In the present studies we have explored the link between food hypersensitivity and IgA nephropathy (IgAN) and evaluated treatment options in primary and recurrent disease. Approximately one third of our IgAN patients had a rectal mucosal sensitivity to gluten, as demonstrated by increased local mucosal nitric oxide production and/or myeloperoxidase release after gluten challenge. The gluten sensitivity seemed to be an innate immune reaction unrelated to the pathogenesis of celiac disease. Approximately half of the patients had a rectal mucosal sensitivity to soy or cow’s milk (CM). The levels of IgG antibodies to alfa-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, indicating that an adaptive immune response might be involved in addition to the innate immune reaction observed. With the knowledge of gastrointestinal reactivity enteric treatment was considered as a potential new treatment approach of IgAN. A 6-month prospective trial demonstrated proof-of-concept for the use of enteric budesonide targeted to the ileocaecal region of IgAN patients. We observed a modest, but significant reduction in urine albumin, a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation. eGFR calculated from the Cockcroft-Gault formula and cystatin C was not changed. In a retrospective study recurrence of IgAN and graft loss was evaluated in Norwegian and Swedish patients having received a primary renal transplant due to IgAN. Adjusting for relevant covariates, a multiple Cox-regression analysis on time to IgAN recurrence showed that use of statins was associated with reduced risk of recurrence and reduced risk of graft loss. The time lag from diagnosis to first transplantation and female gender were also associated with lower risk of recurrence. Improved graft survival was associated with related donor, low donor age and no or low number of acute rejection episodes.

The overall aim of this thesis is to investigate health-related quality of life (HRQoL), anxiety and depression in patients with endocrine gastrointestinal (GI) tumours. Patient as well as staff perceptions were assessed. HRQoL was studied with the EORTC QLQ-C30, and anxiety and depression with the Hospital Anxiety and Depression Scale. In addition, patient perceptions of the importance of and satisfaction with selected HRQoL aspects were investigated. Semi-structured interviews with open-ended questions were conducted to identify disease- and treatment-related distress, what constitutes a good quality of life and strategies to "keep a good mood" among these patients. Patients reported a relatively good HRQoL and low levels of anxiety and depression. However, they reported a lower HRQoL than could be expected for healthy people of similar age and gender. Staff gave a more pessimistic view of patient satisfaction with HRQoL aspects than did patients, and staff did not accurately judge individual patients' levels of anxiety and depression. Importance>satisfaction discrepancies for HRQoL aspects may identify patients with a low quality of life. HRQoL, anxiety and depression did not change substantially during the first year of treatment. Categories identified through content analysis of interview data concerning distress and quality of life were referred to physical, emotional or social dimensions. Identified strategies to "keep a good mood" were classified as Internal or External. Most categories of distress that were identified are covered by the EORTC QLQ-C30 and/or the HADS, but some additional emotional and social aspects of distress emerged from the interview data. Receiving good care was identified as a strategy to "keep a good mood". This result indicates a possible and potentially important relation between the quality of care and patient HRQoL.

Background and aims: Unrecognized intestinal mucosal ischemia in severely ill patients may trigger development of multiple organ failure. Such ischemia can be evaluated by intraluminal tonometry reflecting mucosal PCO2 and intramucosal pH (pHi). The aims were to develop an apparatus for continuous saline tonometry (CST), to analyse circulatory control mechanisms during intestinal hypoperfusion and to evaluate the effect of dopexamine on intestinal circulation. Methods: A modified standard tonometry catheter was integrated in a closed system with circulating saline. By measuring saline PCO2 in a measurement unit pHi could be calculated. This novel system was tested in vitro and in vivo. In a porcine study, CST was evaluated against standard saline tonometry, tissue oxygenation (PO2 TISSUE), jejunal mucosal perfusion (laser doppler flowmetry; LDF) and mesenteric net lactate flux during graded reductions of superior mesenteric arterial pressure (PSMA). Local control mechanisms for maintenance of intestinal oxygenation were analysed. Effects of dopexamine on the intestinal vascular bed were explored. Mucosal lactate production was assessed by microdialysis. Results: CST measured accurate PCO2 values and changes in pHi during restricted intestinal circulation and at reperfusion. Local control mechanisms were insufficient at a PSMA of 30 mmHg, pHi was reduced to 7.10 and intestinal net lactate production was demonstrated. Absence of anaerobic intestinal metabolism was verified at PSMA ≥ 50 mmHg, pHi ≥ 7.22 and a PCO2 gap ≤ 15.8 mmHg. Dopexamine induced negative regional metabolic effects at the lowest PSMA, as expressed by decreased PO2 TISSUE and pHi, increased PCO2 gap and intestinal net lactate production. Conclusions: CST reflected changes in pHi, induced by intestinal hypoperfusion and at reperfusion. Levels of PSMA, pHi and PCO2 gap as indicators of aerobic conditions were defined. Dopexamine induced a decrease of PO2 TISSUE and pHi as well as an increase in lactate flux at the lowest PSMA level.

