The research investigated the combined effects of protein deficiency (PD) and a gastrointestinal nematode infection, Heligmosomoides bakeri , on immunopathology and nutritional status in BALB/c mice. The acute phase of a primary infection reduced resting metabolic rate, but PD did not. Early challenge infection led to temporary anorexia and cessation of weight gain in both protein-sufficient (PS) and PD mice. / Among PS mice, a challenge dose of 200 L3 caused more active worm expulsion than infection with 100 L3. Both serum monocyte chemotactic protein-5 and gut fluid leakage were positively correlated with worm expulsion whereas numbers of mucosal mast cells, eosinophils, goblet cells and Paneth cells were unaffected by doses. Among PD mice, worm survival was prolonged and no dose-dependent worm expulsion was observed. In addition, a wide range of Th1 inflammatory cytokines including leptin was elevated in infected PD mice suggesting (1) that PD mice are unable to mount the appropriate Th2 inflammation and (2) that infection in PD mice induces a Th1 inflammation that allows continuing persistence of the parasite. / The shift to Th1 inflammatory responses in PD mice may also explain modifications in mineral distributions in tissues. Despite adequate dietary intakes of minerals in both PD and PS mice, serum iron concentrations were lower after H. bakeri challenge infection. Infection also reduced calcium and iron concentrations as well as the Ca/Zn ratio in the spleen. In contrast, PD resulted in increased iron and calcium concentrations as well as increased Ca/Zn ratio in the spleen and Fe/Zn ratio in the liver, but reduced calcium, zinc, copper and sulfur concentrations, and the Cu/Zn ratio in the liver. / Re-feeding PD mice with a PS diet restored parasite expulsion, regardless of whether the PS diet was provided during the primary or challenge infection. Thus, although PD mice have suppressed Th2 responses and elevated Th1 inflammation, their response to the primary infection is sufficient to ensure that parasite expulsion occurs once protein status is restored. / Together, these studies show that the shift toward Th1 inflammation plays a key role in prolonged parasite survival and mineral redistribution in protein deficient, infected mice.

The loss of muscle mass leading to cachexia is rarely identified in early lung cancer. Fasting blood and muscle biopsy were collected in 59 non-small cell lung cancer (NSCLC) and 16 non-cancer patients, at the beginning of thoracic surgery. Serum C-reactive protein (CRP), and IL-6 were higher in NSCLC. In weight-losing NSCLC, food intake and serum albumin were lower, CRP, and TNF-alpha were higher. Although the expression of genes of the ubiquitin-proteasome system was not different, ubiquitinated-protein levels were lower and negatively correlated with ph-FOX01 in weight-losing patients. This would suggest lower muscle proteolytic rates in the early stages of NSCLC. Ph-FOXO1 also related to the degree of weight loss and stage of NSCLC. These data suggest that in early stages of the disease, weight and muscle loss could be mainly due to reduced food intake, rather than accelerated proteolysis, which reinforces the potential for successful dietary interventions to prevent or delay the onset of cachexia.

Cardiovascular disease (CVD) risk can be lowered by introduction of plant sterols (PS) in the diet, since PS have been shown to reduce low-density lipoprotein cholesterol (LDL-C). Given that the efficacy of PS as cholesterol-lowering agents depends on their appropriate solubilization, the cholesterol-lowering efficacy of PS in non-traditional matrices needs to be determined. The primary aim of this thesis was to examine the consumption of PS (a) in an oil rich in medium chain triglycerides (MCT) or (b) low-fat yogurt with or without a meal, on changes in lipid parameters. Additional objectives were: (1) to assess the effects of MCT with PS on body composition and energetics, (2) to compare the effects of PS in low-fat matrix consumed with or without a meal on cholesterol synthesis, (3) to evaluate the risks of PS in low-fat matrix on blood levels of carotenoids and fat-soluble vitamin, and (4) to investigate the relationship between the response to PS, cholesterol kinetics and genotyping. For this purpose two randomized, controlled, crossover-feeding trials were conducted. First, 23 overweight, hyperlipidemic men consumed PS in MCT or olive oil control for six weeks each. In the second trial, 26 hyperlipidemic subjects consumed a placebo yogurt, a PS-enriched yogurt consumed with a meal, or afternoon PS-enriched yogurt as a snack for four weeks each. PS, mixed within a MCT matrix, lower plasma total cholesterol (TC) and LDL-C without changing the high-density-lipoprotein cholesterol concentrations. However, no changes in body composition or energetics were observed. Secondly, a PS-enriched low-fat yogurt as snack lowered TC, along with a lowering trend in LDL-C, to greater extent compared to when consumed with a meal without any risk of deficiency in fat-soluble antioxidants. An increase in cholesterol biosynthesis was also observed in both PS phases compared to control phase. In addition, three non-responsive subjects to PS intervention who had higher cholesterol absorption rates were observed; however, no recognizable pattern of genetic polymorphisms was detected. Overall, these novel matrices for PS incorporation consumed with or between meals may be an effective way of decreasing the risk of CVD; however, some individuals respond better to PS intervention.

