ABSTRACT
Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug.
ABSTRACT
PURPOSE: An experimental study was undertaken in order to estimate the angiogenic activity in different free grafts and pedicle flap in urethral reconstruction in an animal model. METHODS: Twenty-eight white New Zealand rabbits were randomly divided into five groups (O, A, B, C and D). A ventral urethral defect was created in all groups. In the group O, (n = 4), a simple closure of the defect was performed. Free penile skin graft (group A, n = 6), buccal mucosal graft (group B, n = 6), bladder mucosal graft (group C, n = 6), and pedicle penile skin graft (group D, n = 6) were used to bridge the urethral defect as an onlay patch. The animals were euthanized on the 21st postoperative day. The angiogenic activity was assessed with immunohistochemistry, using the anti-CD31 MoAb and the alkaline phosphatase antialkaline phosphatase procedure. The native vascularity of penile skin as well as buccal and bladder mucosa was assessed in rabbits from group O (n = 3). Statistical analysis was performed using one-way ANOVA. RESULTS: The angiogenesis seen with a magnification of x 200 in groups O, A, B, C, and D was 34.1 +/- 4.1 (mean +/- SD), 61.7 +/- 6.4, 94.3 +/- 6.4, 91.5 +/- 7.2, and 30.8 +/- 5.2 vessels per optical field, respectively. There were statistically significant differences (p < 0.001) between group O and groups A, B, C and between group A and groups B, C, D, but not (p > 0.5) between groups B and C and groups O and D. The native vascularity of penile skin, buccal mucosa and bladder mucosa was 23.3 +/- 3.0, 24.6 +/- 3.7 and 17.0 +/- 2.6 vessels per optical field, respectively. CONCLUSION: Buccal and bladder mucosal grafts exhibit a higher angiogenic activity than free and pedicle penile skin flap when transplanted in urethral defects. As the buccal mucosal graft showed the higher angiogenic activity and its harvesting is easier than bladder mucosa, we propose that in urethral reconstruction surgery the use of this graft might offer more reliable results.
