Erythrocytes anion transport and oxidative change in beta-thalassaemias.

beta-Thalassaemia is characterized by a decrease in globin beta-chain synthesis and an excess in free alpha-globin chains. This induces alterations in membrane lipids and proteins resulting from a reduction in spectrin/band 3 ratio, partial oxidation of band 4.1 and clustering of band 3. The membrane injury provokes hyperhaemolysis and bone marrow hyperplasia. The pathophysiology of thalassaemia is associated with iron overload that generates oxygen free radicals and oxidative tissue injury with ocular vessel alterations. The aim of this research is to investigate the influence of oxidative stress on band 3 efficiency, which is an integral membrane protein of RBCs (red blood cells). Band 3 protein, of which there are more than 1 million copies per cell, is the most abundant membrane protein in human RBCs. It mediates the anion exchange and acid-base equilibrium through the RBC membrane. Some experiments were performed on thalassaemic cells and beta-thalassaemia-like cells and tested for sulfate uptake. To test the antioxidant effect of Mg(2+), other experiments were performed using normal and pathological cells in the presence of Mg(2+). The oxidant status in thalassaemic cells was verified by increased K(+) efflux, by lower GSH levels and by increased G6PDH (glucose-6-phosphate dehydrogenase) activity. The rate constant of SO(4)(2-) uptake decreases in thalassaemic cells as well as in beta-thalassaemia-like cells when compared with normal cells. It increases when both cells are incubated with Mg(2+). Our data show that oxidative stress plays a relevant role in band 3 function of thalassaemic cells and that antioxidant treatment with Mg(2+) could reduce oxidative damage to the RBC membrane and improve the anion transport efficiency regulated by band 3 protein.

Botulinum toxin vs. topical glyceryl trinitrate ointment for pain control in patients undergoing hemorrhoidectomy: a randomized trial.

PURPOSE: The maximum resting pressure in the anal canal is greatly raised after hemorrhoidectomy. This increase is likely to be the cause of postoperative pain, which is still the most troublesome early problem after hemorrhoidectomy. This study was designed to compare, after hemorrhoidectomy, the effects of intrasphincter injection of botulinum toxin vs. application of glyceryl trinitrate ointment in improving wound healing and reducing postoperative pain at rest or during defecation. METHODS: Thirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 40 days after hemorrhoidectomy. One group received one injection containing 20 IU of botulinum toxin, whereas the other an application of 300 mg of 0.2 percent glyceryl trinitrate ointment three times daily for 30 days. RESULTS: Five days after hemorrhoidectomy, maximum resting pressure was significantly reduced compared with baseline values in both groups (85 +/- 15 vs. 68 +/- 11 mmHg for the group treated with botulinum toxin, 87 +/- 11 vs. 78 +/- 11 mmHg for the group treated with glyceryl trinitrate ointment). Overall analysis of postoperative pain at rest showed a significant reduction in the botulinum toxin group vs. glyceryl trinitrate group, whereas pain during defecation and time of healing were similar. Adverse effects, such as headaches, were observed only in the glyceryl trinitrate group. Forty days after hemorrhoidectomy in the glyceryl trinitrate group, maximum resting pressure values were similar to preoperative ones, whereas the values were still reduced in the botulinum toxin group. CONCLUSIONS: A single intrasphincter injection of botulinum toxin was more effective and safer than repeated applications of glyceryl trinitrate in reducing early postoperative pain at rest but not during defecation.