Rozprawy doktorskie na temat „Therapeutic use of wine”

The use of wine as a medicine is not a new idea, but one that has been rediscovered and given credibility due to current research findings. This research examines the use of wine as a medicine in the past and currently. The whole question of wine and health is put into a more balanced and proper perspective, instead of the ill-informed, negative anti-alcohol view. The aim of the thesis is to document the history of the uses of wine as a medicine, particularly in Australia. The author uses a social ecology framework,which is concerned with the interrelationships between the domains of the personal, social and environmental, with a critical, holistic transdisciplinary understanding approach. One aim of the research is to change the perception of wine from one of a drink for special occasions to one of a daily health drink taken in moderation with a meal
Doctor of Philosophy (PhD)

The use of wine as a medicine is not a new idea, but one that has been rediscovered and given credibility due to current research findings. This research examines the use of wine as a medicine in the past and currently. The whole question of wine and health is put into a more balanced and proper perspective, instead of the ill-informed, negative anti-alcohol view. The aim of the thesis is to document the history of the uses of wine as a medicine, particularly in Australia. The author uses a social ecology framework,which is concerned with the interrelationships between the domains of the personal, social and environmental, with a critical, holistic transdisciplinary understanding approach. One aim of the research is to change the perception of wine from one of a drink for special occasions to one of a daily health drink taken in moderation with a meal

Thesis (MSc)--University of Stellenbosch, 2001.
ENGLISH ABSTRACT: Monoterpene alcohols (monoterpenols) play an important role in the flavour and aroma of grapes and wine. This is especially applicable to wines of a muscat variety, but these flavour compounds are also present in other non-muscat grape varieties, where they supplement other varietal flavours and aromas. These monoterpenols can be found in grapes and wine as free, volatile and odorous molecules, as well as in flavourless, nonvolatile glycosidic complexes. These complexes most often occur as 6-0-a-L-arabinofuranosyl-p-D-glucopyranosides (vicianosides), 6-0-P-D-xylopyranosyl- P-D-gluco-pyranosides (primverosides), 6-0-P-D-glucopyranosyl-p-D-glucopyranosides (gentio-biosides ), 6-0-a-L -rhamnopyra nosyl-p-D-g lucopyra nos ides (rutinos ides), or 6-0-p-D-apiofuranosyl-p-D-glucopyranosides of mainly linalool, geraniol, nerol, a-terpineol and hotrienol. These precursors are, however, hydrolyzed only to a limited extent by endogenous glycosidases during the fermentation process, as they exhibit very low activity in wine conditions. The monoterpenols can be released from their sugar moieties by one of two methods: either an acid or an enzymatic hydrolysis. The enzymatic hydrolysis mechanism is fully understood, and the process functions in two successive steps: firstly, depending on the precursor, the glycosidic linkage is cleaved by an a-L-arabinofuranosidase, an a-L-rhamnosidase, a p-D-xylosidase, or a p-D-apiosidase. The second step involves the liberation of the monoterpene alcohol by a p-glucosidase. This enzymatic hydrolysis does not influence the intrinsic aromatic characteristics of the wine, as opposed to acid hydrolysis. As the endogenous grape glycosides of Vitis vinifera and the yeast Saccharomyces cerevisiae show very low activity towards these aromatic precursors during the handling of the juice and winemaking processes, the focus has increasingly fallen on introducing exogenous p-glucosidases to wines and juices. Genes encoding p-glucosidases and a-L-arabinofuranosidases have been cloned from various organisms, including bacteria, fungi and yeasts. However, the activities and properties of these enzymes are not always suitable for exploitation under winemaking conditions, where a low pH, low temperatures, and high ethanol and glucose concentrations prevail. A genetically engineered wine yeast strain of S. cerevisiae that expresses glycosidases that are active in these conditions would be useful in improving the flavour and aroma of wines, thereby adding to the complexity and value of the wine. Two p-glucosidase genes, BGL 1 and BGL2 from Saccharomycopsis fibufigera, were subcloned into two Escherichia coli-yeast shuttle vectors. A dominant selectable marker gene (SMR1) was also inserted onto these plasmids. These plasmids were designated pBGL 1 (containing the BGL 1 gene) and pBGL2 (containing the BGL2 gene) respectively. Introduction of the two plasmids into two strains of S. cerevisiae then followed. A laboratory strain, L1278, was transformed to confirm the effective secretion of the expressed protein. An industrial yeast strain, VIN13, was subsequently transformed by making use of the selectable marker (resistance against sulfometuron). Enzyme assays with the synthetic substrate p-nitrophenol-j3-D-glucopyranoside (pNPG) were performed to determine the activity of the j3-glucosidases over a period of days, as well as at certain temperatures and pH values. The stability of the enzymes was also investigated. These recombinant yeasts were able to degrade the pNPG efficiently. They showed promising results concerning pH optima, with a substantial amount of activity found at the pH levels as found in the wine environment. There was also a slight increase in specific activity at lower temperatures. The recombinant yeast strains were also tested in smallscale fermentations. Three wines were made, of which two were from white cultivars (Chenin blanc and GewOrtztraminer) and one from red (Pinotage). Results obtained from micro-extraction from the finished wines showed that the terpenol content did increase, although this was not the only wine component influenced. Other flavour compounds also showed increases, especially the esters. This also played a role in the flavour increase in the wine. Future work would include optimizing the available results. This would entail the addition of another glycosidic enzyme, such as a-L-arabinofuranosidase, to the genome of the wine yeast to aid the further breakdown of glycosidic bonds. The cloning or engineering of a j3-glucosidase enzyme that is more active at low temperatures would also yield better results and release even more of the aroma of the wine.
AFRIKAANSE OPSOMMING: Monoterpeenalkohole (monoterpenole) speel 'n belangrike rol in die geur en aroma van druiwe en wyn. Dit is veral van toepassing op wyne van Muskaat-varieteite, maar hierdie geurkomponente is ook teenwoordig in ander nie-Muskaat druifsoorte, waar dit bydra tot die varieteitsqeur en aroma. Hierdie monoterpenole kom voor in druiwe as vry, vlugtige en aromatiese molekules, of as geurlose, nie-vlugtige glikosidies-gebonde komplekse. Hierdie komplekse is meestal in die vorm van 6-0-a-L-arabinofuranosiel-~-D-glukopiranosiede, 6- O-~-D-xilopiranosiel-~-D-glukopiranosiede (primverosiede), 6-0-~-D-glukopiranosiel-~-Dglukopiranosiede (gentiobiosiede), 6-0-a-L-ramno-pyranosiel-~-D-glukopiranosiede (rutinosiede), of 6-0-~-D-apiofuranosiel-~-D-glukopirano-siede van hoofsaaklik linalool, geraniol, nerol, a-terpineol en hotrienol. Hierdie geurvoorlopers word egter slegs tot In beperkte mate tydens die proses van fermentasie deur die endogene glikosidase ensieme gehidroliseer, aangesien hulle baie min aktiwiteit toon onder wynbereidingstoestande. Die monoterpenole kan op een van twee wyses van hul suikermolekules vrygestel word: 'n suurhidrolise, of ensiematiese hidrolise. Die ensiematiese hidroliseproses word baie goed begryp en behels twee opeenvolgende stappe: eerstens, afhangende van die aard van die voorloper, word die glikosidiese verbinding deur In a-L-arabinofuranosidase, In a-L-ramnosidase, In ~-D-xilosidase, of 'n ~-D-apiosidase gebreek. In die tweede stap word die monoterpeenalkohol deur In ~-glukosidase vrygestel. Hierdie ensiematiese afbraakproses verander nie die intrinsieke aromatiese kenmerke van die wyn, soos wat met suurhidrolise die geval is nie. Omdat die endogene glikosidases van Vitis vinifera en die van die gis Saccharomyces cerevisiae baie lae aktiwiteit ten opsigte van die aromatiese voorlopers gedurende die hantering van die druiwesap en wynmaakprosesse toon, val die fokus al hoe meer op die inkorporering van eksogene ~-glukosidases in wyn en sappe. Gene wat vir ~- glukosidases en a-L-arabinofuranosidases kodeer, is al vanuit verskeie organismes gekloneer, insluitende bakteriee, fungi en giste. Die aktiwiteite en kenmerke van hierdie ensieme is egter nie altyd wenslik vir hul gebruik in wyn nie, aangesien dit In omgewing is met 'n lae pH, lae temperatuur, en hoe etanolvlakke en glukose-konsentrasies. In geneties veranderde wyngis van S. cerevisiae wat in staat is om glikosidases uit te druk wat onder hierdie kondisies aktief is, sal baie handig te pas kom in die verbetering van die geur en aroma van wyne, om daardeur die kompleksiteit en die waarde van die wyn te verhoog. Twee ~-glukosidasegene, BGL 1 en BGL2 vanaf die gis Saccharomycopsis fibuligera , is in twee afsonderlike Esccherichia coli-gis-pendelplasmiede gesubkloneer. In Dominante selekteerbare merkergeen (SMR1) is ook in hierdie plasmiede gekloneer. Hierdie plasmiede word onderskeidelik pBGL 1 (met die BGL 1-geen) en pBGL2 (bevattende die BGL2-geen) genoem. Hierdie twee plasmiede is hierna apart na twee rasse van S. cerevisiae getransformeer. Eerstens is 'n laboratoriumras, L1278, getransformeer om te bevestig dat effektiewe sekresie en uitdrukking van die proteTen plaasvind. Hierna is 'n industriele gisras, VIN13, getransformeer deur gebruik te maak van die selektiewe merker (bestandheid teen sulfometuron). Ensiem-bepalings met behulp van die sintetiese substraat p-nitrofeniel-p-O-glukopiranosied (pNPG) is gedoen om die aktiwiteit van die p-glukosidqses oor 'n aantal dae te bepaal, asook om die aktiwiteit by sekere temperature en pH-vlakke te meet. Die stabiliteit van die ensieme is ook bepaal. Hierdie rekombinante giste was in staat om pNPG effektief af te breek. Hulle het belowende resultate betreffende die pH-optima getoon, met 'n aansienlike hoeveelheid aktiwiteit by die pH-vlakke soos dit in die wynomgewing voorkom. Daar was ook 'n effense verhoging in die ensieme se aktiwiteite by laer temperature. Die rekombinante gisrasse is ook in kleinskaalse wynfermentasies gebruik. Drie verskillende wyne is gemaak, waarvan twee wit kultivars was (Chenin blanc en GewOrtztraminer) en een 'n rooi kultivar (Pinotage). Resultate wat deur die mikro-ekstraksie van die voltooide wyne verkry is, het getoon dat die terpenolinhoud wei verhoog het, alhoewel dit nie die enigste wynkomponente was wat beinvloed is nie. Ander geurkomponente het ook 'n verhoging in konsentrasie getoon, veral die esters. Hierdie verbindings het ook 'n rol in die verhoging van geur in die wyne gespeel. Toekomstige werk sal die beskikbare resultate verder optimaliseer. Dit sal insluit die byvoeging van nog 'n glikosidiese ensiem, soos a.-L-arabinofuranosidase, tot die genoom van die wyngis, om verdere afbraak van glikosidiese verbindings teweeg te bring. Die klonering of verandering van 'n p-glukosidase-ensiem met verhoogde aktiwiteit by laer temperature sal ook beter resultate toon en meer geur in die wyn kan vrystel.

