Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Rostock, 1934.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (M.S.)--University of Wisconsin--La Crosse, 2002. / Includes bibliographical references.

No description available.

Abstract The effects of dietary sucrose and systemic glucocorticoid treatment on the response of the pulpodentinal complex to dental caries were examined in an experimental rat model. The possible role of dentinal caries on dentin formation was also examined. After 5-6 weeks of a dietary and/or medication period, the areas of dentin formation and dentinal caries were quantified in the molars of growing animals. Also the number and severity of caries lesions were estimated. The 43% sucrose diet significantly reduced dentin formation and increased dentinal caries progression. Although glucocorticoid medication alone reduced dentin formation, without dietary sucrose it did not have an effect on caries. In combination of these two, glucocorticoids further increased the progression of dentinal caries, however without significant increase in the number of caries lesions. The cariogenic bacterial inoculation of rats fed a sucrose or control diet increased the progression of dentinal caries. The relationship between cariogenic bacteria and caries was not strong, but there was a stronger relationship between the total amount of dietary sucrose and dentinal caries. In addition to the overall reduction of dentin formation there was no difference in the amount of dentin formed between intact and carious fissures in the sucrose diet group. On the contrary, rats receiving the control diet positively responded to the dentinal caries by increasing dentin formation to prevent pulpal exposure. Whereas the high sucrose diet impaired both the deposition and mineralization of the dentin matrix, glucocorticoids affected matrix formation only. These results indicate that the functional alterations in the pulpo-dentinal complex might contribute to dentinal caries progression in a cariogenic environment, irrespective of the causative mechanism.

Dietary composition can impact colonization and composition of gut microbiota. The first aim of this dissertation was to evaluate the effect of dietary Se deprivation, sex and, aging on taxonomic composition of gut microbiota in mice. We have previously shown that long-term dietary Se deprivation promotes health span deteriorate including type-2 diabetes like symptoms in later state Terc-/- mice carrying humanized telomeres. In the present study, the data suggested that the dietary Se deprivation and aging significantly and comparably altered the gut microflora composition. The ratio of Firmicutes/Bacteroidetes was decreased by dietary Se deprivation or aging in both sexes. Abundance of selective gut bacteria genus was associated with dietary Se status and aging as evidenced by heat map and principal coordinate analyses. Moreover, the abundance of Akkermensia muciniphila, a bacterium in association with obesity, differed by Se-deprivation, aging and sex. Taken together, changes in gut microbiota composition by dietary Se deprivation may accelerate mouse aging in a sex-specific manner. The second aim of this dissertation was to investigate the effects and underlying mechanism of fecal fermentation of non-digestible fibers isolated from common beans on adipocyte differentiation and fat accumulation to elucidate the cellular mechanisms. Treatment of 3T3-L1 murine preadipocytes with fermented product resulted in a reduction of triglyceride accumulation in a dose- and time-dependent manner. The fermentation product exhibited antiipogenic effects through suppression of the adipogenesis-associated key transcription factors or activators peroxisome proliferator-activated receptor gamma (Ppar gamma), CCAAT enhancer-bind protein alpha (C/ebp alpha) and fatty acid binding protein 4 (Fabp4). Moreover, the mRNA expression lipolytic genes including peroxisome proliferator-activated receptor delta (Ppar delta) and mitochondrial uncoupling protein 2 (Ucp2) were induced by the fermentation products of non-digestible fiber isolated from common beans counteract adipogenesis through regulation of key targets.Altogether, optimizing gut microbiota by nutritionally adequate level of dietary Se and non-digestible fiber appears to represent a promising strategy to control or prevent early onset of aging and age-related metabolic diseases.

Yes / Patients with adenomatous colonic polyps are at increased risk of developing further polyps suggesting field-wide alterations in cancer predisposition. The current study aimed to identify molecular alterations in the normal mucosa in the proximity of adenomatous polyps and to assess the modulating effect of butyrate, a chemopreventive compound produced by fermentation of dietary residues. A cross-sectional study was undertaken in patients with adenomatous polyps: biopsy samples were taken from the adenoma, and from macroscopically normal mucosa on the contralateral wall to the adenoma and from the mid-sigmoid colon. In normal subjects biopsies were taken from the mid-sigmoid colon. Biopsies were frozen for proteomic analysis or formalin-fixed for immunohistochemistry. Proteomic analysis was undertaken using iTRAQ workflows followed by bioinformatics analyses. A second dietary fibre intervention study arm used the same endpoints and sampling strategy at the beginning and end of a high-fibre intervention. Key findings were that keratins 8, 18 and 19 were reduced in expression level with progressive proximity to the lesion. Lesional tissue exhibited multiple K8 immunoreactive bands and overall reduced levels of keratin. Biopsies from normal subjects with low faecal butyrate also showed depressed keratin expression. Resection of the lesion and elevation of dietary fibre intake both appeared to restore keratin expression level. Changes in keratin expression associate with progression towards neoplasia, but remain modifiable risk factors. Dietary strategies may improve secondary chemoprevention. / Food Standards Agency (Ref N12017), EPSRC (EP/E036252/1), University of Sheffield

