Interaction between Fusarium mycotoxins and cytochrome P450 drug metabolizing enzymes/ABC drug transporters in a porcine animal model

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Characterization of porcine hepatic and intestinal drug metabolizing CYP450 : comparison with human orthologues from a quantitative, activity and selectivity perspective

Over the past two decades, the pig has gained attention as a potential model for human drug metabolism. Cytochrome P450 enzymes (CYP450), a superfamily of biotransformation enzymes, are pivotal in drug metabolism. Porcine CYP450 has been demonstrated to convert typical substrates of human CYP450. Nevertheless, knowledge and insight into porcine CYP450 quantity and substrate selectivity is scant, especially regarding intestinal CYP450. The current study aimed to map the quantities of hepatic and intestinal CYP450 in the conventional pig by using a proteomic approach. Moreover, the selectivity of the six most common used probe substrates (phenacetin, coumarin, midazolam, tolbutamide, dextromethorphan, and chlorzoxazone) for drug metabolizing enzyme subfamilies (CYP1A, CYP2A, CYP3A, CYP2C, CYP2D and CYP2E respectively), was investigated. Hepatic relative quantities were 4% (CYP1A), 31% (CYP2A), 14% (CYP3A), 10% (CYP2C), 28% (CYP2D) and 13% (CYP2E), whereas for the intestine only duodenal CYP450 could be determined with 88% for CYP3A and 12% for CYP2C. Furthermore, the results indicate that coumarin (CYP2A), midazolam (CYP3A), tolbutamide (CYP2C), and dextromethorphan (CYP2D) are as selective for porcine as for human CYP450. However, phenacetin (CYP1A2) and chlorzoxazone (CYP2E1) are less selective for the specific enzyme, despite similarities in selectivity towards the different enzymes involved compared to humans

Optical Fiber Distributed Sensing System Applied in Cement Concrete Commixture Research

DTS are unique optical-fiber distributed systems for measuring of temperature or mechanical tension. These systems use non-linear properties of optical fibers. Optical fiber can therefore be used not only for telecommunication purposes, as is currently the case, but also as a sensor. Optical fiber used by the DTS system can be therefore imagine as thousands of sensors placed along the route, taking all advantages of optical fiber, such as resistance to electromagnetic radiation, safe use in flammable and explosive environments, resistance to aggressive environments, small sizes, easy installation and maintenance-free operation. The properties of DTS system mentioned above seem to be ideal for detailed mapping of the hydration heat of concrete mix in the transition to a rigid structure. Values based on measurements will be used to better understanding of the processes inside the concrete mixture (individual samples) and will serve to develop better and more durable mixture

Backscattering Behavior of Vulnerable Road Users Based on High-Resolution RCS Measurements

Automotive radars, along with optical sensors such as cameras or lidars, offer a reliable way of obtaining the 3-D information about the environment. Of particular interest in autonomous driving (AD) is the reliable detection of particularly vulnerable road users (VRUs). Modern radar sensors are able to detect, distinguish, and track targets with high resolution. Relying on that, a backscattering model of complex traffic targets can be generated from the reflected signals of their scattering points (SPs). These models can be employed in the radar channel simulations for verification methods of advanced driver assistance systems. Therefore, in this work, different persons as the most vital VRUs are measured with high radial and high angular resolution. The necessary signal processing steps are explained in detail for the determination of the relevant SPs. Thus, the corresponding radar cross section (RCS) values can be assigned to certain body regions. In addition to real persons, further measurements are compared with a dummy of the corresponding size. Based on the measurement results, not only accurate models of road users can be derived, but also the measurement results can be employed for calculating wave propagation in traffic scenarios. From the measured SPs, the classification of the persons by size and stature is derived

Automated Dialogue Generation for Behavior Intervention on Mobile Devices

AbstractCommunication in the form of dialogues between a virtual coach and a human patient (coachee) is one of the pillars in an intervention app for smartphones. The virtual coach is considered as a cooperative partner that supports the individual with various exercises for a behavior intervention therapy. To perform its supportive behavior, the coach follows a certain interaction model and its requirements, such as alignment, mutual commitment and adaptation. In this paper, we propose E-Coach MarkUp Language (ECML), a standard XML specification for scripting discourses that define how the virtual coach maintains a dialogue with a coachee following the interaction model. The format of the language allows messages to be tailored at a fine-grained level. Each sentence is synthesized based on the inferred goals of the coaching process and the current beliefs of the user, incorporating everything that has been said previously in the conversation. The design enables inexpensive implementation on mobile devices for a flexible, seamless coaching dialogue. With expert-based evaluations, we validated the language using scenarios on implemented ECML in the field of insomnia therapy

Pediatric pharmacology of desmopressin in children with enuresis : a comprehensive review

Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication-nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration-time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 mu g tablet and 120 mu g lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additional information should be collected about the clinical relevance of the double absorption peak, the food effect, the bioequivalence/therapeutic equivalence, the pediatric adapted dosing regimens, the study endpoints and the difference between performing studies at daytime or at nighttime. To fill in these gaps, additional well designed pharmacokinetic and pharmacodynamic studies in children should be performed

Studentenparticipatie als een strategie om leiderschapskwaliteiten te ontwikkelen

België is een van de weinige landen ter wereld waar de graad van studentenparticipatie in de opleiding geneeskunde zo hoog ligt. In deze studie gaan we na in hoeverre de studentenparticipatie kan bijdragen aan het ontwikkelen van leiderskwaliteiten die van belang zijn voor een arts. Studentenvertegenwoordigers uit de opleiding geneeskunde aan de Vlaamse universiteiten werden een vragenlijst voorgelegd. Uit de vragenlijst blijkt dat bepaalde competenties aangeleerd worden dankzij het engagement van de student. Deze vaardigheden kunnen bijdragen tot een goede ontwikkeling van een arts die kan inspelen op de noden van de maatschappij

Recommandations pour l'éducation et l'accueil des jeunes enfants (EAJE) dans les trois Communautés de Belgique

Ce document, produit par le groupe OMEP Belgique (Organisation Mondiale d'Education Préscolaire), composé d'acteurs et actrices de l'accueil de la petite enfance, de l'école maternelle, de la formation et de la recherche des trois communautés linguistiques de Belgique propose six recommandations pour développer la qualité des services d'éducation et d'accueil des jeunes enfants en accord avec les recommandations internationales et les orientations à privilégier localement.Organisation Mondiale pour l’Education Préscolaire (OMEP) - Belgiqu