xxiii, 222 leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1992

[Formulae and special characters can only be approximated here. Please see the pdf version of the abstract for an accurate reproduction.] Iron is vital for almost all living organisms by participating in a wide variety of metabolic processes, including oxygen transport, DNA synthesis, and electron transport. However, iron concentrations in body tissues must be tightly regulated because excessive iron leads to tissue damage, as a result of formation of free radicals. In mammals since no controlled means of eliminating unwanted iron has evolved, body iron balance is maintained by alterations in dietary iron intake. This occurs in the duodenum where most dietary iron is absorbed. Absorption involves at least two steps, uptake of iron from the intestinal lumen and then its transport into the body, processes that occur at the apical and basal membranes of enterocytes, respectively. In chapter one of this thesis the background information relevant to iron absorption is described. Despite numerous studies, the role of these proteins in iron absorption remains unclear, partly because many studies have reported them in non-enterocyte cell lines where the expression of the proteins involved in iron absorption is unlikely and therefore the physiological significance of the findings uncertain. Therefore, the study of iron absorption would value from additional cell lines of intestinal origin being used, preferably derived from a species used to comprehensively study this process in vivo, namely the rat. Validation of such a model would enable comparisons to be made from a molecular level to its relevance in the whole organism. In chapter 3 of this thesis, the rat intestinal cell line 6 (IEC-6) was examined as a model of intestinal iron transport. IEC-6 cells expressed many of the proteins involved in iron absorption, but not the ferrireductase Dcytb, sucrase or αvβ3 integrin. In addition, in IEC-6 cells the expression of the apical transporter divalent metal transporter 1 (DMT1), the iron storage protein ferritin, the uptake of Fe(II) and Fe(III) were regulated by cellular iron stores as is seen in vivo. This suggests that IEC-6 cells are of a lower villus enterocyte phenotype. Presented in chapter 4 is the study of the uptake of iron from Fe(II):ascorbate and Fe(III):citrate by IEC-6 cells in the presence of a blocking antibody to the putative basolateral transporter ferroportin1 and of colchicine and vinblastine, different pHs, and over-expression of DMT1. It was shown that optimal Fe(II) uptake required a low extracellular pH and was dependent on DMT1. Uptake of Fe(III) functioned optimally at a neutral pH, did not require surface ferrireduction, and was increased during over-expression of DMT1. These observations suggest that intravesicular ferrireduction takes place before transport of Fe(II) to the cytoplasm by DMT1. This pathway was not blocked by a functional antibody against αvβ3 integrin but was inhibited by competition with unlabeled iron citrate or citrate alone. Surprisingly, a functional antibody against ferroportin1 had no effect on efflux but significantly reduced (p<0.05) uptake of Fe(II) by 40-50% and Fe(III) by 90%, indicating two separate pathways for the uptake of iron from Fe(II)-ascorbate and from Fe(III)-citrate in IEC-6 cells. Presented in chapter 5 is the development and validation of a technique for the removal of freshly isolated enterocytes from the rat duodenum and their use to study iron transport processes that enabled comparisons to be made between these cells, IEC-6 cells and the human enterocyte cell line Caco-2 cells. In chapter 6 a blocking antibody to ferroportin1 was shown to inhibit uptake of Fe(II) but not release of iron in freshly isolated duodenal enterocytes from rats and Caco-2 cells supporting the findings obtained with IEC-6 cells described in chapter 4. Fe(II) uptake was reduced only when the antibody was in contact with the apical membrane indicating its expression at the microvillus membrane. Confirming this, ferroportin1 was shown along the microvillus membrane of Caco-2 cells, in enriched microvillus membrane preparations and in enterocytes of duodenum tissue of rats where it co-localised with lactase. The significant findings to emerge from this thesis are that the IEC-6 cell is a valid model to study iron absorption producing results consistent with those found in freshly isolated enterocytes and in human enterocyte-like cells. In particular, ferroportin1 functions in the uptake of iron at the apical membrane possibly by modulating surface binding of Fe(II) to DMT1 or the activity of DMT1. In addition to this in Fe(II) uptake from Fe(III) ferroportin1 may also affect the number of Fe(III): citrate binding sites. Preliminary studies further characterizing the function of ferroportin1 at the apical membrane and at intracellular sites of IEC-6 cells along with integration of these data are discussed in chapter 7.

The two neuron types that initially degenerate with Alzheimer's Disease are the cholinergic projections from the septum to the hippocampus and from the substantia innominata to the cortex, and the somatostatinergic neurons in the hippocampus and cortex. The functional relationship between these two types of neurons was investigated using folic acid, a neuro-excitant, and cysteamine, a somatostatin depleter. Folic acid causes a neuron to fire at a much higher rate than normal (Spector, 1971). Folic acid was injected into either the septum or the substantia innominata, and the long-term effect of the resulting acute hyperactivity of the cholinergic neurons on somatostatin neurons was measured as somatostatin-like immunoreactivity in the hippocampus and cortex. Glutamic acid decarboxylase activity, a marker for gamma-amino butyric acid (GABA) neurons, was also measured because it has been shown to decrease in the cortex after injection of folic acid into the substantia innominata. The administration of folic acid to the cholinergic neurons did not have a significant long-term effect on somatostatin-like immunoreactivity nor glutamic acid decarboxylase activity; therefore, a hyperactivity of the cholinergic neurons did not result in degeneration of GABAergic nor somatostatinergic neurons. Cysteamine causes a short-term depletion of somatostatin. Cysteamine was injected subcutaneously and the effect of an acute decrease of brain somatostatin on the cholinergic neurons was studied by measuring high affinity choline uptake, an indicator of cholinergic activity. Administration of cysteamine had no measured effect on high affinity choline uptake in the hippocampus or frontal cortex; therefore, a depletion of somatostatin did not effect cholinergic activity. The assay for high affinity choline uptake was tested by injection of pentobarbital, a drug known to decrease high affinity choline uptake. We detected a decrease in high affinity choline uptake after pentobarbital administration, indicating that if cysteamine were decreasing high affinity choline uptake, the assay would have detected it. / Master of Science

