Selective functionalizations of dimethyl 4-cyclohexene-l,2-dicarboxylate (1) and acyclic olefins 5 into the corresponding epoxides 2 and 6, bromohydrins 3 and 7, and 1,2-dibromides 4 and 8 were performed by electrolysis in a MeCN-H20-NaBr-(Pt) system. Lower Br" concentration (less than 0.05 M) facilitates the formation of 2 in neutral medium and of 3 in acidic medium, whereas higher Br" concentration (more than 1.5 M in acidic medium) produced exclusively 4. The effective C-C bond cleavage of the epoxy group of 2, leading to the corresponding diacetal 10, was also accomplished by electrolysis in a Me0H-H2S04-(C) system.

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Nociceptive responses in an animal model of peripheral nerve injury were studied. The left common sciatic nerve was exposed, tightly ligated at two locations and transected between the ligatures. A bilateral decrease in the nociceptive threshold to mechanical stimulation was observed within 3 h after the operation. The skin of the lateral dorsal part of the injured paw was hypoalgesic, while the medial dorsal paw innervated by the intact saphenous nerve and the contralateral dorsal paw exhibited hyperalgesia. Amitriptyline, an antidepressant, at 25, 50 and 100 mg/kg per day, p.o., and gabapentin, an anticonvulsant, at 30, 100 and 300 mg/kg per day, p.o., significantly inhibited the decrease in the mechanical nociceptive threshold in the injured and uninjured paws. The effects of amitriptyline at 25 and 50 mg/kg were evident at doses that did not cause neurologic deficits as assessed by the inclined screen test. Indomethacin, a cyclooxygenase inhibitor, and morphine (except at the highest dose of 30 mg/kg, s.c.) showed no analgesic effects in this model. The tail-flick latency was also significantly decreased compared with intact rats. Similar bilateral hyperalgesia was observed when axotomy was performed using silk thread instead of chromic gut. When this axotomy model was applied to mice, the nociceptive thresholds in both paws immediately showed a significant decrease in the same manner as in rats. The bilateral and systemic hyperalgesia observed in this axotomy model, which resembles the clinical features of chronic neuropathic pain, suggests the involvement of the central nervous system in the maintenance of the chronic pain state.

Haemocirculatory and metabolic changes in seemingly normal brain tissue following radiochemotherapy including nimustine hydrochloride (ACNU) and tegafur (FT) were analyzed using oxygen-15 and fluorine-18 positron emission tomography (PET) in seven patients with gliomas. At an early stage (within one month) after radiochemotherapy, marginal increases in regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) were found contralateral to the tumour in gray matter which was apparently normal brain structure, as seen on computerized tomography (CT). The oxygen extraction fraction (rOEF) decreased significantly (p less than 0.05 by a paired-t test) from that of the pretreatment study, due to surgical decompression and radiochemotherapy. At the late stage (three to thirty-one months with a mean of thirteen months), rCBF decreased significantly from the early stage study (p less than 0.05); oxygen consumption (rCMRO2) fell in all cases significantly from the pretreatment study (p less than 0.01) and from the early stage study (p less than 0.05); consequently, rOEF remained unchanged at a level similar to the early stage study. Glucose consumption (rCMRG1) increased slightly as compared with the early stage study but failed to be restored to the level of the pretreatment study. Noteworthy was a coupling reduction of rCBF and rCMRO2--presumably, a late delayed effect of radiochemotherapy. These preliminary results indicate that with PET studies it may be possible to predict damage to normal brain tissue after radiochemotherapy.