No description available.

Fifty percent of the diagnosed cases of coronary heart disease in the United States are of unknown etiology. This study proposed that five personality traits— achievement, dominance, aggression, succorance and Critical Parent—differentiate individuals with coronary heart disease manifestations. The ultimate goal of this research was to formulate a predictive profile of at-risk individuals of developing coronary heart disease. Cardiac rehabilitation units' participants from across the United States were recruited as subjects. Randomly selected cardiac rehabilitation units were sent an initial letter inquiring whether their staff would be willing to participate in the study by administering the instruments to their participants. Eight units from each of the 50 states were contacted. A total of fourteen units agreed to participate. One hundred sixty-nine subjects completed the Demographic Data Questionnaire and the Adjective Check List. Five scale scores, representing the five personality differentials, were analyzed. Comparison of the male subject population (n=135) and the male normative population (n=198) revealed no significant differences in terms of the five traits. Comparison of diagnostic subgroups of the subject population also revealed no significant differences. It was concluded that the subject population did not differ significantly from the normative population in terms of the five traits assess by the instrument used. The goal of a predictive profile was not realized due to this lack of findings. / Master of Science / incomplete_metadata

The dysregulation of immune system function has been centrally implicated in numerous age-related and neurodegenerative disorders, including Alzheimer’s disease (AD). Genetic susceptibility studies have positioned microglia, brain-resident immune cells, as critical actors in the development and the progression of the disease. Microglia are highly plastic cells with diverse functions across many modalities, and the appropriate regulation of their activities are a prerequisite for central nervous system homeostasis and cognitive health. Aging and pathogenic contexts are posited to modify microglial behavior, inhibiting their neuroprotective function and promoting a dysfunctional state that drives disease. However, the mechanisms underlying these pathogenic alterations in microglial state and function are complex and poorly understood. This thesis identifies three elements that are altered in the AD brain and investigates how these mechanisms may serve as triggers producing microglial dysregulation in AD. Chapter 3 examines the role of expression of the transposable element LINE-1 in AD-related microglial dysfunction. Chapter 4 explores the regulation of PLCG2, which encodes a critical AD-associated signaling enzyme. Chapter 5 investigates the role of the AD-linked sorting receptor SORL1 in microglia. Together, these data expand our understanding of mechanisms driving altered microglial pathophysiology in AD and illuminate pathways of interest with potential therapeutic applications meriting deeper exploration.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Seedling blight of maize has significantly influenced field crop stands and seedling vigour over various localities and seasons. The extent of the problem is influenced by a number of factors which includes soil temperature (generally below 13 °C), waterlogged soils, inadequate fertilization, herbicide damage and fungal pathogens. The fungi generally causing seedling damping off are often involved in a complex and succession over time varying in importance depending on the field circumstances at a given time. These generally include the Pythium spp., Rhizoctonia spp. and various Fusarium spp. These have been recorded in a number of studies conducted by local researchers in the late 1980’s and early 1990’s on sorghum but to a lesser degree on maize. Uncertainty regarding the status of the etiology of maize seedling blights as maize production practices have changed dramatically in the last 10 years with increased plant populations, reduced tillage, increased crop rotation options and new short season maize hybrids. It is therefore essential to determine the present status of seedling blights in South Africa to confirm the