Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients.

BACKGROUND: Patients with Parkinson's disease (PD) and chronically treated with L-DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after discontinuation of 1-month folate supplementation given to normalize plasma tHcy levels. METHODS: Plasma tHcy, cobalamin and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years) stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day. RESULTS: After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2-month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper-tHcy. CONCLUSIONS: One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD.

Polyamines are involved in retinoic acid-mediated induction of tissue transglutaminase in human peripheral blood monocytes.

The differentiation of human peripheral blood monocytes (HPBM) into macrophages, when cultured in vitro, has been associated with an increase in the expression of tissue transglutaminase (TGc). Retinoic acid (RA) addition to 5-day-old cultured monocytes, 36 h later induced about 5-folds increase of TGc content. The preliminary exposure of cultured monocytes to alpha-difluoromethylornithine (DFMO) significantly reduced TGc induction caused by RA. DFMO alone does not induce significant changes in the time-course of TGc activity. In cultured monocytes exposed to DFMO, putrescine and spermidine, but not spermine were significantly depleted. The supplementation of putrescine (1 mM) or spermidine (0.5 mM) to culture medium reversed the inhibiting effect of DFMO on RA-mediated induction of TGc. However, the addition of polyamines in the absence of RA or DFMO did not mimic the induction of TGc by RA. We conclude that TGc induction by RA during in vitro maturation of monocytes to macrophages may be modulated by polyamine availability.

Excess of taurine supplementation in rat: effects on GABA-related amino acids in developing nervous tissues.

The effects of taurine supplementation on GABA-related amino acid homeostasis in developing nervous tissues of suckling rats were studied. In the first two weeks of postnatal growth, cerebral cortex and cerebellum appear more accessible to taurine supplementation in comparison to retina; in addition, different changes in excitatory/inhibitory amino acids were observed. After the 5th day of life, in the retina and cerebellum of taurine-supplemented pups a decrease in GABA levels was found; in contrast, in cerebral cortex GABA content significantly increased throughout 20 days of postnatal growth. In all nervous tissues studied (except for cerebellum) glutamine concentration increased at the 5th day; then in cerebellum and in retina, but not in cerebral cortex, a significant decrease until the 20th day occurred. Furthermore, in cerebellum and retina taurine supplementation decreased glutamate levels, in comparison to controls, at the 10th and until the 20th day of postnatal life, respectively, whereas in cerebral cortex an increase in glutamate level was observed only at the 5th day. In conclusion, taurine supplementation, in excess to the usual amount from the mother's milk, affected the glutamate compartments in various cell types. The changes in GABA-related amino acid concentrations in cerebral cortex, cerebellum, and retina may depend on the different pattern of the metabolic processes at different maturative stages.

Cerebral GABAergic control of arterial blood pressure and heart rate in diabetic rats.

Cardiovascular responsiveness to intracerebroventricular (icv) administration of dopamine (50, 100 and 200 micrograms/kg), muscimol (1 and 2 micrograms), and ethanolamine-O-sulphate (EOS; 5, 10, 20 and 40 mumol) as well as GABA content in several brain areas were examined in rats, made diabetic by an intravenous (iv) injection of streptozotocin (STZ; 40 mg/Kg). Citrate buffer (pH 4.5) treated animals were used as controls. Experiments were carried out in conscious rats with chronically implanted icv cannulae and iv and intraarterial catheters, 1 and 3 weeks after STZ injection. Diabetic rats exhibited: 1) higher hyperglicaemia after 1 week than after 3 weeks; 2) normal mean arterial pressure (MAP) both after 1 and 3 weeks, and 3) bradycardia only after 3 weeks. Icv injections of muscimol, a GABA receptor agonist, and EOS, an inhibitor of GABA breakdown, caused a dose-dependent decrease in MAP and heart rate (HR), which was significantly higher than that elicited in control animals. GABA content was reduced in the hypothalamus (already after 1 week), and in the brainstem (but only after 3 weeks). No changes in GABA content were detected in other brain areas. Icv injection of dopamine elicited a dose dependent decrease in MAP and HR either in diabetic or in control rats, with no difference between groups. The results suggest that diabetes alters cerebral GABAergic control of arterial blood pressure and heart rate in the rat.

Effect of intraventricular putrescine on adenosylmethionine decarboxylase in rat hypothalamus and caudate nucleus.

Effects of intracerebroventricularly injected putrescine on adenosylmethionine decarboxylase activity in rat hypothalamus and caudate nucleus were studied. Doses that lacked the capacity to produce behavioral and electrocortical epileptogenic disorder caused a significant activation of enzyme occurring between 10 and 15 min after injection. The changes in hypothalamic and caudate nucleus enzyme activity after putrescine administration were dose-dependent, and they supported the assumption that limiting putrescine concentration in vivo may play a role in adenosylmethionine decarboxylase regulation.