This thesis analyses the impact that the European Community had on table wine growers in the Midi region of France in the 1970s. This work is divided into the following parts: the negotiations leading to the creation of the Common Wine Policy (CWP) in 1970, its operation in the early 1970s until its first major crisis in 1975-1976, its drastic transformation from liberal policy to one of restrictive control in the late 1970s, the reaction of table wine producers in Languedoc-Roussillon to these changes over the decade, and the change in political relationships and governance at three levels - Brussels, Paris, and Languedoc-Roussillon - as a result of this process. It argues that the first decade of the CWP changed relationships between different groups at the European, national, and local level in two major ways: first, national French government institutions voluntarily decreased their power over a key national industry – this was the most marked feature in the French wine industry of this time period. Second, the CWP helped facilitate the rise of sub-national and non-state actors in policy circles from which they were previously excluded. Empowered by the new responsibilities given to them by the French government, particularly via a newly-created national office of wine, French vignerons began attempting to bypass the national French bottleneck to the Community and directly lobby European-level institutions, either via their own organisations or as part of transnational endeavours. Given the French government’s particularly adamant control of who represented the country at the Brussels levels in the 1960s, this change in only a decade was a significant shift. In analysing this process, this thesis also makes broader comments on the integration process as a whole, adding particularly to the literature on the Community’s agricultural integration, and is the first comprehensive review of the history of the Common Wine Policy, and the first to make an extensive assessment of the impact on local farmers in the Midi during this time in relation to the European Community’s policies.

A number of experimental studies have implied a link between diabetes-induced lipid accumulation in the myocardium and the development of cardiomyopathy. Since diabetics excrete large amounts of myo-inositol which is a lipotropic agent, this study was undertaken to investigate the effects of myo-inositol on the elevated myocardial lipid levels and the depressed cardiac performance of diabetic rats. Diabetes was induced in female Wistar rats (190-215 g) with streptozotocin (STZ) (55 mg/kg, i.v.). Three days after diabetes induction, myo-inositol was administered in the drinking water (2.5 g/kg/day) for a 8 week period. Untreated diabetics exhibited a loss of body weight, hyperglycemia, hypoinsulinemia and hypothyroidism. These effects were not altered after myo-inositol treatment. STZ-diabetes also produced a significant elevation of plasma and myocardial triacylglycerol, cholesterol and phospholipid. Myo-inositol treatment decreased these lipid levels. In addition, hearts from diabetic animals had a decreased ability to develop left ventricular developed pressure (LVDP) and both the rate of pressure rise (+dP/dt) and the rate of pressure decline (-dP/dt) were also reduced. Hearts from myo-inositol-treated diabetic animals showed a partial but definite improvement of cardiac function. As diabetes-induced hypothyroidism was not altered after myo-inositol supplementation, a combination treatment of both myo-inositol (2.5 g/kg/day, p.o. daily) and T₃ (30 ug/kg/day, s.c. daily) was then undertaken to determine whether heart function of diabetic rats could be further improved. STZ-diabetic rats were characterized by a loss of body weight, hyperglycemia and hypoinsulinemia; none of which were altered by either T₃ or myo-inositol plusT₃ treatment. T₃ treatment normalized the thyroid state of diabetic animals as shown by Tahiliani and McNeill (1984). However, plasma and myocardial triacylglycerol, cholesterol and phospholipid levels of diabetic rats either remained elevated or were further increased with T₃ or myo-inositol plus T₃ treatment. In addition, T₃ treatment alone did not prevent cardiac dysfunction in diabetic rats. There was, however, some improvement in heart function in the groups treated with both myo-inositol and T₃, but the improvement was not as pronounced as with myo-inositol treatment alone.
Pharmaceutical Sciences, Faculty of
Graduate

