Simulation program of a cytotoxic compounding robot for monoclonal antibodies and anti-infectious sterile drug preparation.

The aim of this study was to develop a specific simulation program for the validation of a cytotoxic compounding robot, KIRO® Oncology, for the preparation of sterile monoclonal antibodies and anti-infectious drugs. The impact of excipient formulations was clearly measured using simulation accuracy tests with worst case excipient (i.e. viscous, foaming) and allowed to correct the robotic settings prior to real production. Corrections brought accuracies within the acceptable range of ±5%. KIRO® Oncology robot has also the capacity of self-cleaning and a simulation combining media fill test, and environmental monitoring was able to validate the aseptic process including simulation of worst case conditions and highlighting the areas not accessible to self-cleaning to be corrected by additional manual cleaning measures. The risk of chemical contamination was simulated by using fluorescent dye of the process with high-risk excipient formulation and overpressure vials. Quality control reliability was simulated by using a model drug, and final concentration was determined by high-performance liquid chromatography-ultraviolet detection. Finally, productivity was simulated using different models of production showing the impact of the type of drug, the number of vials and the poor standardization of the process.

[Monitoring of heparinization in cardiac surgery with ACT: accreditation of the point-of-care test in the Bordeaux University Hospital Centre]. / Surveillance de l'héparinisation en chirurgie cardiaque par l'ACT : accréditation de l'analyse en biologie délocalisée au CHU de Bordeaux.

ACT (Activated Clotting Time) is a point of care test (POCT) on whole blood, used to monitor the heparinization of patients in the operating room in cardiac surgery (ExtraCorporeal Circulation ECC) and in interventional cardiology (TAVI, AF ablation). The ACT is concerned both by the ISO 22 870 standard and French regulations regarding POCT. We performed an important work at the Bordeaux CHU on its accreditation, by rationalizing and making the park uniform (11 HemochronTM Signature Elite), standardizing the training and the habilitation of operators in medical units, introducing periodic quality controls, centralizing in the laboratory the management of the devices and reagents and by connecting it to the laboratory's computer system (Middleware, SIL et expert softwares). One year after, we have some positive feedbacks with only a few technical problems and with only few remarks raised during internal audits.

Leishmania donovani: differential activities of classical topoisomerase inhibitors and antileishmanials against parasite and host cells at the level of DNA topoisomerase I and in cytotoxicity assays.

Different classes of topoisomerase (TOP) inhibitors and antitrypanosomatid agents exhibited variable efficacies against Leishmania donovani parasites and human mononuclear cells both at the level of DNA topoisomerase I (TOPI) catalytic activity and in cytotoxicity assays. Bis-benzimidazoles and the diamidine diminazene aceturate exhibited uniformly high efficacies against parasite and host enzymes as well as against parasite and mononuclear cells, but pentamidine showed around 2 orders of magnitude greater specificity for Leishmania TOPI and amastigote cells (P<0.05). The protoberberine coralyne and the flavonoid quercetin were highly potent, but non-selective, inhibitors in vitro, although the latter showed slight selectivity for parasite TOPI. Camptothecin was selective for mononuclear cells at both levels (P<0.05) and sodium stibogluconate was selective only at the enzyme level displaying 30-fold greater potency against parasite TOPI (P<0.05). These data suggest that at least part of pentamidines' leishmanicidal activity may be mediated through TOPI inhibition, and support the feasibility of exploiting differences between Leishmania and human TOPs to develop modified compounds with improved selectivity.