Publications of Thomas Dubrowski
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See detailTriamcinolone acetonide after intra-articular injection in knee in sheep
Legrand, Nathalie ULiege; Tian, Jin; Douny, Caroline ULiege et al

Poster (2018, October 26)

Intra-articular injections of glucocorticoids aim to control pain and inflammation caused by osteoarthritis. There is a lack of evidence and pharmacokinetics (PK) studies to support the empirical ... [more ▼]

Intra-articular injections of glucocorticoids aim to control pain and inflammation caused by osteoarthritis. There is a lack of evidence and pharmacokinetics (PK) studies to support the empirical currently used dosage regimens. This study aimed 1) to determine the PK of triamcinolone hexacetonide (TH) and triamcinolone acetonide, its active metabolite (TA), in synovial fluid after intra-articular administration of a suspension of TH at 40mg and 10mg in sheep and 2) to compare the profiles of TA after injection of suspensions of TA or TH, both at 40mg. Twelve sheep were randomly allocated to three groups receiving respectively 40 mg TA (n=4), 40 mg TH (n=4) or 10 mg TH (n=4) in the left knee. Synovial fluids were sampled from day 1 up to day 21. The concentrations of TA and TH were measured by ultra-performance liquid chromatography mass spectrometry. TA concentrations measured after one day were higher in the group TA-40 mg (537762.3ng/ml) compared to those recorded in the group TH-40mg (22743.4ng/ml), On day 21, the corresponding values were 2.5 and 33.5 ng/ml due to a significant higher value of T1/2β of TA in group TH-40 mg (6.0 versus 1.9 days). The differences between the mean values of AUC and T1/2β of TA were not significantly different between the groups TH-10 and -40 mg but T1/2β of TH was significantly higher in the group TH-40mg. In conclusion, TH injection maintains TA concentrations for a longer period of time than TA administration. Due to a possible saturation of esterases, the PK profiles associated to the high and low doses of TH were rather close suggesting that a dose of 10mg could provide an optimal benefit-risk. [less ▲]

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See detailValidation d’une méthode UHPLC/MS-MS pour le dosage plasmatique du 15-F2t-isoprostane, biomarqueur du stress oxydant, en vue de l’établissement de valeurs de référence en routine clinique
Dubrowski, Thomas ULiege; PINCEMAIL, Joël ULiege; Vigor, Claire et al

Poster (2017, October)

Objectif : Cela fait des décennies que l’implication des isoprostanes dans le stress oxydant est mise en évidence dans la littérature. Malgré cela, il y a peu de concordances entre les différentes valeurs ... [more ▼]

Objectif : Cela fait des décennies que l’implication des isoprostanes dans le stress oxydant est mise en évidence dans la littérature. Malgré cela, il y a peu de concordances entre les différentes valeurs de référence publiées dans ces mêmes articles. Cela peut s’expliquer par le très grand nombre de composés apparentés à cette famille de molécules. L’Unité GLP-AEPT s’est concentrée sur le 15-F2t-isoprostane, biomarqueur « gold standard » de la peroxydation lipidique, afin de développer et valider une méthode de dosage fiable et utilisable en routine clinique. Cette méthode a ensuite été appliquée à l’analyse du plasma prélevé chez 61 volontaires sains en vue de déterminer les valeurs de référence pour ce biomarqueur du stress oxydant. Méthodes : Les échantillons plasmatiques sont purifiés par extraction liquide-solide avant d’être analysés par chromatographie liquide à ultra haute pression couplée à la spectrométrie de masse en tandem (UHPLC/MS-MS) au moyen du système UPLC Xevo TQ-S (Waters). Résultats : La méthode a été validée avec succès sur une gamme de concentrations allant de 25 à 2000 pg/ml en appliquant une stratégie basée sur l’erreur totale de mesure (incluant l’expression de la justesse et de la fidélité intermédiaire) et les profils d’exactitude. Les limites d’acceptation ont été fixées à ± 20 % pour les concentrations inférieures à 30 pg/ml et ± 15 % pour les concentrations égales ou supérieures à cette valeur. Cette approche garantit que seules 10 % des futures mesures d’échantillons inconnus seront en dehors de ces limites. Les concentrations obtenues pour les 61 volontaires sains sont distribuées selon une courbe gaussienne classique. L’intervalle de valeurs de référence pour le 15-F2t-isoprostane a été calculé et est compris entre 152 et 368 pg/ml [1]. Plusieurs corrélations ont ensuite pu être mises en évidence entre ce biomarqueur et d’autres paramètres biologiques connus pour affecter le niveau de stress oxydant de l’organisme (rapport Cu/Zn et glutathion total entre autres) [1]. Conclusion : Une méthode d’analyse fiable et compatible avec une application en routine clinique est à présent disponible afin de mesurer la concentration plasmatique en 15-F2t-isoprostane. Grâce à l’intervalle de valeurs de référence qui a été déterminé pour ce biomarqueur, le niveau de stress oxydant du patient peut être évalué. Références : 1. Pincemail J. et coll. Validated routine-ready UHPLC/MS-MS method for the reference range determination in human plasma of 15-F2t-isoprostane, biomarker of the oxidative stress. FRBM. 2017; 108 (1): page S42. [less ▲]