Dissertation (PhD)--University of Stellenbosch, 2004.
ENGLISH ABSTRACT: Wine is the product of a complex biological and biochemical interaction between grapes and different microorganisms (fungi, yeasts, lactic acid bacteria and acetic acid bacteria, as well as the mycoviruses and bacteriophages affecting them) in which yeasts play the most important role regarding the alcoholic (primary) fermentation. These wine-associated yeasts can be divided into Saccharomyces and non-Saccharomyces yeasts. During fermentation, there is a sequence of dominance by the various non-Saccharomyces yeasts, followed by Saccharomyces cerevisiae, which then completes the fermentation. This is especially evident in spontaneously fermenting must, which has a low initial S. cerevisiae concentration. Some non- Saccharomyces yeasts can also be found throughout the fermentation. The non- Saccharomyces presence in the fermentation can affect wine quality, either positively or negatively. A positive contribution could be especially useful to improve wines produced from grape varieties with a neutral flavour profile due to non-optimal climatic conditions and/or soil types. As part of a comprehensive South African research programme, the specific objectives of this study were: the isolation of indigenous non-Saccharomyces yeasts from vineyards and musts; the identification of these isolates; the characterisation and evaluation of predominant species under winemaking conditions; and the development of a protocol for their use in enhancing wine quality. Initially, 720 isolates representing 24 different species, were isolated from grape (vineyard) and must samples taken over three vintages from four distinctly different wine producing regions. The isolates were characterised and grouped utilising biochemical profiles and DNA karyotyping, whereupon representative isolates were identified. The yeast species that had the highest incidence of predominance in the vineyard was Kloeckera apiculafa. However, some vineyard samples were characterised by low numbers or absence of this yeast, which is not according to generally accepted norms. Other species that also predominated in a few of the vineyard samples were Candida pulcherrima, Kluyveromyces thermofolerans, Rhodotorula sp. and Zygosaccharomyces bailii. Generally, there was a greater diversity of yeasts in the processed must than from the vineyard samples. Furthermore, while each sample showed a different yeast population, no pattern linking species to climatic zone was observed. Four species i.e. Candida collieulosa, Candida pulcherrima, Candida stel/ata and Kloeckera apiculata, were found to predominate in grape must samples. Representative strains consequently received further attention during laboratory and small-scale winemaking trials. A protocol was developed whereby individual species could be used in co-inoculated fermentations with S. cerevisiae in the small-scale production of wine. An improvement in wine quality was achieved and it was found that there was a link between specific species and grape cultivar. The ability of C. pulcherrima to improve Chenin blanc wine quality was investigated further. Results over three vintages showed that the wine produced by the co-inoculated fermentation was superior to that of a reference wine (produced by S. cerevisiae only). The improvement in wine quality was not linked to increased ester content nor were the standard chemical analyses adversely affected. The effects of pH and wine production parameters i.e. 802, fermentation temperature and use of di-ammonium phosphate (DAP), on this yeast followed the same pattern as that known for S. cerevisiae. This study was successfully completed and the developed protocol can be used for the improvement of Chenin blanc wine where additional aroma and quality is needed.
AFRIKAANSE OPSOMMING: Wyn is die produk van 'n komplekse biologiese en biochemiese interaksie tussen druiwe en mikroorganismes (swamme, giste, melksuurbakterieë, asynsuurbakterieë, asook die mikovirusse en bakteriofage wat hul beïnvloed) waar gis die belangrikste rol speel ten opsigte van die alkoholiese (primêre) fermentasie. Die betrokke giste kan in Saccharomyces- en nie-Saccharomyces-giste verdeel word. Tydens gisting vind daar 'n opeenvolging van dominansie deur die verskillende nie-Saccharomyces giste plaas, gevolg deur Saccharomyces cerevisiae, wat dan die gisting voltooi. Dit is veral in spontaan fermenterende mos, waarin aanvanklik lae konsentrasies S. cerevisiae-gisselle voorkom, waarneembaar. Sekere nie-Saccharomyces-giste kan ook regdeur die verloop van fermentasie gevind word. Die teenwoordigheid van nie-Saccharomyces-giste kan 'n bydrae maak tot wynkwaliteit, hetsy positief of negatief. 'n Positiewe bydrae kan veral nuttig wees vir die verbetering van wyn geproduseer van druifsoorte met neutrale geurprofiele as gevolg van nie-optimale klimaatstoestande en/of grondtipes. As deel van 'n uitgebreide Suid-Afrikaanse navorsingsprogram, was die doelwitte van hierdie studie soos volg: die isolasie van inheemse nie-Saccharomyces-giste vanuit wingerde en mos; die identifikasie van hierdie isolate; die karakterisering en evaluering van spesies wat tydens wynbereiding oorheers; en die ontwikkeling van 'n protokol waarin geselekteerde nie- Saccharomyces-giste gebruik kan word vir die verbetering van wynkwaliteit. Druif- en mosmonsters is oor drie oestye vanuit vier duidelik onderskeibare wynproduserende gebiede geneem en 720 isolate, verteenwoordigend van 24 verskillende spesies, is hieruit geïsoleer. Hierdie isolate is volgens biochemiese profiele en DNA-kariotipering gekarakteriseer en gegroepeer waarna verteenwoordigende isolate geïdentifiseer is. Die gisspesie wat die meeste in wingerde voorgekom het, was Kloeckera apiculata. Sommige wingerde is egter deur lae getalle of afwesigheid van dié gis gekenmerk, In feit wat afwyk van die algemeen aanvaarde norm. Ander spesies, nl. Candida pulcherrima, Kluyveromyces thermotolerans, Rhodotorula sp. en Zygosaccharomyces bailii, het ook in enkele gevalle in die wingerdmonsters oorheers. Oor die algemeen was daar 'n groter diversiteit van giste in die geprosesseerde mos as in die wingerdmonsters. Verder is elke monster gekenmerk deur verskillende gispopulasies, maar geen verband tussen gisspesie en klimaatsone is waargeneem nie. Vier spesies, nl. Candida collieulosa, Candida pulcherrima, Candida stel/ata en Kloeckera apiculata, het in hoë getalle in die druiwemosmonsters oorheers en verteenwoordigende rasse het verdere aandag tydens laboratorium- en kleinskaalse wynmaakproewe geniet. 'n Protokol, waar hierdie rasse individueel gebruik is in gesamentlike geïnokuleerde fermentasies met S. cerevisiae vir die kleinskaalse produksie van wyn, is ontwikkel. 'n Verbetering in wynkwaliteit is verkry en daar is 'n verband tussen spesifieke gisspesies en druifvariëteit gevind. Gevolglik is die vermoë van C. pulcherrima om die gehalte van Chenin blanc wyn te verbeter, verder ondersoek. Resultate oor drie oesjare het gewys dat die wyn wat met die C. pulcherrima / S. cerevisiae kombinasie geproduseer is, beter was as 'n verwysingswyn (deur slegs S. cerevisiae geproduseer). Die waargenome verbetering in wynkwaliteit was egter nie aan 'n verhoging in esterinhoud te danke nie en die standaard chemiese analises het geen negatiewe afwyking uitgewys nie. Verder is gevind dat die effek van pH en wynproduksieparameters, nl. die gebruik van S02, fermentasietemperatuur en die gebruik van di-ammoniumfosfaat (DAP), dieselfde patroon as die bekend vir S. cerevisiae gevolg het. Die ontwikkelde protokol kan nou aangewend word waar verhoogde Chen in blanc wynaroma en kwaliteit verlang word.

Includes bibliographical references.
A three phase investigation into the utility of wine consumer opinion as a viable source of information to wine consumers in South Africa. The research demonstrates that existing marketing and expert opinion is inappropriately constructed, using paradigms that are overly simplistic or language that is not valued by consumers. The paper further investigates the use of visual representations of wine to communicate the "tasting notes" of consumers, providing a first access trigger which can be quickly and accurately interpreted into an assessable taste for the wine. Lastly it examines the benefits of using consumers to provide narrative reviews of the wine, in whatever terms they choose, to represent the consumption experience of the wine.

Background: This research was designed to explore the experience and understanding of counsellors' and psychotherapists' engagement with metaphors in the therapeutic process. The aim is to reflect on the experience of therapists involved in therapeutic metaphors from differing perspectives. Methodology: In a heuristic study a group of seven therapists (counsellors and psychotherapists) shared their use of metaphors in their therapy practice. Data were collected through an informal conversational interview that supported the participants to share their experiences in a natural dialogue. Findings: The experience of using metaphor in therapy appears to involve a multi-faceted web of generation, construction and development between the therapist and client. Various levels of depth of metaphor in therapy were identified along with links to transferential and cultural issues. Metaphors of hope also appear to be potentially important. Discussion: The findings suggest that the use of metaphors in therapy is pervasive. Metaphors that reflect an empathic connection and encounter between therapist and client were identified. Dualistic thinking around the origination of metaphors in therapy is challenged and the concept of co-creation and the mutual development of moving metaphors is discussed. Environmental and cultural influences are considered alongside transferential aspects. Conclusion: It appears that the use of metaphor in therapy is pervasive and offers an opportunity for therapeutic change. The consideration of the construction of metaphors and their mutual development may be useful for therapists to consider. This research highlights the need for more investigation with regard to client perspectives, the environmental impacts on metaphors in therapy and who the therapist and client stand for metaphorically for each other.

