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4 edition of Mechanisms of thalidomide teratogenesis found in the catalog.

Mechanisms of thalidomide teratogenesis

Mechanisms of thalidomide teratogenesis

bioactivation by prostaglandin synthetase and glutathione homeostasis in cytoprotection.

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Published by National Library of Canada in Ottawa .
Written in English


Edition Notes

SeriesCanadian theses = Thèses canadiennes
The Physical Object
FormatMicroform
Pagination3 microfiches.
ID Numbers
Open LibraryOL18648388M
ISBN 10031556668X
OCLC/WorldCa25367630

Although teratogenesis has been recognized for a long time, the molecular mechanisms of their effects on embryos are only recently being unraveled. A brief description of thalidomide tragedy and induced teratogenesis is provided here. For details, readers are referred to a standalone chapter on thalidomide elsewhere in this book. This book brings together some of the more recent and important research findings related to the mechanisms and pathogenesis of abnormal develop­ ment. It is not only a documentation of the latest experimental work, but it also points out future directions that seem productive and challenging.

We estimated dispensing rates of medical drugs suspected to be associated with teratogenic mechanisms in our study population. The database includes all pharmacy dispensings for an estimated population of in – and c since In addition, trends in first trimester dispensing rates over time and patterns of receiving multiple drugs associated with . Thalidomide-Induced Teratogenesis: History and Mechanisms Neil Vargesson Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man-made medical disaster ever, where o children were born with a range of severe and debilitating malformations.

Stephens TD, Fillmore BJ, Hypothesis: thalidomide embryopathy-proposed mechanism of action, Teratology, Mars , Vol (3), pp You can also read an article written by Dr. Stephens exclusively for TVAC newsletter, in which he describes its conclusions. ISBN: OCLC Number: Description: 1 online resource ( pages) Contents: 1 Embryonic-fetal localization of drugs and nutrients Antiteratogens as analytical tools Trypan blue induced teratogenesis Congenital skeletal dysplasias --a better understanding via experimental models Current concepts on the mechanisms .


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Mechanisms of thalidomide teratogenesis Download PDF EPUB FB2

Other proposed mechanisms of thalidomide‐induced teratogenesis include effects on chrondrogenesis (Stephens et al., ), nerve toxicity/neural crest loss (McCredie and McBride, ), and DNA intercalation (Jonsson, ; Hague et al., ).

All these proposed mechanisms likely have some involvement; however, in what order?Cited by: 3. We propose that thalidomide affects the following pathway during development: insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF-2) stimulation of the transcription of αv and β3 integrin subunit genes.

The resulting αvβ3 integrin dimer stimulates angiogenesis in the developing limb bud, which promotes outgrowth of the by:   In this commentary, we describe a model to explain the mechanism of the embryopathy of thalidomide.

We propose that thalidomide affects the following pathway during development: insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF Cited by: to act as a primary mechanism of teratogenesis by altering fluid pressures, viscosities and composition in different compartments of the embryo.

Embryos appear to lack much of the homeostatic regulation available to fetal or postnatal by:   Thalidomide caused birth defects, yet it is now being used successfully to treat cancers and other diseases. In this entry, Karl outlines the molecular mechanisms by which such a small drug can have such diverse effects, and discusses the ethical issues that surround the use of thalidomide.

Thalidomide Teratogenic Effects Linked to Degradation of SALL4: After 60 years, researchers have now shed light on the mechanism underlying thalidomide's devastating teratogenic effects.

Mechanisms of thalidomide teratogenesis book. Genet. Dec; (12) [PubMed: ]. Mechanism of Action in Thalidomide Teratogenesis Trent D.

Stephens,* Carolyn J. Bunde and Bradley J. Fillmore DEPARTMENT OF BIOLOGICAL SCIENCES,IDAHO STATE UNIVERSITY,POCATELLO, IDU.S.A. ABSTRACT. In this commentary, we describe a model to explain the mechanism of the embryopathy of thalidomide.

The fifteen or sixteen proposed mechanisms that are plausible at the present time can be roughly grouped into six categories, with thalidomide affecting: (i) DNA replication or transcription, (ii) synthesis and/or function of growth factors, (iii) synthesis and/or function of integrins, (iv) angiogenesis, (v) chondrogenesis, or (vi) cell death or injury.

It may be that many of the. The mechanism by which thalidomide causes limb malformations and other developmental defects is a long-standing question. in thalidomide teratogenesis. Biochem Pharmacol – In this commentary, we describe a model to explain the mechanism of the embryopathy of thalidomide.

We propose that thalidomide affects the following pathway during development: insulin-like growth factor I (IGF-I) and fibroblast growth factor 2 (FGF-2) stimulation of the transcription of alphav and.

The mechanism by which thalidomide causes limb malformations and other developmental defects is a long-standing question. Multiple hypotheses exist to explain the molecular mechanism of thalidomide action. Among them, theories involving oxidative stress and anti-angiogenesis have been widely supported.

Despite a resurgence in interest in thalidomide as a clinical drug, its mechanisms of action to cause teratogenesis are still an enigma. However, given the great interest in thalidomide presently, it will hopefully only be a matter of time that we finally elucidate the full devastating mechanisms.

mechanism of action d thalidomide embryopathy at very high concentrations (Therapontos et al., ). CPS49 is an analog structurally based upon the antian.

An alternative mechanism for teratogenesis due to thalidomide was proposed by Arlen and Wells (), Parman et al. (), and Wells et al. (a,b) where its metabolism may be catalyzed by embryonic prostaglandin H synthase (also known as cyclooxygenase) to reactive free radical intermediates.

These free radicals in the presence of cellular glutathione can induce oxidative stress via ROS generation. It is an immunomodulatory medication and works by a number of mechanisms including stimulating T cells and decreasing TNF-α production.

Thalidomide was first marketed in in West Germany, where it was available over the counter. When first released, thalidomide was promoted for anxiety, trouble sleeping, "tension", and morning sickness. Several decades have passed since the thalidomide disaster, and efforts to explore the mechanism underlying thalidomide-induced teratogenesis have never ceased.

Thalidomide hijacks the CRL4 CRBN E3 ligase to degrade a number of cellular proteins. The degradation of SALL4 and p63 is a new molecular mechanism involved in thalidomide embryopathy. Thalidomide consists of two linked rings, a glutarimide and pthalimide ring (Fig.

(Fig.1A). 1 A). Thalidomide has a chiral carbon, which is unstable and allows two enantiomers to coexist, which can interswitch between the two states rapidly in bodily fluids and in water (Smith et al., ; Franks et al., ).

One of the enantiomers is teratogenic, the S‐enantiomer. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level.

As the precise molecular mechanisms of thalidomide teratogenicity remains unclear, thalidomide prescription is strictly controlled by a program called the Thalidomide Risk Evaluation and Mitigation Strategy (REMS), formerly known as the System for Thalidomide Education and Prescribing Safety (STEPS) [ 17, 18 ].

Mechanisms of teratogenesis. Annu Rev Pharmacol Toxicol. title = "Thalidomide-induced Teratogenesis: History and Mechanisms", abstract = "Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man-made medical disaster ever where over children were born with a range of severe and debilitating malformations.

Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear.

Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level.In the late s and early s, the use of thalidomide in pregnant women in 46 countries resulted in the "biggest man‐made medical disaster ever," with o children born with a range of severe deformities, such as phocomelia, and thousands of miscarriages.

Thalidomide was introduced in and was aggressively marketed by the German pharmaceutical company Chemie Grünenthal as a.