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20. The neonatal and juvenile pig in pediatric drug discovery and development

Author

Ayuso, M, Buyssens, L, Stroe, M, Valenzuela, A, Allegaert, Karel, Smits, A, Annaert, P, Mulder, A, Carpentier, S, Van Ginneken, C, Van Cruchten, S, Ayuso, M, Buyssens, L, Stroe, M, Valenzuela, A, Allegaert, Karel, Smits, A, Annaert, P, Mulder, A, Carpentier, S, Van Ginneken, C, and Van Cruchten, S

Abstract

Pharmacotherapy in pediatric patients is challenging in view of the maturation of organ systems and processes that affect pharmacokinetics and pharmacodynamics. Especially for the youngest age groups and for pediatric-only indications, neonatal and juvenile animal models can be useful to assess drug safety and to better understand the mechanisms of diseases or conditions. In this respect, the use of neonatal and juvenile pigs in the field of pediatric drug discovery and development is promising, although still limited at this point. This review summarizes the comparative postnatal development of pigs and humans and discusses the advantages of the juvenile pig in view of developmental pharmacology, pediatric diseases, drug discovery and drug safety testing. Furthermore, limitations and unexplored aspects of this large animal model are covered. At this point in time, the potential of the neonatal and juvenile pig as nonclinical safety models for pediatric drug development is underexplored.

Published
2021

37. Abstracts of papers

Author

Rollema, H., Grol, C. J., Feenstra, M. G. P., van Oene, Joop C., Houwing, Hendrik A., Horn, Alan S., Ijzerman, A. P., Bultsma, T., Timmerman, H., Zaagsma, J., van der Graaff, M., Vermeulen, N. P. E., Joeres, R. P., Breimer, D. D., Tsantili-Kakoulidou, A., van der Valk, F., Rekker, R. F., Bijloo, G. J., Zoetemelk, C. E. M., van Hoven, W., van Meeteren-Wālchli, B., van der Gen, A., Mohn, G. R., Buijs, W., Breimer, D. D., Onkenhout, W., de Jong, H. J., Rog, A. A., van Ginneken, C. A. M., Lentjes, E. G. W. M., Bast, A., Savenije-Chapel, E. M., Noordhoek, J., Beld A. J., Rodrigues de Miranda J. F., van Ginneken C. A. M., van der Giesen, W. F., Dröge, J. H. M., Wilting, J., Janssen, L. H. M., van Amsterdam J. G. C., van Buuren, K. J. H., Wijnne, H. J. A., Nolet, M. R. A., Kremer, J. M. H., Bakker, G., van der Heijden, P. J. C. M., van der Schaar, M. W. G., Bank, C. M. C., Eriks, J. Ch., Gaisser, H. -D., van der Goot, H., Sterk, G. J., Zaagsma, J., Lock, F. M., de Vries, J., Mullink, H., van Bree, L., Redegeld, F. A. M., Grolleman, C. W. J., de Visser, A. C., Wolke, J. G. C., Buchan, P., and Burns, J. W.

Published
1982
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39. The preterm pig as a model of premature infant gait ataxia

Author

Bergström, A., Ryom, K., Vanden Hole, C., Andersen, A. D., Skovgaard, Kerstin, Van Ginneken, C., Thymann, T., Sangild, P. T., Bergström, A., Ryom, K., Vanden Hole, C., Andersen, A. D., Skovgaard, Kerstin, Van Ginneken, C., Thymann, T., and Sangild, P. T.

Abstract

Aims/background Compromised gait, balance and motor coordination (ataxia) as observed in cases of cerebral palsy is a serious complication to premature birth. The cerebellum is a central region with regards to these brain functions and its development shows high sensitivity to premature birth. Our group has over many years refined a pig model of premature birth focusing on gut and immune system development. Phenotypically, we have observed distinct motoric problems e.g. falls, tiptoe walking and swaying in preterm pigs relative to term born counterparts, indicating compromised brain function. The aim of this study was to compare gait patterns and cerebellar neurodevelopmental gene expression of preterm and term piglets. Methods We compared gait patterns and T-maze performance of caesarean born preterm (3 litters, 90% gestation) and term born pigs (1 litter, 100% gestation) recorded at five distinct postnatal days. MatLab was used to determine a list of spatiotemporal gait characteristics e.g. stride length/ frequency, ”duty factor” and asymmetry indices. These data were paralleled by qPCR of >60 selected neurodevelopmental genes of isolated cerebellar tissue. Results While most genes did not differ significantly, we found higher (fold change [1,5-2]) mRNA levels of Midkine, Doublecortin, Neurotrophin3, p75 and Ephrin-B1 in preterms. Preliminary results from gait and T-maze showed significant functional differences between terms and preterms. Conclusions The preterm pig shows functional delays relative to terms, yet the limited cerebellar gene expression differences (mainly related to angiogenesis) suggest other brain regions e.g. motor cortex and basal ganglia to also be involved in compromised gait.