Due to their rising popularity, herbal supplements have created a specific niche for themselves between the food and the drug industry. Due to their categorization as dietary supplements, they lack scientific seriousness where as on the other hand they act like unregulated drugs with potential effects. Finding scientific data of questionable accuracy for herbal supplements is not uncommon, which is usually designed to sell products rather then provide unbiased information. Hence, development of performance standards based on the bioavailability of the active components of herbal extracts promises to be an attractive solution towards regulating the inflow of meaningful products in the herbal supplement market. Solubility, partition coefficient and permeability are the fundamental properties for studying drug absorption. Top selling herbal extracts from the United States that included Kava, Ginkgo biloba, Milk thistle, Ginseng, Black cohosh, Garlic, Valerian, and Echinacea were selected and in silico descriptors such as CLogP, minimal cross-sectional area, polar surface area and in vitro permeability using the Caco-2 cell model and SimBioDAS® of their active components, determined. Based on the interparameter relationships between the minimal cross sectional area, CLogP, polar surface area and the in vitro permeability of the active components, bioavailability/bioequivalence markers were predicted for Kava, Ginkgo biloba and Milk thistle. Kawain was predicted as a marker for Kava, Ginkgolide B for the ginkgo terpenes and quercetin for the flavonol glycosides in Ginkgo biloba and silycristin as a marker for Milk thistle (silymarin). Silymarin comprising of isomers silycristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B was selected as a representative extract for further confirmation of marker prediction. Equilibrium solubility, experimental octanol-water partition coefficient values, and assay and in vitro dissolution profiles were determined for each of the active isomers in extract and market products respectively. The pharmacokinetics and absolute bioavailability of each of the active isomers was determined in male Sprague Dawley rats following intravenous and oral administration of the silymarin extract. Equilibrium solubility values indicated that all the silymarin isomers were practically insoluble, and silycristin and silydianin had relatively higher solubility values as compared to the other isomers. Experimental partition coefficient values correlated with the predicted partition coefficient (CLogP) with an r² of 0.834. Based on their equilibrium solubility and the partition coefficient (experimental and predicted) the active isomers were classified according to the Biopharmaceutic Classification System (BCS). Thus, isomers silybin A, silybin B, isosilybin A and isosilybin B were classified as Class II compounds (High PermeabilityLow Solubility) where as silydianin was classified as a Class IV compound (Low Permeability-Low Solubility). Silycristin was classified as a intermediate between Class II and Class IV. Absolute bioavailability (F) for silycristin was found to be the lowest (0.15±0.1), followed by silybin A (0.20±0.04) followed by silybin B (0.62±0.08). Silycristin being one of the least permeable and bioavailable component, was selected as a marker for silymarin, further confirming its prediction based on the correlations between the in silico descriptors and in vitro permeability. Pharmacokinetic parameters such as area under the curve, half life, volume of distribution, clearance and F for the components suggest significant differences between not only the silymarin isomers but also diastereomers of silybin (A and B) and isosilybin (A and B). Selection of bioavailability-bioequivalence markers, based on their least permeability/bioavailability, proves to be the most conservative and meaningful approach towards standardization of complex mixtures such as herbal extracts and supplements.

The objective was to conduct a systematic review and meta-analysis of randomized feeding trials to assess the effect of dietary pulses (beans, chickpeas, lentils, peas) on established lipid targets of cardiovascular disease (CVD) and perform a secondary analysis of our randomized feeding trial to assess whether dietary pulses as a means of lowering the glycemic index offer further CVD protection by reducing oxidative stress. The meta-analysis of 26 trials (n=1013) found dietary pulse interventions significantly lowered LDL-C compared with isocaloric control interventions (mean difference=-0.17mmol/L [95% CI: -0.25, -0.09]; p<0.0001). No treatment effects were observed for Apo-B and non-HDL-C. Our feeding trial found no significant differences between the high-dietary pulse diet and high-fibre control diet on markers of oxidative stress, including thiobarbituric acid reactive substances (TBARS), conjugated dienes (CDs), and protein thiols. Overall, the results suggest dietary pulses reduce LDL-C but not oxidative stress as a means of reducing cardiovascular risk.