M.Sc. (Zoology) / There has been an increasing concern worldwide regarding the possible adverse effects of pharmaceutical supplements present in our aquatic ecosystems and whether or not they modify the physiological functioning in humans and wildlife. Trenbolone acetate (TBA) and zeranol (Z) for example, are two commonly used synthetic anabolic growth promoting hormones in cattle production. TBA is metabolized into trenbolone-β and excreted as both trenbolone-α and -β. In liquid manure trenbolone-β has a half-life of over 270 days and Z, 120 days. Therefore if released into the surrounding environment there is the possibility for long-term severe ecological impacts i.e. fish reproduction and general health. The aim of this study was to determine the physiological effects of several growth promoting hormones used as growth promoting hormones in cattle production on the Mozambique Tilapia – Oreochromis mossambicus. The growth promoting hormones assessed in this study were; Trenbolone acetate, Methyltestosterone, Diethylstilbestrol and Zeranol. The aim was accomplished by making use of histology (gills, liver and gonads) and three biomarker assays; Glutathione-S-transferase (GST), Uridine-Diphosphate Glucuronosyltransferase (UDPGT) and Cellular Energy Allocation (CEA). Stock solutions of Trenbolone acetate (14 μg/l and 15 μg/l), Methyltestosterone (7 μg/l and 7.5 μg/l), Zeranol (2.8 μg/l and 3 μg/l) and Diethylstilbestrol (0.28 μg/l and 0.29 μg/l) were prepared. Fish were exposed under controlled conditions for a period of 24-hours, 4-, 15- and 30-days respectively using a flow-through system. The aquarium water was changed (45 L removed and replaced with 45 L of prepared growth hormone containing bore-hole water) every 48 – 72 hours to remove all waste material thus ensuring the aquariums were clean. Upon performing the necropsies, gills, liver and gonads were removed and examined using standard histological techniques. Muscle tissue was used to determine the CEA, liver and kidney tissue was used for both GST and UDPGT assays. The results obtained from the histology revealed that the gills and liver were not severely affected by exposure to the growth promoting hormones although possible exposure related alterations were evident. The gonads results indicated that exposure to the growth promoting hormones severely affected the morphology and functioning of the organs to the point where reproduction is questionable. The results obtained from the hepatosomatic index (HSI) and gonadosomatic index (GSI) revealed no significant differences (p<0.05) although a trend of increasing HSI and decreasing GSI was evident in the male fish exposed to the androgens. With regards to the biomarker assays there were minor decreases in CEA in the exposed fish but no significant differences (p<0.05) could be established. The GST assay revealed that Zeranol prompted a significant increase (p<0.05) in GST activity in the kidney after 4- and 15-days of exposure while the liver displayed no change in GST activity. The UDPGT assay revealed minor fluctuation in UDPGT activity in both the kidney and liver throughout the study, however, no significant differences (p<0.05) could be established. To conclude, exposure to these growth promoting hormones at the selected concentrations and exposure periods severely compromised the fish’s reproductive capabilities thus challenging the fish’s fitness. Further studies examining the energy metabolism and xenobiotic detoxification pathways of the Mozambique tilapia and other indigenous fish species are recommended to better comprehend the effects that these growth promoting hormones may possess.

Statins induce beneficial vascular effects. How statins induce beneficial vascular effects is yet to be determined. Here we examine Simvastatin and vascular endothelial growth factor (VEGF) acting through the phosphoinositide 3-kinase (PI3K) pathway in human coronary artery endothelial cells (HCAEC). While Simvastatin and VEGF both activated mediators in the PI3K pathway, the proteins and the rates of activation were not always consistent. This suggests that although Simvastatin and VEGF share a common PI3K pathway in HCAEC and similar vascular effects, the agonists diverge in the induction of cellular signaling cascades. Simvastatin also was shown to induce phosphoinositide 3, 4, 5-triphosphate (PIPS) organization and PI3K p110 gamma (y) perinuclear localization. Beneficial, non-lipid lowering effects of statins may occur through the PI3K pathway through activation of distinct mediators from those of VEGF. Better understanding of the pathways associated with statins is necessary for the discovery of better treatments for cardiovascular disease (CVD). / Department of Biology

Includes bibliographical references. / 1 v. (various foliations) : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Indicates that retarded fetal growth in sheep, associated with restricted supply of substrates to the fetus, is accompanied by reduced concentrations of insulin-like growth factor I in fetal blood and its decreased production in several major fetal tissues. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1995

Bibliography: leaves 175-203. / xxix, 203 leaves, [14] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates whether cytokines influence the development of the embryo prior to implantation. / Thesis (Ph.D.)--University of Adelaide, Depts. of Obstetrics and Gynaecology and Microbiology and Immunology, 1993