Postprandial urea production in subjects with insulin dependent diabetes mellitus (IDDM) on conventional insulin therapy is normal when the previous diet is high in protein, but there is an incomplete adaptive reduction in urea production following protein restriction. To evaluate the nutritional implications of restricted protein intake in human diabetes mellitus, it is first necessary to establish a reliable method to measure changes in urea production and amino acid catabolism in response to changes in dietary protein intake. We therefore tested (1) the accuracy of the urea production rate (Ra) to depict changes in urea production, (2) whether sulfate production can be accurately depicted using tracer or nontracer approaches, after establishing the use of electrospray tandem mass spectrometry to measure sulfate concentrations and 34SO4 enrichments following administration of the stable isotope tracer sodium [34S]sulfate, (3) the reproducibility of urea and sulfate measurements following a test meal low in protein (0.25 g/kg) in subjects previously adapted to high (1.5 g/kg.d) and low (0.3 g/kg.d) protein intakes, and compared the metabolic fate of [ 15N]alanine added to the test meal with that of [15N] Spirulina platensis, a 15N-labeled intact protein, and (4) whether we could identify the differences in postprandial urea and sulfate productions between normal subjects and persons with IDDM receiving conventional insulin therapy previously adapted to high protein intake, when the test meal was limiting in protein. Under basal conditions, steady state urea Ra is an accurate measure of urea production. Following changes in urea production, both the tracer and nontracer methods seriously underestimated total urea Ra. The tracer method overestimated sulfate production by 20%, but the nontracer method provided an accurate measure of sulfate production and, hence, sulfur amino acid catabolism. Postprandial changes in urea and sulfate productions following normal ada

The aim of this research was to determine the influence of iron deficiency on both the efficacy and metabolic patterns of albendazole in mice infected with Heligmosomoides polygyrus. Anthelmintic efficacy was markedly decreased in iron-deficient mice; the deficiency was also associated with a decrease in body weight, altered hematological parameters and a decreased net egg output; worm establishment in the deficient group was not affected by the deficiency. Although anthelmintic efficacy was significantly decreased by the iron deficiency, plasma concentration profiles of the main metabolites, albendazole sulphoxide and albendazole sulphone, were not changed by the deficiency. Levels of intestinal cytochrome P-450, the main metabolizing enzyme of albendazole however, was significantly depressed in iron-deficient mice. These observations suggest that although pharmacokinetic parameters are not affected by iron deficiency, nutritional status has the potential to influence anthelmintic efficacy and thus warrants further study.

In the past 20 years, boron has been identified as an essential trace element for animals and humans but also as an increasingly important industrial pollutant. We examined first whether boron influenced survival of the gastrointestinal nematode Heligmosomoides bakeri. Female Balb/c mice were fed deficient (0.1 mug B/g), marginal (2.0 mug B/g) or control (12.0 mug B/g) diets, and infected with third-stage larvae. Although liver boron concentrations did not differ among diet groups, dietary boron deficiency impaired survival of the parasite and modulated a broad range of cytokines and chemokines. On the other hand, infection history altered liver mineral concentrations. Second, we examined whether elevated boron concentrations would exert toxic effects on H. bakeri in vitro. Boron toxicity was evidenced by reduced motility, fecundity, infectivity and survival. Feeding stages and free-living stages were more sensitive than non-feeding stages and parasitic stages respectively in a dose-dependent manner.

Intrauterine growth restriction (IUGR) reduces bone mass by 10-30% and impairs arachidonic (AA) and docosahexaenoic (DHA) acid status in infants. Because AA and DHA enhance neonatal bone mass, the aim of this study was to determine the effects of dietary 0.5% AA and 0.2% DHA (w/w) prior to weaning on bone and growth. 40 guinea pigs were randomized to either a control (C) or low-protein diet (LP) during pregnancy and the C diet or the C diet with AA+DHA during lactation. Measurements included bone mass, metabolism, and strength, and erythrocyte lipid of sows and offspring from birth to 16 wk post-partum. The LP diet induced IUGR, while the AA+DHA increased bone mass by 5-20% in sows and offspring and corrected growth and bone mass in IUGR pups. Thus, AA+DHA provided in lactation rescues the growth trajectory in an IUGR state and is beneficial to maternal and neonatal bone mass.

