Development and Training of Spatial Ability in Children

Krabbendam, A.C. [Promotor]Jolles, J. [Promotor]Huizinga, M. [Copromotor

Performance of the Roche Total Mycophenolic Acid® assay on the Cobas Integra 400®, Cobas 6000® and comparison to LC-MS/MS in liver transplant patients

Background: Mycophenolic acid (MPA) is an immunosuppressant for which therapeutic drug monitoring (TDM) is performed for optimal prophylaxis and avoidance of toxicity in transplant patients. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is ideally suited for TDM of MPA. There have been several method comparisons of the Roche Total MPA assay, but none have been performed with respect to liver transplant patients. Methods: We validated the Roche Total MPA assay on the Cobas Integra 400 and Cobas 6000 and compared it to a validated LC-MS/MS (API 2000 (TM)) method. Fifty-five EDTA plasma samples from liver transplant patients were measured with the Roche assay on these platforms and compared to the LC-MS/MS results. Results: Validation of the LC-MS/MS, Cobas Integra 400 and 6000 was performed with good results. The LC-MS/MS/Integra 400/Cobas 6000 were linear up to 30, 15 and 17 mg/L, respectively. Imprecision was <10% for LC-MS/MS and <7% for the Roche assay on both platforms. The samples showed good agreement with LC-MS/MS. Passing-Bablok regression analysis showed Cobas Integra (mg/L) = 1.02 x LC-MS/MS (mg/L)-0.50 and Cobas 6000 (mg/L) = 0.98 x LC-MS/MS-0.47. Conclusions: The Roche Total Mycophenolic Acid-assay is suitable for measuring total MPA in plasma from liver transplant patients and is a good alternative for LC-MS/MS

In vitro antileishmanial and cytotoxicity activities of essential oils from Haplophyllum tuberculatum A. Juss leaves, stems and aerial parts

Background: Plants used for traditional medicine produce diverse and complex secondary metabolites exhibiting various medicinal properties. The medicinal plant Haplophyllum tuberculatum is used by native people against malaria and parasitic infections. Methods: In this study and in order to contribute for the search of new natural drugs for leishmaniasis, the essential oils of H. tuberculatum leaves, stems and aerial parts (leaves+stems) collected in two different periods, 2013 and 2015, and their components by GC/FID and GC/MS analyses were investigated. Those collected in 2013 were also re-analyzed two years later. The extracted oils were screened in vitro for anti-leishmanial activity on Leishmania mexicana mexicana (L.m.m.) promastigotes and cytotoxicity on the Chinese Hamster Ovary (CHO) cell line. Limonene (1.5 – 8%), its isomers (R- (+)-limonene and S-(-)-limonene), linalool and octanol were also tested. Results: Results showed that the chemical composition varied according to the year of collection. Though major compounds remain almost the same, qualitative and quantitative variations in the composition of the EOs can be observed between the two years of collection, with some minor compounds identified only in one type of samples. Variation in the composition were also observed in the re-analyzed volatile oils, showing stability concerns. The essential oils and R-(+)-limonene showed moderate anti-leishmanial activity. Their IC50 range from 6.48 to 50.28 μg/ml. Cytotoxicity assays for theses volatile extracts, R- (+)-limonene and S- (-)-limonene on CHO cells showed relatively potent cytotoxicity with a selectivity index <10. Their CC50 range from 27.79 to 82.56 μg/ml. Conclusions: The findings of the present study demonstrated that H. tuberculatum might not be considered as a natural source for production of new anti-leishmanial agents without further analyzing its eventual in vivo toxicity as well as that of major pure compounds

Robustness testing in the determination of seven drugs in animal muscle by liquid chromatography–tandem mass spectrometry

In this work, the robustness of the sample preparation procedure for the determination of six tranquilizers (xylazine, azaperone, propionylpromazine, chlorpromazine, haloperidol, and azaperol) and a beta-blocker (carazolol) in animal muscle by LC/MS–MS was assessed through the experimental design methodology. A 2III7 − 4 fractional factorial design was performed to evaluate the influence of seven variables on the final concentration of the seven drugs in the samples, in accordance with what is laid down in Commission Decision No 2002/657/EC. The variation considered for each of those seven factors is likely to happen when preparing the samples, being the values chosen as level − 1, the nominal operating conditions. The results of the experimentation were evaluated from different statistical strategies, such as hypothesis testing using an external variance previously estimated, Lenth's method, and Bayesian analysis. Both Lenth's and Bayes' approaches enabled to determine the effect of every variable even though no degrees of freedom were left to estimate the residual error. The same conclusion about the robustness of the extraction step was reached from the three methodologies, namely, none of the seven factors examined influenced on the method performance significantly, so the sample preparation procedure was considered to be robust.Ministerio de Ciencia e Innovación (CTQ2011-26022) and MINECO (CTQ2014- 53157-R)

Prevalence of osteochondrosis in Warmblood horses in Wallonia

peer reviewedOsteochondrosis (OC), a developmental orthopaedic disease, is consecutive to a defect in the endochondral ossification process, and can result in formation of an osteochondral fragment (osteochondrosis dissecans). Our objective is to establish the prevalence of osteochondrosis in Wallonia, and describe the main observed lesions. One hundred forty-two Warmblood horses, aged from 12 to 36 months, underwent a systematic X-ray examination. Sixty-three of these horses (44.4 %) presented one or more OC lesions, 46 (32.4 %) of them with an articular fragment. This prevalence is similar to those observed in Dutch Warmblood horses (44.3 %). The localisation of the lesions was as follows: 25 (17.6 %) of the experimental group showed one or more lesions in the hindlimbs fetlocks, 23 (16.2 %) in the hocks, 21 (14.8 %) in the stifles and 14 (9.9 %) in the forelimbs fetlocks. The medial ridge of the talus is the most frequently injured anatomical site in our study. This lesion was observed in 12 horses (8.4 %), a prevalence that is by far higher than those observed in Dutch Warmblood horses (2.9 %). Not any significant difference was observed between males and females. The high prevalence and the clinical and economic consequences of this disease in the horse’s industry fully justify further research in order to improve the understanding of its pathogenic process.Ann. Méd. Vét., 2008, 152 (3), pp 131-137 Prévalence de l’ostéochondrose chez le cheval de sport en Wallonie VANDER HEYDEN L., SERTEYN D., CAUDRON I., VERWILGHEN D., DELIEGE B., LEJEUNE J.-P. Résumé : L’ostéochondrose (OC) est une affection ostéo-articulaire juvénile, consécutive à une non-ossification de l’os endochondral et pouvant entraîner la présence de fragments ostéochondraux (ostéochondrose dissécante). L’objectif de notre étude est d’établir la prévalence de cette affection en région wallonne, et de décrire les principales lésions observées. Cent quarante-deux poulains de sport nés en Wallonie, âgés de 12 à 36 mois, ont été radiographiés. Soixante-trois de ces poulains (44,4 %) montrent une ou plusieurs lésions d’OC, 46 (32,4 %) d’entre eux avec un fragment articulaire. Cette prévalence est assez proche de celle observée chez les chevaux demi-sang néerlandais (44,3 %). Au niveau localisation, vingt-cinq (17,6 %) de nos chevaux montrent une ou plusieurs lésions au niveau des boulets postérieurs, vingttrois (16,2 %) au niveau des jarrets, vingt-et-un (14,8 %) au niveau des grassets et quatorze (9,9 %) au niveau des boulets antérieurs. La lèvre médiale de la trochlée du talus est le site anatomique du jarret présentant le plus de lésions d’OC avec douze poulains atteints (8,4 %) ; cette proportion est nettement supérieure aux 2,9 % observées chez les demi-sang néerlandais (Vos, 2008). Aucune différence significative n’a été observée entre les mâles et les femelles. La prévalence élevée et les répercussions importantes de cette affection, tant du point vue clinique qu’économique dans la filière équine, justifient pleinement l’approfondissement des études qui sont réalisées sur le sujet