Graduation date: 1993

No description available.

No description available.

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Based on the findings from breast cancer cells and nude mouse assays, we noticed that fatty acid metabolism was influenced by BDE-47 exposure. To have a comprehensive understanding of the impact, we performed targeted metabolomics analysis of fatty acids. Short-chain fatty acids (SCFAs) and hydroxylated short-chain fatty acids (OH-SCFAs) are crucial intermediates related to a variety of diseases, such as bowel disease, cardiovascular disease, renal disease and cancer. We developed a global profiling method to screen SCFAs and OH-SCFAs by tagging these analytes with d0/d6-N, N-dimethyl-6,7-dihydro-5H-pyrrolo[3,4-d] pyrimidine-2-amine (d0/d6-DHPP) and UHPLC-MS/MS in parallel reaction monitoring (PRM) mode. The derivatization procedure was simple and rapid. The targeted compounds could be derivatized within three minutes under mild condition and analyzed without the need of further purification. The derivatization significantly improved the chromatographic performance and mass spectrometry response. The d6-DHPP tagged standards were used as internal standards, which remarkably reduced the matrix effects. The use of high resolution PRM mode made it possible to identify unknown SCFA and OH-SCFA species. The developed method was successfully applied to the analysis of mouse feces, serum, and liver tissue samples harvested from the breast cancer nude mice that had been exposed to BDE-47. By using the developed method, 40 analytes (10 SCFAs and 30 OH-SCFAs) were characterized. Semi-quantitative analysis indicated that the exposure of BDE-47 to the mice altered the SCFA and OH-SCFA metabolism, especially in the high dose group. In addition, medium- and long-chain fatty acids (MLFAs) are essential energy sources in cells and possess vital biological functions. Characteristics of MLFAs in biosamples can contribute to the understanding of biological process and the discovery of potential biomarkers for relevant diseases. However, there are obstacles of the MLFAs determination because of the poor ionization efficiency in mass spectrometry and structural similarity. Herein, a derivatization strategy was developed by labeling with d0-DHPP and detecting with UHPLC-MS/MS in multiple reaction monitoring (MRM) mode. The parallel isotope labeled internal standards were generated by tagging d6-DHPP to MLFAs. The simple and rapid derivatization procedure and mild reaction conditions greatly reduced the potential of MLFA degradation. With the methodology, the chromatography performance was greatly improved, and the mass spectrum response was enhanced up to 1, 600 folds. Finally, the developed derivatization method was applied to serum samples to analyze the alteration of MLFAs induced by BDE-47 exposure in breast cancer nude mice. The semi-quantitative results demonstrated that the BDE-47 exposure significantly influenced the MLFA metabolism. Together, mass spectrometry-based targeted and nontargeted metabolomics of in vitro and in vivo studies suggested that BDE-47 impacted multiple metabolic pathways and was positively associated with breast tumor growth in mice. This study might further our understanding of the health risks of BDE-47 to breast cancer.;Polybrominated diphenyl ethers (PBDEs) are commonly used to prevent the development of fire in various factory products. Due to the adverse effects on human health and bio-accumulation capacity, PBDEs are considered as one kind of persistent organic pollutants. 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is one of the most frequently detected PBDE congeners in humans. Although numerous studies have shown the close connection between BDE-47 and human health, few reports were related to breast carcinoma. In vivo study of the association between BDE-47 and breast cancer was also scarce. In this study, both in vitro and in vivo experiments were conducted to explore the influence of BDE-47 to breast cancer. Firstly, we performed the in vitro study by exposing different concentrations of BDE-47 (5, 10 µM) to MCF-7 breast cancer cells. Nontargeted metabolomics analysis was conducted by using ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Results showed that the toxicity to MCF-7 cells gradually increased when the concentration of BDE-47 exceeded 1 µM in the medium. Pyrimidine metabolism, purine metabolism and pentose phosphate pathway (PPP) were the most influenced metabolic pathways, and the metabolites in the three metabolic pathways were significantly downregulated. Moreover, the increase of reactive oxygen species was detected by using the 2',7'-dichlorodihydrofluorescein diacetate staining assay. Results suggested that the BDE-47 induced oxidative stress by downregulating the NADPH generation in PPP. The pyrimidine metabolism and purine metabolism might be downregulated by the downregulation of mRNA transcripts. Therefore, BDE-47 could induce oxidative stress in breast cancer cells by inhibiting PPP and disordering the metabolism of the entire cell subsequently. Secondly, we constructed a breast cancer nude mouse model, performed in vivo exposure of BDE-47 to the mice, and conducted mass spectrometry-based metabolomics and lipidomics analysis to investigate the metabolic changes in mice. Results showed that the tumor sizes were positively associated with the dosage of BDE-47. Metabolomics and lipidomics profiling analysis indicated that BDE-47 induced significant alterations of metabolic pathways in livers, including glutathione metabolism, ascorbate and aldarate metabolism, and lipids metabolism, etc. The upregulations of phosphatidylcholines and phosphatidylethanolamines suggested the membrane remodeling, and the downregulations of Lyso-phosphatidylcholines and Lyso-phosphatidylethanolamines might be associated with the tumor growth. Targeted metabolomics analysis revealed that BDE-47 inhibited fatty acid β-oxidation (FAO) and induced incomplete FAO. The inhibition of FAO and downregulation of PPARγ would contribute to inflammation, which could promote tumor growth. In addition, BDE-47 elevated the expression of the cytokines TNFRSF12A, TNF-α, IL-1β and IL-6, and lowered the cytokines SOCS3 and the nuclear receptor PPARα. The changes of cytokines and receptor may contribute to the tumor growth of mice.

