Melatonin is a product of the pineal gland and is postulated to play an antigonadotropic role in the reproductive system of mammals. The reproductive system of non-seasonally breeding mammals is believed to be not as responsive to melatonin treatment as that of seasonally breeding mammals. Recently, there has been increasing support from in vivo and in vitro studies, for the hypothesis that melatonin has negative effects on sperm physiology, especially on sperm motility. High and/or low seminal concentrations of melatonin have been associated with abnormalities in human sperm motility and concentration. In this study, I examined the effects of melatonin on the testis, epididymis and sperm physiology, using in vivo and in vitro experiments, in a non-seasonally breeding mammal. Treatment, in vivo, with exogenous melatonin for six weeks did not inhibit testosterone production or spermatogenesis, nor did it affect the mass of the testes and epididymides at dissection, the concentration the morphology of speimatozoa. However, melatonin in vivo had a small, but significant negative effect on sperm motility and sperm motility index. In vitro incubation of spermatozoa Fith melatonin reduced the percentage (%) of forward progressive movement (fpm), increased the % reduction in fpm, reduced the vigor or quality of sperm motility, reduced the sperm motility index, and delayed and/or prolonged the transition of one pattern of sperm motility to the subsequent patterns. Melatonin increased the pH of the culture medium, and the increased pH, and the ethanol utilized as a solvent for melatonin, both negatively affected all the sperm motility parameters that were assessed in my study. The effects of ethanol increased with time, and the effects of pH increased with both time and increasing pH. Melatonin in vitro did not inhibit capacitation and the acrosome reaction, but it delayed the onset and the progression of capacitation and the acrosome reaction. These results suggest that while melatonin did not inhibit spermatogenesis in the Wistar rat, it may influence sperm motility. Therefore, the presence of high concentrations of melatonin in the reproductive fluids may inhibit sperm motility. With further detailed research, melatonin may have a potential use as a contraceptive drug.

Diabetes is a serious condition that affects all the body’s systems including kidneys, heart, eyes and limbs. This alone makes type II diabetes a life threatening disease; an expensive disease and economic burden that many individuals struggle to cope with.The rapid growth type II diabetes in South Africa is associated with the change of life style, and environmental factors brought by westernized way of life living in rural areas. Despite the technical advances in diagnosis and therapy of diabetes many people still use alternative forms of therapy due to the cost, traditional reasons and religion. Some of the people use the conventional medication together with the alternative therapy without informing their doctor and knowing the pathological changes. The aim of the study was to investigate pathological changes in male Wistar rats after co-treatment of type II diabetes with metformin and Sutherlandia frutescens and the possible synergistic and antagonistic effects. The thirty five rats were divided into five groups, seven in each group. There were two control groups and three test groups. Only the first control group was on a low fat diet (normal rat pellets) and second control group and test groups were on a high fat diet which induces obesity, insulin resistance and leads a typical prediabetic state for 12 weeks (Buettner et al., 2006). After 11.5 weeks medication was administered by oral gavaging to the test groups for 4 weeks and control groups received water. Blood was collected for determination of glucose, insulin, lipid profile and the concentrations of the liver enzymes. Pancreas, liver and kidney tissue were removed and used for histology. Urine was collected from the bladder for creatinine analyses. The plant + metformin group co-treatment was better in managing hyperglycemia, liver damages were minimal and also weight control was better when compared to metformin alone.

The anti-estrogenic properties of birdsfoot trefoil (Lotus corniculatus) and yellow pine (Pinus ponderosa) needles were studied. Oral administration of a water-soluble fraction of an acetone extract of birdsfoot trefoil was found to decrease uterine weight of immature female mice. The estrous cycles of rats receiving this extract in the ration, were not disturbed. Specially prepared aqueous fractions of an acetone extract of yellow pine needles decreased the uterine weight of mice. In further experiments, immature female mice were fed 0.040 mcgms. and 0.020 mcgms. diethylstilbestrol (D.E.S.) per gram of feed. When a water-soluble fraction of pine needle extract was administered, it did not affect uterine weight significantly in the 0.040 mcgm. D.E.S. group, but markedly and significantly decreased uterine weight in the 0.020 mcgm. D.E.S. group. This pine needle extract also interrupted the estrous cycles of mature rats, causing a prolonged diestrus. Chromatographic studies indicated that the pine extracts probably do not owe their anti-estrogenic activity to pinosylvin or its mono-methyl ether. / Land and Food Systems, Faculty of / Graduate

With the advent of the atomic age, a great deal of attention has been given to the effects of radiation of various types on the living organism. Some emphasis was placed also on the particular effects damaging radiation has on the central nervous system. Of particular importance was the dis -covery of the high resistance to irradiation exhibited by the central nervous system, and the observation of a latent period after exposure, during which the individual appears normal, followed by deterioration and death. Explan - ations of this unique reaction have caused some controversy and, currently, one of two theories are supported by most workers: (1) vascular damage is the primary cause of brain damage, precedes it, and causes necrosis; (2) direct damage is caused to nerve tissue by radiation and vascular damage is of secondary importance. Both theories have good supporting evidence as will be reported later.

