In vivo and in vitro antioxidant properties of furosemide.

The aim of this study was to investigate in vivo and in vitro antioxidant properties of furosemide. In vitro, human red blood cells were submitted to oxidative stress (AAPH), in absence or in presence of different concentrations of furosemide. Potassium efflux was measured in order to quantify the oxidative stress after the action of AAPH on red blood cells. Allophycocyanin assay was also used to investigate antioxidant capacities of furosemide. For the in vivo experiment, male Wistar rats were used. A control group (n = 5) was treated by a daily intraperitoneal injection of saline solution (0.2 ml); 2 other groups (J0 and J+) were treated for 7 days by one daily intraperitoneal injection of furosemide (0.10 mg/kg/day). In the J+group, the injection of furosemide was done one hour before the experiment, while in the J0 group the last injection of furosemide was done on the 6th day and an injection of saline was performed one hour before the experiment. On the day of experiment, a laparotomy was performed under general anesthesia and blood was collected from abdominal aorta. Oxidative stress and antioxidant capacities were evaluated on Wistar rat red blood cells and plasma. In vitro results (oxidative challenge with AAPH) showed that oxidative stress was decreased in presence of furosemide. This was due to a potent free radical scavenging effect of furosemide. In vivo studies confirmed that furosemide had antioxidant properties. These data may be of great relevance in clinical practice, considering the use of large doses of furosemide in patients presenting pathology involving the production of free radicals.

[Thalidomide with or without dexamethasone for refractory multiple myeloma]. / Intérêt du thalidomide avec ou sans dexaméthasone dans le myélome multiple réfractaire.

It was shown in 1999 thalidomide could induce a therapeutic response in patients with refractory multiple myeloma. Between March 2000 and January 2002, we treated 21 patients with refractory multiple myeloma with thalidomide (Thalidomide) at initial dose of 400 mg a day. Response rate (Intergroupe Francophone du Myélome criteria) was 33 percent and median progression-free survival estimated to 15 months. All patients suffered from drowsiness and constipation requiring lowest doses. Five patients developed a sensitive neuropathy. Eight refractory patients were treated by a combination of their prior maximally tolerated dose of thalidomide and monthly dexamethasone (Soludécadron) alone (n = 4) or associated to cyclophosphamide (Endoxan) and étoposide (Etopophos) (n = 4). Six patients on 8 were responders. Our results suggest that the combination thalidomide/dexamethasone should be compared to thalidomide alone in a prospective, randomized study in patients with refractory multiple myeloma.

Decrease in Candida albicans strains with reduced susceptibility to fluconazole following changes in prescribing policies.

This study was undertaken to identify prescribing policies likely to favour or limit fluconazole resistance within a clinical department. Fluconazole exposure within the infectious diseases and clinical haematology units was investigated, and data were compared with in vitro susceptibility of Candida albicans isolates obtained in these units. Fluconazole utilization was determined by the number of fluconazole treatment-days per 100 hospitalization days (penetration index). In the infectious diseases unit, separate evaluations for low-dose fluconazole (50 mg) prescribed as intermittent or prolonged treatment, and for higher-dosing schedules (fluconazole 200 mg) were made. Susceptibility of C. albicans isolates was surveyed in a broth microdilution assay by measuring the inhibitory concentration 50% (IC50). The penetration index (PI) for fluconazole 50mg declined from 1992 to 1977 in infectious diseases (P= 0.0048). In the meantime, total usage of fluconazole increased, due to increased prescribing of fluconazole 200 mg (P = 0.0724). The IC50 of C. albicans isolates tested in infectious diseases decreased between 1994 and 1996 from 7.33 mg/ml to 1.64 mg/ml (P = 0.0075). In clinical haematology, declines in C. albicans IC50 and fluconazole PI were not significant (P = 0.35 and P = 0.07, respectively). These data suggest that prolonged or repeated exposure to low-dose fluconazole, rather than total cumulative use, was associated with fluconazole resistance in the infectious diseases unit. Moreover, restoration of a normal ecology was observed when low-dose prolonged or intermittent prescriptions were reduced.