Calf scours are caused by a variety of infectious agents. Oral rehydration therapy solutions are formulated with the objective of correcting dehydration and acidosis. Currently, oral rehydraton therapy does not promote gut healing in diarrheic calves. However, investigators are examining the role of nutrition in promoting gut healing. Previous work has shown that the amino acid glutamine is important in nitrogen transport between tissues and is an indispensable nutrient for rapidly dividing cells such as lymphocytes, fibroblasts and enterocytes. Small intestinal epithelial cells depend mainly on glutamine, glucose, and ketone bodies for their energy under normal physiological conditions. The oxidative substrate preferred by large intestinal epithelial cells appears to be butyrate, followed by acetate, glutamine, and glucose. Research shows that glutamine supplementation increases intestinal protein synthesis. This may be one of the mechanisms by which glutamine exerts its protective effect on gut integrity and mucosal barrier function during critical illness. However, questions concerning the optimum dose and route by which glutamine is to be administered have yet to be addressed. A surgical model was developed to chronically study the nutrient concentration differences across the portal-drained viscera of preruminant calves. The experimental design consisted of a series of infusions conducted on four different study days in each calf. On the study days, 4 separate 1h infusions of acetate, glucose, glutamine, saline (control) were administered intravenously via the jugular vein at 200 mmol/L/h in a different order. Venous and arterial blood were collected over the last 15 min of each 1h infusion. Blood flow was also measured. Intestinal uptake in ìmol/kg^0.75/min was 0.3 ± 1.1 for glutamine and 1.9 ± 3.1 for glucose during saline infusion. During acetate, glucose, and saline infusions, glucose was a greater source of energy than glutamine for the intestine. However, during glutamine infusion, intestinal glutamine uptake (29.9 ± 11.2 ìmol/kg^0.75/min) increased significantly which was associated with a rise in ammonia production (7.0 ± 0.5 ìmol/kg^0.75min). A second experiment was designed to determine if glutamine uptake could be further stimulated either by longer term intravenous infusion or by chronic oral supplementation in neonatal calves. Intestinal metabolism was investigated by measuring nutrient uptake during three intravenous infusions of glutamine over a 5 h period after an overnight fast. Prior to the first infusion, calves diet consisted of milk only. Diet was supplemented with oral glutamine for the second and third infusions. Glutamine was administered via the jugular vein at a rate of 200 mmol/L/h. Venous and arterial blood was collected in duplicate every hour for 5 h. Blood flow was also measured. During glutamine infusion, there was an absolute increase in PDV uptake of glutamine associated with a significant production of ammonia. Feeding glutamine orally did not alter the PDV glutamine uptake. Glutamine infusion did not increase the intestinal uptake of essential amino acids. Neither chronic oral supplementation with glutamine, or infusion for periods longer than an hour, further increased intestinal glutamine uptake. Arterial leucine concentration and intestinal uptake declined during glutamine infusion suggesting that its supply became limiting. Thus glutamine supplementation may require the provision of a mixture of amino acids to be effective.

Thesis (M.Tech.: Biotechnology)- Dept. of Biotechnology, Durban University of Technology, 2007 xv, 127 leaves / The human gut microbiota play a major role in host health, and attempts are being made to manipulate the composition of the gut microbiota-increase the composition of bacterial groups, such as lactobacilli and bifidobacteria that are perceived as exerting health promoting properties. These bacteria defined as food supplements (probiotics) beneficially affect the host by improving the intestinal microbial balance, and have been used to change the composition of the colonic microbiota. However, such changes may be transient, and the implantation of exogenous bacteria therefore becomes limited. In contrast, prebiotics are naturally occurring carbohydrates that are classified as non-digestible oligosaccharides present in edible plants. These carbohydrates enter the colon as intact compounds, elicit systemic physiological functions and act as fermentable substrates for colonic microflora-influencing the species composition and metabolic characteristics of intestinal microflora providing important health attributes. Currently, a widely marketed prebiotic, inulin is extracted from plants of the family Asteraceae. There are many unexploited plants that are regularly consumed and that may have a prebiotic effect or can have very high levels of inulin which could make them commercially viable. In this study, we investigated prebiotic compounds, especially inulin from locally growing, non-commercialised leafy plants. The aqueous extracts of 22 plants from the families Asparagaceae, Alliaceae, Asteraceae, Solanaceae, Cucurbitaceae, Amaranthaceae, Acanthaceae, Polygonaceae, Portulaceae, Fabaceae, Chenopodiaceae, Pedaliaceae and Apiaceae from Kwa-Zulu Natal were investigated for a prebiotic effect using a modified batch-culture technique with Lactobacillus bulgaricus, Lactobacillus lactis, Lactobacillus reuteri and Bifidobacterium longum, four common probiotics and the inulin content of the plants was determined using high performance liquid chromatography. Of the 22 plants studied, Solanum nigrum, Amaranthus spinosus, Amaranthus hybridus, Asystasia gangetica, Senna occidentalis, Cerathoteca triloba, Asparagus sprengeri, Tulbaghia violacea, Sonchus oleraceus and Taraxacum officinale exhibited a prebiotic effect. The prebiotic effect of the Taraxacum officinale, Sonchus oleraceus and Asparagus sprengeri extracts on L. lactis and L. reuteri was higher than or equivalent to inulin-a commercial prebiotic. In this study, Sonchus oleraceus exhibited the best prebiotic effect-was the only plant to stimulate all the probiotics including B. longum. Of all the plants analysed, Asparagus sprengeri tuber contained the highest amount of inulin (3.55%).

