Thyroxine was observed to stimulate the incorporation of radio labeled amino acids into protein of cell-free Liver systems from treated normal and hypothyroid rats. However, the in vitro addition of the hormone only had a stimulatory effect, though quite erratic in magnitude, on the normal system. This difference in response has not been explained. The hypothyroid rat was also characterized by lowered liver ribonucleic acid levels. It WEB found that thyroxine pretreatment resulted in increased ribonucleic acid levels only in the hypothyroid rat with the greater increase occurring in microsomal ribonucleic acid. No change was observed in the ribonucleic acid base ratios of the hypothyroid rat when compared to those of the normal. However, thyroxine pretreatment cf the hypothyroid rat did alter the rate of incorporation of radio phosphorus into the various nucleotides, although there was little difference in the total amount of incorporated label. / Ph. D.

This study was undertaken to determine whether immunoreactive atrial natriuretic peptide (irANP) concentrations in plasma and atrial tissue are altered in experimental diabetes mellitus (DM), and to compare the response of the DM and normal groups to exogenous administration of ANP. OM was induced by intraperitoneal injection of 45 mg/kg streptozotocin in male Sprague-Dawley rats. After three weeks of established OM (glucosuria and blood glucose> 250 mg/dl), plasma irANP levels were 149.6 ± 19.4 pg/ml in the OM group (n = 18) and 86.3 + 12.9 pg/ml in the normal group en = 12, P <0.01). Atrial tissue irANP levels were significantly lower in the OM group (38.1 ± 7.8 ng/mg, n = 7) than in the normal group (60.1 ± 1.3 ng/mg, n = 4, P < 0.02). In response to intravenous infusion of ANP (2.5 ug/kg prime, followed by 0.1 ug/kg/min for 30 minutes), urine flow rate and urine sodium and potassium excretion rates increased significantly in the normal group (n = 6, P < 0.05), while no significant responses were found in the OM group (n = 6). It is concluded that plasma levels of ANP are significantly elevated in streptozotocin-induced diabetes in rats, and that atrial tissue stores are significantly depleted in this diabetic model. In addition, the renal response to exogenously administered ANP appears to be diminished in streptozotocin-induced OM. / Master of Science

Chiu Chi Pang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 121-134). / Abstracts in English and Chinese. / DECLARATION --- p.i / ACKNOWLEDGEMENTS --- p.ii / ABBREVIATIONS --- p.iii / ABSTRACT --- p.vi / 摘要 --- p.viii / Chapter CHAPTER 1: --- GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- Cholesterol --- p.1 / Chapter 1.1.1 --- History of cholesterol --- p.1 / Chapter 1.1.2 --- Structure of cholesterol --- p.1 / Chapter 1.1.3 --- Biological function of cholesterol --- p.3 / Chapter 1.1.4 --- Sources of cholesterol in our body --- p.3 / Chapter 1.2 --- Lipid hypothesis --- p.4 / Chapter 1.2.1 --- Relationship between dietary cholesterol and plasma cholesterol --- p.4 / Chapter 1.2.2 --- "Hypercholesterolemia , atherosclerosis and coronary heart disease (CHD)" --- p.4 / Chapter 1.2.3 --- Individual variation --- p.5 / Chapter 1.3 --- Cholesterol homeostasis --- p.7 / Chapter 1.3.1 --- SREBPs up-regulates the