necessity of fungicide seed treatments to ensure adequate plant densities and seedling vigour. Cob and tassel smut caused by Sphacelotheca reiliana is a disease of maize that was a problem in the 1970’s. Due to improved fertilisation, fungicide seed treatments and hybrid resistance this disease was reduced to such levels that the disease was only found to occur on research farms where seedlings were inoculated. Since 2007, the disease was reported to reach epidemic proportions on the heavy clay soils in the Standerton area. This disease has since spread over the last seven seasons to a range including northern KwaZulu/Natal, namely as far as Underberg/Swartberg, the Witbank, Ermelo, Middelburg and Delmas area in Mpumalanga and to Harrismith in the eastern Free State maize production area. This may be due to susceptible hybrids coming onto the local market or the inability of traditional fungicide seed treatments to contain infection. New and unregistered seed treatments available will be tested for their ability to control cob and tassel smut in two fields over two seasons. The aims of this dissertation were to determine the extent of the seedling blight problem in commercial fields throughout the maize industry. To determine the efficacy of fungicide seed treatments for the control of maize seedling blights using both field and greenhouse studies, and to determine the efficacy of fungicide seed treatments for the control of cob and tassel smut of maize in field trials. A total of 101 localities were sampled throughout the maize producing region of South Africa with root discolouration varying from 0 to 90 % root discolouration. Seventy different fungal species were isolated from the maize seedlings roots which include species such as Aspergillus, Clonostachus, Fusarium, Trichoderma and Penicillium. The most commonly isolated fungi which included Aspergillus niger, Fusarium solani, Fusarium verticillioides and Fusarium oxysporum were evaluated in glasshouse studies to determine their pathogenicity. Pathogenicity differed between isolates of the same fungal species, which were collected from different geographical regions, in the glasshouse studies. Field trials for seedling blight disease showed significant differences between the localities (P < 0.001) the trials were planted at, and between seed treatments. Significant season (P < 0.001) and locality (P < 0.05) differences were also found for cob and tassel smut trials planted at Potchefstroom, North-West province and Greytown, KwaZulu/Natal Province respectively. Fungicide seed treatments also showed significant differences for cob and tassel smut regarding plants infected (P < 0.001) and yield loss (P < 0.05). Overall seed treatments can be seen as an effective controlling agent for the control of seed- and soil-borne fungi on maize. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

Seedling blight of maize has significantly influenced field crop stands and seedling vigour over various localities and seasons. The extent of the problem is influenced by a number of factors which includes soil temperature (generally below 13 °C), waterlogged soils, inadequate fertilization, herbicide damage and fungal pathogens. The fungi generally causing seedling damping off are often involved in a complex and succession over time varying in importance depending on the field circumstances at a given time. These generally include the Pythium spp., Rhizoctonia spp. and various Fusarium spp. These have been recorded in a number of studies conducted by local researchers in the late 1980’s and early 1990’s on sorghum but to a lesser degree on maize. Uncertainty regarding the status of the etiology of maize seedling blights as maize production practices have changed dramatically in the last 10 years with increased plant populations, reduced tillage, increased crop rotation options and new short season maize hybrids. It is therefore essential to determine the present status of seedling blights in South Africa to confirm the necessity of fungicide seed treatments to ensure adequate plant densities and seedling vigour. Cob and tassel smut caused by Sphacelotheca reiliana is a disease of maize that was a problem in the 1970’s. Due to improved fertilisation, fungicide seed treatments and hybrid resistance this disease was