Dissertation (PhD)--University of Stellenbosch, 2004.
ENGLISH ABSTRACT: This thesis provides the first scientific evidence on the cancer modulating properties of two unique South African herbal teas, rooibos (Aspalathus Iinearis) and honeybush (Cyclopia intermedia) utilizing in vitro as well as in vivo carcinogenesis assays by: • Demonstrating the in vitro antimutagenic activity of aqueous extracts of the herbal teas against the metabolic activated mutagens, 2-acetylaminofluorene (2- AAF) and the mycotoxin, aflatoxin B1 (AFB,) as well as, to a certain extent, against the direct acting mutagen, hydrogen peroxide, utilizing the Salmonella typhimurium mutagenicity assay. • Increasing the activity of hepatic drug metabolizing enzymes, glutathione Stransferase alpha and UPD-glucuronosyl transferase, and reduced the oxidative stress by stabilizing the level of reduced glutathione (GSH) resulting in an increased hepatic reduced to oxidized glutathione ratio (GSG:GSSG). No toxic effects were noticed in rats consuming the herbal teas for 10 weeks as their sole source of drinking fluid. • Demonstrating the ex vivo modulation of 2-AAF- and AFB1-induced mutagenesis by sub- cellular hepatic fractions of rats consuming the herbal teas in the Salmonella mutagenicity assay. Hepatic cytosolic fractions protected against mutagenesis of both mutagens, while the microsomal fractions exhibited a reduced capacity to metabolize AFB1 to its active mutagenic metabolite. • Providing evidence for the in vivo modulation of tumour promotion using the liver as well as the two-stage skin carcinogenesis animal models. The unprocessed herbal teas arrested proliferation of the placental form of glutathione-Stransferase (GSTP+) altered cells as well as reduced the total number of enzyme altered foci in the liver of rats. Topical application of polyphenolic fractions of the various herbal teas prior to 12-0-tetra-decanoylphorbol-13-acetate (TPA) tumour promotion, reduced tumour formation in mouse skin initiated with 7,12-dimethylbenz[ ajanthracene (DMBA). The protective effect was illustrated by a decreased tumour incidence, a reduction in tumour volume as well as a delayed onset of tumour development. The f1avanol/proanthocyanidin content of the fractions could playa major role in the protection against skin tumour promotion. • Proposing possible mechanisms whereby rooibos and honeybush herbal teas could exert their cancer modulating properties with respect to in vitro and ex vivo antimutagenicity, in vivo oxidative status and reduced tumour promotion. • Providing evidence that the herbal teas mimic the cancer modulating properties of green and black teas although differences exist, presumably due to differences in the polyphenolic constituents. • Suggesting that rooibos and honeybush herbal teas may play an important role as chemopreventive agents in the modulation of cancer.
AFRIKAANSE OPSOMMING: Hierdie tesis bevat die eerste ondersoek na die effek van waterige en polifenoliese ekstrakte van rooibos (Aspalathus Iinearis) en heuningbos (Cyclopia intermedia) op verskeie aspekte van kankerontwikkeling. Die twee kruietees is uniek aan Suid-Afrika en kan 'n belangrike rol speel in die voorkoming van kanker. Verskillende in vitro so wei as in vivo studies het die volgende getoon: • Antimutageniese aktiwiteite teen die metabolies-geaktiveerde mutagene, 2- asetielaminofluoreen (2-AAF) en die mikotoksien, aflatoksien B1 (AFB1) in die Salmonella fyphimurium mutagenisiteitstoets. 'n Beperkte mate van beskerming is ook verleen teen die oksidatiewe mutageen, waterstofperoksied, sonder metaboliese aktivering. • Verhoogde aktiwiteite van die fase II ensieme, glutatioon S-tranferase alfa en UDP-glukuronidase, wat liggaamsvreemde verbindings metaboliseer. Die kruietees verlaag die oksidasietoestand soos weerspieel word deur 'n toename van gereduseerde glutatioon tot die geoksideerde vorm in die lewer van rotte wat 10 weke hierdie kruietees gedrink he!. Die kruietees het geen toksiese uitwerking op die rotte gehad nie. • Antimutageniese aktiwiteite van subselluiE~re fraksies van die lewer teenoor 2- AAF en AFB1 in die Salmonella toets. Die sitosolfraksie van die rotlewer bied beskerming teen die ge"induseerde mutagenese van beide mutagene, terwyl die mikrosomale fraksie ook die metaboliese aktivering van AFB1 na die aktiewe mutageniese metaboliet verminder. • In vivo modulering van kankerpromosie met behulp van bekende rotlewer en muisvel kankerontwikkelingsmodelle. In die lewermodel het die ongeprosesseerde kruietees beide die ontwikkeling en getal van GSTP+ fokusse onderskeidelik vertraag en verminder. In die geval van die velkankermodel het aanwending van polifenoliese fraksies van die kruietees beskerming gebied teen die ontwikkeling van velkankers by muise. Die aantal en grootte van die tumors het afgeneem terwyl die verskyning daarvan ook vertraag is. • Verskeie meganismes waardeur rooibos- en heuningboslee moonllik kanker kan moduleer word voorgeslel. Verskille in die polifenoliese sameslelling asook hul onderskeie konsenlrasies kan 'n belangrike rol speel in die kankerveranderende effekle van die lees. • Oal gereelde inname van rooibos- en/of heuningboslee moonllik 'n belangrike rol kan speel in die voorkoming van dieel- en omgewings-geYnduseerde kankers.

The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2008-2009
published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy

Sucralfate is a drug that effectively heals duodenal, gastric and oesophageal ulcers. It is not absorbed systemically and it has been shown to act locally by coating the ulcer base. However when it was also shown to prevent stress ulcers and ethanolinduced gastric mucosa! lesions, it seemed likely that it acted in some way to improve the effectiveness of the gastric mucosa! barrier. Some investigators suggested that it did so by stimulating local prostaglandin release. The Slomiany group, on the basis of in vitro work on the effects of Sucralfate on pig gastric mucus, claimed that Sucralfate acted by altering the physico-chemical properties of mucus to increase the viscosity and retard the back diffusion of H+ ions. The work described in this dissertation set out to verify, in vivo, these claimed effects on mucus, using an experimental porcine model of peptic ulceration, the bile duct ligated pig. In addition, the effects of Sucralfate were compared with those of Famotidine and Misoprostol, and changes in mucous prostaglandins, gastric juice pepsin and gastric flora were sought. By way of introduction, the known and postulated actions of Sucralfate, current understanding of gastric mucus physiology and pathogenesis of peptic ulceration, have been reviewed, as have experimental animal models of peptic ulceration, in order to justify using the bile duct ligated pig model.

This study explored the use of rituals in substance abuse counseling. Data were obtained from a total of 25 mental health workers in the substance abuse field from the northern region of Utah. Four research questions were asked about rituals and their use in substance abuse counseling: (I) Are addictions therapists using rituals? (2) How did therapists determine when to use rituals? (3) What types of rituals do they use? and (4) How do therapists assess ritual effectiveness? Results indicated that about three fourths of the mental health workers questioned were using rituals in their treatment protocol with substance abuse clients. The most common methods used for determining when to implement rituals into treatment were (a) clients were emotionally stuck, (b) client's cognitive ability, and (c) therapist's perception. The findings also suggested that therapists presented means of assessing the effectiveness of the rituals they implemented, but the data also supported past literature findings that showed little empirical means of assessment.

Wine production is one of the farming practices with the highest negative environmental impacts, mainly due to a heavy use of pesticides, why it is important to find more sustainable wine production practices. One such practice is organic farming, but the transition is slow and the number of organic certified vineyards remain low. The purpose of this study is to map what motives and barriers Swedish wine farmers perceive in using organic practices in their production, and to what extent the decision to do so is guided by intrinsic or extrinsic motivation. This was studied by visiting 11 Swedish vineyards and conducting interviews with the wine farmers. The theoretical framework used in this thesis builds on the Self-determination theory about motivation together with previous research on motives and barriers to convert to organic farming. The results show that despite that only 5% of the Swedish vineyards are organically certified, all visited vineyards almost exclusively use organic practices in their production. The main motives to use organic practices were identified to be soil protection and long-term scope of the vineyard, biodiversity and ecosystem protection, lower exposure to agrochemicals, to produce an honest product, and the possibility of increased sales. Perceived barriers with using organic practices among Swedish wine producers were increased workload and labour costs, lack of access to knowledge about organic viticulture, difficulties with weed and pest control, and lower harvest yields. The decision to use organic practices are mainly guided by inner beliefs about producing the wine in harmony with nature, not causing unnecessary damage, producing a high-quality product they can be proud of, and the desire to get a professional challenge and develop as winemakers, consequently indicating that Swedish wine farmers are motivated by intrinsic motivation. Only weak indicators of extrinsic motivation were found in the study. Furthermore, the study found that the climate in southern Sweden is facilitating for organic viticulture which together with a lack of regulations regarding grape- and vine varieties could act as a foundation for Sweden to become a leader in sustainable wine production, but that a lack of knowledge and the strict regulation on sales of alcohol might prevent this.

