No description available.

No description available.

The aim of this dissertation was to study the absorption, and subsequent toxic side effects of transition metal based pharmaceuticals following oral administration to rats. Administration of cisplatin (30mg/kg), carboplatin (37mg/kg) and iproplatin (42mg/kg) by oral gavage resulted in their rapid absorption so that respective peak blood levels of 2.63mug platinum/ml, 1.48mug platinum/ml and 3.13mug platinum/ml were achieved within 2-4 hours. Approximately 3-4% of the dose was excreted in the urine, but the major route of elimination was the faeces (>75%). This indicated that although rapid, absorption was relatively poor. Absorption was enhanced by employing a period of starvation prior to administration. A series of novel platinum (IV) mixed amines were absorbed to a greater extent than cisplatin and its congeners, carboplatin and iproplatin. However, absorption was somewhat slower with peak blood levels being attained some 24 hours after administration. Of the other transition metal complexes studied, auranofin and ruthenium acetylacetonate were particularly well absorbed so that peak blood levels of 12.53mug gold/ml and 6.4mug ruthenium/ml were achieved respectively. Urinary clearance of the ruthenium complex was especially significant with up to 45% of the administered dose being eliminated by this pathway within 48 hours. In vitro everted gut sac and in situ perfusion techniques confirmed the in vivo finding that cisplatin is absorbed from the small intestine more readily than carboplatin. No evidence for active or carrier-mediated transport was found and kinetic studies confirmed that absorption was by passive diffusion. Toxicology studies after oral administration of cisplatin (57 or 30mg/kg) or carboplatin (282mg/kg) indicated that the toxicities associated with the perenteral use of the complexes would also apply to the oral route. This was exemplified by the fact that oral cisplatin was profoundly nephrotoxic, whereas carboplatin was not. In addition, gastro-intestinal toxicity manifested as acute necrotizing enteritis and ulcerogenicity of the stomach was potentiated by the oral route. Studies in the ferret indicated that cisplatin is significantly more emetogenic than carboplatin. Examination of liver morphology indicated changes, such as mitochondrial swelling and vesiculation of the endoplasmic reticulum, that might indicate a higher incidence of hepatotoxic responses associated with administration of platinum complexes by the oral route. Both cisplatin and carboplatin induced a degree of myelosuppression but the most pronounced haematological lesion associated with oral administration was severe erythrocytosis which occurred as a result of a dehydration related decrease in plasma volume. Electrothermal atomic absorption analysis of tissues excised from cisplatin and carboplatin rats indicated that platinum deposition was highest in the kidney. In an attempt to explain the prolonged retention of cisplatin in this organ, the intracellular location of the compound was studied using electron microprobe analysis and subcellular fractionation. The various lysosome populations of the proximal tubule were identified as sites of concentration of platinum and it was hypothesised that sequestration within these organelles might be an important mechanism of detoxification.

Drug-induced gingival overgrowth is a disfiguring condition that is a side effect encountered in susceptible responder patients common to three groups of drugs - immunosupressants, calcium channel blockers and anticonvulsant agents. The altered overgrown gingiva can be aesthetically displeasing but in severe cases it can cause functional problems and such patients may eventually require excision of excess tissue. The underlying mechanisms that mediate drug-induced gingival overgrowth is uncertain and the various investigations into the pathogenesis of this disease suggest that it is multifactorial. This study investigated the effects of exogenous addition of cycJosporin and amlodipine on the growth and proliferation of human gingival fibroblasts and the production of collagen by these cells. Results showed that these drugs have a direct stimulatory effect on the gingival fibroblasts of responder patients in vitro and there seems to be a synergistic effect between the two drugs. Findings of this study have important relevance as it suggests that fibroblast proliferation and collagen production must play a significant role in the pathogenesis of drug-induced gingival overgrowth. / Dissertation (MSc (Odontology))--University of Pretoria, 2006. / Dental Management Sciences / unrestricted

Typescript (photocopy). / Digitized by Kansas Correctional Industries

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No description available.