A major challenge for the pig industry is to formulate starter diets that primarily fit the digestive capacity, maintain GIT health and promote growth without recourse to in-feed antimicrobials. Experiments were conducted to evaluate the efficacy of carbohydrase enzymes (CE) targeting non-starch polysaccharides (NSP) in enhancing gut health and function in piglets. First, an experiment was conducted to evaluate the effects of adding CE in piglet diets on growth performance, GIT bacterial activity and nutrient digestibility. Pigs fed diets containing CE had a higher ileal lactobacilli count, total organic acids concentrations, NSP digestibility and low ammonia compared with control. The effectiveness of CE targeting NSP was further evaluated using enterotoxigenic E. coli (ETEC) in a challenge model to evaluate the impact on gut health and function. Two approaches for the ETEC challenge were adopted; an in situ small intestine segments perfusion model and an in vivo model. Initially, a pilot study was conducted to establish and validate the in situ model. In the pilot study, conventional anti-diarrhea agents; fumaric acid, ZnO, egg yolk antibodies against ETEC K88 fimbriae and carbadox, attenuated fluid losses in ETEC-infected jejunal segments. Following the establishment of the in situ model, four experiments were conducted to study the effects NSP hydrolysis products (HP) from various feedstuffs (i.e. wheat, soybean meal, canola meal and flaxseed) on ETEC-induced secretory diarrhea. The results demonstrated that HP protected against ETEC-induced fluid and electrolyte losses. A further study was conducted to investigate the response of piglets fed diets containing HP and EYA singly or in combination upon oral challenge with ETEC. Feeding HP and EYA alone or in combination attenuated ETEC-enteritis symptoms such that piglets fed additives showed less pronounced acute phase responses and superior performance. Piglets fed diets containing additives had lower gastric pH, fewer ETEC adhered to ileal mucosa and lower incidence of diarrhea. Overall, reduction of intestinal pathogens or toxic bacterial metabolites contributes to enhanced GIT health and function. These novel results expand the scope of enzyme technology in animal nutrition within the new paradigm of dietary approaches to gut health and function.

Whole yellow pea flour (WPF) and fractionated yellow pea flour (FPF) are novel functional food ingredients that vary in nutritional composition. Consequently, the health benefits of WPF and FPF remain undefined. The purpose of this research was to identify the effects of WPF and FPF on risk factors and morbidities associated with cardiovascular disease, diabetes and obesity as well as the gastrointestinal microbiome. Using USDA recommended dosages of WPF and FPF, clinical endpoints and the colonic microbiome were investigated using a human clinical trial engaging a cross-over design and a diet and energy controlled paradigm. Humans were also utilized to investigate post-prandial glycemic responses and sensory characteristics of novel functional foods formulated with WPF. Finally, Golden Syrian hamsters were used to assess the impact of high doses of WPF and FPF on clinical endpoints and caecal microbial abundance. Results reveal that USDA recommended dosages of WPF and FPF in humans decreased (p<0.05) fasting insulin and estimates of insulin resistance compared to white wheat flour (WF). Android-to-gynoid fat ratios in women were lower (p=0.027) in the WPF group compared to the WF group. FPF decreased (p<0.05) post-prandial energy expenditure alongside a tendency (p<0.075) to reduce carbohydrate oxidation. Novel biscotti and banana bread formulated with WPF induced low post-prandial glycemic responses which were similar to boiled whole yellow peas and significantly lower (p<0.05) than white bread. Sensory analysis of novel WPF biscotti and banana bread demonstrated that WPF-based food products are palatable and acceptable for human consumption. Hamsters consuming diets containing 10% WPF and FPF induced similar reductions (p<0.05) in fasting insulin levels compared to controls. However, animals consuming WPF increased (p<0.05) oxygen consumption while FPF decreased (p<0.05) fasting glucose levels. In addition, terminal restriction fragment length polymorphism analysis revealed that WPF and FPF induced distinct shifts in caecal microbial populations within the phyla Firmicutes. Finally, pyrosequencing analysis of human fecal microbiota demonstrated that FPF and WPF induced shifts in bacterial genera, primarily within Bacteroidetes and Firmicutes. In conclusion, whole and fractionated yellow pea flours are functional food ingredients and can be utilized to manage risk factors for lifestyle-related diseases in humans.