Prompted by the successful clinical application of cisplatin in cancer therapy, worldwide efforts have been devoted to develop new metal-based drugs for anticancer treatment. Gold(III) complexes at first received attention as anti-cancer drug candidates because of their square-planar geometry which resembles that of platinum(II) complexes. Subsequent studies revealed that various gold(III) complexes displayed promising anti-cancer activities with different biological mechanisms. Although some achievements have been obtained in the development of anti-cancer gold(III) complexes, challenges including the improvement of bioavailability, stability and selectivity, elucidation of the action mechanisms, and the development of novel delivery approaches of gold(III) complexes to reduce systematic toxicity, remain to be exploited. A panel of anti-cancer complexes [AuIII(R-C^N)(L)]n+ (wherein HC^N is 2-phenylpyridine, L is biguanide or biuret) have been identified and described in Chapter 3. Biguanide or biuret have been employed to improve the solubility of the complexes in aqueous solutions. Meanwhile, the lipophilicity could readily be adjusted by varying the R group to obtain a balance between lipophilicity and aqueous solubility. Among the synthesized complexes, the cationic complexes, [AuIII(butyl-C^N)biguanide]Cl (3.1) and [AuIII(C^N)biguanide]Cl (3.2) are soluble in aqueous solutions with solubility over 5 mg/mL. Besides, introduction of butyl groups to 3.1 and [AuIII(butyl-C^N)biuret] (3.3) resulted in higher cellular uptake of gold, which might enhance their cytotoxic activities (IC50 values: 1.5–17 μM) compared with 3.2 and [AuIII(C^N)biuret] (3.4) (IC50 values: 9.4–47.3 μM). Moreover, 3.1 was also found to induce cell cycle arrest in S-phase and endoplasmic reticulum (ER) damage in human cervical epithelial carcinoma (HeLa) cells, and display significant anti-angiogenic activity at its sub-cytotoxic concentrations. In Chapter 4, a series of gold(III) complexes with dithiocarbamate and 2-phenylpyridine ligands to target deubiquitinases (DUBs), have been designed. These complexes achieved significant inhibition on purified DUBs. Notably, [AuIII(2-(4-nbutylphenyl) pyridyl)(diethyldithiocarbamate)]PF6 (4.1) inhibited both the purified (IC50 values: 46–223 nM) and cell-based DUBs activities with high efficiency. Its interaction with DUB UCHL1 and peptides which are present in several types of DUBs and contain active cysteine residue were confirmed by mass spectrometric analysis. All complexes displayed significant cytotoxicities, and those containing diethyldithiocarbamate ligand displayed specific cytotoxicity on breast cancer cells. Accumulation of a tumor suppressor p53, cell-cycle arrest, and apoptotic cell death were induced in breast cancer cells by 4.1. Besides, 4.1 also showed anti-angiogenic effects. These biological activities might be related with DUBs inhibition. In Chapter 5, a cytotoxic complex [AuIII(C^N^C)(4-dpt)](CF3SO3) (5.1, HC^N^CH = 2,6-diphenylpyridine; 4-dpt = 2,4-diamino-6-(4-pyridyl)-1,3,5-triazine) has been designed to self-assemble into supramolecular polymers (5.1-SP) in acetonitrile. In physiologically relevant solutions, 5.1-SP displayed a sustained-release property of the anti-angiogenic ligand 4-dpt, and in the presence of glutathione (GSH), [AuIII(C^N^C)-GSH] adduct(s) were also gradually released. The supramolecular polymers 5.1-SP also showed selective cytotoxicity toward cancerous cells, and could act as drug-carriers of other cytotoxic agents to achieve sustained-release behavior.
published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy

In a 6-week rat model it was demonstrated that a small dose of peri-implant zoledronic acid (ZA) increased local bone formation 3-fold compared with controls. Ancillary in vitro studies using 14C-labeled ZA implant doses demonstrated biphasic elution profiles for implants coated with hydroxyapatite; complete ZA release occurred within one to three weeks in serum compared with only 60% ZA release after 12 weeks in water. Implants without hydroxyapatite coating showed more burst-type release profiles and full ZA elution within 24 hours of hydration in serum or water. Canine studies at 6 weeks using implants with 14C-labeled ZA showed that the compound remained localized, with the greatest ZA concentration immediately adjacent to the implant. Although there was evidence of skeletal ZA distribution via diffusion into the circulation, the levels were two orders of magnitude less than at the implant site.

Thesis submitted in fulfilment of the requirements for the degree Magister Technologiae: Chemistry in the Faculty of Applied Sciences at the CAPE PENINSULA UNIVERSITY OF TECHNOLOGY 2014
The solid state modification of a given active pharmaceutical ingredient is a desired way to alter its physicochemical properties, such as solubility or bioavailability. The solubilitymelting point relationship of the ensuing co-crystal or salt is not fully understood. In this thesis, a series of model co-crystals and pharmaceutical co-crystals and salts of baclofen were investigated. The model co-crystals were prepared from 4,4’-bipyridine (BIPY) and 1,2-bis(4-pyridyl)ethane (ETBIPY) used as host compounds which were combined with a series of carboxylic acids as co-formers, such as p-toluic acid (PTA), rac-phenylbutyric acid (racPBA), racemic and S-phenylsuccinic acid (racPSA and S-PSA, respectively). In the second part, six new multicomponent crystals of baclofen (BAC, (RS) 4-amino-3-(4- chlorophenyl)-butanoic acid), were prepared with mono- and dicarboxylic acids: two pharmaceutical co-crystals obtained with benzoic acid (BAC•BA) and p-toluic acid (BAC•PTA) and four pharmaceutical salts with 1-hydroxy-2-naphthoic acid, (BAC+)(HNA-), oxalic acid, 2(BAC+)(OA2-), maleic acid, (BAC+)(MA-) and p-toluene sulfonic acid, (BAC+)(PTSA-)•IPA. The compounds prepared were analysed by single crystal and powder X-ray diffractometry, differential scanning calorimetry and their solubility was measured in water and ethanol. From the analysis of the model co-crystals it was concluded that their aqueous solubility is inversely related to the melting point values and this can be explained by packing features. Also, the introduction of a chiral building block, compared to its racemic counterpart, is a valuable way to limit the formation of the intermolecular interactions in the new multicomponent crystal and thus decrease the efficiency of the packing which eventually leads to lower melting points and better solubility. The analysis of the baclofen crystals suggests that a strong, robust and predictable hydrogen bonding network with a combination of molecular building blocks which show acceptable molecular flexibility is a good recipe for successful co-crystal design.

In this paper the goal was to optimize the scheduling of vats for the wine fermentation process considering demand, time and quality constraints in order to minimise the production cost. The method that was used during the project was to start of with a simple model that only took the basic parameters in to account, verify that it worked, and then add up parameters until the model was completed. An integer program was formed to obtain the optimal solution to the problem och to test the programs accuracy a small example that could be tested by hand was made. It showed that the program worked as expected and a conclusion that was drawn was therefore that the program would work for larger problems, that are more based in reality, as well. After testing the program for larger problems another conclusion that was drawn was that for instance a larger vintage period and an increased frequency of supply led to an increase in the solving time.
Syftet med den här rapporten var att optimera schemaläggningen av kärl för vinfermenteringsprocessen med avseende på efterfrågan, tid och kvalitet för att minimera produktionskostnaden. Tillvägagångssättet under projektet var att utgå ifrån en enkel model som endast tog de grundläggande parametrarna i åtanke, verifiera att den fungerade, och sedan lägga till parametrar tills att modellen var fulländad. Ett dynamiskt program togs fram för att finna den optimala lösningen och för att testa dess tillförlitlighet användes ett mindre exempel. Det visade sig att programmet fungerade som det skulle och därmed drogs slutsatsen att programmet även ska fungera för större, mer verklighetstrogna, problem. Efter att ha testat programmet för större problem drogs även slutsatsen att faktorer som bland annat längre perioder och högre frekvens på tillförsel av druvor leder till större lösningstider.

Thomas Hobbes’s knowledge of religious doctrine, typology, and use religious rhetoric in his writings is often glossed over in an over-eager attempt to establish his preeminence as a founder of modern political theory and the social contract tradition. Such action, however is an injustice to Hobbes himself, who recognized that in order to establish a new, and arguably radical, political position founded upon reason and nominalist materialism he had to reform people’s understanding of religious revelation, and Christianity specifically. Rather than merely move to a new epistemological foundation, Hobbes was aware that the only way to ensure religion does become a phoenix was to examine and undermine the foundations of religious thought in its own terms. This reformation of religious language, critique of Christianity, and attempt to eliminate man’s belief in their obligation to God was done in order to promote a civil society in which religion was servant of the state. Through reforming religious language, Hobbes was able to demote religion as a worldview; removing man’s fear of the afterlife or obligation to obey God over a civil sovereign. Religious doctrine no longer was in competition with the civil state, but is transformed into a tool of the state, one which philosophically founds the modern arguments for religious toleration.