Insulin-like growth factor I (IGF-I) is a polypeptide protein hormone similar to insulin. It plays an important role in growth and anabolic effects in life. Most circulating IGF-I is bound to high-affinity insulin-like growth factor binding protein-3 (IGFBP-3), to form a complex (IGF-I/IGFBP-3) that can treat growth hormone insensitivity syndrome (GHIS) and can lower plasma glucose in diabetic patients. Its side effects can be reduced without affecting the therapeutic efficacy. Human insulin-like growth factor binding protein 3 (hIGFBP-3) alone is an anti-tumor agent. It has been shown to have anti-proliferation effect on numerous cancer cells, such as breast, prostate and liver cancers. / Our previous study has demonstrated that recombinant hIGF-I (rhIGF-I) and hIGFBP-3 (rhIGFBP-3) could be synthesized in transgenic tobacco plant. In the present study, we propose to establish an efficient bioreactor platform for mass production of hIGF-I and hIGFBP-3 in rice, as rice grain contains 8-15% of protein by dry weight. In order to enhance rhIGF-I and rhIGFBP-3 stability and yield, and to control their glycosylation, various constructs were designed and transformed into rice by Agrobacterium-mediated transformation. Protein targeting signal sequence (KDEL) was fused to direct the target proteins to specific compartments in rice grain for glycosylation in the Golgi apparatus or for stable accumulation without complex glycan processing in the endoplasmic reticulum. These expression constructs were driven by seed-specific glutelin promoter (Gt1pro). Western blot analysis showed that the rhIGF-I and rhIGFBP-3 were successfully expressed in transgenic rice grains. Biological activity of rhIGF-I was evidenced by the induction of membrane ruffling in L6 rat skeletal muscle cells, while rhIGFBP-3 was effective in inhibiting the effect of IGF-I on membrane ruffling of L6 cell. Moreover, rhIGFBP-3 was also found to inhibit the growth of human breast cancer MCF-7 cells. Biological activity results showed that the active expression levels of rhIGF-I and rhIGFBP-3 were found to be 10 ug and 7.36 ug per 1 g of rice seed respectively. These findings suggested that both rice-produced rhIGF-I and rhIGFBP-3 were biologically active. / Cheung, Chun Kai. / "September 2007." / Adviser: Peter Tong Chun Yip. / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4555. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 209-243). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Background: Different types of cardiomyopathies are associated with variable hypertrophic response. <p>A number of growth factors are thought to play a role in pathologic cardiac remodeling. <p>Aims: We compared the modulation of the TGF-ƒÒ superfamily and IGF-1 signaling pathways and their target genes, the cell cycle regulatory proteins in tachycardia-induced dilated cardiomyopathy, a model with no detectable hypertrophy and in ischemic cardiomyopathy, a model with a marked hypertrophic reaction. <p>Methods: In the first study, endomyocardial biopsies were obtained weekly in 15 dogs, during the development of tachycardiomyopaty. Genes involved in the myostatin-TGF-ƒÒ-Activin-A/Smad signaling pathway, p21 and cyclin D were quantified and correlated to echocardiographic measures of hypertrophy. In the second study, myocardial tissue samples were obtained in 8 dogs with a healed myocardial infarction, in 8 dogs with heart failure induced by overpacing and in 7 healthy dogs. We measured gene expression of IGF-1, its receptor (IGF-1R) and cyclins A, B, D1, D2, D3 and E and correlated them to the level of hypertrophy. <p>Results: Tachycardiomyopathy was characterized by chambers dilation with no identifiable hypertrophy. Ischemic cardiomyopathy was characterized by eccentric hypertrophy. In tachycardiomyopathy, Activin-A mRNA was 4-fold higher than at baseline. Smad7 was overexpressed in severe heart failure; p21, a direct target gene of the Smad pathway was upregulated 8-fold and cyclin D1 was down-regulated. In that model, IGF-1 was overexpressed but neither IGF-1R nor any of the cyclins studied.<p> In ischemic cardiomyopathy, IGF-1, IGF-R, and cyclins B, D1, D3 and E gene expression were upregulated.<p> In tachycardiomyopathy, Activin-A and p21 were inversely correlated to the thickness of the interventricular septum. In normal dogs and in the both models of cardiomyopathy, IGF-1R was correlated to the thickness of the interventricular septum and to cyclins. <p>Conclusions: Taken together, these results agree with the notion that Activin-A, IGF and cyclins are involved in the modulation of hypertrophic response observed in cardiomyopathies. <p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished