Met-enkephalin-Arg6-Phe7 in spinal cord and brain following traumatic injury to the spinal cord: influence of p-chlorophenylalanine. An experimental study in the rat using radioimmunoassay technique

The possibility that trauma to the dorsal horn may affect the release and distribution of enkephalin was examined using the opioid peptide Met-Enk-Arg6-Phe7 (MEAP) as a marker in a rat model. The peptide content of samples of spinal cord and whole brain was measured using a radioimmunoassay (RIA) technique. In addition, the possible functional relation between this peptide and serotonin was evaluated using a pharmacological approach that included depletion of endogenous serotonin. A focal trauma to the right dorsal horn in the T10-11 segments (2 mm deep and 5 mm long) markedly modified the content of MEAP of the adjacent rostral and caudal segments of the cord, as well as the content of MEAP of the brain. Depletion of serotonin with p-CPA (an inhibitor of the synthesis of serotonin) significantly elevated the content of MEAP in the whole brain without affecting the regions of the spinal cord (except T9 level which showed a 25% decrease from an intact control group). Trauma to the spinal cord in the serotonin-depleted animals did not alter the content of MEAP further, as compared to a p-CPA-treated but untraumatized group. These results indicate that enkephalin (i) participates in the pathophysiology of spinal cord trauma and (ii) suggest that the peptide is somehow functionally related with serotonin.     

An evaluative study of the short-term effects of once-daily, sustained-release theophylline on sleep in nocturnal asthmatics

OBJECTIVE: To examine the effects of once-daily, sustained-release theophylline on sleep patterns in nocturnal asthmatics. DESIGN: Double-blind, randomised, cross-over, placebocontrolled trial over 22 days. Seven-day period to establish therapeutic levels of theophylline (11.8 +/- 3 mg/l); 8-day cross-over period of 4 days' placebo or theophylline; 7-day baseline period. Electrophysiological sleep patterns, overnight bronchoconstriction and arterial O2 saturation monitored on nights 7, 11 and 15. SETTING: Sleep Laboratory, Medical School, University of the Witwatersrand. PATIENTS: Twelve volunteers who met the criteria for asthma, had previously used theophylline, were clinically stable and had a history of nocturnal awakenings caused by asthma were enrolled. OUTCOME MEASURES: Sleep-onset latency (SOL), within-sleep wakefulness (WSW), rapid eye movement sleep (REM), slow-wave sleep (SWS), peak expiratory flow rate (PEFR) and arterial oxygen saturation. RESULTS: SOL increased on theophylline--12 minutes (range 7-9 minutes) compared with placebo--6 minutes (range 3-11 minutes); WSW increased from 33 minutes (range 17-66 minutes) on placebo to 72 minutes (range 35-150 minutes) on theophylline. REM sleep was unaltered. SWS decreased in 10-12 patients, but this difference was not significant. Early morning PEFR was significantly better on theophylline in all study limbs. CONCLUSION: Our findings show that while once-daily, sustained-release theophylline improves bronchodilation in nocturnal asthmatics, it increases nocturnal wakefulness and decreases sleep efficiency during short-term treatment. This may, however, not be a long-term effect.