Dissertation (PhD(Agric)) -- Stellenbosch University, 2005.
ENGLISH ABSTRACT: Due to increased consumer demand for products labelled by origin, and the requirement that these labels are a guarantee of both quality and product character, there is an increasing global focus on delimitation of denominations of origin. The integrity of denominations of origin and their defensibility can be ensured through the use of terroirs as a basis for delimitation. The aims of this study were to establish the dominant environmental criteria that affect the viticultural behaviour and wine character of two important cultivars (Cabernet Sauvignon and Sauvignon blanc) in the Stellenbosch Wine of Origin District, to use an appropriate methodology to identify viticultural terroirs in this district based on these criteria and with the use of a geographic information system, and finally to use these viticultural terroirs to identify denominations of origin within the same area. A terroir can be defined as a grouping of homogenous environmental units, or natural terroir units, based on the typicality of the products obtained. Identification and characterisation of terroirs depends on knowledge of environmental parameters, the functioning of the grapevine and the characteristics of the final product. Field studies, resulting in point data, are necessary to investigate the functioning of the grapevine but in order for this information to be of use within zoning studies it must be placed in a spatial context. As a first phase in data acquisition, the Stellenbosch Wine of Origin District was characterised and natural terroir units were identified using existing digital data and a geographic information system. A natural terroir unit (NTU) can be defined as a unit of land that is characterised by relatively homogenous topography, climate, geological substrate and soil. A total of 1389 NTUs were identified in the Stellenbosch Wine of Origin District (84 537 ha). The identified NTUs were homogenous with respect to terrain morphological unit, altitude, aspect and soil type. Each of the identified units was further described with respect to the extent of the expected sea breeze effect and, for certain of the soil types, the associated parent material. As a second phase of data acquisition, a network of plots of Sauvignon blanc and Cabernet Sauvignon were delimited in commercial vineyards in proximity to weather stations and their viticultural and oenological response monitored for a period of seven years. Regression tree analyses were performed on the complete data set and the relative importance of the environmental and management related variables determined for each dependent variable. Excepting for scion clone, which had a high relative importance for bunch mass of Sauvignon blanc and yield to pruning mass index of Cabernet Sauvignon, no other non-environmental variable included in the analyses appeared to have a strong effect on grapevine performance and wine character. The performance of Cabernet Sauvignon was affected by the potassium content of the subsoil and the climate of the season. The performance of Sauvignon blanc appeared to be related to soil texture, wind exposure and temperature, both during the green berry growth stage and the month prior to ripening. From the results presented, it appears that environmental parameters have an overriding effect on the performance of both Cabernet Sauvignon and Sauvignon blanc, but that these two cultivars react differently to environmental stimuli. A knowledge-driven model used the rules generated in the regression tree analyses to directly classify natural terroir units with respect to expected response of Cabernet Sauvignon and Sauvignon blanc in the Stellenbosch Wine of Origin District. The natural terroir units were thus grouped into terroir units that were homogenous with respect to predicted viticultural and oenological response for each cultivar. The use of representative sites to determine the response of the grapevine to its environment is time consuming and costly and limits terroir studies to research related investigations. Vineyard managers were therefore surveyed with respect to the functioning of established Sauvignon blanc vineyards in the Stellenbosch Wine of Origin District in an attempt to obtain the necessary data. Comparison of the data generated with these questionnaires to measured data in commercial vineyards suggested that the vineyard managers were able to characterise the performance of vineyards with respect to vigour, signs of drought stress and yield. Each vineyard was mapped and the responses were linked to modelled environmental variables. Classification and regression trees were used to construct decision trees, which could be applied to environmental data in a geographic information system to determine viticultural terroirs for production of Sauvignon blanc. These terroirs, although fewer, were comparable to those generated using field data. Data gathered during terroir studies, and the identified viticultural terroirs for Cabernet Sauvignon and Sauvignon blanc, were used to revisit the boundaries of the Stellenbosch Wine of Origin District and the Simonsberg-Stellenbosch ward. Modifications were proposed based on expected wine characteristics. Boundaries for two new wards in the Helderberg basin were proposed. It was also possible to identify vineyards within a ward for the production of terroir specific wines.
AFRIKAANSE OPSOMMING: Toenemende verbruikersaanvraag vereis produkte waarvan die etikette nie net die oorsprong aandui nie, maar ook kan dien as ‘n waarborg vir die produk se kwaliteit en kenmerkendheid. Hierdie tendens verklaar die toenemende wereldwye fokus op afgebakende areas van oorsprong. Die integriteit van die afgebakende areas van oorsprong sowel as hul verdedigbaarheid kan gewaarborg word deur terroirs as basis vir afbakening te gebruik. Die doelstellings van die studie was om die oorheersende omgewingseienskappe wat wingerdprestasie en wynkarakter van twee belangrike cultivars, naamlik Cabernet Sauvignon en Sauvignon blanc, in die Stellenbosch Wyn van Oorsprongsdistrik bemvloed, te bepaal; tweedens om ‘n toepaslike metodologie te gebruik om terroirs in die die distrik te bepaal wat gebaseer is op die geidentifiseerde omgewingseienskappe met die gebruik van ‘n geografiese inligtingstelsel; en, ten slotte, om hierdie terroirs vir wingerbou te gebruik om afgebakende areas van oorsprong in dieselfde omgewing te identifiseer. ‘n Terroir kan gedefinieer word as ‘n samestelling van homogene omgewingseenhede, of natuurlike terroir-eenhede (NTE), wat gebaseer word op die kenmerkende eienskappe van die produkte wat daaruit verkry word. Identifisering en karakterisering van terroirs sal afhang van kennis van die omgewingsparameters, die funksionering van die wingerdstok en die eienskappe van die finale produk. Veldstudies waaruit puntdata verkry word, is noodsaaklik om die funksionering van die wingerdstok te ondersoek. Dit is egter noodsaaklik om eers hierdie inligting in ruimtelike konteks te plaas alvorens die inligting vir soneringstudies gebruik kan word. As 'n eerste fase van datagenerering, was die Stellenbosch Wyn van Oorsprongsdistrik gekarakteriseer en NTE’s geidentifiseer deur gebruik te maak van bestaande digitale data en ‘n geografiese inligtingstelsel. ‘n NTE kan gedefinieer word as ‘n landseenheid wat gekarakteriseer word deur ‘n relatiewe homogene topografie, klimaat, geologiese substraat en grondtipe. ‘n Totaal van 1389 NTE’s is geidentifiseer in die Stellenbosch Wyn van Oorsprongsdistrik (84 537 ha). Die geidentifiseerde NTE’s was homogeen met betrekking tot die terrein morfologiese eenheid, hoogte bo seespieSI, hellingsaspek en grondtipe. Elk van die geidentifiseerde eenhede was verder beskryf volgens die omvang van die seewindinvloed en, vir toepaslike grond tipes, die geassosieerde moedermateriaal. As ‘n tweede fase van datagenerering is ‘n netwerk van persele van Cabernet Sauvignon en Sauvignon blanc afgebaken binne bestaande kommersiele wingerde in die nabyheid van weerstasies. Hul wingerd- en wynkundige respons is vir ‘n periode van sewe jaar gemonitor. Regressieboomanalises is gebruik om die volledige stel data te analiseer en om die relatiewe belang van omgewings- en bestuurspraktykverbonde veranderlikes te bepaal. Die bostokkloon (wat 'n hoe relatiewe belang vir die trosmassa van Sauvignon blanc en die oes- tot snoeimassa verhouding van Cabernet Sauvignon het) is die enigste van die nie-omgewingsparameter wat ‘n sterk invloed op wingerdprestasie of wynkarakter blyk te he. Die prestasie van Cabernet Sauvignon is beTnvloed deur die kaliuminhoud van die ondergrond sowel as die seisoensklimaat. By Sauvignon blanc het dit voorgekom of die prestasie verband hou met grondtekstuur, windblootstelling en temperatuur tydens die groen fase van korrelgroei sowel as die maand voor rypwording. Alhoewel dit blyk uit die resultate dat omgewingsparameters 'n oorheersende invloed op die prestasie van beide Cabernet Sauvignon en Sauvignon blanc uitoefen, reageer die twee cultivars verskillend op omgewingsprikkels. ‘n Kennisgedrewe model waarvan die riglyne uit resultate van die regressieboomanalise saamgestel is, word gebruik om NTE direk te klassifiseer ten opsigte van die verwagte respons van Cabernet Sauvignon en Sauvignon blanc in die Stellenbosch Wyn van Oorsprongsdistrik. Die NTE is dus gegroepeer om terroir eenhede te vorm wat homogeen was ten opsigte van die verwagte wingerd- en wynkundige respons vir elke cultivar. Die gebruik van verwysingspersele om die respons van die wingerdstok teenoor sy onmiddelike omgewing te bepaal, is tydrowend en duur en beperk sodoende terroir studies tot navorsing. Gevolglik is ‘n opname onder wingerdbestuurders gemaak om inligting oor die prestasie van Sauvignon blanc in die Stellenbosch Wyn van Oorsprongsdistrik in te win en sodoende die nodige data te verkry. Na vergelyking van die ingewinde data, wat uit die opname verkry is, met gemete data vanaf kommersiele wingerde, kon afgelei word dat wingerdbestuurders by magte is om die prestasie van wingerde ten opsigte van groeikrag, tekens van droogtestres en opbrengs te karakteriseer. Elke wingerd is gekarteer en die respons is gekoppel aan die gemodeleerde omgewingsparamters. Klassifikasie en regressiebome is gebruik om besluitnemingsmodelle saam te stel wat toegepas kon word op omgewingsdata in ‘n geografiese inligtingstelsel om terroirs vir die produksie van Sauvignon blanc te bepaal. Hierdie terroirs, alhoewel minder, was vergelykbaar met die wat gegenereer was met behulp van veldstudies. Data verkry met terroirstudies, sowel as gei'dentifiseerde terroir-eenhede, was gebruik om die grense van die Stellenbosch Wyn van Oorsrongsdistrik en die Simonsberg-Stellenbosch wyk te herbepaal. Voorgestelde modifiserings was gebaseer op verwagte wyneienskappe. Grense vir twee nuwe wyke in die Helderbergkom is voorgestel. Dit was ook moontlik om wingerde binne ‘n wyk te identifiseer vir die produksie van terroir-spesifieke wyne.