expression of LDL-receptor and HMG-CoA reductase --- p.7 / Chapter 1.3.2 --- HMG-CoA reductase as the rate-limiting enzyme in cholesterol synthesis --- p.11 / Chapter 1.3.3 --- LDL-receptor as the major protein removing plasma cholesterol …… --- p.12 / Chapter 1.3.4 --- LXR-α as an activator of CYP7A1 --- p.14 / Chapter 1.3.5 --- CYP7A1 controls the classical pathway for the elimination of hepatic cholesterol --- p.16 / Chapter 1.3.6 --- Bile acids as the metabolites of CYP7A1 --- p.17 / Chapter 1.4 --- Previous works in our laboratory --- p.20 / Chapter 1.5 --- Objective of this project --- p.22 / Chapter CHAPTER 2: --- INCREASED EXPRESSION OF LDL-RECEPTOR IS RESPONSIBLE FOR THE HYPO-RESPONSIVENESS OF RATS TO DIETARY CHOLESTEROL --- p.23 / Chapter 2.1 --- Introduction --- p.23 / Chapter 2.2 --- Objective --- p.24 / Chapter 2.3 --- Methods and materials --- p.25 / Chapter 2.3.1 --- Animals --- p.25 / Chapter 2.3.2 --- Diets --- p.25 / Chapter 2.3.3 --- Determination of serum cholesterol --- p.26 / Chapter 2.3.4 --- Western blot --- p.26 / Chapter 2.3.5 --- Probe production for LDL-receptor --- p.27 / Chapter 2.3.5.1 --- Extraction of total RNA --- p.27 / Chapter 2.3.5.2 --- Reverse-transcription reaction of total RNA --- p.28 / Chapter 2.3.5.3 --- Polymerase chain reaction (PCR) of LDL- receptor fragment from cDNA template --- p.28 / Chapter 2.3.5.4 --- Separation and purification of PCR products --- p.29 / Chapter 2.3.5.5 --- Polishing of purified PCR products --- p.29 / Chapter 2.3.5.6 --- Ligation of PCR products and pPCR-script Amp SK(+) cloning vector --- p.30 / Chapter 2.3.5.7 --- Transformation --- p.30 / Chapter 2.3.5.8 --- Preparing glycerol stocks containing the bacterial clones --- p.31 / Chapter 2.3.5.9 --- Plasmid DNA preparation --- p.31 / Chapter 2.3.5.10 --- Clones confirmation by restriction enzyme digestion --- p.32 / Chapter 2.3.5.11 --- Clones confirmation by automatic sequencing --- p.32 / Chapter 2.3.5.12 --- Linearization of the plasmid DNA --- p.33 / Chapter 2.3.5.13 --- DIG-labeling of RNA probe --- p.35 / Chapter 2.3.5.14 --- Testing of DIG-labeled probe --- p.35 / Chapter 2.3.6 --- Probe production for HMG-CoA reductase --- p.36 / Chapter 2.3.7 --- Probe production for GAPDH --- p.37 / Chapter 2.3.8 --- Northern blot --- p.38 / Chapter 2.3.9 --- Determination of hepatic cholesterol --- p.39 / Chapter 2.3.10 --- Statistics --- p.40 / Chapter 2.4 --- Results --- p.42 / Chapter 2.4.1 --- Growth and food intake --- p.42 / Chapter 2.4.2 --- Effect of cholesterol supplements on serum cholesterol --- p.42 / Chapter 2.4.3 --- Effect of cholesterol supplements on liver cholesterol content --- p.45 / Chapter 2.4.4 --- "Stimulatory effect of high cholesterol diet on nSREBP-2, LDL-receptor and HMG-CoA reductase in rats" --- p.45 / Chapter 2.4.5 --- "Effect of high cholesterol diet on nSREBP-2, LDL-receptor and HMG-CoA reductase in hamsters" --- p.49 / Chapter 2.4.6 --- The regulation of LDL-receptor and HMG-CoA reductase existed at transcriptional level --- p.54 / Chapter 2.5 --- Discussion --- p.59 / Chapter CHAPTER 3: --- RATS ARE HYPO-RESPONSIVE TO DIETARY CHOLESTEROL DUE TO EFFICIENT ELIMINATION OF CHOLESTEROL --- p.67 / Chapter 3.1 --- Introduction --- p.67 / Chapter 3.2 --- Objective --- p.69 / Chapter 3.3 --- Methods and materials --- p.70 / Chapter 3.3.1 --- Animals and diets --- p.70 / Chapter 3.3.2 --- Western blot --- p.70 / Chapter 3.3.3 --- Probe production for CYP7A1 and LXR-α --- p.71 / Chapter 3.3.4 --- Northern blot --- p.71 / Chapter 3.3.5 --- Determination of fecal neutral and acidic sterols --- p.71 / Chapter 3.3.5.1 --- Separation of neutral and acidic sterols --- p.71 / Chapter 3.3.5.2 --- Neutral sterols analysis --- p.72 / Chapter 3.3.5.3 --- Acidic sterols analysis --- p.72 / Chapter 3.3.5.4 --- GLC analysis of neutral and acidic sterols --- p.73 / Chapter 3.3.6 --- Statistics --- p.73 / Chapter 3.4 --- Results --- p.76 / Chapter 3.4.1 --- Effect of cholesterol supplements on fecal total neutral sterols --- p.76 / Chapter 3.4.2 --- Effect of cholesterol supplements on fecal total bile acids --- p.76 / Chapter 3.4.3 --- CYP7A1 protein on rats showed a concentration-dependent increase with response to dietary cholesterol while hamsters did not --- p.79 / Chapter 3.4.4 --- The regulation of CYP7A1 was at transcriptional level --- p.79 / Chapter 3.4.5 --- LXR-α demonstrated a parallel changes in its expression at both translational and transcriptional level --- p.84 / Chapter 3.5 --- Discussion --- p.88 / Chapter CHAPTER 4: --- MECHANISM FOR INDIVIDUAL VARIATION OF SERUM CHOLESTEROL LEVEL IN RATS AND HAMSTERS FED A HIGH CHOLESTEROL DIET --- p.94 / Chapter 4.1 --- Introduction --- p.94 / Chapter 4.2 --- Objective --- p.96 / Chapter 4.3 --- Methods and materials --- p.97 / Chapter 4.3.1 --- Diet and animals --- p.97 / Chapter 4.3.2 --- Western blot --- p.97 / Chapter 4.3.3 --- Statistics --- p.97 / Chapter 4.4 --- Results --- p.99 / Chapter 4.4.1 --- Growth and food intake --- p.99 / Chapter 4.4.2 --- Change of serum cholesterol --- p.99 / Chapter 4.4.3 --- Correlation between various protein expression and serum cholesterol --- p.99 / Chapter 4.4.3.1 --- Correlation between LDL-receptor and serum total cholesterol in rats --- p.99 / Chapter 4.4.3.2 --- Correlation between CYP7A1 and serum total cholesterolin rats --- p.99 / Chapter 4.4.3.3 --- Correlation between nSREBP-2 and serum total cholesterolin rats --- p.105 / Chapter 4.4.3.4 --- Correlation between LXR-a and serum total cholesterol in rats --- p.105 / Chapter 4.4.3.5 --- Correlation between HMG-CoA reductase and serum total cholesterol in rats --- p.105 / Chapter 4.4.3.6 --- Correlation between LDL-receptor and serum total cholesterol in hamsters --- p.105 / Chapter 4.4.3.7 --- Correlation between CYP7A1 and serum total cholesterolin hamsters --- p.109 / Chapter 4.4.3.8 --- Correlation between nSREBP-2 and serum total cholesterolin hamsters --- p.109 / Chapter 4.4.3.9 --- Correlation between HMG-CoA reductase and serum total cholesterol in hamsters --- p.109 / Chapter 4.5 --- Discussion --- p.114 / Chapter CHAPTER 5: --- CONCLUSION --- p.117 / REFERENCES --- p.121

The neurochemical effects of partial D2-like agonists (i.e., terguride) to alter striatal DOPA accumulation under high and low dopaminergic tone was examined in preweanling rats. The results indicate that terguride has agonist-like (quinpirole-like) effects under a low dopaminergic tone and antagonist-like (haloperidol-like) effects under a high dopaminergic tone during the preweanling period.

