Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

by Chiu Pui Yu. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 86-118). / Abstracts in English and Chinese. / Title Page --- p.i / Abstract --- p.ii-iv / Acknowledgement --- p.v / Table of Contents --- p.vi-viii / List of Tables --- p.ix / List of Figures --- p.x-xii / List of Abbreviations --- p.xiii / Chapter Section I: --- Introduction / Chapter Chapter 1: --- Overview --- p.1-2 / Chapter Chapter 2: --- Teratogenic Effects of Hyperglycemia / Chapter 2.1 --- What is Hyperglycemia --- p.3 / Chapter 2.2 --- Teratogenic Effects of Hyperglycemia --- p.4-6 / Chapter 2.2.1 --- Human Studies / Chapter 2.2.2 --- Animal Studies / Chapter 2.3 --- Timetables for Embryogenesis: Rats versus Humans --- p.7 / Chapter 2.4 --- Mechanisms of Hyperglycemia Induced Teratogenesis --- p.8-12 / Chapter 2.4.1 --- What are Free Radicals? / Chapter 2.4.2 --- Major Free Radical Species Involvedin Hyperglycemic Teratogenesis / Chapter 2.4.3 --- Molecular Damage Induced by Reactive Oxygen Species / Chapter 2.4.4 --- Supporting Evidence of Reactive Oxygen Species Causing Anomalies / Chapter 2.4.5. --- Hyperglycemia and Formation of Free Radicals / Chapter Chapter 3: --- Caffeine as Teratogen and Antioxidant / Chapter 3.1 --- Popularity of Caffeine --- p.13 / Chapter 3.2 --- Basic Metabolism of Caffeine --- p.14 / Chapter 3.3 --- Biological Actions of Caffeine --- p.15 / Chapter 3.4 --- Teratogenicity of Caffeine --- p.16-20 / Chapter 3.4.1 --- Animal Studies / Chapter 3.4.1.1 --- Teratogenic Effects of Caffeine in Animals / Chapter 3.4.1.2 --- Teratogenic Dose of Caffeine / Chapter 3.4.1.3 --- Interspecies Sensitivity / Chapter 3.4.2 --- Human Studies / Chapter 3.5 --- Possible Mechanisms for the Teratogenic Actions of Caffeine --- p.21 / Chapter 3.6 --- Caffeine as an Antioxidant --- p.22 / Chapter 3.7 --- Combined Effects of Caffeine with Other Substances --- p.23 / Chapter Chapter 4: --- Combined Effects of Hyperglycemia and Caffeine on Early Embryogenesis- A Question to be Answered / Chapter 4.1 --- Possible Links between Hyperglycemia and Caffeine --- p.24 / Chapter 4.2 --- Objectives of the Present Study --- p.25 / Chapter 4.3 --- Hypothesis --- p.26 / Chapter Section II: --- Research Designs and Methods / Chapter Chapter 5: --- Materials and Methods / Chapter 5.1 --- Licenses --- p.27 / Chapter 5.2 --- Overall Study Design --- p.28-40 / Chapter 5.2.1 --- Whole Embryo Culture Model / Chapter 5.2.1.1 --- Animals / Chapter 5.2.1.2 --- Explantation of Embryos and Serum Collection / Chapter 5.2.1.3 --- Preparation of Serum / Chapter 5.2.1.4 --- Culture Media / Chapter 5.2.1.5 --- Embryo Culture / Chapter 5.2.2 --- Experimental Groups / Chapter 5.2.3 --- Morphological Assessment / Chapter 5.2.4 --- Quantitation of Oxidative Stress / Chapter 5.2.5 --- Protein Assay / Chapter 5.3 --- Statistical Evaluation --- p.41 / Chapter Chapter 6: --- Laboratory Considerations / Chapter 6.1 --- Whole Embryo Culture Model --- p.42-43 / Chapter 6.1.1 --- Subjects / Chapter 6.1.2 --- Time Mating / Chapter 6.1.3 --- Culture Medium / Chapter 6.1.4 --- Gas Phase and Rotating Bottle Culture Method / Chapter 6.2 --- Quantification of Oxidative Stress --- p.47-49 / Chapter 6.2.1 --- 8-Isoprostaglandins F2a as a Marker / Chapter 6.2.2 --- Assay for 8-Isoprostaglandins F2a / Chapter 6.2.2.1 --- Enzyme Immunoassay versus Gas Chromatography/ Mass Spectrometry / Chapter Section III: --- Results / Chapter Chapter 7: --- Results / Chapter 7.1 --- Justifications of Methods of Statistical Analysis --- p.50 / Chapter 7.2 --- Effects of Hyperglycemia on Early Embryogenesis --- p.51-56 / Chapter 7.2.1 --- Effects of Hyperglycemia on Morphological Development / Chapter 7.2.2 --- Effects of Hyperglycemia on Production of 8-isoprostaglandins F2a / Chapter 7.2.3 --- Effects of Hyperglycemia on Total Protein Content / Chapter 7.3 --- Effects of Caffeine on Early Embryogenesis --- p.57-61 / Chapter 7.3.1 --- Effects of Caffeine on Morphological Development / Chapter 7.3.2 --- Effects of Caffeine on Total Protein Content / Chapter 7.4 --- Combined Effects of Hyperglycemia and Caffeine on Early Embryogenesis --- p.62-66 / Chapter 7.4.1 --- Combined Effects of Hyperglycemia and Caffeine on Morphological Development / Chapter 7.4.2 --- Combined Effects of Hyperglycemia and Caffeine on Production of 8-isoprostaglandins F2a / Chapter 7.4.3 --- Combined Effects of Hyperglycemia and Caffeine on Total Protein Content / Chapter Section IV: --- Discussion and Conclusions / Chapter Chapter 8: --- Discussion --- p.67-83 / Chapter Chapter 9: --- Conclusions and Future Directions --- p.84 / Appendices --- p.85 / References --- p.86-118

