5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.
The present study demonstrates that with the use of corneal electrodes mice can be kindled to minimal convulsions by repeated 60-Hz electroshocks. The efficacy of kindling was found to be dependent upon several stimulus parameters, including duration and intensity as well as the intertrial interval. Because the complexity and generalization of the minimal convulsions increased with the number of electroshock treatments, it was apparent that such kindling had quantitative as well as qualitative characteristics. Moreover, the fact that 50% of the mice remained completely kindled to minimal convulsions 8 weeks after cessation of repeated stimulation indicated that the phenomenon is relatively long-lived. Finally, the increase in CNS excitability associated with kindling extended to some, but not all, chemo- and electroshock tests of excitability. Altogether, the results show that mice kindled by corneal electrode stimulation have many features in common with animals kindled by stimulation of discrete brain areas. Because the procedure can readily and rapidly yield large numbers of kindled animals, an important application for the method will be in the evaluation of drug effects on kindled animals.
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