To create a cleanroom controlled environment using a mobile air decontamination unit for the preparation of antineoplastic drugs.

OBJECTIVES: To use a mobile air decontamination unit (MADU) for a microbial destruction and decreased particle burden making a cleanroom controlled environment in a Centralized Chemotherapy Preparation Unit (CCPU). Good manufacturing practices (GMP) in France specify that the ambient air in the vicinity of a class III biosafety cabinet (isolator) complies with air cleanliness ISO 8 level in CCPU. This guideline has a significant impact because implementing a dedicated air handling unit (AHU) brings some engineering constraints and generates substantial additional costs. METHODS: Authors have previously studied some technical and economical aspects to evaluate the feasibility of the MADU option. RESULTS: Using a MADU was the chosen option. Qualification of the CCPU showed that results were in compliance with the French GMP. After one year of use, the efficiency of the MADU was confirmed. According to these results, using a MADU constitutes a beneficial option for CCPU previously equipped with an isolator when compared to renovation work involving a standard built-in AHU.

Effects of various osmolarity on human red blood cells in terms of potassium efflux and hemolysis induced by free radicals.

OBJECTIVES: To study in an in vitro model of erythrocytes exposed to free radicals the effects of hyperosmolarity and hypoosmolarity on the induced potassium efflux and hemolysis. DESIGN SETTING: Erythrocytes were separated from plasma and suspended in 3 different phosphate buffer solutions (HYPO, ISO, and HYPER) containing, respectively, 100, 150 and 200 mmol/l of Na. Free radicals were generated from 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). Potassium efflux (flame photometry) and hemolysis (Drabkin method) were measured. Measurements were expressed in % (versus total) and area under % versus time curves were calculated (% min). An ANOVA was used for statistical analysis. RESULTS: In presence of AAPH, hemolysis was significantly greater in HYPO (732.45+/-40% min) and lower in HYPER (578.97+/-15% min) as compared to ISO (608.30+/-42% min). Potassium efflux was significantly increased in HYPER (7508.04+/-85% min) as compared with HYPO (5308.74+/-62% min) and ISO (6561.39+/-62% min). DISCUSSION: Our data suggest that hyperosmolarity increases the resistance of the red blood cells when exposed to free radicals as shown by the decreased hemolysis. In such conditions, the potassium efflux analysis appears to be inappropriate to evaluate the free radical effects on erythrocytes.

Determination of acid base balance and oil water partition coefficient of an atopy patch test of levofloxacin.

Levofloxacin, a quinolone used in the treatment of an upper respiratory tract infection is involved in skin reactions. Patch tests are helpful for the aetiological diagnosis. Unfortunately, they are known for their lack of sensibility. A weak transcutaneous penetration due to the physicochemical characteristics of tested drugs is a well-known cause of false negative results but these characteristics are usually unknown. The aim of the present study was to evaluate physicochemical parameters by potentiometric method in order to optimize the transcutaneous penetration of a preparation for patch test. This method is applicable to a medium such as the preparation for patch test. In order to value the stability of the preparation, qualitative and quantitative analysis of the level of levofloxacin was effectuated. In our study, spectrophotometric and potentiometric data at T0 and six months later with the preparation showed the stability of the preparation. The proportions of non-ionized (45%) and ionized levofloxacin (55%) were not modified. Further experiments are needed to choose the minimal efficient dose of the suspected molecule able to detect a positive reaction in cases of allergic reaction. In addition, this method could be useful in qualitative and quantitative control of preparations made at hospital.

Comparison of three methods for oxidative stress-induced potassium efflux measurement.

The aim of the study was to compare the potassium efflux measurements (flame photometry (FP), specific electrode (SE) and atomic absorption photometry (AAP)) using a model of erythrocytes exposed to an oxidative stress in various conditions of osmolarity. Human erythrocytes were incubated in 3 different values of osmolarity and in the presence of 50mM AAPH, potassium efflux was measured by FP, SE and AAP at t=0 and every 30min for 2h. These methods were similar for the measurement of global potassium efflux. However, SE detected important amounts of potassium at the beginning of the experiment or in absence of AAPH in comparison with AAP and FP. It is noteworthy that these different methods of measurements were not altered by the osmolarity. FP and AAP make it possible to study the potassium efflux during oxidative stress while SE should be used only for global measurements.

Impact of inflammation on the duodenal mRNA expression of CYP3A and P-glycoprotein in children with Crohn's disease.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic and invalidating inflammatory bowel disease of unknown etiology. The coordinated action of the cytochrome metabolizing subfamily CYP3A and the transport protein P-glycoprotein (P-gp) in the enterocyte results in a reduced bioavailability of drugs administered orally. Cytokines modulate the expression and functionality of CYP3A and P-gp. Although P-gp results are in disagreement between animal and Caco-2 cell studies, all authors report a decrease in CYP3A levels after exposure to proinflammatory agents. In humans, CYP3A and P-gp mRNA, protein, and functionality levels were higher in various tissues in patients with CD as compared with control groups. Our study's aim was to analyze the impact of systemic inflammation on the expression of CYP3A and P-gp in duodenal normal tissue. MATERIALS AND METHODS: We compared CYP3A and P-gp mRNA expression in 19 noninflamed duodenal biopsies from children with CD with 19 normal biopsies. We used a real-time reverse-transcription-polymerase chain reaction technique. RESULTS: There was a high variability in the expression of the 3 CYP3A isoforms and P-gp. CYP3A4, CYP3A5, and P-gp levels were significantly higher in the CD group than in the control group. DISCUSSION AND CONCLUSIONS: CYP3A and P-gp are involved in the metabolism and transport of many drugs prescribed in CD including corticosteroids. Changes occurring in their duodenal and hepatic expression may explain important interindividual differences in the bioavailability and response to treatment. Further explorations considering protein and activity must be undertaken to understand how such changes affect drug absorption and bioavailability.