 Hepatocellular carcinoma (HCC) is the primary cancer of liver. It is the fifth common malignant tumor in men while seventh common in women. Aetiology of HCC is complex; however, it is now believed that sustained chronic liver injury and fibrosis are critically involved in the development of HCC. Prevention and treatment of HCC is far from desirable and prognosis remains poor. Coptis is a Chinese herbal Medicine which has been used for more than thousands years for clearing heats, dampness and toxics. Recently, studies from our group reported the hepatoprotective effect of Coptis and its major active component, berberine, on acute liver injury and berberine was extensively studied for their anti-tumor effect. However, there’s no comprehensive investigation focusing on the preventive and curative potential of berberine on HCC. Hence, here we hypothesized Coptis and berberine exhibits both preventive and curative effects on HCC. The prevention of HCC by berberine and Coptis may rely on their effects on chronic liver damage and fibrosis, and the curative action may depend on their actions on the angiogenesis, tumor growth and invasion of HCC. Both in vitro cell models and in vivo animal system were used in our study and some molecular events were investigated. We found that berberine and Coptis could significantly attenuate the chronic liver injury and fibrosis by restoring the anti-oxidative enzyme SOD activity in CCl4-, bile duct ligation- and alcohol-induced liver injury and fibrosis model. Recovery of SOD activity prevents the hepatocytes from apoptosis by inhibiting the oxidative stress-induced Erk1/2 signaling activation. The prevention of berberine and Coptis on chronic liver injury and fibrosis may contribute to its preventive effect against HCC. Then we found that berberine (as representative to Coptis) could suppress the angiogenesis of HCC, in which berberine does not directly act on the blood vessel formation, but suppress the expression and secretion of pro-angiogenic factors VEGF in HCC cells, and Id-1 inhibition by berberine plays a central role in the suppression of HIF-1α/VEGF and NF-κB pathways. We also found that berberine could induce both apoptotic and autophagic cell death in HCC, and the mitochondria related-caspases activation confers the apoptosis while mTOR inhibition initiates autophagy in berberine treated- cells. We found that berberine could suppress the migration and invasion of HCC cells as well, and Rho-GTPases/ROCK signaling is the particular target in berberine’s anti-invasive action. Finally, to dig out some molecular events involved in berberine’s action on HCC, we studied critically the mechanism underlying berberine’s inhibition on Cyclin D1 in HCC. We found berberine may promote the IKKα-induced Cyclin D1 phosphorylation at T286, and this may initiate the ubiquitination-dependent proteasomal degradation of Cyclin D1 in berberine-treated HCC cells and contribute to berberine’s anti-HCC action. Critical clinical trials and OMICS techniques were planned to further our comprehensive study on Coptis and berberine’s effects on HCC. In all, we found that berberine targets on different stages and molecules and exerts preventive and curative potential against HCC. Our study sheds light on the clinical application of berberine in HCC treatment.
published_or_final_version
Chinese Medicine
Doctoral
Doctor of Philosophy

Background: A study of the impact of yoga and aerobic exercise and psychosis was conducted in 2012 by Lin et al., from The University of Hong Kong. The study indicated significant improvement in the aspects of physical fitness, cognitive functions, psychosocial and emotional functioning in patients with psychosis after a 12-week yoga or aerobic intervention program. Long-term effect of exercise intervention, however, had yet been determined. The aim of the present study was to evaluate the long-term effects of yoga and aerobic exercise on cognitive functioning and clinical symptoms in early psychosis. Patients who originally participated in Lin et al.’s 2012 study were recruited and re-assessed in this current 18-month follow-up study. Methods: Two intervention groups (yoga and aerobic exercise group) and one control group (wait-list control group) of a total 57 subjects from the initial study were recruited in this follow-up study. Cognitive functioning and clinical symptoms were assessed at three time points (T1:Baseline, T2:12-week, T3:18-month). Results: No significant changes or significant deterioration were found in cognitive functioning, clinical symptoms and depression between T2 (12-week) and T3 (18-month) in both intervention groups (yoga and aerobic group). Significant improvement of clinical symptoms was observed in wait-list control group at T3. Conclusions: Although there is no significant finding in this current study, it is still recommended that further study on the relationship between physical exercise intervention and psychosis should carried out in order to explore other adjunct, and especially low cost, treatment to antipsychotics in treating people with psychosis.
published_or_final_version
Psychological Medicine
Master
Master of Psychological Medicine

G. pentaphyllum (Thun.) Makino (Cucurbitaceae) is a perennial climbing herb, mainly found in southern tropical areas of Asia. Traditional use of the herb dates back 500 years and includes treatment for chronic tracheitis, bronchitis, infectious hepatitis, pyelitis and gastroenteritis. Its numerous medicinal applications include anti-inflammatory, anti-toxic, anti-tussive and expectoratory actions. The plant is not endemic to Australia and, as far as the author knows, has never been cultivated in this region. Therefore, cultivation of G. pentaphyllum was undertaken in Sydney, Australia in order assess its growth in a new environment and to provide local material for further chemical and biological assessment (Chapter 2). It was observed that G. pentaphyllum adapted successfully to the Sydney soil, light and water conditions and the yields provided ample supply of material for extraction purposes.

The present project investigated the effect of glucose, high dose insulin and normoglycemia (GIN) therapy in patients undergoing coronary revascularization surgery. A reduction in myocardial injury as measured by cardiac troponin I was the primary end point. Cardiac function based on hemodynamics and vasoactive drug requirements as well as clinical outcome were evaluated. Hormones and metabolites and cardiac metabolism were investigated concurrently as potential mechanisms of GIN therapy. The major findings of the present study are that GIN therapy reduced post-operative myocardial injury and myocardial dysfunction leading to a decrease in major complications following coronary artery bypass grafting surgery. The mechanism of the overall improvement in cardiac function and decreased morbidity following CABG with GIN therapy is likely to be multi-factorial, but from the present results, is influenced by improved myocardial metabolism. GIN therapy is thus an effective diet for the ischemic heart.

Thesis (MTech (Consumer Sciences: Food and Nutrition))--Cape Peninsula University of Technology, 2006
Fruit and vegetables are the major antioxidant contributors to the diet Antioxidants assist in the prevention of oxidative damage in the body and may as a result prevent the causation of degenerative diseases. Thermal household processing plays an integral part in South African consumers' lives, as most fruit and vegetables consumed are processed at home. Consumers' perceptions that food processing causes nutrient losses, especially of vitamin C, have been corroborated by studies that investigated thermal household processing of single foods or that of industrial processing. No studies have determined the effect of thermal household processing on mixed dishes. A popular consumed South African mixed dish, namely, stewed tomato and onion flavoured with parsley, was investigated by using three recipes, each using a different preparation method. The traditional recipe for the preparation of stewed tomato and onion was modified (control recipe) to contain parsley. Two other recipes (Recipe 1 and 2) were compiled based on the recipe formulation of the control recipe but differed in the preparation methods used. In Recipe 1, raw onion was added to cooked tomato and in Recipe 2, sauteed onions were added to cooked tomato.