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See detailDelirium and oxidative stress
PINCEMAIL, Joël ULiege; CHRISTELBACH, Sophie ULiege; GILLAIN, Sophie ULiege et al

Poster (2015, June)

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See detailAn HPLC-MS method for the analysis of 26 non-enzymatic metabolites of PUFAs in biological samples
Dupuy, Anne; Pinot, Edith; Vigor, Claire et al

Poster (2014, September)

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See detailEffect of New Synthetic PEGylated Ferulic Acids in Comparison to Ferulic Acid and Commercial Surfactants on the Properties of Wheat Flour Dough and Bread
Nicks, Francois ULiege; Richel, Aurore ULiege; Dubrowski, Thomas ULiege et al

in Journal of the Science of Food and Agriculture (2013), 93(10), 2415-2420

BACKGROUND: Ferulic acid esterified with poly(ethylene glycol) with three different average molecular weights (200, 400 and 1000 g/mol) was studied in breadmaking. The effects of these antioxidants on the ... [more ▼]

BACKGROUND: Ferulic acid esterified with poly(ethylene glycol) with three different average molecular weights (200, 400 and 1000 g/mol) was studied in breadmaking. The effects of these antioxidants on the properties of wheat flour dough and bread were analyzed and compared with those obtained with ferulic acid and two commercial surfactants, diacetyl tartaric acid ester of mono- and diglycerides and sodium stearoyl lactylate. Farinographic and alveographic methods as well as weight, volume and bread firmness measurements were used for this purpose. <br /> <br />RESULTS: Such as ferulic acid, when the PEGylated derivatives were implemented in the dough (5000 ppm), it accelerated its breakdown and decreased its rheological properties. However, it allowed to avoid the important diminution of loaf volume observed when dough supplemented with ferulic acid was baked. That decrease in volume was related to the inhibition of the yeast (Saccharomyces cerevisae) by the unesterified ferulic acid. Moreover, two of the PEGylated ferulic acids even contributed to an increase of loaf volumes (5-6%) and demonstrated crumb softener properties. <br /> <br />CONCLUSION: The addition of ferulic acid in wheat flour dough caused the inhibition of the yeast, which resulted in decreased bread volume. That effect could be avoid by the esterification of ferulic acid with poly(ethylene glycol). [less ▲]

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See detailContribution à la recherche et à l’étude d’améliorants de panification
Dubrowski, Thomas ULiege

Master's dissertation (2011)

This work takes place in the current trend aiming to find new substances that, once added to the formulation of bread, improve its characteristics. To do this, a homologous series of three emulsifiers ... [more ▼]

This work takes place in the current trend aiming to find new substances that, once added to the formulation of bread, improve its characteristics. To do this, a homologous series of three emulsifiers, synthesized from glucuronic acid on which were grafted hydrocarbon chains of different lengths (from 14 to 18 carbon atoms), was obtained by glycosylation. The purification of these three surfactants is also described as feasible, with an almost complete separation of the two anomers obtained through this synthesis. Then these three synthesized products were applied to bakery by conducting laboratory tests (farinograph, alveograph) followed by micropanification tests in real conditions. In order to compare their results, two commercial references (DATEM and SSL) have also been used. It appears that none of the alkyl glucuronolactone possesses a “dough strengthener” effect while a “crumb softener” effect was noted (P < 0.05) for GlcA-O-C14 and -C16 in comparison with the “control”, with in the latter case, a greater decrease of firmness than with SSL, already popular for its action. The role of these molecules on staling was also analyzed and it seems that they slow down the hardening of bread after 27 h (P < 0.05) more than the commercial references, whereas after 48 h, only GlcA-O-C18 retains an advantage against the formulation without any emulsifier, even if it is no longer significant. [less ▲]

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