Diabetic wounds frequently undergo impaired and prolonged wound healing due to a multitude of factors including hypoxia, impaired angiogenesis, hyperglycaemia, formation of ROS and AGEs, and infection - all of which may lead to cellular dysfunction. To date, however, treatment options for individuals suffering from impaired diabetic wound healing are limited, non-specific, and generally unsuccessful. The search for new and effective treatment strategies is severely hampered by the availability of adequately characterized screening models which comprehensively mimic the complexity of the diabetic wound healing process. In order to explore natural products as potential therapeutics to treat diabetic wounds and to encourage more research on this topic, this study sought out to develop and characterize a more convenient and cost effective in vitro screening assay which mimics the effects of protein glycation on the healing process of diabetic wounds. As proof of principal, this model was subsequently used to screen the potential of five wild mushroom species (P. tinctorius, R. capensis, B. badius, P. ostreatus and G. lucidum) as suitable diabetic wound healing therapies. The glycated gelatin model developed during this study was found to suitably mimic the diabetic state as it successfully simulated the major cellular dysfunctions in macrophages (NO production, phagocytosis, macrophage polarization, NF-ĸB translocation and COX-2 expression) and fibroblasts (proliferation and migration) documented during diabetic wound healing. Together these findings provide confidence that the model may serve as a valuable tool to study the poorly understood mechanisms which characterize cellular dysfunction in response to AGE accumulation and also to aid the identification of novel therapeutic agents to treat this pathology. Screening a number of mushroom extracts revealed that the ethanol extracts of R. capensis and P. ostreatus had the greatest potential for attenuating chronic inflammation due to their ability to promote macrophage phagocytosis, increased M2 activation (R. capensis) and decreased M1 activation (P. ostreatus) as well as reduced COX-2 expression while the water extract of G. lucidum proved to be the most promising candidate for stimulating fibroplasia as it was the most successful at promoting both fibroblast proliferation and migration. Different mushroom species were thus shown to promote different stages of the wound healing process providing sufficient evidence to support further studies related to the use of macrofungi as therapeutic agents in the search for more cost-effective and efficient treatment strategies for impaired diabetic wound healing.

HSPC1 (Hsp90), a member of the anti-apoptotic Heat Shock Protein (HSP) family appears to play a pivotal role in the development and maintenance of several tumour cell characteristics and as a result has become a target for novel anti-cancer therapies. HSPC1 inhibitors have been tested in clinical trials on a wide variety of cancer types with moderate success. However, despite recent advantages in HSPC1 inhibitor development, the effects of these drugs are not consistent. A number of factors may play a role in determining cell sensitivity to these inhibitors. As Chronic Lymphocytic Leukaemia (CLL) is such a heterogeneous disease with great variation in baseline HSP levels and other proteins amongst the patient cohort, it would not be unreasonable to assume that HSPC1 inhibitors may have varying success as a treatment strategy for this disease. The present study examined the effects of four HSPC1 inhibitors on primary CLL cells, as well as cells from healthy control subjects, and analysed a number of HSPC1 client proteins to assess the efficacy of these inhibitors. Great variation in cellular response to these drugs was observed in both CLL and healthy control subjects. Analysis of HSPC1 client proteins in these cells including ZAP-70, Akt, NF-kB and HSPA1A, revealed that HSPC1 inhibitors do not effect client protein levels in all samples. The results suggest that these inhibitors should not be considered as a universal treatment strategy for CLL and provide a basis for further study into elucidating the mechanisms behind HSPC1 inhibitor resistance. The final aim of this work was to investigate the role of the microenvironment in CLL progression, where a co-culture system was used as an in-vitro tool. Whilst consistent data was obtained using cell lines, and showed that microenvironmental factors promoted resistance to HSPC1 inhibitors, use of primary CLL cells in this model produced inconsistent data, again highlighting the heterogeneity of the disease.

