locking bolts 30 per cent broke 8-10 weeks after partial weight bearing was allowed. Electron microscopy investigations showed that failure of the bolts was due to fatigue. It was not associated with any clinical problems with regard to union times or incidence of malunion. Bolt failure is however a problem if you try to remove the nail. (C) 1996 Elsevier Science Lt