The protective action of chlorpromazine on the spinal cord of rabbits submitted to ischemia and reperfusion is dose-dependent.

BACKGROUND: Chlorpromazine (CPZ), at high doses, has been shown to protect the central nervous system in experimental models of ischemia and reperfusion. The purpose of this study was: 1) to investigate the protection afforded by different doses of CPZ on the spinal cord of rabbits submitted to ischemia and reperfusion. 2) to correlate the motor impairment of the hind limbs and the percentage of damaged neurons in the anterior horns of the lumbar spinal cord in treated and untreated animals. METHODS: Seventy-two New Zealand white rabbits were divided into 6 equal groups (n=12): sham operation, control and 4 study groups. Spinal cord ischemia was obtained by clamping the abdominal aorta caudally to the renal arteries for 30 min, after which it was released and the animals were observed for a period of 48 hrs. The control animals received 3 ml/kg of 0.9% NaCl, i.v., 10 min before aorta clamping. The experimental animals received CPZ, i.v., at doses of 2, 1 and 0.5 mg/kg, 10 min before aorta clamping. In one group 1 mg/kg of CPZ was given 10 min before aorta clamping and the same dose was repeated 2 hrs after the beginning of reperfusion. The spinal cord of the control animals and of those who received one CPZ dose of 2 mg/kg was processed for light microscopy examination. RESULTS: Motor scores of the hind limbs, graded 0 to 4, obtained 48 hrs after the beginning of reperfusion showed that CPZ was effective at doses of 2 and 1 mg/kg. No significant difference was observed with the dose of 0.5 mg/kg. However, the best results were obtained with the dose of 2 mg/kg administered in a fractionated manner. Histological examination revealed that at the dose of 2 mg/kg, CPZ protected a significant number of neuronal cells and that motor recovery hardly occurred when the number of damaged neurons exceeded 50%. CONCLUSIONS: 1) The neuroprotective action of CPZ is dose-dependent in the ischemic spinal cord of rabbits. The lower protective dose is 1 mg/kg, which is too high for human beings. 2) There is an inverse correlation between motor recovery and percentage of damaged neurons, and the critical point seems to be between 30% and 50%.

Salivary cortisol for screening of Cushing's syndrome in children.

OBJECTIVE: Cushing's syndrome (CS) is characterized by changes in diurnal cortisol variation and total or partial resistance to cortisol suppression by dexamethasone (DEX). Diagnosing CS is a challenge especially in childhood and requires differentiation from primary obesity. The aim was verify the efficacy of salivary cortisol in differentiating primary obesity from CS in children. SUBJECTS AND METHODS: We studied 11 patients with CS confirmed by standard laboratory investigation and surgical findings aged 1-16 years, and 21 age-matched primary obese controls. Salivary samples were collected at 0900 h, 2300 h, and after an overnight DEX suppression test (20 microg/kg up to 1 mg). Salivary cortisol was measured by RIA. RESULTS: Diurnal variation of salivary cortisol levels was observed in all controls, as opposed to only 5 of 11 patients with CS. Suppression of salivary cortisol was detected in all controls but in no CS patient after the overnight DEX test. Mean salivary cortisol levels were higher in the CS than in the control group both at 2300 hours and at 0900 hours after DEX but no difference was observed at 0900 hours of the first day. The sensitivity and specificity of salivary cortisol at 0900 h, 2300 hours and after-DEX in diagnosing CS were 27% and 95.2%, 100% and 95. 2%, and 100% and 95.2%, respectively. Sensitivity and specificity of 100% were obtained by combining the data for 2300 hours and after-DEX. CONCLUSION: The combination of salivary cortisol determination at 2300 hours and after-Dexamethasone is an easily performed and noninvasive method with high specificity and sensitivity for diagnosing Cushing's syndrome in children.