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Rats received access to either distilled water, sucrose, quinine, hydrochloric acid, saline, or the three flavors of sucrose, quinine, and hydrochloric followed one or 28-days later by testing for neophobia and training and testing for conditioned taste aversion to saline. At the one-day interval, preexposures to saline, hydrochloric, or multiple flavors attenuated neophobia to saline while only preexposures to saline attenuated the conditioned aversion to saline. At the 28-day interval, none of the preexposure conditions attenuated neophobia to saline while preexposures to saline attenuated the conditioned aversion to saline. / M.S.

Thesis (MScMedSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Diabetes Mellitus is a metabolic disease characterized by the loss of beta cells from the islets, thereby disrupting islet composition and architecture which are important components that influence islet function. The experimental technique of pancreatic duct ligation (PDL), which is thought to induce the regeneration of beta cells within the adult pancreas, was investigated as a novel treatment strategy for diabetes. This study aimed at investigating the possibility that the PDL model may have the capacity to restore normal islet composition and architecture in diabetic animals, which could make it an effective approach to reverse diabetes. Male Wistar rats (n=55) were divided into three study groups: the normal control (NC) group, the diabetic control (DC) group consisting of five subgroups (day 0, 3, 5, 10 and 30) and the experimental (EX) group consisting of four subgroups (day 3, 5, 10 and 30). The experimental group was exposed to PDL. All pancreata were divided into a P1 portion (proximal to the point of ligature) and P2 portion (distal to the point of ligature) for histological assessment. Animals’ non-fasting blood glucose levels (BGLs) and body weights were monitored. The general morphology of the tissue was studied, while an immunohistochemical (IHC) study was performed to determine insulin, pancreatic polypeptide, glucagon and somatostatin protein expression in the P1 and P2 portions of the pancreas. From the IHC slides hormone fractions, staining intensity and distribution were determined as indication of islet composition and architecture. Despite apparent morphological recovery in the islet 30 days post-PDL, islet composition and architecture remained disrupted. Compared to diabetic animals, the proximal portion of the pancreas in experimental animals had a decreased beta cell fraction and increased delta cell fraction thirty days following PDL. These observed changes in islet composition in the part of the pancreas proximal to the ligature are novel findings. There was no change in the diabetic islet composition in the portion of the pancreas distal to the ligature thirty days following PDL. Furthermore, pancreatic duct ligation did not restore body weight or normoglycemia. We conclude that STZ disrupts islet composition and architecture and this could not be restored using PDL; we therefore suggest that a comparative study using a Type 2 diabetic model, where there is limited damage to pre-existing beta cells, may yield different results. / AFRIKAANSE OPSOMMING: Diabetes Mellitus is ʼn metaboliese siekte wat deur die verlies van beta selle uit die eilande van Langerhans gekarakteriseer word. Hierdie verlies van beta selle ontwrig eiland komposisie en argitektuur, twee belangrike komponente van eiland funksie. Die eksperimentele tegnieke van pankreatiese buisafbinding (in Engels PDL), wat moontlik beta sel regenerasie in die volwasse pankreas kan induseer, is ondersoek as behandelings-strategie vir diabetes. Hierdie studie het ten doel gehad om die moontlikheid te ondersoek dat die PDL model die kapasiteit het om normale eiland komposisie en argitektuur te herstel in diabetiese diere, wat dit ʼn effektiewe benadering vir die omkeer van diabetes kan maak. Manlike Wistar rotte (n=55) was in 3 studie groepe verdeel: die normale kontrole (NC) groep, die diabetiese kontrole (DC) groep wat uit vyf subgroepe bestaan (dag 0, 3, 5, 10 en 30) en die eksperimentele (EX) groep wat uit vier subgroepe bestaan (dag 3, 5, 10 en 30). Die eksperimentele groep is aan PDL blootgestel. Alle pankreata is verdeel in ʼn P1 porsie (proksimaal tot die afbinding) en ʼn P2 porsie (distaal tot die afbinding) vir histologiese assessering. Die diere se nie-vastende bloed glukose vlakke en liggaamsgewig is gemonitor. Die algemene morfologie van die pankreas weefsel is bestudeer, terwyl ’n immunohistochemiese (IHC) studie gedoen is om insulien, pankreatiese polipeptied, glukagon en somatostatien proteïen uitdrukking in die P1 en P2 porsies van die pankreas te bepaal. Vanaf die IHC snitte is hormoon fraksie, kleur intensiteit en verspreiding bepaal as aanduidings van eiland komposisie en argitektuur. Ten spyte van ooglopende morfologiese herstel in die eilande op dag 30 na PDL, het eiland komposisie en argitektuur versteur gebly. In vergelyking met die diabetiese diere, het die proksimale deel van die pankreas van eksperimentele diere verlaagde beta sel fraksie en verhoogde delta sel fraksie getoon dertig dae na PDL. Die waarneming van veranderde komposisie in die deel van die pankreas proksimaal tot die afbinding is nuut. Daar was geen verandering in diabetiese eiland komposisie in die deel van die pankreas distaal tot die afbinding dertig dae na PDL nie. Verder het PDL nie liggaamsgewig of bloedsuiker genormaliseer nie. Ons gevolgtrekking is dat STZ eiland komposisie en argitektuur ontwrig en dat dit nie met PDL herstel kon word nie; daarom stel ons ʼn vergelykende studie in ʼn tipe 2 diabetes model voor, waar die skade aan reeds bestaande beta selle beperk is, wat ander resultate mag lewer.

Thesis (PhD)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: A high fat diet (HFD) reduces beta-cell mass, impairs glucose signalling and is involved in the development of Type 2 diabetes. Malnutrition during gestation is hypothesized to irreversibly damage beta-cell development. The transcription factors Pdx-1 and Pax 4 are involved in islet cell development. Pdx-1 is reported to regulate expression of GLUT-2, glucokinase (GK) and the insulin gene. Aims The aim of this study is to investigate, in the neonatal and weanling rat, the effect of exposure to a HFD in utero and/or lactation on weight, glucose and insulin concentrations, islet cell development, pancreatic transcription factors and glucose sensing genes. Methods Neonatal and weanling rats were exposed to a maternal HFD for defined periods of gestation and/or lactation. After termination, pups were weighed and glucose and insulin concentrations determined. mRNA expression of Pdx-1, Pax 4, GLUT-2 and GK was quantified by LightCycler PCR. Pancreatic sections were immunostained for insulin and glucagon (islet cell development), and for Pdx-1, GLUT-2 and GK (beta-cell function) followed by image analysis. Results: Exposure to an in utero HFD throughout gestation resulted in hyperglycaemic pups with reduced beta-cell volume and number, Pdx-1 and GK immunoreactivity. In contrast the alpha-cell volume, number and size were augmented in neonates exposed to a HFD throughout gestation. Most weanlings were hyperglycaemic and hypoinsulinaemic. In some weanlings, reduced beta-cell number and beta- and alpha-cell size was observed. Pdx-1 mRNA was overexpressed in weanlings exposed to a maternal HFD for the final week of gestation or throughout both gestation and lactation, but reduced in those only exposed throughout lactation. Pax 4 mRNA was reduced in weanlings exposed to a maternal HFD for the first or final week of gestation, throughout gestation or throughout lactation. In most of the weanlings, GLUT-2 mRNA expression was reduced whereas immunoreactivity for GLUT-2 was increased. Both GK mRNA expression and immunoreactivity were reduced in most of the weanlings. Conclusions • Exposure to an in utero HFD throughout gestation induced hyperglycaemia in neonates. The reduced Pdx-1 expression appears to play a role in the compromised beta-cell development, and concomitant with the reduced GK levels, contributes to the hyperglycaemia in these neonates and may make them susceptible to beta-cell failure. • In most weanlings exposed to a HFD in utero and/or during lactation the hyperglycaemia and hypoinsulinaemia suggest compromised beta-cell function. The GK mRNA expression and immunoreactivity were reduced thereby impairing glycolysis which would result in reduced insulin secretion contributing to the hyperglycaemia. Furthermore, beta-cell development is