Climate change predictions suggest that the continent most vulnerable to climate change is Africa. The impacts of potential changes which include increases in air temperatures and rainfall variability are negative with potential species extinctions projected throughout southern Africa. A number of climate models have been applied to examine the consequences of climate change for ranges of South African animal species. One such model frequently predicted range shifts from west to east, which is realistic considering the marked aridity gradient in an east-west direction across the country, but the authors suggested that these shifts may not be as marked if species are able to use physiological and behavioural methods to adapt to an increase in aridity. Information on the degree to which behavioural and physiological flexibility affect species range in southern Africa is scant which is surprising given its importance with regard to climate change. Thallomys nigricauda occurs along an east-west aridity gradient in southern Africa, inhabiting mesic, semi-xeric and xeric regions. One would expect phenotypic flexibility in physiological and behavioural traits in response to the diverse environmental conditions to be related to the success and range of the species. The wide distribution and arboreal habits, suggesting that T. nigricauda is exposed to greater extremes of temperature than fossorial rodents, makes T. nigricauda an ideal species to test this assumption. Hence I expected that T. nigricauda would exhibit variation in physiological and behavioural traits measured along an aridity gradient. This has important implications in predicting the survival of small mammal species in the light of climate change in southern Africa. Thallomys nigricauda were live-trapped in winter 2006 and 2007 and summer 2007 using Elliot traps in three sites: mesic site Weenen Game Reserve (KwaZuluiv Natal Province, South Africa); semi-xeric site Haina Game Farm (Botswana) on the northern boundary of the Central Kalahari Desert and xeric site Molopo Nature Reserve (southern Kalahari savannah, North-West Province, South Africa). I studied the home-range size of T. nigricauda by radiotracking 12 males and 16 females in winter 2006, 2007 and summer 2007. Home ranges were estimated using 100% and 95% minimum convex polygons and 95% and 50% fixed kernels. Home ranges varied widely, from 166 to 80199m2 for males and from 46 to 8810m2 for females. Males had larger home ranges than females, which supports a promiscuous mating system reported for the species. Although range size was reduced in both sexes in winter, this was not significant. I found no significant difference in home range size along the aridity gradient. It is suggested that a combination of precipitation, habitat productivity and breeding system influences the size of home range of the species, and that this species displays phenotypic flexibility in terms of its behavioural responses to these factors. I measured the urine concentrating ability (UCA), as indicated by urine osmolality and relative medullary thickness (RMT), and water turnover rate (WTR) of T. nigricauda. There was no significant difference in RMT between sites or sex and no difference in osmolalities when site, season and sex were taken into account. In addition, specific WTR was not significantly influenced by season. Lack of significant differences could be the result of the high degree of individual variation in the traits measured, an indication of the flexibility in UCA and WTR. However, higher urine osmolality and lower WTR’s were recorded in the dry winter months. I quantified the thermal environment perceived by a small, arboreal, mammalian endotherm using a number of methods at three study sites in winter and summer. Our area of interest was how well these methods accurately portrayed the actual temperatures that small mammals are exposed to. Temperature differences between the methods were largest during the midday, when temperatures were highest. All methods recorded a greater range of temperatures during photophase than during scotophase. Black-bulb and model temperatures produced more accurate, rapid measurements when compared to measurements produced by direct temperature recording devices, particularly during photophase, when solar radiation is the major influence of heating. Other methods lagged behind black-bulb measurements. Although the mean temperatures of some of the methods were significantly different, there was a high degree of correlation between all methods, even after randomization and generation of 25% and 10% subsamples. Computed thermal indices and blackbulb temperatures produced similar thermal profiles. In studies requiring accurate time series measurements, it is suggested that black-bulb or copper models be employed rather than direct temperature recording devices. Simpler measurement devices would suffice for studies requiring an estimate of the temperature variation and trends in the microclimate of small mammalian endotherms, particularly arboreal or cavity dwelling species. In the wild, across an aridity gradient, I measured abdominal body temperarture (Tb) of T. nigricauda using implanted iButtons®. All but three T. nigricauda displayed significant 24 h Tb rhythmicity. The Tb range for free-living T. nigricauda was 32.33-40.63 oC (n = 13) and 32.69-40.15 oC (n = 17) in winter and summer respectively. Although there was variation in Tb profiles, T. nigricauda generally displayed a bimodal distribution of Tb, with high and low Tb values during scotophase and photopase respectively. Body temperature range was significantly greater in winter, when T. nigricauda reduced its minimum Tb. It was shown that the maximum amplitude of circadian rhythms of body temperature was on average 259.6% of expected values. To determine the extent to which the microclimate of T. nigricauda cavities assists in the maintenance of Tb, I measured the temperatures of cavities across the gradient, providing an indication of the degree of buffering provided by refugia. I measured the temperatures of shallow and deep regions of cavities using iButtons® in summer and winter and recorded operative and shade temperatures for comparison. Compared with operative temperature, cavities had stable microclimates, displaying smaller ranges in temperature. Mean minimum and maximum cavity temperatures differed significantly to operative temperature and between seasons, whereas there was no significant difference between shallow and deep measurements in cavities. Differences in the buffering capacities of the cavities between seasons were not significant. To determine whether T. nigricauda alter its length of exposure in response to lower ambient temperatures in winter as a means of maintaining Tb, I measured the activity of T. nigricauda, defined as the proportion of fixes outside the home cavity of the individual. Males spent a greater proportion of the active phase away from their home cavity in summer, and significantly in winter when compared with females, but there were no differences between seasons. It is suggested that T. nigricauda realize energy savings by lowering its Tb during their rest phase during the day, allowing them to maintain nocturnal activity and overall energy balance. Thus, besides the larger male home range, a result of the reproductive pattern, the physiological and behavioural traits of T. nigricauda measured in this study did not differ between aridity sites or seasons. The results of this study, in highlighting the variation in physiological and behavioural responses of subpopulations of T. nigricauda to diverse conditions, suggest that this variation is due to phenotypic flexibility. Understanding the extent and nature of this flexibility is critical to our comprehension of the consequences climate change. By defining the presence and extent of intraspecific variation in physiology and behaviour, this study resolved the necessary first step towards this understanding for the widely distributed T. nigricauda in southern Africa. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.

Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2015. / Diabetes mellitus (DM) has been reported to be one of the greatest global public health threats. Statistics of the fertility status of modern society has linked increased DM to a decrease in fertility rates. Hyperglycaemia is characteristic of DM that results in a disturbance of proteins, lipids and carbohydrate metabolism leading to an increase production of reactive oxygen species (ROS). In the case where ROS overwhelms antioxidant mechanisms, the body goes into state of oxidative stress (OS). OS plays a vital role in the progression of DM which leads to dysfunction and damage of various organs including that of the reproductive system. Os has shown to cause damage to the sperm membraneby oxidation of polyunsaturated fatty acids (PUFA’s) as the sperm membrane are rich in PUFA’s. This damage contributes to reduced sperm motility, concentration, morphological abnormalities and the sperms ability to fuse with the ZP of the oocyte. DM has been observed to cause testicular degeneration by interrupting sertoli cell production and maintenance thus resulting in a disturbance of the normal functioning of the reproductive system. Experimental studies have targeted more natural sources for treating DM and its complications of the reproductive system. Plants and natural dietary substances have shown to have high antioxidant contents that combat DM induced oxidative stress. This study explored the effect the Hypoxis hemerocallidea (H. hemerocallidea) supplementation on testicular and epididymal tissue, sperm motility and reproductive hormones in male wistar rats. The experiment were conducted for 6 weeks and the rats (230-260 grams) were randomly divided into 5 groups (n=12 per group). Diabetes was induced in 3 of the 5 groups. The first group was the normal control group (A), second the diabetic control group (B), third was the diabetic group treated with 800mg/kg H. hemerocallidea (group C), fourth the diabetic group treated with 200mg/kg H. hemerocallidea (group D) and fifth the non-diabetic group supplemented with 800mg/kg H. hemerocallidea (group E). Blood glucose showed a significant increase in the diabetic group when compared to the normal control and treated groups. H. hemerocallidea showed improvement in sperm motility and sperm morphology more at 800mg/kg when compared to diabetic group and diabetic group treated with 200mg/kg. Body, testicular and epipidymal weights of diabetic control were significantly lower when compared to the other groups. Testicular and epididymal Malondialdehyde levels were decreased in normal control, diabetic groups treated with different doses of H. hemerocallidea and the non-diabetic group supplemented with H. hemerocallideaon comparing with the diabetic control group. Antioxidants such as Superoxide dismutase, Catalase and total Glutathione activity was observed to be dosage dependent in certin groups but most showed a significant increase when compared to the diabetic control group. The total antioxidant capacity was measured using Oxygen radical absorbance capacity (ORAC) and Ferric ion reducing antioxidant power (FRAP); increase was observed when normal control group and treated groups were compared to the diabetic group. Testosterone and estradiol levels were also increased when the normal control group and treated groups were compared to the diabetic control group. Based on our findings it can be concluded that H. hemerocallidea supplementation can potentially be used to counteract deleterious effects of DM on the male reproductive system.

Methylenedioxymethamphetamine (MDMA) popularly known as "Ecstasy" continues to gain popularity as a recreational drug that has been shown to increase serotonin and dopamine levels. The present study has demonstrated that repeated exposure to MDMA produces long-term damage to serotonergic and dopaminergic neurons in various regions of the rat brain.

The purpose of this study was to investigate whether a partial D₂-like dopamine agonist (i.e. terguride) would block the induction or expression of cocaine-induced behavioral sensitization in pre-weanling rats. The ability of terguride to induce behavioral sensitization was also examined, as partial D₂-like agonists have agonistic actions in cases of low dopaminergic tone.

A study of low-cost Texas diets to support reproduction, lactation, and iodine needs in animals.

It was hypothesized that 192 IgG-saporin lesions of the basal forebrain cholinergic system (BFCS) would disrupt differential reinforcement of low rate (DRL) learning in an uncued DRL task, but would not impair acquisition and performance in the cued version of the task. Results suggest that BFCS lesions impair vigilance to the external cues despite continued practice in the cued DRL, whereas continuous attention to internally produced cues recovers with extended practice in the uncued DRL.

Graduation date: 1993