L-threonine in the treatment of spasticity.

Preclinical data indicate that the administration of the amino acid L-threonine increases glycine levels in rat spinal cord. In order to investigate glycinergic mechanisms in spasticity, and other signs of the upper motor syndrome, we gave 4.5 and 6.0 g/day of L-threonine to 18 patients with familial spastic paraparesis (FSP) according to a double-blind, crossover protocol. The response to treatment at the end of each 2-week period was based upon three measures: the physician's global impressions; the patients' global impressions; and semiquantitative ratings of strength, muscle tone, DTRs, walking, hopping, and running. Blood and CSF were collected during each treatment period for amino acid analyses. Based upon the severity rating scales, there was a statistically significant (p less than 0.02) decrease in motor impairment and spasticity during L-threonine administration compared to placebo treatment; significant treatment effects were not found on the physician's and patients' global impressions. Plasma and CSF levels of threonine increased significantly during L-threonine treatment but glycine levels did not change. These data indicate that L-threonine significantly suppressed the signs of spasticity even though the benefits were not clinically valuable.

The circadian rhythm of plasma melatonin during the normal menstrual cycle and in amenorrheic women.

Plasma melatonin, PRL, and LH levels were measured in samples collected every 2 h for 24 h from 14 normally cycling women during the early follicular, periovulatory, and luteal phases of their menstrual cycles. Plasma melatonin levels also were measured in samples collected at the same interval from 7 patients with hypothalamic amenorrhea. A distinct daily rhythm in plasma melatonin was evident in all subjects, with peaks occurring around 0300 h. Each woman's rhythm was remarkably consistent throughout the menstrual cycle (in terms of the phase, amplitude, and total melatonin secreted). Plasma PRL levels also exhibited daily rhythms which did not change during the menstrual cycle; the nocturnal peak plasma PRL level tended to occur 1-2 h after that for melatonin. Among the amenorrheic women, both daytime and nighttime melatonin levels were significantly higher (P less than 0.005) than in the normal women. Their plasma PRL levels were similar to those in the normal women. We conclude that, as for PRL, the circadian rhythm of melatonin secretion does not change significantly during the normal menstrual cycle. The elevated plasma melatonin levels in women with hypothalamic amenorrhea suggest that the hormone may be involved in the neuroendocrine pathology underlying this disorder.