Cell-cycle progression in mammalian cells is coordinated by a series of control points. The D-type cyclins are a family of key cell cycle regulators that are controlled largely by mitogens and their association with and activation of cdk 4 and 6 at the G1 phase of the cell cycle. This study seeks to first analyze cyclins D1, D2, and D3 expression patterns in preimplantation mouse embryos using in vivo studies and then analyze the effects of Dilantin on the cyclin D1 expression pattern in cultured embryos. Antibody staining against cyclin D1, D2, and D3 via indirect immunofluorescence using a Zeiss Confocal Microscope and analysis of individual embryo staining intensities using Zeiss computer software were employed to evaluate expression patterns throughout the first three cell cycles. The data showed that all three D cyclins were present throughout the first three cell cycles. Cyclin D1 had peak average fluorescence intensity at the G2 phase of the second cell cycle with a decrease at the G1 in the third cell cycle. Cyclin D2 had a consistent increase of fluorescence intensity throughout all three cell cycles. Cyclin D3 had peak average fluorescence intensity at the G2 phase of the second cell cycle with an immediate decrease at the Gl phase in the third cell cycle. Cyclin D1 was localized to the nucleus in G1 phases of the cell cycle. In contrast, cyclin D2 was found in the nucleus during G2 phases of the cell cycle rather than in G1. Cyclin D3 was not localized to the nucleus in either cell cycle phase throughout the first three cell cycles. These unique nuclear staining patterns seen by D1, D2, and D3 may reflect a function in the cell cycle. Embryos cultured in the presence of l0gg/ml of Dilantin were found to be slowed in development indicated by the absence of transition from the one-cell to the two-cell stage when compared to the controls. Since the Dilantin cultured embryos never reached G1 of the second cell cycle the increase in fluorescence intensity seen was still considered to be a representation of the G2 phase of the first cell cycle. Cyclin Dl's fluorescence intensity was affected by Dilantin and accompanied with unstained nuclei during the G2 phase of the first cell cycle. The peak average fluorescence intensity occurred during the G1 phase of the second cell cycle for cyclin D1 stained CZB control, while the vehicle control, 0.001N NaOH, remained constant. Both CZB and 0.001N NaOH had similar expression patterns seen previously in the cyclin D1 in vivo data. The information gained from the in vivo and in vitro experiments will help to better understand what causes the problems associated with exposure to Dilantin, and also the effects Dilantin has on the cell cycle. / Department of Biology

in English This thesis is a review of substances contained in medicinal plants, the side effects and complications that they provoke. The adverse drug reactions are directly related to the constituents contained in each plant. Information for this work was taken from sources published from 1965 until 2013, especially from The Essential Guide To Herbal Safety and from the databases webmd.com and ncbi.nlm.nih.gov. It is discussed how the use of natural medicinal drugs affect vital organs in the human organism and in which cases their consumption is contraindicated. Central nervous, cardiovascular, urinary, gastrointestinal, endocrine, haemopoietic, respiratory, urinary systems are affected and allergic reactions are possible to occur as complications. Hypericum perforatum is typical for causing gastrointestinal irritations and Chamaemelum nobile and Achillea millefolium are found to cause dermatic complications. Finally, Piper methysticum may induce extreme sedation, since it has anxiolytic and antiepileptic properties. Keywords: side effects, contraindications, medicinal plants, uses, constituents.

M.Tech. / In spite of the improvement in the delivery of anti-cancer treatments over the past decade, side effects from these treatments remain inevitable. A common, distressing side effect that all cancer patients experience is fatigue. However, cancer related fatigue (CRF) remains one that is under-reported and under-treated. CRF is a topic that has received very limited attention in the South African context. Regardless of the amount of literature available on CRF, many questions continue to go unanswered. CRF has been identified as a side effect that is associated with physical, mental and psychological elements. Consequently, it has the ability to cause a delay in treatment schedules, impinge on daily functioning and impact negatively on the quality of life (QoL) in the cancer patient. Effective management strategies for patients during and after radiation treatment are thus essential to improve QoL. The aim of the study was to investigate the general pattern of fatigue experienced by patients diagnosed with various types of cancers during a radical course of radiotherapy. For the purpose of this study fatigue was defined according to the National Comprehensive Cancer Network (NCCN) Practice Guidelines in Oncology (www.nccn.org): “a distressing persistent subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning” A cross-sectional, theory-generating study was conducted to explore and describe the prevalence of fatigue, factors that could influence fatigue scores, strategies being used to alleviate this side effect and the impact of fatigue on QoL. One hundred and eighty patients were asked to complete a self-developed questionnaire in three oncology centres in Gauteng, South Africa. The NCCN Clinical Practice Guidelines in Oncology were used as a framework to direct the study. The results of the study illustrate that fatigue scores increased as radiotherapy progressed. However, not all the variables explored in the study significantly impacted on fatigue scores. The study revealed, though, that all cancer patients do experience CRF irrespective of the diagnosis. Management of the causes of CRF is thus essential to improve QoL for cancer patients.