AFRIKAANS: In hierdie proefskrif word wapenbeheer en ontwapening 5005 dit na die Koue Oorlog op globale-, streek-(spesifiek Afrika) en nasionale (spesifiek Suid-Afrika) vlakke toegepas is ondersoek en ontleed. Die doel van die studie is om bestaande kennis op 'n oorsigtelike gekonsolideerde wyse, veral ten opsigte van Afrika en Suid-Afrika uit te brei omdat 'n behoefte in die opsig met die indiening van die navorsingsvoorstel geïdentifiseer is; om aan te toon dat wapenbeheer en ontwapening selfs na die beëindiging van die Koue oorlog steeds wëreldwyd van kardinale belang is; en dat daar na die Koue Oortog ongekende sukses op globale vlak, in Afrika tot 'n mindere mate, en in Suid-Afrika groot sukses met wapenbeheer en ontwapening behaal is. 'n Radikale verandering in binnelandse en buitelandse beleid deur Suid-Afrika het tot gevolg gehad dat Suid-Afrika in die vroeë negentigerjare die eerste staat in die wêreld geword het wat kemontwapening algeheel toegepas het. Suid-Afrika se chemiese en biologiese oorlogvoe¬ringprogramme is ook in die vroeë negentigerjare beëindig. Die demokratisering van die politieke bestel in Suid-Afrika in 1994 het ook grootskaalse betrokkenheid van die Suid¬-Afrikaanse regering by wapenbeheer en ontwapening op globale-, streek- en nasionale vlakke tot gevolg gehad. Die doel van die studie is ook om aan te toon tot watter mate die bëeindiging van die Koue Oortog 'n invloed op wapenbeheer en ontwapening gehad het. Die beëindiging van die Koue Oorlog was 'n resultaat van 'n radikale verandering in binnelandse en buitelandse beleid deur die voormalige Sowjet-Unie. Die studie aangaande wapenbeheer en ontwapening na die Koue Oorlog word voorafgegaan deur 'n ontleding van die teoretiese konsepte van wapenbeheer en ontwapening en die ontwikkeling van die konsepte deur teoretici van die twintigste eeu. Die benaderings met wapenbeheer en ontwapening soos deur hierdie teoretici ontwikkel, word dan ook in die studie toegepas op die verdrae en ooreenkomste wat na die Koue Oorlog onderteken en/of geratifiseer is. Die metode van ondersoek wat vir die bestudering van die onderwerp gevolg is, is histories-beskrywend en analities van aard. Die doeI hiermee was om die verskillende wapenkategorieë en tydperke af te baken en dan vas te stel tot hoe 'n mate wapenbeheer en ontwapening globaal, en meer spesifiek op streek-(Afrika) en nasionale (Suid-Afrika) vlakke na die Koue Oorlog toegepas is. Wapenbeheer en ontwapening soos voor en na die Koue Oorlog toegepas, word ooreenkomstig die teorie, soos in hoofstuk 1 uiteengesit, beoordeel. Die prosedure wat met die navorsing gevolg is, is soos volg: selektering van boeke, dokumente, tydskrifte, nuusblaaie en publikasies van verskillende aard; dataversameling en bestudering van tekse; data-ontleding ten einde vas te stel watter toepaslik is; die proses van vertolking en interpretering van die inligting; toepassing van inligting; evaluasie; en die vorming van gevolgtrekkings. ENGLISH: In this dissertation the processes of arms control and disarmament as implemented at global, regional (Africa) and national (South Africa) levels are investigated and analysed. The purpose of the study is to widen existing knowledge in a consolidated manner, especially with regard to Africa and South Africa. A need in this regard was identified with the submission of the proposal for the study. A further purpose of the study is to indicate that arms control and disarmament, even after the end of the Cold War, is still of utmost importance; and that success of formerly unknown proportions was obtained with arms control and disarmament after the Cold War on the global level, to a lesser extent in Africa, and with great success in South Africa. A radical change in internal as well as foreign policy by the South African government resulted in South Africa being the first state in the world to implement total nuclear disarmament in the early nineties. South Africa's chemical and biological warfare programs were also terminated in the early nineties. The democratisation of the political environment in South Africa in 1994 resulted in South Africa becoming involved in arms control and disarmament at global, regional and national levels. The purpose of the study is also to illustrate to what extent the ending of the Cold War had an influence on arms control and disarmament. The end of the Cold War was a result of a radical change in internal as well as foreign policies of the former Soviet Union. The study of arms control and disarmament after the Cold War is preceded by an analysis of the theoretical concepts of arms control and disarmament by twentieth century theorists. The approaches to arms control and disarmament, as developed by these theorists, are then applied to treaties and agreements, which were signed/ ratified before and after the Cold War. The method of investigation that was followed for the study was historically descriptive and analytical of nature. The purpose was to differentiate between the different categories of weapons and the different periods during which arms control and disarmament were implemented since the earliest times and during and after the Cold War. The approaches to arms control and disarmament, during and after the Cold War, are also assessed according to the theory as explained in chapter 1. The procedure which was followed whilst doing research for the study was as follows: The selection of books, documents, magazines, newspapers, and publications of various nature; compilation and studying of data; analysis of data to establish which would be appropriate to use; the process of interpretation of the information; application; evaluation and forming of conclusions. <p / Thesis (DPhil (International Politics))--University of Pretoria, 2006. / Political Sciences / unrestricted

X–linked adrenoleukodystrophy (X–ALD) is the most common peroxisomal enzyme deficiency disorder, characterized by inborn mutations in the ABCD1 gene, an ATP–binding cassette (ABC) half–transporter. The ABCD1 gene encodes the adrenoleukodystrophy protein (ALDP), the transporter for the very–long–chain fatty acids (VLCFA; C > 22:0) from the cytosol into the peroxisomes to enter the peroxisomal B–oxidation pathway. The diagnostic disease marker is the elevated levels of VLCFAs which accumulate in different tissues and body fluids, leading to inflammatory demyelination, neuro–deterioration and adrenocortical insufficiency. At present, there is no satisfactory therapy for X–ALD available. However, another peroxisomal ABC half–transporter, ALDRP can compensate for the functional loss of ALDP and is encoded by the ABCD2 gene. This prompted a new approach to treatment strategies. Phenylbutyric acid (PBA) over–expresses the ABCD2 gene, leading to an increased expression of ALDRP and PBA decreases VLCFA levels by increasing peroxisomal B–oxidation. This study had a dual aim: to determine the antioxidant capacity of PBA and to verify known and identify new metabolites of PBA. In vitro, HeLa cells were cultivated and treated with 0.5 mM, 1 mM, 2 mM and 5 mM PBA for 48 hours. The ROS, lipid peroxidation, apoptosis and cell viability were determined using fluorescein–based flow cytometry. Images were taken to visualize the peroxisome proliferation. In vivo, a vervet monkey was given a single dose of 130 mg/kg PBA. Blood was collected before treatment and 15 minutes, 30 minutes, 1, 2 and 3 hours after treatment. ROS, apoptosis and lipid peroxidation were determined by fluorescein–based flow cytometry. Urine was collected before treatment and 15 minutes, 30 minutes, 1, 2, 3, 7 and 24 hours after PBA treatment. A standardised method, employing gas chromatography–mass spectrometry (GC/MS), was used to analyse the organic acids in the urine and fatty acids in the blood. In vitro results showed decreased levels of ROS and lipid peroxidation with increased concentrations of PBA. PBA showed a protective effect towards the HeLa cells with reduced apoptosis and a high number of viable cells. In vivo levels of ROS en lipid peroxidation decreased over time of treatment with PBA. The fluorescence microscope images confirmed an increased number of peroxisomes after PBA treatment. The short term effect of PBA showed an initial, but small decrease in the levels of the fatty acids, suggesting induction over a longer period rather than activation of peroxisomal B–oxidation. New metabolites of phenylbutyrate were identified in the urine of a vervet monkey. These new metabolites originated from monooxygenase, N–phenylacetyl–glutamine synthases and B–oxidation byproducts. Recently discovered metabolites in humans and rats were also verified and confirmed in the vervet monkey. We therefore propose that treatment with PBA, on account of its beneficial effects of restoring VLCFA levels and reducing oxidative stress, could be considered a novel approach for the treatment of X–ALD. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.

X–linked adrenoleukodystrophy (X–ALD) is the most common peroxisomal enzyme deficiency disorder, characterized by inborn mutations in the ABCD1 gene, an ATP–binding cassette (ABC) half–transporter. The ABCD1 gene encodes the adrenoleukodystrophy protein (ALDP), the transporter for the very–long–chain fatty acids (VLCFA; C > 22:0) from the cytosol into the peroxisomes to enter the peroxisomal B–oxidation pathway. The diagnostic disease marker is the elevated levels of VLCFAs which accumulate in different tissues and body fluids, leading to inflammatory demyelination, neuro–deterioration and adrenocortical insufficiency. At present, there is no satisfactory therapy for X–ALD available. However, another peroxisomal ABC half–transporter, ALDRP can compensate for the functional loss of ALDP and is encoded by the ABCD2 gene. This prompted a new approach to treatment strategies. Phenylbutyric acid (PBA) over–expresses the ABCD2 gene, leading to an increased expression of ALDRP and PBA decreases VLCFA levels by increasing peroxisomal B–oxidation. This study had a dual aim: to determine the antioxidant capacity of PBA and to verify known and identify new metabolites of PBA. In vitro, HeLa cells were cultivated and treated with 0.5 mM, 1 mM, 2 mM and 5 mM PBA for 48 hours. The ROS, lipid peroxidation, apoptosis and cell viability were determined using fluorescein–based flow cytometry. Images were taken to visualize the peroxisome proliferation. In vivo, a vervet monkey was given a single dose of 130 mg/kg PBA. Blood was collected before treatment and 15 minutes, 30 minutes, 1, 2 and 3 hours after treatment. ROS, apoptosis and lipid peroxidation were determined by fluorescein–based flow cytometry. Urine was collected before treatment and 15 minutes, 30 minutes, 1, 2, 3, 7 and 24 hours after PBA treatment. A standardised method, employing gas chromatography–mass spectrometry (GC/MS), was used to analyse the organic acids in the urine and fatty acids in the blood. In vitro results showed decreased levels of ROS and lipid peroxidation with increased concentrations of PBA. PBA showed a protective effect towards the HeLa cells with reduced apoptosis and a high number of viable cells. In vivo levels of ROS en lipid peroxidation decreased over time of treatment with PBA. The fluorescence microscope images confirmed an increased number of peroxisomes after PBA treatment. The short term effect of PBA showed an initial, but small decrease in the levels of the fatty acids, suggesting induction over a longer period rather than activation of peroxisomal B–oxidation. New metabolites of phenylbutyrate were identified in the urine of a vervet monkey. These new metabolites originated from monooxygenase, N–phenylacetyl–glutamine synthases and B–oxidation byproducts. Recently discovered metabolites in humans and rats were also verified and confirmed in the vervet monkey. We therefore propose that treatment with PBA, on account of its beneficial effects of restoring VLCFA levels and reducing oxidative stress, could be considered a novel approach for the treatment of X–ALD. / Thesis (M.Sc. (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2011.