Class of 2006 Abstract / Objectives: To assess perceived efficacy and patient satisfaction at a single point in time during a course of therapy with a compounded topical formulation containing at least ketoprofen in an anhydrous gel base. Methods: Patients aged 18 and older, currently using one of the topical pain relief compounds of interest obtained from Reed’s Compounding Pharmacy in Tucson, Arizona were recruited and then interviewed (in person or by telephone) for this study. Data collected during patient interviews were recorded on a form designed solely for the purposes of this study. Interview questions pertained to the nature of the participant’s pain, their assessment of their pain both before treatment with the medication of interest and at the time of the interview, frequency and duration of patient use of the pain relief gel, disclosure of any other pain relief medications the patient was using at the time, and their overall satisfaction with the medication. Results: Interviews were conducted with a total of 50 patients with chronic pain conditions representing several different etiologies and anatomical locations. The average pain assessment score at the time of the interview (representing perceived patient pain after use of the topical pain relief compound) was significantly lower than the average before treatment pain assessment score (p<0.001). After treatment with the gel had commenced, perceived pain scores dropped by average of 3.56 units (SD 2.28), or 44%. Increased frequency of application of the topical pain relief gel was not associated with greater pain relief or changes in overall patient satisfaction with the product. A longer duration of use of the topical pain relief was also not associated with greater pain relief or overall patient satisfaction with the product. Whether or not a patient utilized other pain relief medication(s) while undergoing treatment with the topical pain relief gel had no bearing on the assessment of their pain either before use of the gel or at the time of interview. The average overall patient satisfaction with the topical pain relief compound was rated at 6.6 out of a possible 10 units (SD 3.13). Thirty-six patients (72%) rated their satisfaction with the topical medication of interest with a satisfaction score of ≥ 6, 10 patients (20%) rated their satisfaction with a score of 10 (completely satisfied), and 6 patients (12%) rated their satisfaction with a score of 0 (not at all satisfied). It was observed that the lower the perceived pain assessment score at the time of the interview (after using the gel), the greater the patient satisfaction with the product. Additionally, patients were observed to be more satisfied with the product if the difference between their perceived pain assessment scores (before and after) was greater (i.e.: greater patient satisfaction with greater pain relief). Conclusions: Treatment of chronic pain with a topical pain relief compound containing at least ketoprofen in an anhydrous gel base is associated with patient satisfaction and perceived analgesic benefits. During the one-time interview, most patients reported a significant improvement in their pain relief, and the great majority of patients were very satisfied with the compounded topical treatment they received from Reed’s Compounding Pharmacy.

Chronic pulmonary aspergillosis (CPA) is a serious disease that occurs secondary to tuberculosis and is estimated to affect 1.2 million persons globally. Pulmonary aspergillosis is found in 2-3% of all AIDS autopsies, but 90% of cases go undiagnosed ante-mortem. Here the sensitivity and specificity of optimal diagnostic thresholds for CPA have been defined in relation to six Aspergillus-specific IgG assays. The prevalence of CPA in an area of high tuberculosis prevalence has been measured. Receiver operating characteristic (ROC) curves were used to compare results of testing with six Aspergillus-specific IgG assays in 241 patients with CPA and 100 healthy controls. ThermoFisher Scientific ImmunoCAP and Siemens Immulite had ROC area under curve (AUC) results of 0.995 and 0.991 respectively. Both were statistically significantly superior to all other assays. Both had a sensitivity of 96% and specificity of 98% using diagnostic cut offs of 20 mg/L and 10 mg/L respectively. Eighty patients with allergic bronchopulmonary aspergillosis (ABPA) were also assessed. ROC AUC results were 0.959 for ImmunoCAP and 0.932 for Immulite. The new thresholds produced specificities of 98% for both assays and sensitivities of 78% and 81% respectively. Levels in ABPA patients were also compared to asthmatic controls.398 patients with treated tuberculosis in Gulu, Uganda were assessed in a cross-sectional survey. CCPA diagnostic criteria were; 1 – Cough or haemoptysis for one month, 2 – Progressive cavitation on serial chest X-ray or either paracavitary fibrosis or aspergilloma on CT scan and 3 – Raised Siemens Immulite Aspergillus-specific IgG. All three were required for diagnosis. CCPA was present in 5.7% of patients and simple aspergilloma in 0.7% of patients. There was a non-significant trend to less frequent CCPA in HIV positive patients (p=0.18). Aspergillus-specific IgG levels were measured in stored sera from two adult in patient groups at Mulago Hospital, Kampala, Uganda. 26% of 39 patients with HIV infection and subacute respiratory illness and no diagnosis after extensive investigation had raised levels. 47% of 57 patients with proven active pulmonary tuberculosis had raised levels. The Immulite and ImmunoCAP assays both have good sensitivity and specificity for the diagnosis of CPA. New diagnostic thresholds improve the performance of all assays. CCPA has been shown to complicate pulmonary tuberculosis in Gulu, Uganda. Subacute invasive pulmonary aspergillosis is likely to affect many patients with AIDS and subacute respiratory illness. CPA may begin during active pulmonary tuberculosis infection. CPA associated with tuberculosis constitutes a significant unrecognized public health problem, which is probably being incorrectly identified as ‘smear-negative tuberculosis’ clinically and in public health data. Prospective studies are now needed to confirm the prevalence of CPA secondary to tuberculosis and define the optimal strategy for routine CPA screening, followed by studies to define optimal treatment regimes for use in research poor-settings, where most cases of CPA are likely to occur.