There is no abstract available for this thesis. / Department of Family and Consumer Sciences

Objective The main objective of this thesis was to explore the effects of diet on gastrointestinal symptoms in prostate cancer patients treated with local curative radiotherapy, by evaluating dietary intake prior to treatment (Study I), the psychometric properties of a new questionnaire on patient-reported gastrointestinal side effects (Study II), and the effect of a dietary intervention on acute and long-term gastrointestinal symptoms up to 2 years after radiotherapy completion (Study III-IV). Methods A total of 130 men with localized prostate cancer referred to dose-escalated radiotherapy (ED2 87-102 Gy, α/β=3 Gy) were recruited to a dietary intervention trial. Patients were randomized to receive either standard care plus the dietary intervention of a fibre- and lactose-restricted diet (intervention group, IG; n=64) or standard care alone (standard care group, SCG; n=66). Data on gastrointestinal symptoms and dietary intake were collected pre-treatment and at seven time points during a follow-up period of 26 months. Results Prior to treatment, grain products and milk products were major sources of energy. Unbalanced fatty acid intake and low intake of selenium were observed (Study I). Validation of the Gastrointestinal Side Effects Questionnaire (GISEQ) revealed satisfactory internal consistency, moderate concurrent validity and adequate responsiveness (Study II). There were no significant effects of the intervention on acute or long-term gastrointestinal symptoms, but a tendency towards lower prevalence and severity of bloating and diarrhoea in the IG compared to the SCG during radiotherapy. Gastrointestinal symptoms were predominantly mild, and the frequency of clinically relevant symptoms was merely a few percent. Dietary adherence in the IG was initially good, but tended to decline beyond 12 months post-radiotherapy (Study III-IV). Conclusions A fibre- and lactose-restricted diet was not superior to the habitual diet in reducing gastrointestinal symptoms in patients undergoing high-dose, small-volume radiotherapy for localized prostate cancer. The GISEQ enables assessment of patient-perceived change in symptoms, but further work is needed to strengthen its psychometric qualities. It is suggested that continued research in this area target patient categories referred to irradiation of larger pelvic volumes with a higher risk of gastrointestinal symptoms, and that dietary interventions incorporate established strategies to enhance adherence and effectiveness.

A major challenge for the pig industry is to formulate starter diets that primarily fit the digestive capacity, maintain GIT health and promote growth without recourse to in-feed antimicrobials. Experiments were conducted to evaluate the efficacy of carbohydrase enzymes (CE) targeting non-starch polysaccharides (NSP) in enhancing gut health and function in piglets. First, an experiment was conducted to evaluate the effects of adding CE in piglet diets on growth performance, GIT bacterial activity and nutrient digestibility. Pigs fed diets containing CE had a higher ileal lactobacilli count, total organic acids concentrations, NSP digestibility and low ammonia compared with control. The effectiveness of CE targeting NSP was further evaluated using enterotoxigenic E. coli (ETEC) in a challenge model to evaluate the impact on gut health and function. Two approaches for the ETEC challenge were adopted; an in situ small intestine segments perfusion model and an in vivo model. Initially, a pilot study was conducted to establish and validate the in situ model. In the pilot study, conventional anti-diarrhea agents; fumaric acid, ZnO, egg yolk antibodies against ETEC K88 fimbriae and carbadox, attenuated fluid losses in ETEC-infected jejunal segments. Following the establishment of the in situ model, four experiments were conducted to study the effects NSP hydrolysis products (HP) from various feedstuffs (i.e. wheat, soybean meal, canola meal and flaxseed) on ETEC-induced secretory diarrhea. The results demonstrated that HP protected against ETEC-induced fluid and electrolyte losses. A further study was conducted to investigate the response of piglets fed diets containing HP and EYA singly or in combination upon oral challenge with ETEC. Feeding HP and EYA alone or in combination attenuated ETEC-enteritis symptoms such that piglets fed additives showed less pronounced acute phase responses and superior performance. Piglets fed diets containing additives had lower gastric pH, fewer ETEC adhered to ileal mucosa and lower incidence of diarrhea. Overall, reduction of intestinal pathogens or toxic bacterial metabolites contributes to enhanced GIT health and function. These novel results expand the scope of enzyme technology in animal nutrition within the new paradigm of dietary approaches to gut health and function.