The breast cancer resistance protein, also known as ABCG2, is one of the most studied ATP-binding cassette (ABC) transporters, due to its ability to confer multidrug resistance1,2. The lack of information on the physiological roles of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr), and that individuals of the Jr(a−) blood type have inherited two null alleles of ABCG2. We thus identified 5 frameshift and 3 nonsense mutations in ABCG2. Furthermore, we show that the prevalence of the Jr(a−) blood type in the Japanese and European Gypsy populations is related to the mutations p.Q126X and p.R236X, respectively. The identification of ABCG2−/− (Jr(a−)) individuals, who appear phenotypically normal, is an essential step towards targeting ABCG2 in cancer, but also understanding the physiological and pharmacological roles of this promiscuous transporter in humans.

The main object of our study was to investigate whether the resazurin metabolism assay is a sensitive surfactant and alcohol toxicity test in isolated pig cornea and to compare this recently developed fluorometric assay with the data collected in the eye irritation reference chemical data bank. Resazurin is a substrate that changes color in response to metabolic activity. Isolated pig corneas were immersed for 10 min in surfactants and alcohol irritant solutions. After incubation, resorufin fluorescence was read and corneal viability was assessed. This corneal viability was compared with the maximal modified average score published in the report of ECETOC. This assay highlighted different concentration-dependent irritation potentials of the three surfactants tested, and the same results were obtained with corneas treated with the alcohols. We observed that the degree of surfactant- and alcohol-induced decrease in corneal viability, using the resazurin reduction test, was correlated with the in vivo irritancy measurements as determined by the Draize test and scored with the Modified Maximum Average Score (MMAS). This assay allowed us to classify the ocular irritancy of the tested surfactants and alcohols in the same ranking order as the Draize classification. Corneal viability measurement can be used as a potential alternative for the toxicological assessment of surfactants and alcohols. The nontoxic, nonradioactive resazurin metabolism assay allows rapid assessment of many samples with simple equipment and at reduced cost for continuous monitoring of corneal viability. This assay seems to be suitable as a toxicological screening test for eye irritation determination.

The purpose of this study was to investigate whether maximal muscle power production in humans is influenced by the habitual time of training to provide recommendations for adapting training hours in the month preceding a competition. Sixteen participants performed maximal brief squat and countermovement jumps and short-term cycle sprints tests before and after 5 weeks of training. Subjects were randomly assigned to either a Morning-Trained Group (MTG, 7:00-9:00 hr) or an Evening-Trained Group (ETG, 17:00-19:00 hr). They trained and performed the evaluation tests in both the morning and evening in their naturally warm and moderately humid environment. The results indicated a significant increase in performance (approximately 5-6% for both tests) after training for both groups but failed to show any time-of-day effect on either performance or training benefit. These findings could be linked to the stabilization of performances throughout the day because of the passive warm-up effect of the environment. In summary, our data showed that anaerobic muscle power production could be performed at any time of day with the same benefit.

Background: Three-dimensional culture or human corneal equivalents for safety testing are difficult to investigate with classic cytometric or biochemical methods. So a fluorometric method is proposed using resazurin probe. Methods: Absorbance and fluorescence spectra of the oxidized and reduced forms of resazurin were performed to determine optimal measurement conditions. More than 100 enucleated porcine eyes were used for this experiment. Twelve corneas were immersed in resazurin solution and fluorescence was measured hourly from 1 to 10 h. Ninety benzalkonium chloride-treated corneas and control corneas were used as toxicity controls, and corneal viability was compared with in vivo rabbit eye irritation. Results: After analysis of spectra, the optimal measurement condition of resazurin metabolism proved to be a fluorescence measurement using 570 nm excitation wavelength and 590 nm emission wavelength. The reduction of

BackgroundWipes containing chlorhexidine and azole derivates have been recommended for veterinary use. No study has been published about their activity against Malassezia pachydermatis.Hypothesis/ObjectivesTo evaluate the in vivo and in vitro activity of wipes soaked in a chlorhexidine, climbazole and Tris-EDTA solution against Malassezia pachydermatis.AnimalsFive research colony shar-pei dogs.MethodsWipes were applied once daily onto the left axilla, left groin and perianal area (protocol A), and twice daily on the right axilla, right groin and umbilical region (protocol B) for 3 days. In vivo activity was evaluated by quantifying Malassezia colonies through contact plates on the selected body areas before and after wipe application. The activity of the solution in which the wipes were soaked was assessed in vitro by contact tests following the European Standard UNI EN 1275 guidelines.ResultsSamples collected after wipe application showed a significant and rapid reduction of Malassezia yeast CFU. No significant difference in the Malassezia reduction was found between protocols A and B. In vitro assay showed 100% activity against Malassezia yeasts after a 15 min contact time with the wipe solution.Conclusions and clinical importanceWipes containing chlorhexidine, climbazole and Tris-EDTA substantially reduced the M. pachydermatis population on the skin of dogs. The results, although this was an uncontrolled study performed on a small number of dogs, suggest that these wipes may be useful for topical therapy of Malassezia dermatitis involving the lips, paws, perianal area and skin folds.RésuméContexteDes lingettes contenant de la chlorhexidine et des dérivésazolés ont été recommandés en médicine vétérinaire. Aucune étude n'a été publiée sur leur activité contre Malassezia pachydermatis.Hypothèses/ObjectifsEvaluer l'activité in vivo et in vitro de lingettes imprégnées d'une solution de chlorhexidine, climbazole et Tris-EDTA contre Malassezia pachydermatis.SujetsCinq colonies de shar-pei de recherche.MéthodesLes lingettes ont été appliquées une fois par jour au niveau du pli axillaire gauche, le pli inguinal droit et de la zone périanale(protocole A) et deux fois par joursur le pli axillaire droit, le inguinal droit et l'ombilic (protocole B) pendant 3 jours. L'activité in vivo a été évaluée par quantification des colonies de Malassezia par disques de contact sur les zones corporelles choisies avant et après application des lingettes. L'activité de la solution d'imprégnation des lingettes a été testée in vitro par tests de contact suivant les recommandations de l'European Standard UNI EN 1275.RésultatsLes échantillons prélevés après application ont montré une diminution importante et rapide des CFU des levures Malassezia. Aucune différence significative dans la diminution des Malassezia n'a été mise en évidence entre les protocoles A et B. Des tests in vitro ont montré 100% d'activité contre les Malassezia après un temps de contact de 15 minutes avec la solution des lingettes.Conclusions et importance CliniqueLes li...

No abstract

Objectives The aims of the study were to determine the in vitro drug release of guar gum-coated capsules of ronidazole, and to evaluate the pharmacokinetics and efficacy of this formulation for the treatment of cats naturally infected with Tritrichomonas foetus. Methods The pharmacokinetics of ronidazole were evaluated in five healthy cats and five cats infected with T foetus. In a second step, the clinical efficacy of these capsules was evaluated by a controlled, randomised, double-blind clinical trial performed in 47 infected cats from French catteries. In this study, cats were randomly allocated to either the ronidazole treatment group (n = 25) or a placebo group (n = 22). Ronidazole (30 mg/kg) q24h for 14 days was administered to the treated cats. After 14 days of treatment, the presence of T foetus was tested by conventional PCR assay. Results In the pharmacokinetic study, a delayed peak plasma concentration was observed in healthy and infected cats, with no significant difference between these two groups (mean geometric mean of 9 h for time to maximum plasma concentration [T], 21.6 µg/ml for time to maximum plasma concentration [C] and 467.4 μg/h/ml for the area under the curve [AUC] in healthy cats; and 9.4 h for T, 17.1 µg/ml for C and 481 μg/h/ml for AUC in infected cats). In the clinical trial, T foetus was detected in 16% of cats from the treated group and 82% of cats from the placebo group at the end of the study ( P <0.001). No clinical signs of adverse drug reactions were observed. Conclusions and relevance Oral administration of guar gum-coated capsules of ronidazole at a dose of 30 mg/kg once daily for 14 days delays the peak plasma concentration and eradicates infection in most cases.

No abstract