To test the hypothesis that maternal glucose restriction (GR) would compromise small intestine (SI) growth and development, we used a diet induced model of IUGR. Pregnant rats and offspring were fed isoenergetic diets {0% (deficient), 12, 24% (restricted), 60% (adequate) glucose) from gestation day (gd) 0 through adolescence. SI tissue was collected at gd20, birth, 12--24h, postnatal day (pd) 7, 15, 21, 28, 35, 49 and in controls. GR affected pup weight at early timepoints, resulting in IUGR; beyond effects due to differences in body wt, GR compromised SI length at 12--24h and promoted SI growth during peak lactation (pd15; total and distal wts). Dietary glucose regulated in utero (gd20) expression of sodium-dependent glucose co-transporter (SGLT1) protein. Diet-induced precocious maturation of lactase and sucrase was observed in glucose deficient animals. In summary, there were periodic but no permanent effects of dietary glucose intake on gut growth and development.

Weight loss is a common occurrence in patients with human immunodeficiency virus (HIV) and contributes to further debilitation in the acquired immune deficiency syndrome (AIDS). Wasting syndrome (WS) is defined as 10% or more unintentional weight loss from usual body weight. The etiology of WS includes alterations in metabolism, which contribute to loss of lean body mass. Cytokine driven oxidative stress may play a critical role in the metabolic pathways that lead to HIV wasting. Studies have shown that that patients infected with HIV may have a depleted antioxidant (AO) defense system, the integrity of which is needed to efficiently scavenge reactive oxygen species (ROS). It has been theorised that low AO intake may contribute to a depressed AO defense system, which drives oxidative stress (OS). In this study we examined 16 subjects who had documented WS but no active infectious process, stratified into 10 to 15% weight loss (n = 7) and over 15% weight loss (n = 9) groups, and reported on oxidative stress measures and AO intake. (Abstract shortened by UMI.)

Background: Breastfeeding is known to have benefits both for maternal and child health. Some questions around the benefits and risks of breastfeeding in the presence of HIV infection still remain unclear. Aims: To study the effects of infant feeding mode by HIV-positive mothers, on maternal and child health. In addition, to assess the effect of nutritional supplementation to HIV-positive lactating mothers on nutritional and health status of mothers and their infants and on the quality of breastmilk. Methods: The study had 2 components; a prospective study to examine the impact of infant feeding mode on nutritional and health indices in mothers and their infants and within it a nested randomized controlled clinical trial to study the impact of a daily 50 g soya/peanut based supplement during breastfeeding on the above parameters. The measurements included anthropometry; body composition indicators (using both deuterium dilution and BIA); haematology and biochemical markers; as well as incidence rates of opportunistic infections and clinical disease progression. Breastmilk was analysed for both macro and micronutrients. Cervical screening was offered to all the women. Results: AFASS criteria were fulfilled by 38.7% of the formula feeding mothers. No significant differences between the formula feeding and breastfeeding groups in terms of haematological, immunological and body composition changes were seen. Breastfeeding mothers had significantly lower events with high depression scores (p=0.043). Longer duration of breastfeeding was observed to be significantly associated with a mean increase in CD4 count (74 cells/μL) and better health outcomes. The supplement made no significant impact on any maternal or child outcomes except for a limited effect on mothers with low BMI, where it was significantly associated with preventing loss of lean body mass (p=0.026). Breastfeeding infants had a significantly lower risk of diarrhoea and hospitalisation at 3 months (p=0.006 and 0.014 respectively). Both breastfeeding and longer duration of breastfeeding was significantly associated with better development scores and growth parameters. Supplementation made no impact on breastmilk composition. Of the 86 mothers who agreed for cervical screening, 27.6% had human papilloma virus infection. Conclusions: Breastfeeding is not harmful to the mother despite the presence of HIV infection. On the contrary we observed both breastfeeding and longer breastfeeding duration to be associated with better maternal and child outcomes. Mothers are still choosing formula feeding inappropriately presumably because of the availability of free formula and/or sub-optimal counseling. The new (2010) local PMTCT guidelines based on WHO recommendations should reverse this. Food insecurity was prevalent amongst 32% of our study population, highlighting the need to include sustainable and empowering solutions to encounter this problem. Less sustainable solutions such as nutritional supplementation should be targeted to the malnourished and in emergency situations. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2012.