[Study of four kits used for titration of tetanus antibody for selection of plasma donors intended to fractionation]. / Etude de quatre trousses de titrage des anticorps antitétaniques pour la sélection des plasmas destinés au fractionnement (LFB).

UNLABELLED: Antitetanus antibodies titration is carried out by French National Blood Services (FNBSs) with the aim of seeking donors whose title of antibodies are greater or equal to 8 IU/ml. Different kits are used: ELISA antitetanus toxoid IgG (The Binding Site), ELISAT (Diagast), tetanus toxoid IgG ELISA (Diamed), ELISA IgG tetanus (Ingen). As the results obtained using these different reagents show some discrepancies with the control results carried out by the Laboratoire Français des Biotechnologies (LFB), it appeared necessary to harmonize the selection practices. With this intention a study of the different kits was initiated. METHOD: Different samples were used during this evaluation: (1) the Reference Control (RC) used by the FNBS; (2) a serum sample of high title; (3) a range of dilution of national standard. The following tests were carried out: (1) robustness with the evaluation of the contamination and the board effect; (2) linearity and repeatability (eight deposits of each standard, RC and points of national standard dilutions); (3) reproducibility; (4) homogeneity. After automatic dilution of the samples, the plates were then processed according to the protocol of the manufacturer. RESULTS: The study gives the CV in percentage of repeatability and reproducibility, the values of the standards provided as well as the bias compared to the RC and the uncertainty of measurements. CONCLUSION: This study gave the possibility to rank each kit compared to RC and to specify the variations which surround each result. This variation can explain the discrepancy of conformity of plasma when title is close to the threshold of selection.

[Organization for the coverage of the transfusional needs of patients with hemoglobinopathy at the Établissement français du sang Bretagne]. / Organisation de la prise en charge des besoins transfusionnels des patients atteints d'hémoglobinopathie à l'Établissement français du sang Bretagne.

UNLABELLED: Brittany is a low prevalence region for hemoglobinopathies. Despite of that, the number of patients is increasing each year. In 2013, 140 patients were known at the EFS Bretagne, and medical consultations are growing for 50% each year since 2011. The consequence is an increase of needs of 22% of compatible packed red blood cells. To anticipate the announced progress, various actions were implemented as study groups, creation of a new informatic prescription for red blood cells phenotyping, promotion of donation, transfusion organisation. RESULTS: Fifthty-nine percent of the 400 ABO RH-KELL, FY, JK, MNS 3, 4, red blood cells were realised on the basis of this new informatic prescription, as the 99% of the packed red blood cells identified Fy (a- b-). So, 92% of the compatible transfused packed red blood cells were already in stock when the patients needed them. CONCLUSIONS: In Brittany, that organisation leads to assume qualitative and quantitative transfusion for sickle cell disease in more than 90% of cases, with fast distribution. In the same time promotion of donation is done to increase the diversity of donors.

The sulphonylurea glibenclamide inhibits multidrug resistance protein (MRP1) activity in human lung cancer cells.

1. Glibenclamide, a sulphonylurea widely used for the treatment of non-insulin-dependent diabetes mellitus, has been shown to inhibit the activities of various ATP-binding cassette (ABC) transporters. In the present study, its effects towards multidrug resistance protein 1 (MRP1), an ABC efflux pump conferring multidrug resistance and handling organic anions, were investigated. 2. Intracellular accumulation of calcein, an anionic dye substrate for MRP1, was strongly increased by glibenclamide in a dose-dependent manner in MRP1-overexpressing lung tumour GLC4/Sb30 cells through inhibition of MRP1-related calcein efflux. By contrast, glibenclamide did not alter calcein levels in parental control GLC4 cells. Another sulphonylurea, tolbutamide, was however without effect on calcein accumulation in both GLC4/Sb30 and GLC4 cells. 3. Glibenclamide used at 12.5 microM was, moreover, found to strongly enhance the sensitivity of GLC4/Sb30 cells towards vincristine, an anticancer drug handled by MRP1. 4. Efflux of carboxy-2',7'-dichlorofluorescein, an anionic dye handled by the ABC transporter MRP2 sharing numerous substrates with MRP1 and expressed at high levels in liver, was also strongly inhibited by glibenclamide in isolated rat hepatocytes. 5. In summary, glibenclamide reversed MRP1-mediated drug resistance likely through inhibiting MRP1 activity and blocked organic anion efflux from MRP2-expressing hepatocytes. Such effects associated with the known inhibitory properties of glibenclamide towards various others ABC proteins suggest that this sulphonylurea is a general inhibitor of ABC transporters.

Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486.

Multidrug resistance-associated protein (MRP) and P-glycoprotein (P-gp) are drug efflux pumps conferring multidrug resistance to tumor cells. RU486, an antiprogestatin drug known to inhibit P-gp function, was examined for its effect on MRP activity in MRP-overexpressing lung tumor GLC4/Sb30 cells. In such cells, the antihormone compound was found to increase intracellular accumulation of calcein, a fluorescent compound transported by MRP, in a dose-dependent manner, through inhibition of cellular export of the dye; in contrast, it did not alter calcein levels in parental GLC4 cells. RU486, when used at 10 microM, a concentration close to plasma concentrations achievable in humans, strongly enhanced the sensitivity of GLC4/Sb30 cells towards two known cytotoxic substrates of MRP, the anticancer drug vincristine and the heavy metal salt potassium antimonyl tartrate. Vincristine accumulation levels were moreover up-regulated in RU486-treated GLC4/Sb30 cells. In addition, such cells were demonstrated to display reduced cellular levels of glutathione which is required for MRP-mediated transport of some anticancer drugs. These findings therefore demonstrate that RU486 can down-modulate MRP-mediated drug resistance, in addition to that linked to P-gp, through inhibition of MRP function.