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Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that the experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.
Since the thalidomide (Contergan) tragedy about 30 years ago the induction of prenatally-induced morphological or functional defects has been an area of extensive research. Risk assessment of prenatally-induced adverse health effects is still a difficult task from both experimental data as well asfrom observations in humans. In the contributions to this book three major aspects are dealt with: - Quantitative extrapolations of experimental data to the situation possibly relevant for man. - The significance for a risk assessment with respect to man of minor or rare structural abnormalities observed in experimental studies - The future need to assess congenital dysfunctions (e.g. of the hormone or the immune system) beside the present evaulation of structural defects. Limitations as well as gaps of the present knowledge in this area of basic and applied research are pointed out. Since the results of prenatally-induced lesions may manifest themselves not only pre- but often not before late postnatally, numerous aspects of structural and functional abnormaldevelopment must be studied in experimental and clinical investigations.
Having received the invitation from Springer-Verlag to produce a volume on drug-induced birth defects for the Handbook of Experimental Pharmacology, we asked ourselves what new approach could we offer that would capture the state of the science and bring a new synthesis of the information on this topic to the world's literature. We chose a three-pronged approach, centered around those particular drugs for which we have a relatively well established basis for understanding how they exert their unwanted effects on the human embryo. We then supplemented this information with a series of reviews of critical biological processes involved in the established normal developmental patterns, with emphasis on what happens to the embryo when the processes are perturbed by experimental means. Knowing that the search for mechanisms in teratology has often been inhibited by the lack of understanding of how normal development proceeds, we also included chapters describing the amazing new discoveries related to the molecular control of normal morphogenesis for several organ systems in the hope that experimental toxicologists and molecular biologists will begin to better appreciate each others questions and progress. Several times during the last two years of developing outlines, issuing invitations, reviewing chapters, and cajoling belated contributors, we have wondered whether we made the correct decision to undertake this effort.
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