adversely affected by the HFD in some weanlings. This would contribute to reduced beta-cell function and may eventually result in beta-cell failure. GLUT-2 immunoreactivity was increased in some, suggesting a compensatory adaptative mechanism to restore glucose homeostasis. • A maternal HFD has adverse effects both in neonates and weanlings on beta-cell development, transcription factor and glucose sensing gene expression and induced hyperglycaemia and hypoinsulinaemia in some of the offspring. Ways to ameliorate the HFD-induced attenuation of key beta-cell genes to ensure normal beta-cell function are important for future research in Type 2 diabetes. / AFRIKAANSE OPSOMMING: ‘n Hoe vet diet (HVD) verminder beta-sel masse, glukose signale en speel ‘n rol in Tipe 2 diabetes. Die hipothese is dat wanvoeding gedurende swangerskap lei tot onomkeerbare betasel beskadiging. Die transkripsiefaktore Pdx-1 en Pax 4 speel rolle in eilandselontwikkeling. Daar is bewyse dat Pdx-1 die uitdrukking van die GLUT-2, glucokinase (GK) en insulin gene reguleer. Doelstelling: Die doel van hierdie studie is om, in die pasgebore en gespeende rot, die effek van ’n HVD in utero en/of laktasie op gewig, glukose en insulin konsentrasies, eilandselontwikkeling, pankreatiese transksripsiefaktore en op glukosewaarnemingsgene te ondersoek. Metodes: Pasgebore en gespeende rotte is vir bepaalde periodes van gestasie en/of laktasie blootgestel aan ’n HVD van die moeder. Na terminase, is kleinjies geweeg en die glukose- en insulienkinsentrasies bepaal. mRNA uitdrukking van Pdx-1, Pax 4, GLUT-2 en GK is geoes met LightCycler PCR. Snitte van die pankreas is gekleur met insulien en glukagon (eilandsontwikkeling) en vir Pdx-1, GLUT-2 en GK (betaselfunksie) gevolg deur beeldanalise. Resultate: Bloodstelling aan ’n in utero HVD regdeur gestasie het hiperglisemie versoorsaak in pasgebore rotte met verlaagde betasel volume en aantal, Pdx-1 en GK immunoreaktiwiteit. In teenstelling daarmee was die alfasel se volume, aantal en grootte verhoog in pasgebore rotte wat regdeur gestasie aan 'n HVD blootgestel was. Meeste van die gespeende rotte was hiperglisemies en hipoinsulinemies. In sommige gespeende rotte, was daar ’n verlaging van betasel hoeveelheid en grootte en in alfasel groote. Oormatige uitdrukking van Pdx-1 mRNA het plaasgevind in speenlinge wat aan ’n HVD van die moeder vir die laaste week van gestasie of regdeur gestasie en laktasie blootgestel was, maar dit was verlaag in die speenlinge wat net tydens laktasie blootgestel was. Pax 4 mRNA was verlaag in speenlinge wat aan ’n HVD van die moeder blootgestel was vir die eerste of laaste week van gestasie, regdeur gestasie of regdeur laktasie. In meeste van die speenlinge is onder-uitdrukking van GLUT-2 mRNA, maar ’n verhoging van GLUT-2 immunoreaktiwiteit gevind. Beide GK mRNA uitdrukking en immunoreaktiwiteit was laer in meeste van die speenlinge. Gevolgtrekkings: • Blootstelling aan ’n in utero HVD regdeur gestasie lei tot hiperglisemie in pasgebore rotte. Die verlaagde Pdx-1 immunoreaktiwiteit speel klaarblyklik ’n rol by die geaffekteerde betaselontwikkeling. Dit, saam met die verlaagde immunoreaktiwiteit vir GK, kan bydra tot die hiperglisemie in hierdie pasgebore rotte. In die meeste van die speenlinge wat aan ’n HVD blootgestel was, dui die hiperglisemie en hipoinsulinemie op geaffekteerde betaselfunksie. Die GK mRNA uitdrukking en immunoreaktiwiteit is verlaag, wat weer glikolise benadeel, en dit sal lei tot verminderde insulienafskeiding wat bydra tot die hiperglisemie. Betaselontwikkeling word voorts negatief beinvloed deur die HVD, wat blyk uit die verlaagde aantal en grootte van betaselle. Dit sal bydra tot verminderde betaselfunksie. Dit kan uiteindelik tot betaselversaking lei. GLUT-2 immunoreaktiwiteit was verhoog in hierdie speenlinge, wat dui op ’n kompenserende aanpassingsmeganisme om glukose homeostase te herstel. ’n HVD van die moeder het ’n negatiewe uitwerking op betaselontwikkeling, transkripsiefaktor en glukosewaarneming geenuitdrukking in beide die pasgebore en gespeende rotte, en geinduseerde hiperglisemie en hipoinsulinemie in sommige kleintjies. Dis belangrik vir toekomstige Tipe 2 diabetes navorsing dat daar na gekyk moet word om die HVD-geinduseerde verlaging van sleutel betaselgene te verbeter vir optimale betaselfunksie.