Published
2016

41. [Untitled]

Author

A. Weyns, De Smet M, Van Meir F, and Van Ginneken C

Subjects
Whole mount, Cuprolinic blue, Pathology, medicine.medical_specialty, Nucleolus, Cell Biology, Biology, Molecular biology, Staining, medicine.anatomical_structure, Cytoplasm, medicine, Anatomy, Nucleus
Abstract

Encouraged by the knowledge that microwaves have a beneficial effect on immunohistochemical reactions, the present study aimed to find out whether microwaves could improve the Cuprolinic Blue staining of enteric neurons as well as the actual method that has been developed for gastrointestinal whole-mount preparations. In addition to incorporating a microwave application in the method described by Holst and Powley (1995), some other modifications were made: two incubations before incubation in the staining solution and free-floating incubations. In the whole-mount preparations, most, if not all, enteric neurons were stained by Cuprolinic Blue. These neurons appeared as blue–green cells with non-reacting nuclei and neuronal processes. At higher magnification, the cytoplasm was characterized by a fine blue– green granulation, and the nucleolus in the nucleus appeared as a blue iridescent structure. Non-specific staining occurred in fibrocy tes and epithelial cells but, because of their location and appearance, they could easily be distinguished from neurons. The modified incubations and the incorporation of a microwave application into the conventional Cuprolinic Blue staining method turn the method into an easy-to-use one that seems to visualize most, if not all, enteric neurons in whole-mount preparations of the pig jejunum.

Published
1998
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45. Abstracts of papers

Author

v. d. Wouw, P. A., v. Rooy, H. H., Koster, R. W., Porsius, A. J., van Wayjen, R. G. A., van den Ende, A., van Tol, R. G. L., MacGregor, T. R., Mooy, J., Arends, B. c., Böhm, R., v. Kemenade, J., v. Baak, M., Rahn, K. H., Koopmans, P. P., Thien, Th., Thomas, C. M. C., Gribnau, F. W. J., Timmer, J. G., Vyth, A., Kok, W. Th., de Jong, J. M. B. V., den Hartog Jager, W. A., Overdiek, J. W. P. M., Merkus, F. H. H. M., van Bàak, M. A., de Ryckc, D., Teirlynck, O., Bogaert, M. G., Smits, P., van 't Laar, A., van Schaik, B. A. M., Geyskes, G. G., Roos, J. C., Mees, E. J. Dorhout, Navis, G. J., de Jong, P. E., Donker, A. J. M., v. d. Hem, G. K., Zeeuw, D. de, van den Meiracker, A. H., Veld, A. J. Man in't, Ritsema, C. J. R., van Eck, Derkx, F. H. M., Schalekamp, M. A. D. H., Berkelmans, J. H. M., Wollersheim, H., Dullemond-Westland, A. C., Neijt, J. P., Nortier, J. W. R., Sitsen, J. M. A., Vermeij, P., Edelbroek, P. M., Ferrari, M. D., Buruma, O. J. S., de Wolff, F. A., Elferink, F., van der Vijgh, W. J. F., Klein, I., ten Bokkel Huinink, W. W., Pinedo, H. M., Raghoebar, M., Tiemessen, H. L. G. M., van Kiel, P. L. C. M., van den Berg, W. B., and van Ginneken, C. A. M.

Published
1985
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46. Abstracts of papers pharmacological meeting

Author

Beckorinqh, J. J., Korstanje, C., van Zwieten, P. A., Boddeke, H. W. G. M., Jonkman, F. A. M., Daemen, M., van Essen, H., Smits, J., Thljssen, H., de Bruijn, E. A., Driessen, O., Hermans, J., de Graeff, P. A., Kingma, J. H., van Gilst, W. H., Bel, K., de Langen, C. D. J., Wesselinq, H., Doods, H. N., Davidesko, D., Mathy, M. -J., Batink, H. D., de Jonge, A., Ellenbroek, B., Klockgether, T., Turskit, L., Schwarz, M., Cools, A., Franken, N. A. P., van Delft, J. L., van Langevelde, A., Dubbelman, T. M. A. R., Oosterhuis, J. A., Star, W. M., Marljnissen, J. P. A., Journée-de Korver, J. G., Pauwels, E. K. J., Haenen, G. R. M. M., Bast, A., de Vries, J., Vcrmeulen, N. P. E., Timmerman, H., Hugtenburg, J. G., Beckeringh, J. J., Janssen, B. J. A., Struyker-Boudier, H. A. J., Smits, J. F. N., Jonkman, P. A. M., Man, P. W., Knape, J. T. A., Lambalk, C. B., van Kessel, H., van Rees, G. P., Schoemaker, J., Lammers, J. H. C. M., Meelis, W., Kruk, M. R., van der Poel, A. M., Lippens, F. J. P., van Valkenburg, C. F. M., van der Krogt, J. A., Krick, E. W. C., Belfroid, R. D. M., Noach, E. L., Loesberg, C., Woutersen-v. Nijnanten, F. M. A., Nijkamp, F. P., Molenaar, P. C., Pen, B. S., Polak, R. L., Nievelstein, H. N. M. W., Tijssen, C. M., Smits, J. F. M., Plant jé, J. F., Stoof, J. C., Maikel Kaghoebar, Jan A., Huisman, M., van Ginneken, Cees A. M., Rahusen, F. D., Robillard, G. T., Wildevuur, Ch. R. N., Russel, F. C. M., van der Linden, P. E. M., Vermeulen, W. G., van Ginneken, C. A. M., Smits, R. P. J. H., Steinhusch, H. U. M., Mulder, A. H., ten Brink, E. M. J., van der Plas, J., van Giersbergen, P. L. M., Wlegant, V. M., de Jong, W., van Koppen, C. J., Hermanussen, M. W., Verrijp, C. N., Rodrigues de Miranda, J. F., Beld, A. J., Lammers, J. W. J., van Oosterhout, A. J. M., Vulto, Arnold G., Sharp, Trevor, Ungerstedt, Urban, Wolterink, G., and van Ree, J. M.

Published
1985
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50. Abstracts of papers medicinal chemical meeting

Author

Damsma, G., Westerink, B. H. C., de Vries, J. B., Horn, A. S., Rettenmayr, N., de Miranda, J. F. Rodrigues, Lambrecht, G., Mutschler, E., Russel, F. G. M., van Galen, P. J. M., van Viijmen, H. W. Th., Ijzerman, A. P., Soudijn, W., Vromans, R. M., van de Straat, R., Groeneveld, M., Vermeiden, N. P. E., Siero, H. L. M., van Zwam, A. J. G., de Miranda, J. F. Rodriques, van Ginneken, C. A. M., Willems, P. H. G. M., de Pont, J. J. H. H. M., van Gelderen, J. G., Pruijn, F. B., Bast, A., de Zwart, M. A. H., van der Goot, H., Timmerman, H., Kramer, K., Voss, H. P., Grimbergen, J. A., Goeptar, A. R., Haenen, G. R. M. M., Veerman, M., Vermeulen, N. P. E., Boom, S. P. A., Koper, J. G., Leurs, J. N. L. Go. R., Rekka, E., Sterk, G. J., van der Weide, Jan, Tendijck, H., Tepper, P. G., Horn, A. B., Bosker, F. J., van Bussel, F. J., Plug, M. J., Dijk, J., Tepper, P., Möller, W., Leusen, F. J. J., van Vlijmen, H. W. Th., de Kaste, D., van Amsterdam, J. G. C., Llorens-Cortes, C., Vleeming, W., v. d. Wouw, P. A., v. Rooij, H. H., Wemer, J., Porsius, A. J., Lusthof, K. J., de Mol, N. J., Janssen, L. H. M., Bakri, Aziz, Janssen, Lambert H. M., Wilting, Jaap, Kelder, P. P., Kuit, M. C. A. W., van Sterkenburg, E. L. M., Wilting, J., Bos, O. J. M., and Fischer, M. J. E.

Published
1987
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