This thesis project will investigate the effects of fasting on the serum levels of two key regulatory hormones, insulin and thyroid hormone (T3) and the effects of these hormones on the trafficking of Glut4 on soleus muscle.

The experiment tested the hypothesis that 192 IgG-saporin lesions of the nucleus basalis magnocellularis (NBM) in rats would impair performance in a biconditional visual discrimination task, which requires configural association learning. Experiment used 22 male Long-Evan rats (Harlan Sprague-Dawley). Behavioral testing was conducted in two identical T-mazes. Rats were randomly assigned to either a bilateral 192 IgG-saporin lesion group (n = 10) or to a control group (n = 12). Results support the hypothesis that NBM is critically involved in configural but not simple association learning and suggest that NBM may be involved more generally in cognitive flexibility.

Call number: LD2668 .T4 1985 E44 / Master of Science

Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Background: Athletes use androgenic anabolic steroids (AAS) to enhance their physical performance. The abuse of AAS is however associated with a host of side effects including sudden death due to cardiac arrest. The use of AAS leads to myocardial hypertrophy, which possibly makes the heart more prone to ischaemia/reperfusion injury, since it often develops in the absence of proper vasculature development. Chronic AAS use also disrupts myocardial p-adrenoreceptor function and possibly cAMP, signalling in the heart. Drugs increasing cAMP and decreasing cGMP levels in the ischaemic myocardium exacerbate myocardial ischaemia/reperfusion injury. We also know that AAS causes coronary artery disease secondary to the deleterious alteration of lipid profiles by increasing the LOL cholesterol and decreasing the HOLcholesterol levels. AAS treatment may increase systemic TNFa levels by stimulating lymphocyte TNFa secretion that has been implicated in the depression of myocardial function, myocardial hypertrophy and the worsening of ischaemia/reperfsuion injury. Aims: To determine whether chronic AAS treatment in trained and untrained rats influences: 1) heart function and susceptibility to ischaemia/reperfusion injury, 2) myocardial cyclic nucleotide levels (cAMP and cGMP) and 3) myocardial TNFa levels. Material and methods: Male Sprague-Dawley rats (n=100) were divided into 4 groups: sedentary vehicle (placebo) treated group, sedentary AAS treated group, exercise vehicle (placebo) treated group, and exercise AAS treated group. Steroid treated animals received an intramuscular injection of nandrolone laureate (0.375 mg/kg) once a week, for six weeks. Training consisted of swim sessions 6 days a week for 6 weeks. Swim time was incrementally increased up to a maximum of 50 minutes a day. For biometric parameters heart weight and body weight were documented. Hearts were mounted on a l.anqendorff perfusion apparatus and left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF) was monitored. The hearts were subjected to a period of 20 minutes of global ischaemia, followed by 30 minutes of reperfusion. Functional parameters was again monitored and documented. For biochemical analysis, blood was collected for the determination of serum lipid levels and myocardial tissue samples were collected before, during and after ischaemia for the determination of myocardial TNFa, cGMP and cAMP levels and p38 activity. Conclusions: Results obtained would suggest that AAS exacerbate exercise induced myocardial hypertrophy. It also prevents the exercise-induced improvement in cardiac function. AAS use reduces reperfusion function in treated hearts, which may suggest