[Mesenteric ischemia following a left radical nephrectomy]. / Infarctus mésentérique dans les suites d'une néphrectomie élargie gauche.

The nephrectomy of a dialyzed renal insufficient patient is a frequent operation. Nevertheless, the vascular complication risks are increased for these patients. We report the case of a patient who had presented a mesenteric ischemia after a left nephrectomy. The cause of this ischemia was plurifactorial with, on one hand, a splanchnic hypoperfusion due to post-procedure hypovolemia caused by an important depletion during the dialysis as well as the use of vasoactive amines and, on the other hand, the peripheral mesenteric microvascularisation occlusion due to a kayexalate crystal deposit.

[Functional evaluation of the orthotopic Z-shaped ileal detubulated neobladder with a minimal 5-year follow-up]. / Evaluation fonctionnelle de la néovessie iléale détubulée orthotopique en Z avec cinq ans de recul minimum.

OBJECTIVE: Study and evaluate the orthotopic Z-shaped neobladder in the long term and life quality of patients bearing this type of replacement. METHODS: Based on 162 medical records of patients who have undergone total cystoprostatectomy and orthotopic Z-shaped replacement because of bladder cancer with a minimal 5-year follow-up. Forty patients (113-month average follow-up) residing in the region were notified for a clinical consultation and were the basis for the target population of this study. A physical examination, a Pad test and a specific consultation allowed for continence evaluation whereas three validated surveys allowed for life quality appreciation. RESULTS: Continence was satisfactory for 82% of the patients during the day and 55% during the night. There was a significant negative correlation between a patient's age at the time of the cystoprostatectomy and diurnal continence. Life quality was estimated as good in the long term. CONCLUSION: The functional results of the Z-shaped ileal detubulated neobladder in the long term are satisfactory. It allows for good urination quality and satisfactory quality of life for patients subject to total cystoprostatectomy because of cancer as well as body schema's conservation.

Microsomal catalyzed N-hydroxylation of guanfacine and reduction of N-hydroxyguanfacine.

Guanfacine 1 is a well known centrally acting alpha 2-adrenoceptor agonist with antihypertensive activity. The drug belongs to the guanidine class of compounds. The N-oxidative biotransformation of guanfacine was investigated in vitro in the presence of hepatic microsomal fractions from rabbits, pigs, and humans. The N-hydroxylated derivative N-hydroxyguanfacine 2 had to be synthesized as reference for the identification of the metabolite. The corresponding in vitro retroreduction of N-hydroxyguanfacine 2 was also investigated using the same set of enzyme sources. A new HPLC analytical method was developed in order to isolate and quantify the metabolites. A complete metabolic cycle involving the oxidative metabolism of guanfacine could only be observed in the presence of microsomal fractions from rabbitt livers, whereas enzyme sources of all species under investigation catalyzed the N-reduction of N-hydroxyguanfacine 2.

Formation of guanoxabenz from guanabenz in human liver. A new metabolic marker for CYP1A2.

The in vitro N-hydroxylation of guanabenz as well as the corresponding N-dehydroxylation of guanoxabenz has been previously detected in biotransformation studies with microsomal fractions of different species including human hepatic microsomes. Furthermore, the N-hydroxylation of guanabenz was found to be catalyzed by enriched cytochrome P450 (P450) fractions in reconstituted systems. Strong correlations between 7-ethoxyresorufin O-deethylation (r = 0. 96; p < 0.001), caffeine N-demethylation (r = 0.92; p < 0.001), respectively, and guanabenz N-hydroxylation activities were demonstrated in 10 human liver microsomal preparations. Studies with microsomes from human B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes proved that CYP1A2 is the major isozyme responsible for this metabolic pathway. Further, P450 isozymes did not show any detectable conversion rates. The reaction was inhibited in presence of the potent CYP1A2 inhibitors alpha-naphthoflavone (7, 8-benzoflavone) and furafylline. The N-reduction of guanoxabenz to guanabenz exhibits a significant correlation to the benzamidoxime N-reduction after incubation with 10 human liver microsomal preparations (r = 0.97; p < 0.001). The formation of benzamidine from benzamidoxime was described previously to be catalyzed by the benzamidoxime reductase. These results suggest that the guanabenz N-hydroxylation is mediated via CYP1A2, whereas the corresponding guanoxabenz N-reduction is catalyzed by an enzyme system composed of cytochrome b5, NADH cytochrome b5-reductase, and benzamidoxime reductase. The high affinity of guanabenz to CYP1A2 and the distinct selectivity of this P450 isozyme toward guanabenz confirms the in vitro guanabenz N-hydroxylation to be a suitable metabolic marker for CYP1A2 in biotransformation studies.

Microsomal catalyzed N-hydroxylation of guanabenz and reduction of the N-hydroxylated metabolite: characterization of the two reactions and genotoxic potential of guanoxabenz.

The N-reduction of the centrally acting alpha 2-adrenoreceptor agonist guanoxabenz (Benzérial), an N-hydroxyamidinohydrazone, to the amidinohydrazone guanabenz (Wytensin, Hipten, Rexitene) by microsomal fractions from rabbits, pigs and humans has been detected in vitro. The conversion rates with rabbit microsomal fractions were markedly slower than those in the cases of fractions from humans and pigs. It was also possible to demonstrate the N-oxidation of guanabenz to guanoxabenz by the use of microsomal fractions from rabbits, pigs, and humans. Furthermore, the oxidation was also observed in reconstituted systems in the presence of enriched cytochrome P450 fractions, purified isoenzyme P450 2C3, and heterologously expressed P450 2C3 of the subforms 6 beta H and 6 beta L. The analyses were performed with a newly developed HPLC technique and were confirmed by LC-MS methods. The kinetic parameters determined for the metabolic cycle (bioreversible reactions) are indicative of a predominance of the reduction of guanoxabenz to guanabenz in vivo. Accordingly, guanoxabenz in part constitutes a prodrug of guanabenz. Examination of guanabenz and guanoxabenz for mutagenicity by means of the Ames test revealed that guanoxabenz has pronounced mutagenic effects in the strains TA 98 and TA 1537. Guanabenz did not exhibit mutagenicity so that the N-reduction of guanoxabenz has significance in terms of detoxification.