reduced to such levels that the disease was only found to occur on research farms where seedlings were inoculated. Since 2007, the disease was reported to reach epidemic proportions on the heavy clay soils in the Standerton area. This disease has since spread over the last seven seasons to a range including northern KwaZulu/Natal, namely as far as Underberg/Swartberg, the Witbank, Ermelo, Middelburg and Delmas area in Mpumalanga and to Harrismith in the eastern Free State maize production area. This may be due to susceptible hybrids coming onto the local market or the inability of traditional fungicide seed treatments to contain infection. New and unregistered seed treatments available will be tested for their ability to control cob and tassel smut in two fields over two seasons. The aims of this dissertation were to determine the extent of the seedling blight problem in commercial fields throughout the maize industry. To determine the efficacy of fungicide seed treatments for the control of maize seedling blights using both field and greenhouse studies, and to determine the efficacy of fungicide seed treatments for the control of cob and tassel smut of maize in field trials. A total of 101 localities were sampled throughout the maize producing region of South Africa with root discolouration varying from 0 to 90 % root discolouration. Seventy different fungal species were isolated from the maize seedlings roots which include species such as Aspergillus, Clonostachus, Fusarium, Trichoderma and Penicillium. The most commonly isolated fungi which included Aspergillus niger, Fusarium solani, Fusarium verticillioides and Fusarium oxysporum were evaluated in glasshouse studies to determine their pathogenicity. Pathogenicity differed between isolates of the same fungal species, which were collected from different geographical regions, in the glasshouse studies. Field trials for seedling blight disease showed significant differences between the localities (P < 0.001) the trials were planted at, and between seed treatments. Significant season (P < 0.001) and locality (P < 0.05) differences were also found for cob and tassel smut trials planted at Potchefstroom, North-West province and Greytown, KwaZulu/Natal Province respectively. Fungicide seed treatments also showed significant differences for cob and tassel smut regarding plants infected (P < 0.001) and yield loss (P < 0.05). Overall seed treatments can be seen as an effective controlling agent for the control of seed- and soil-borne fungi on maize. / MSc (Environmental Sciences), North-West University, Potchefstroom Campus, 2015

The aim of this study is to demonstrate how the complementary concepts of stability and change could manifest during the therapeutic process, specifically with clients showing the symptom of dependency. The study is guided by a literature study on systems/cybernetic theory with a focus on the cybernetic complementarity of stability and change. A brief description is provided of the symptom of dependency from a more traditional lineal perspective as well as a non-lineal (systemic) perspective. A single case study is utilized to describe how both stability and change could manifest in the therapeutic process. From this description the relevance and usefulness of addressing both stability and change during the therapeutic process emerge and are outlined. / Social Work / M. A. (Social Science Mental Health)

Thesis (MScMedSc (Pathology. Medical Virology))--University of Stellenbosch, 2010. / Bibliography / ENGLISH ABSTRACT: Throughout history disease entities have been described which match the description of diseases now known to be caused by hantaviruses; however these viruses were first identified as the aetiologic agent in 1976, the first species named Hantaan virus after the river near which its natural host, the rodent species Apodemus agrarius, was captured. Since then numerous species in the Hantavirus genus, family Bunyaviridae, have been found, with today more than 30 species worldwide being known. Hantaviruses are hosted by rodents from the Muridae and Cricetidae families and by shrews (insectivores) in the Soricidae family. There are two types of hantavirus disease, Haemorrhagic fever with renal syndrome (HFRS) in the Old World and Hantavirus cardiopulmonary syndrome (HCPS) in the New World. The first two African hantaviruses were identified in 2006 in Guinea, West Africa; Sangassou virus (SANGV) in a rodent, the African wood mouse (Hylomyscus simus), and Tanganya virus (TGNV) in Therese’s shrew (Crocidura theresae). In this study, rodents and shrews were trapped at localities in the Western Cape and Northern Cape provinces of South Africa, and in the southern regions of Namibia. RNA was extracted from their lungs and screened for hantavirus sequences by RTPCR, using degenerate primers designed to detect all members of the Hantavirus genus. In addition, an in-house IgG ELISA assay was set up, based on recombinant N antigen from Dobrava virus, DOB-rN, and Puumala virus, PUU-rN. The assay was used to screen patient sera collected in an anonymous convenience serological survey using residual serum samples left over from routine testing at NHLS laboratories in the Western Cape for hantavirus-specific antibodies. RNA from 576 animal specimens was screened by RT-PCR; no hantavirus genome was detected in any of the specimens. Sera from 161 patients were screened for hantavirus antibodies; 11.18% of the sera were reactive to DOB-rN, 4.97% against PUU-rN and 2.48% against both antigens. v Though no virus was detected in the animals screened, this does not necessarily mean that there are no hantaviruses present in Southern Africa. A previous seroepidemiological survey conducted in South Africa reported on the presence of hantavirus specific antibodies by IFA in two species of rodents trapped in the Western Cape and Northern Cape Aethomys namquensis and Tatera leucogaster. Our was the second known study in South Africa conducted that determined and proved the presence of hantavirus specific antibodies in humans. / AFRIKAANSE OPSOMMING: Dwarsdeur die geskiedenis was daar beskrywings van siektes wat ooreenstem met die beskrywing van hantavirus simptome, maar die eerste etiologiese oorsaak van die siekte is eers in 1976 geïdentifiseer en Hantaan virus genoem, vernoem na die rivier waar naby die gasheer, Apodemus agrarius, gevang is. Van daar af het die soektog na nuwe hantavirusse intensief gevorder en vandag is daar meer as 30 spesies wêreldwyd wat aan die Hantavirus genus, ’n lid van die Bunyaviridae familie, behoort. Knaagdiere van die Muridae en Cricetidae families, sowel as spitsmuise (insekvreters) in die Soricidae familie is gasheer vir hantavirusse. Twee tipes hantavirus siekte is bekend, hemorragische koors met nier sindroom (HFRS) in die Ou Wêreld en hantavirus kardiopulmonale sindroom in die Nuwe Wêreld. Die eerste twee Afrika hantavirusse is in 2006 in Guinee Wes-Afrika geïdentifiseer; Sangassou virus (SANGV) in ’n knaagdier, die Afrika hout muis (Hylomyscus simus) en Tanganya virus (TGNV) in Therese se spitsmuis (Crocidura theresae). In hierdie studie is knaagdiere en spitsmuise op verskeie plekke in die Wes- en Noord-Kaap provinsies, asook die Suide van Namibië, gevang. RNS is onttrek vanuit die longe en hantavirus volgordes is gesoek deur middel RT-PKR deur gebruik te maak van Pan-Hanta primers wat ontwerp is om alle lede van die Hantavirus genus op te spoor. ’n Self-ontwerpde IgG ELISA, gebasseer op rekombinante N antigeen van Dobrava virus, DOB-rN en Puumala virus, PUU rN, is opgestel en gebruik om pasiënt serum, verkry in ’n anonieme serologiese opname, te toets; oorblywende serum, na toetse uitgevoer is deur NHLS laboratoriums in die Wes-Kaap, is verkry en getoets vir hantavirus spesifieke teenliggaampies. RNS van 576 dier monsters is getoets deur middel van RT-PKR en geen hantavirus is in enige van die monsters geïdentifiseer nie. Serum van 161 pasiënte is getoets vir hantavirus teenliggaampies; 11.18% van die serum was reaktief teen DOB-rN, 4.97% teen PUU-rN en 2.48% teen albei antigene. Alhoewel geen virus in die diere geïdentifiseer is nie, beteken dit nie noodwendig dat geen hantavirusse in Suidelike-Afrika voorkom nie. ‘n Vorige sero-epidemiologiese opname wat in Suid-Afrika gedoen is het die teenwoordigheid van hantavirus spesifieke teenliggaampies in twee knaagdier spesies, Aethomys namquensis en Tatera leucogaster gevang in die Wes-en Noord-Kaap, gevind. Ons studie is die tweede studie bekend in Suid-Afrika uitgevoer, wat die teenwoordigheid van hantavirus spesifieke teenliggaampies bevind en bewys het.

Thesis (MScMedSc)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: INTRODUCTION: Glycogen synthase kinase-3 (GSK-3) is a serine-threonine protein kinase that was first discovered as a regulator of glycogen synthase thus playing a role in glycogen synthesis (Embi et al. 1980). GSK-3 has also been shown to down regulate the expression of SERCA-2a (a calcium ATPase pump) thus playing a role in myocardial contractility (Michael et al. 2004). However, SERCA-2a activity is regulated by phospholamban (PLM) and sarcolipin (SLN) (Asahi et al. 2003). GSK-3 is constitutively active in cells and can be acutely inactivated by insulin through phosphorylation by PKB/Akt. However, GSK-3 is known to phosphorylate and inhibit IRS-1 protein, thus disrupting insulin signaling (Eldar-Finkelman et al. 1996). In addition, abnormally high activities of GSK-3 protein has been implicated in several pathological disorders which include type 2 diabetes, neuron degenerative and affective disorders (Eldar-Finkelman et al 2009). This led to the development of new generations of inhibitors with specific clinical implications to treat these diseases (Martinez 2008). GSK-3 inhibition has been shown to improve insulin and blood glucose levels and to be cardioprotective during ischemia/reperfusion (Nikoulina et al. 2002; Kumar et al. 2007). AIMS: To determine whether myocardial GSK-3 protein and its substrate proteins are dysregulated in obesity and insulin resistance, and whether a specific GSK-3 inhibitor can prevent or reverse the cardiovascular pathology found in obese and insulin resistant animals. OBJECTIVES: To correlate the alterations in expression and activation of GSK-3 protein in a well characterised rat model of obesity coupled to insulin resistance with: i) myocardial contractile dysfunction and an inability of hearts to withstand ischemia/reperfusion, ii) the activation and expression of phospholamban and SERCA-2a in the sarcoplasmic reticulum, iii) the activation of intermediates (IRS-1, IRS-2 and PKB/Akt) that lie upstream in the activation pathway of GSK-3 and iv) to determine the effects of inhibition of GSK-3 on the abovementioned parameters. METHODS: Age and weight matched male Wistar rats (controls and diet induced obese (DIO) animals) were used in the present study. Controls were fed normal rat chow, while DIOs were fed a rat chow diet supplemented with sucrose and condensed milk, for 8 or 16 weeks. Half of each group of animals were treated with the GSK-3 inhibitor for 4 weeks (from 12 to 16 weeks). After the feeding and treatment period, animals were weighed, sacrificed, hearts removed and freeze clamped immediately or perfused with Krebs-Henseleit buffer and subjected to low flow ischemia (25 min) followed by 30 min reperfusion. Biometric (body weight, intraperitoneal fat, ventricular weight and tibia length) and biochemical (fasting blood glucose and insulin levels) parameters were determined. Expression of GSK-3, PKB/Akt, IRS-1, IRS-2, SERCA-2a and Phospholamban were determined by Western blotting. Ca2+ ATPase activity was determined spectrophotometrically. RESULTS: At both 8 and 16 weeks DIO animals were significantly bigger than control animals and this was associated with increased intraperitoneal fat in DIOs. In DIO animals: IRS-1 was downregulated at 8 weeks and both IRS-1 and IRS-2 as well as PKB/Akt at 16 weeks. There was an increased tendency of GSK-3 expression at both 8 and 16 weeks in DIO animals while SERCA-2a was severely downregulated from 8 weeks onwards and associated with lower Ca2+-ATPase activity. PLM expression was upregulated but its phosphorylation was attenuated. At 16 weeks, baseline heart rate (225 vs 275 in control, P<0.0001, n=6) and rate pressure product (21000 vs 30000 in control, P=0.019, n=6) were significantly lower in hearts from DIO animals. Functional recovery was unchanged but the time to ischemic contracture development was increased (11.6±0.4 control vs 16.2±0.5 min DIO, P<0.01, n=6). Treatment had no effect on total GSK-3 expression. However, GSK-3 phosphorylation was significantly increased in treated controls, while there was no significant difference in DIO animals. However, there was a tendency for an increased GSK-3 phosphorylation in treated DIO animals. GSK-3 inhibitor, improved hypertrophy in DIO animals, while it led to its development in control animals. GSK-3 inhibitor improved IRS-2 expression in both control and DIO animals while it had no effect on IRS-1 and SERCA-2a expression and activity. However, GSK-3 inhibition increased PKB/Akt and phospholamban phosphorylation in DIO animals. CONCLUSION: These findings show that high calorie diet as well as imbalance between energy intake and expenditure lead to the development of obesity and insulin resistance in male Wistar rats. We showed that GSK-3 and its substrate proteins are dysregulated in obesity and insulin resistance. The reduced SERCA-2a expression at baseline may have a negative impact on cardiac function. By treating the animals with GSK-3 inhibitor, we showed that GSK-3 protein may not be responsible for changes seen at baseline. The decreased IRS-1 and SERCA-2a expression may have been caused by a different mechanism other than the actions of GSK-3. However, according to this study, GSK-3 may play a role in regulation of IRS-2 expression but not in IRS-1. Increased PKB/Akt phosphorylation may contribute to the GSK-3 inhibition. In addition, GSK-3 inhibition may reverse cardiac hypertrophy in DIO animals, thus acting as a negative regulator of hypertrophy. / AFRIKAANSE OPSOMMING: Inleiding: Glikogeen sintase kinase-3 (GSK-3), 'n serien/threonien proteïen kinase, is oorspronklik ontdek as 'n rolspeler in glikogeen sintese, aangesien dit 'n reguleerder van glikogeen sintase is (Embi et al.1980). Intussen is dit ook bevind dat GSK-3 die uitdrukking van SERCA-2a ('n kalsium ATPase pomp) kan afreguleer en dus sodoende 'n rol speel in miokardiale kontraktiliteit (Michael et al. 2004). Die aktiwiteit van SERCA-2a kan egter ook gereguleer word deur fosfolamban (PLM) en sarkolipin (Asahi et al. 2003). GSK-3 is deurgaans aktief, maar kan tydelik geïnaktiveer word onder kondisies van insulien stimulasie deur PKB/Akt gemedieerde fosforilering. Aan die ander kant is dit bekend dat GSK-3 die IRS-1 proteïen kan fosforileer om dus sodoende insulien sein-transduksie af te reguleer (Eldar-Finkelman et al. 1996). Daarmee saam is abnormaal hoë vlakke van GSK-3 aktiwiteit geassosieer met verskeie patologiese versteurings, insluitend tipe 2 diabetes, neuron degeneratiewe en affektiewe versteurings (Eldar-Finkelman et al. 2009). Daar is dus nuwe generasies GSK-3 inhibitore ontwikkel met die kliniese potensiaal om hierdie patologieë te behandel (Martinez 2008). Dit is al bevind dat GSK-3 inhibisie geassosieer kan word met beide die normalisering van plasma insulien- en glukose vlakke, asook kardiobeskerming in die konteks van iskemie/herperfusie (Nikoulina et al. 2002; Kumar et al. 2007). Doelwitte: Om te bepaal of GSK-3 proteïen en sy substraat proteïene gedisreguleer is onder kondisies van obesiteit en insulien weerstandigheid, asook om vas te stel of 'n spesifieke GSK-3 inhibitor die kardiovaskulêre patologie wat gevind word in obese en insulien weerstandige diere kan verhoed of omkeer. Mikpunte: Om veranderinge in uitdrukking en aktiwiteit van GSK-3 proteïen in 'n goed gekarakteriseerde rotmodel van obesiteit, gekoppel aan insulien weerstandigheid, te korreleer met die volgende: i) miokardiale kontraktiele disfunksie en onvermoë om kardiale iskemie/herperfusie besering te weerstaan, ii) aktivering en uitdrukking van PLM en SERCA-2a in die sarkoplasmiese retikulum, iii) die aktivering van intermediêres wat proksimaal geleë is in die insulienseintransduksiepad van GSK-3 (IRS-1, IRS-2 en PKB/Akt) en iv) om die effek van behandeling met 'n spesifieke inhibitor van GSK-3 op die bogenoemde punte te bepaal. Metodes: Ouderdoms- en gewigsgepaarde manlike Wistar rotte (kontrole en dieet geïnduseerde obees (DIO) diere) is in die studie gebruik. Kontrole diere was normale rotkos gevoer, terwyl die DIO diere op 'n dieet van rotkos aangevul met sukrose en kondensmelk geplaas is vir 'n periode van 8 of 16 weke. Helfte van die diere van elke groep is behandel met die GSK-3 inhibitor vir 4 weke (vanaf week 12 tot 16). Na afloop van die voer- en behandelingsperiode is die diere geweeg, doodgemaak en die harte verwyder om dan of onmiddelik gevriesklamp te word, of retrograad geperfuseer te word met Krebs-Hensleit buffer. Ex vivo geperfuseerde harte is dan blootgestel aan 25 minute lae vloei iskemie gevolg deur 30 minute herperfusie. Biometriese (liggaamsgewig, intraperitoneale vet, ventrikulêre gewig en tibia lengte) en biochemiese (vastende bloedglukose en -insulien vlakke) parameters is telkens bepaal. Western klad tegnieke is gebruik om die uitdrukking en fosforilering van GSK-3, PKB/Akt, IRS-1, IRS-2, SERCA-2a en PLM te bepaal. Ca2+-ATPase aktiwiteit is spektrofotometries bepaal. Resultate: Na beide 8 en 16 weke was die DIO diere beduidend swaarder as die kontrole diere. Hierdie gewigstoename was geassosieer met meer intraperitoneale vet in die DIO diere. Verder, in die DIO diere was IRS-1 afgereguleer na 8 weke, terwyl beide IRS-1 en IRS-2 asook PKB/Akt afgereguleer was na 16 weke. GSK-3 uitdrukking het 'n neiging getoon om toe te neem na beide 8 en 16 weke in die DIO diere, terwyl SERCA-2a beduidend afgereguleer was reeds vanaf 8 weke, geassosieer met laer Ca2+-ATPase aktiwiteit. PLM uitdrukking het toegeneem en die fosforilering daarvan was verlaag. Op 16 weke was die basale harttempo (225 vs 275 in die kontrole groep, P<0.0001, n=6) en tempo druk produk (21000 vs 30000 in die kontrole groep, P=0.019, n=6) betekenisvol laer in die DIO diere. Funksionele herstel het onveranderd gebly, alhoewel die tyd tot iskemiese kontraktuur toegeneem het in die DIO groep (kontrole: 11.6±0.4 min vs DIO: 16.2±0.5 min, P<0.01, n=6). Toediening van die inhibitor het geen effek op totale GSK-3 uitdrukking gehad nie. Fosforilering van GSK-3 was egter wel beduidend verhoog in die behandelde kontrole diere, terwyl daar geen verskille in die DIO groep was nie. Die fosforilering van GSK-3 het wel geneig na 'n toename in die behandelde DIO diere. Die GSK-3 inhibitor het kontrasterende effekte op hipertrofie gehad: dit het dit omgekeer in die DIO groep, maar veroorsaak in die kontrole diere. Daarmee saam het die inhibitor die uitdrukking van IRS-2 in beide DIO en kontrole diere gestimuleer, maar geen effek op IRS-1 en SERCA-2a uitdrukking en aktiwiteit gehad nie. GSK-3 inhibisie het wel PKB/Akt en PLM fosforilering in die DIO diere verhoog. Gevolgtrekking: Hierdie bevindinge toon dat 'n hoë kalorie dieet, tesame met 'n wanbalans tussen energie inname en verbruiking, lei tot die ontwikkeling van obesiteit en insulien weerstand in manlike Wistar rotte. Die studie het ook getoon dat GSK-3 en sy substraat proteïene wel gedisreguleer is in obesiteit en insulien weerstandigheid. Die verlaagde basale uitdrukking van SERCA-2a mag dalk 'n negatiewe impak hê op kardiale funksie. Behandeling van die diere met 'n GSK-3 inhibitor het getoon dat GSK-3 moontlik nie verantwoordelik is vir die basislyn veranderinge nie. Die afname in IRS-1 en SERCA-2a uitdrukking kan moontlik toegeskryf word aan ander meganismes buiten die effekte van GSK-3. Hierdie studie toon wel dat GSK-3 moontlik 'n rol speel in die regulering van die uitdrukking van IRS-2, maar nie IRS-1 nie. Verhoogde PKB/Akt fosforilering mag dalk bydra tot die inhibisie van GSK-3. Daarmee saam blyk dit dat GSK-3 inhibisie hipertrofie kan omkeer in DIO diere, om dan sodoende op te tree as 'n negatiewe reguleerder van hipertrofie, maar in normale kontrole diere, hipertrofie in die hand werk. / South African Medical Research Council / University of Stellenbosch, Dept. of medical Physiology

Thesis (MScMedSc)--University of Stellenbosch, 2011. / Please refer to full text to view abstract.