Therapeutic ultrasound employs the acoustic energy carried by high-frequency mechanical wave to induce beneficial effects on living systems. This therapeutic approach is advantageous in that its energy could be remotely focused on the targeted tissue in a non-invasive manner. Although ultrasound therapy has been shown to be feasible and effective in both laboratory experiments and clinical trials, its safety and efficacy are still challenged by the lack of fundamental knowledge of how ultrasound wave exerts physical effects on the cell system and how the cell functionally responds to the ultrasound stimulation. Motivated by the above insight, this thesis aims to provide direct experimental evidence for illustrating the biophysical details of how ultrasound wave (alone or combined with microbubble) interacts with live cells. An acoustic experimental platform with well-calibrated ultrasound field and live-cell imaging modality was developed to observe ultrasound-cell interaction. Based on this platform, a series of single-cell studies was then conducted to monitor the structural and functional changes of the live cell as well as its fluorescently-labelled components over the course of ultrasound exposure. Results obtained in this thesis provided image-level evidence for characterizing the ultrasound-cell interactions in the following three aspects. First, it was found that low-intensity ultrasound pulsing could directly perturb the plasma membrane, the cytoskeletal network and the inner nucleus of live neuroblastoma cells. This cytomechanical perturbation would result in reversible and structural alternations of subcellular components. Second, low-intensity pulsed ultrasound, when applied on neuronal cells, could exert morphological impact through inducing neurite retraction and cell body displacement, and electrophysiological impact in the form of membrane depolarization and calcium influx. This finding verified the potential of ultrasound in modulating neuronal development and excitability. Last, the cell membrane perforation and resealing dynamics induced by the ultrasound-activated microbubble were visualized and characterized. The subsequent cellular responses to this ultrasound-induced sonoporation were also identified at both membrane and cytoskeleton levels. The significance of this study is to provide direct and solid experimental evidence for understanding the biophysical interactions between ultrasound wave and live cell. This advanced scientific interpretation is definitely crucial for establishing the cellular mechanisms of therapeutic ultrasound and for providing technical insights into ultrasound treatment.
published_or_final_version
Electrical and Electronic Engineering
Doctoral
Doctor of Philosophy

Hong Kong’s compacted urban form brings about potential problems including mental illness. Meanwhile stressful life mainly originates from working pressure brought a lot of physical and mental problems for the people themselves and generating serious family and social problems. As more and more people start to aware mental health issue, the current mental health services system is no longer sustainable due to increasing number of patients. This thesis aims to excavate the potential for landscape to become element in healthcare delivery in the context of community as following: refine the definition of therapeutic landscape, define the scope of work, and identify components essential for therapeutic environment. Last but not least, dig out possible interpretation/physical form through set an example of a particular design introduce for a typical site. Therapeutic landscape which introduce to community recreation system will become a new approach to backup mental health service system as well provide people more convenient and broad healthcare service to cultivate healthy personality. Thus promote community organic development to become a thoughtful and institutional environment.
published_or_final_version
Architecture
Master
Master of Landscape Architecture

An in vitro IgG secretion assay was developed to investigate the regulation of the humoral immune response in humans. Pokeweed mitogen (PWM), a plant lectin derived from Phytolacca americana stimulates human peripheral blood mononuclear cells (PBMNC) to divide and resting B-lymphocytes to differentiate into immunoglobulin secreting cells (ISC). This differentiation requires that both monocytes and T-lymphocytes be present in the culture system. The amount of IgG secreted by these differentiated B-lymphocytes in response to PWM appears to be the net result of a balance between the functional activity of the regulatory T-helper and T-suppressor cells. Alterations, qualitative or quantitative in any of these leukocyte subsets could conceivably alter the amount of IgG secreted by the B-lymphocyte subpopulation. We have employed this assay to investigate the immune status in a group of chronic progressive multiple sclerosis (MS) patients and to assess the immunoregulatory effects of interferon (Wellferon R, INF) administered in vivo to this selected group. Their mononuclear cells (MNC) were studied in this PWM induced IgG secretion assay before INF treatment and again after 7 days of daily sub-cutaneous injections (5 X 10⁶ u/day). Twenty patients received the interferon (INF) preparation and eighteen received normal saline. The study was carried out in a double blind manner and the code was broken only after individual results had been calculated.
Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

The high performance of bone implants depends on the positive response of osteoblasts to the surface of the materials manufactured for the implant. Cell response in turn strongly depends on the nature of the initial interaction of macromolecules involved in cell adhesion and proliferation with the atomic structure of the surface of the material used for the implant. The initial interaction between bone specific extracellular matrix proteins and the solid substrate influences cell response at the cell-implant interface. This interaction is crucial for implant stability, long-term durability, and osseointegration. Despite extensive research undertaken to develop high-quality material for implants in order to improve the cell-substrate interaction, little is known about the significance of the atomic structure of the substrate and the role of molecular machinery involved in cell-substrate interaction. Using a combined approach involving material sciences and cell and molecular biology, the objectives of this research are to evaluate the response of pre-osteoblast and fibroblast cell lines to novel bulk polycrystalline and single crystal titanium based material and assess the role of crystal size and orientation.
Novel bulk nano-structured titanium substrates were produced by the process of high-pressure torsion (HPT). These materials have a significant advantage compared to conventional titanium-based materials by having higher surface wettablity, mechanical properties as well as a distinct surface oxide layer and atomic structure. A co-culture system was adapted to investigate the differential response of pre-osteoblast and fibroblast cell lines to titanium and titanium dioxide single-crystal substrates.
The results of this study provide clear evidence that crystal size and specific crystallographic orientation can be used to improve cell adhesion and proliferation. The nanostructured titanium substrates show strong interaction with pre-osteoblast cells as evident by the higher expression of fibronectin and the formation of extensive focal adhesion. Differential cell behaviour of pre-osteoblasts and fibroblasts are observed in cultures grown on the substrates with specific crystallographic orientations. The degree of cell attachment of the pre-osteoblasts is considerably higher on Ti-(1120) crystal face compared with the fibroblasts. These findings have profound implications for the improved osseointegration and inhibition of fibrosis leading to long-term implant consolidation and stability.

This thesis is a step forward in evaluating insulin therapy and defining its role in cardiac surgery first described as Glucose-Insulin-Potassium (GIK) solution 40 years ago.
Chapter (I) includes a review of the literature on insulin therapy in cardiac surgery and illustrates the scientific bases and controversies in this therapy.
Chapter (II) entitled: "Myocardial Protection During Elective Coronary Artery Bypass Grafting Using High Dose Insulin Therapy" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) McGill cardiovascular research day, February 1/2007, Montreal, Canada. (2) Fraser Gurd annual research day, McGill surgery department, May 31/2007, Montreal, Canada. (B) National meetings: (1) 11th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (C) International meetings: (1) 43rd Annual meeting of the Society of thoracic surgeons (STS), January 30/2007, San Diego, United States. A full manuscript was submitted to "The Annals of Thoracic Surgery" for review.
Chapter (III) entitled: "High Dose Insulin Therapy Attenuates Systemic Inflammatory Response in Patients Undergoing Elective Coronary Artery Bypass Grafting" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) Fraser Guard McGill Surgery department annual research day, May 3/2006, Montreal, Canada. (B) National meetings: (1) 10th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (2) Young investigator forum, Canadian Society of Clinical Investigators (CSCI), September 28/2006, Ottawa, Canada. (3) 59 th annual meeting of Canadian Cardiovascular Society (CCS), October 21/2006, Vancouver, Canada. (C) International meetings: (1) American Heart Association (AHA), November 12/2006, Chicago, United states.
Abstracts from this work were published in the following journals: (1) Clinical and Investigative Medicine, Vol. 29, No. 4, August 2006. (2) The Canadian Journal of Cardiology, Vol. 22 supp D, October 2006 (3) Circulation, Vol. 114 supp, No. 18, October 2006.
A full manuscript was submitted to "the journal of thoracic and cardiovascular surgery" for review.

Background. Both basal-like subtype and BRCA1-related breast cancers tend to have a poor overall prognosis and lack of effective treatments. Given that the lung cancer drug gefitinib and the leukemia drug dasatinib inhibit proteins also belonging to the molecular signature of this subtype, we and others hypothesized that they might be useful therapies for those two breast cancer subgroups.
Methods. Eight breast cancer cell lines were characterized by immunohistochemistry and western blotting and were treated with both drugs. Response was measured by using the sulphorhodamine B (SRB) assay.
Results. Two out of six basal-like cell lines were sensitive to gefitinib and five of six to dasatinib. BRCA1-related breast cancers were also responsive to dasatinib (three out of four). Moreover, EGFR and caveolin-1 act as markers for dasatinib sensitivity, but do not appear to be the primary targets of this drug. The presence of SRC but not ABL is necessary to achieve a response to dasatinib.
Conclusion. Dasatinib is more effective in the treatment of basal-like breast cancers than gefitinib and acts by inhibiting SRC and other molecules that are yet to be determined.

From a social constructionist perspective, the self of the therapist is the only tool that she takes into therapy with her. The study of the therapeutic self therefore becomes important as this impacts on the quality of therapy received by the client. This treatise explores the development of the researcher’s therapeutic self through the storying of significant learning experiences in the course of her training in counselling psychology. An analysis of the narrative reveals the substance of some of the soul tattoos that make up her therapeutic self. The study was undertaken from an action research approach, thus emphasising the investigation of the therapeutic self in the field and feeding this information back into the practice of counselling psychology in the course of the research project. The themes extracted in the analysis reveal the process of action learning and what constituted significant learning experiences for the researcher. The researcher found that certain conditions were required for the formation of soul tattoos and that merely obtaining a masters degree in counselling psychology was not sufficient preparation for the practice of counselling psychology.