M.Tech.

This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), macrophage inflammatory protein-1 beta (MIP-1 beta), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-alpha (TNF-alpha) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they were of both sexes, and many had suffered from multiple strokes, we also present findings that reveal how the chronic inflammatory response to stroke is impacted by age, sex, and multiple strokes in mice. Our data indicate that the chronic cytokine and chemokine response to stroke is not substantially altered in 18-month old compared to 3-month old C57BL/6 mice, although T cell infiltration is attenuated. We found a significant correlation in the chronic cytokine response to stroke in males and females. However, the chronic cytokine response to stroke was mildly exacerbated by a recurrent stroke in both C57BL/6 and BALB/c mice.

This research project aims to provide insights into the psychobiology of personality of individuals living with chronic asthma to inform treatment planning. Personal experience in observing emotional and social difficulties in an asthmatic child over years and an article on the effects of asthma medication on the cognitive and psychosocial functioning of asthmatic learners raised awareness of the problem. Medical illnesses, acute and chronic, are often accompanied by a number of disease-related stressors or events that produce stress. Stress-induced changes in the nerve and immune system affect cognitive and emotional functioning that adversely affect personality development and significantly decrease the individual’s quality of life, particularly if sustained over a long period of time. This project followed a quantitative mode of enquiry, and personality profiles were compiled at hand of the 16-PF Questionnaire. The research sample consisted of 11 Afrikaans speaking, 18-year-old asthmatic individuals from the same school. Significantly meaningful characteristics associated with chronic asthma were identified, i.e., a highly tense temperament, accompanied by low resilience, subjective anxiety, low self-worth, as well as surgency or uninhibited behaviour, tempered by moderate spontaneity and warmness. It is envisioned that these insights might significantly inform planning of treatment regimes and lifestyle modification programmes. Stress relief might improve neuroendocrine and immune functioning, delay disease progression, and reduce morbidity and mortality. The focus is thus on a general stress-coping model in order to improve quality of life. / Dissertation (MEd (Educational Psychology))--University of Pretoria, 2007. / Educational Psychology / unrestricted

No description available.

Chronic back pain is a pervasive and debilitating phenomenon contributing to staggering health costs and a host of psychological, medical, vocational, and social consequences. The etiology of chronic back pain remains unclear and traditional biomedical, psychological, and interdisciplinary treatments have not been completely effective at eliminating pain or restoring long-term functionality. Psychodynamic models of chronic back pain have not been fully explored due to methodological difficulties. Explorations of psychodynamic-related constructs such as alexithymia (i.e., lack of emotional awareness) may offer vital clues to help increase the understanding of chronic back pain. The purpose of this study was to serve as a preliminary descriptive analysis of alexithymia among patients seeking interdisciplinary treatment for chronic back pain. First, the prevalence of alexithymia in an interdisciplinary treatment seeking sample of patients with chronic back pain and comparisons to other chronic pain and psychosomatic samples were addressed. Second, the relationship between alexithymia and somatic complaints, pain, anxiety, depression, and health-related quality of life was explored. Finally, a meditational analysis was conducted to examine if the relationship between alexithymia and somatic complaints was mediated by negative affect. Eighty-one patients seeking interdisciplinary treatment for chronic back pain participated in the study. Analyses revealed that 14.8% patients met criteria for alexithymia, which was similar to other chronic pain samples but not significantly different from general medical samples. Higher alexithymia scores were found to be associated with higher levels of somatic complaints, negative affect, and mental-health related quality of life. Unexpectedly, higher alexithymia scores were also associated with better physical-related quality of life. There were no significant relationships between alexithymia and pain. The relationship between alexithymia and somatic complaints was found to be mediated by negative affect, which was consistent with psychodynamic models of chronic back pain. Findings were discussed in relation to clinical implications and future research.

In this study, the use of hypnosis in the treatment of chronic low back pain is described in terms of Ecosystemic thinking, as opposed to traditional conceptualisations of hypnosis. Six case studies were used. Each is described in detail, as well as the therapeutic rationale behind each case, in order to present the reader with an understanding of the thinking behind using Ecosystemic hypnotherapy. / Psychology / M.A. (Psychology)