N-acetylcysteine protects against cuprizone-induced demyelination: histological and immunohistochemical study.

BACKGROUND: Myelination is a sequential process that is tightly controlled by a number of intrinsic and extrinsic factors. Any central nervous system disease in which the neuronal myelin sheath is damaged is referred to as demyelinating disease. The present work was designed to study the histopathological, ultrastructural and immunohistochemical changes in rat brain, mainly corpus callosum (CC), following oral administration of cuprizone (CPZ), and the role of N-acetylcysteine (NAC) in reducing these changes. MATERIALS AND METHODS: Demyelination was induced by CPZ administration for short (4 weeks) and long (8 weeks) periods. NAC was given concomitantly and sequentially for similar periods. Spontaneous recovery after cessation of CPZ followed by no medication was also investigated. At the end of each experimental period, both cerebral hemispheres were extracted and prepared for light and electron microscopic examination and immuno-histochemical study. RESULTS: The obtained results showed a direct proportion between the duration of CPZ administration and the severity of demyelination. The co-administration of CPZ and NAC, had a fair protective impact that was stronger than the sequential administration of the two drugs. Incomplete spontaneous remyelination was observed after cessation of CPZ, being more evident in short than in long period group, indicating that when CPZ administration is prolonged, remyelination is delayed. CONCLUSIONS: In the light of the above results, it could be concluded that NAC has neuroprotective effects and has the potential to be a novel therapeutic approach for the treatment of demyelinating diseases such as multiple sclerosis; however, treatment should begin as soon as the disease manifests.

Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage.

PURPOSE: To assess the feasibility and safety of transpedicular percutaneous vertebroplasty (PVP) using thick bone cement in patients with intractable metastatic vertebral pain and at high risk for cement leakage. METHODS: Unilateral transpedicular PVP using firm bone cement was performed in 77 patients with intractable pain due to vertebral metastases in the thoracolumbar spine, who had one or more relative contraindication to PVP. Primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale and daily morphine consumption. Secondary outcome measures were the degree of disability and the incidence of procedure-related adverse outcomes. The outcome measures were assessed at the preoperative visit and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure. RESULTS: Sixty-three (81.8%) patients completed the 12-week follow-up period. There were 30 men and 33 women, with a mean age of 58±11 (SD) [range: 34-81 years]. Compared with pre-procedure value, all post-procedure pain scores were significantly lower (P<0.0001). Likewise, there was a statistically significant reduction in daily morphine consumption at all follow-up times (P<0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with pre-procedure values (P<0.0001). No serious adverse effects were observed. CONCLUSION: PVP using thick bone cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability.

beta-Endorphin and beta-lipotropin concentrations in umbilical cord blood.

Antisera suitable for human beta-endorphin and beta-lipotropin radioimmunoassay were developed, and radioimmunoassays were established to measure these peptides in umbilical cord plasma, with silicic acid extraction and gel chromatography used to separate the beta-endorphin from the beta-lipotropin fraction. These two peptides were determined in umbilical venous plasma from 64 newborn infants. Umbilical vein beta-endorphin and beta-lipotropin concentrations averaged 38.5 +/- 3.2 and 50.4 +/- 4.1 (+/- SE) fmoles/ml in the 54 newborn infants without and 115 +/- 18 and 110 +/- 25 fmoles/ml in the 10 newborn infants with apparent fetal distress. Neither the presence or absence of labor nor the route or mode of delivery was found to affect umbilical vein beta-endorphin or beta-lipotropin concentrations. However, cord plasma levels of both peptides were significantly elevated in conjunction with fetal distress, as evidenced by prolonged bradycardia, late and prolonged variable fetal heart rate decelerations, or fetal acidosis. In 18 of 22 pairs of simultaneously measured umbilical venous and arterial beta-endorphin and beta-lipotropin concentrations in newborn infants without apparent intrapartum distress, the venous beta-endorphin concentrations, which averaged 40.4 +/- 3.5 fmoles/ml, were significantly higher than the arterial beta-endorphin levels, with a mean of 28.5 +/- 4.2 fmoles/ml. No significant umbilical arteriovenous concentration difference could be observed for beta-lipotropin. This suggests that at least a portion of the coad plasma beta-endorphin is derived from the placenta. The ratio of umbilical arterial to venous beta-endorphin concentrations rose as the absolute cord plasma beta-endorphin levels increased. Furthermore, both the molar umbilical venous and arterial beta-lipotropin to beta-endorphin ratios decreased significantly in association with intrapartum fetal distress. These data indicate tat the stress-related increase in umbilical plasma beta-endorphin exceeds that of beta-lipotropin and may be, at least in part, of fetal origin. Umbilical venous beta-endorphin and beta-lipotropin levels of neonates whose mothers did not receive meperidine or other narcotics agents did not differ from those of neonates whose mothers were given meperidine or other narcotics during labor. Our data, in conjunction with those of others, are consistent with the hypothesis that fetal hypoxia causes the release of neurotransmitters such as beta-endorphin, which may modulate the regulation of fetal heart rate patterns.