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Thesis (M.S.)--University of Michigan, 1963.

Thesis (M.S.)--University of Michigan, 1963.

The aims of the research were to establish whether diphenylhydantoin and phenobarbitone are teratogenic in mice both in vivo and in an in vitro whole embryo culture system, to investigate possible mechanisms of teratogenicity and to examine whether the methods used in this study, may form a basis for developing systems of more extensive drug teratogenicity screening.

Chan Wai-Hon. / "September 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 137-156). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 7 uppsatser.

Hydroxyurea was used as a model teratogen to investigate the role of oxidative stress and stress-response pathways in mediating developmental toxicity. When administered to pregnant mice during early organogenesis, hydroxyurea induced fetal death and growth retardation, as well as external and skeletal malformations. The malformed fetuses displayed hindlimb, vertebral column, and tail defects. Hydroxyurea treatment enhanced the production of 4-hydroxynonenal, a lipid peroxidation end product, in malformation sensitive regions of the embryo. Depletion of glutathione, a major cellular antioxidant, specifically enhanced hydroxyurea-induced malformations and elevated the region-specific production of 4--hydroxynonenal protein adducts in the embryo, without affecting the incidence or extent of hydroxyurea-induced fetal death or growth retardation. The major proteins modified by 4-hydroxynonenal were involved in energy metabolism. Thus, oxidative stress is important in the induction of malformations by hydroxyurea. / Exposure to hydroxyurea stimulated the DNA binding activity of activator protein 1 (AP-1), an early response redox-sensitive transcription factor. Activated AP-1 was composed mainly of c-Fos heterodimers. Glutathione depletion did not change the effects of hydroxyurea on AP-1/c-Fos DNA binding activities despite an augmentation of the incidence of embryo malformations. Mitogen-activated protein kinases (MAPKs) activate AP-1 in response to stress by post-transcriptional phosphorylation of AP-1 proteins. Hydroxyurea treatment dramatically enhanced the activation of stress-responsive p38 MAPKs and JNKs (c-Jun N-terminal protein kinases). Selectively blocking p38 MAPKs enhanced the incidence of fetal death, whereas selective inhibition of JNKs specifically elevated the limb defects induced by hydroxyurea. Thus, activation of stress-response pathways impacts on the response of the embryo to a teratogenic insult.

Source: Dissertation Abstracts International, Volume: 69-10, Section: B, page: 6009. Adviser: Dorothy K. Waller. Includes bibliographical references.