Thesis (MScAgric)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Codling moth, Cydia pomonella (L.), infested fluit were collected in a sprayed, unsprayed and an organic orchard. The time of emergence was monitored to see if there was selection for a delayed emergence caused by different treatments. Moths from fruit collected in the sprayed and unsprayed orchards in Desember 2001, had a peak emergence during January 2002 and a smaller peak during February 2002. Moths from fruit collected during February 2002 from an organic orchard, had a peak emergence during February 2002 and an extended emergence from diapause until January 2003. Moths from fluit collected during March 2002 had a peak emergence during November 2002 with an extended emergence in the sprayed orchards until January 2003. Delayed emergence from diapause was observed. Not all the moths from diapause emerged during the first flight, but overlapped with the second flight in December and January. / AFRIKAANSE OPSOMMING: Kodlingmot, Cydia pomonella (L.), geïnfesteerde vrugte is in 'n onbespuite, chemies behandelde en 'n organiese boord versamel. Die tyd van motuitkoms is gemonitor om te bepaal of verskillende behandelings dalk seleksie in die motpopulasie kan veroorsaak ten op sigte van 'n vertraagde motuitkoms. Motte uit vrugte wat in die gespuite boorde in Desember 2001 versamel is, het 'n piek uitkoms in Januarie en 'n kleiner een in Februarie 2002 gehad. Motte uit die ongespuite boord se vrugte, het ook 'n piek uitkoms in Januarie 2002 getoon. Motte uit vrugte wat in Februarie 2002 in 'n organiese boord versamel is, het 'n piek uitkoms in Februarie 2002 gehad, met 'n verlengde uitkoms vanuit diapause vanaf Oktober 2002 tot Januarie 2003. Motte uit vrugte wat in Maart 2002 versamel is, het 'n piek uitkoms in November 2002 gehad. Daar was ook 'n verlengde motuitkoms vanaf diapause by die chemies behandelde boorde tot Januarie 2003. 'n Vertraagde motuitkoms vanaf diapause is waargeneem. Die motte vanuit diapause maak nie almal deel uit van die eerste vlug nie, maar oorvleuelook met motte van die tweede vlug wat gedurende Desember en Januarie in die veld voorkom.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2007-2008 / published_or_final_version / Biological Sciences / Master / Master of Philosophy

Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Na⁺/K⁺ ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of K⁺-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of K⁺-return relaxation. Another Na⁺/K⁺ ATPase activity, ⁸⁶Rb⁺ uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Na⁺/K⁺ ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began.

The effect of hydrogen cyanamide (H₂CN₂) on budbreak and fruit maturity of 2-year old 'Flame Seedless' table grapes was investigated in a low desert climate in central Arizona. Dormant sprays of H₂CN₂ applied at 2.5 and 5.0% (v/v) concentrations hastened budbreak by at least 16 days with subsequent advancement of fruit maturity by 5 to 10 days. A 5.0% (v/v) dormant application of H₂CN₂ to whole vine, buds only or pruning cuts only advanced budbreak by at least 16 days and advanced fruit maturity by 1 to 5 days, regardless of application site. A more uniform budbreak was observed on H₂CN₂ treated vines, regardless of concentration or site of application when compared to control vines.