that AAS exacerbates ischaemie and reperfusion injury. Furthermore it was seen that AAS elevates basal (preischaemie) cyclic nucleotide levels and basal (pre-ischaemic) as well as reperfusion TNFa levels. This may also contribute to the exacerbation of ischaemic and reperfusion injury. / AFRIKAANSE OPSOMMING: Agtergrond: Androgeniese anaboliese steroïede (AAS) word dikwels deur atlete gebruik om sportprestasie te verbeter. Die misbruik van AAS het egter talle newe effekte, insluitende skielike dood wat gewoonlik toegeskryf word aan hartaanvalle. Die gebruik van AAS lei onder andere tot miokardiale hipertrofie wat opsigself, as gevolg van ontoereikende vaskulêre ontwikkeling tydens die ontwikkeling van hipertrofie, die hart nog meer vatbaar vir isgemie/herperfusie skade maak. Kroniese AAS toediening versteur miokardiale beta-adtenoresepter funksie en moontlik die tweede boodskapper, sAMP, seintransduksie in die hart. Ons weet ook dat AAS koronêre hartvatsiektes veroorsaak. Laasgenoemde is sekondêr tot die nadelige lipiedprofiel verandering, wat 'n verhoging in LDL-C en 'n verlaging in HDL-C insluit. Middels wat miokardiale sAMP vlakke verhoog en sGMP vlakke in die isgemiese miokardium verlaag, vererger miokardiale isgemie/herperfusie skade. AAS behandeling kan moontlik ook sistemiese TNFa vlakke verhoog deur limfosiet TNFa sekresie te stimuleer. Die verhoogde TNFa vlakke word verbind aan die onderdrukking van miokardiale funksie, miokardiale hipertrofie en die verergering van isgemie/herperfusie skade. Doelwitte: Die doelwitte van die studie was om te bepaal of kroniese AAS toediening in geoefende en ongeoefende rotte 1) hartfunksie en die hart se vatbaarheid vir isgemie/herperfusie skade beïnvloed, 2) miokardiale sikliese nukleotiedvlakke (sAMP en sGMP) beïnvloed en 3) miokardiale TNFa-vlakke beïnvloed. Materiale en metodes: Manlike Sprague-Dawley rotte (n=100) is gebruik en in 4 groepe verdeel: 'n ongeoefende placebo groep (kontrole); 'n ongeoefende steroïedbehandelde groep; 'n geoefende placebo groep (kontrole) en 'n geoefende steroïedbehandelde groep. Steroïed behandelde diere het 'n intramuskulêre nandroloon lauraat inspuiting (0.375 mg/kg) een keer per week vir ses weke ontvang. Die oefenprogram het bestaan uit ses swemsessies 'n week vir ses weke. Die swemtyd is geleidelik weekliks verhoog tot by 'n maksimum tyd 50 min. Die waterbadtemperatuur is tussen 30 - 32 oe gehandhaaf. Vir biometriese parameters is hartgewig en liggaamsgewig genoteer. Harte is op 'n Langendorff perfusie apparaat gemonteer en linker ventrikulêre ontwikkelde druk (LVOD), koronêre vloei (KV) en harttempo (HT) is genoteer. Die harte is vervolgens blootgestel aan 20 minute van globale isgemie gevolg deur 'n 30 minute herperfusieperiode. LVOD, KV en HT is weer eens noteer. Vir biochemiese doeleindes is bloed voor perfusie versamelom serum lipied vlakke te bepaal. Miokardiale weefsel is versamel voor, tydens en na isgemie vir die bepaling van TNFa, cGMP en AMP vlakke asook p38 aktiwiteit. Gevolgtrekkings: Na aanleiding van resultate verkry wil dit voorkom asof die gebruik van steroïde oefeningsgeïnduseerde miokardiale hipertrofie vererger. Dit verhoed ook oefeningsgeïnduseerde verbetering in miokardiale funksie. AAS lei tot 'n verlaagde herperfusiefunksie in behandelde harte, wat dalk mag dui op MS verergering van isgemie en herperfusie skade. Verder was daar ook waargeneem dat MS basale (pre-isgemiese) sikliese nukleotiedvlakke en basale TNFa-vlakke sowel as herperfusie TNFa vlakke verhoog. Die verhoging in TNF-a vlakke mag dus moontlik ook bydra tot die verergering van isgemie- en herperfusieskade.

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy