Dissertations / Theses: 'Intestinal absorption'

1

Morgan, Emma Louise. "Intestinal glucose and calcium absorption." Thesis, University of York, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424573.

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2

Patel, Raj B., and Raj B. Patel. "Prediction of Human Intestinal Absorption." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/624487.

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The proposed human intestinal absorption prediction model is applied to over 900 pharmaceuticals and has about 82.5% true prediction power. This study will provide a screening tool that can differentiate well absorbed and poorly absorbed drugs in the early stage of drug discovery and development. This model is based on fundamental physicochemical properties and can be applied to virtual compounds. The maximum well-absorbed dose (i.e., the maximum dose that will be more than 50 percent absorbed) calculated using this model can be utilized as a guideline for drug design, synthesis, and pre-clinical studies.

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3

Ashiru, Diane A. I. "Modulating Intestinal Absorption Using Pharmaceutical Excipients." Thesis, University College London (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509950.

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4

Wheeler, Sarah. "Enhancement of intestinal absorption of peptides." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394924.

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5

Lundin, Pål. "Intestinal permeability a parameter of mucosal dysfunction /." Lund : Dept. of Animal Physiology, Lund University, 1997. http://books.google.com/books?id=wuNqAAAAMAAJ.

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6

Glover, Chris. "Physiological characterisation of piscine intestinal zinc absorption." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272327.

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7

Wang, Chuan. "Pathologically and experimentally induced intestinal barrier changes evaluated by permeability measurements." Lund : Dept. of Animal Physiology, Lund University, 1995. http://books.google.com/books?id=ddlqAAAAMAAJ.

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8

Thiesen, Aducio Leonel. "Glucocorticosteroid effects on the intestinal absorption of nutrients." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq28993.pdf.

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9

Lord, Andrew P. D. "Intestinal absorption of [beta]-casomorphins in newborn animals /." Title page, contents and summary only, 1986. http://web4.library.adelaide.edu.au/theses/09SB/09sbl866.pdf.

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10

Balakrishnan, Anita. "Regulation of the diurnal rhythmicity of intestinal absorption." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539749.

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11

Bell, J. M. "Studies on the intestinal absorption of somatostatin analogues." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.379282.

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12

Shokry, Dina. "Predicting human intestinal absorption using chromatography and spectroscopy." Thesis, University of Huddersfield, 2017. http://eprints.hud.ac.uk/id/eprint/34142/.

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New drug entities (NDE) are constantly being developed with most of them intended for oral administration. For this reason, there is a need to estimate their absorption in order to save time and money that would be lost if the drug enters the clinical stage and is then found to exhibit poor absorption. For many years, the use of animals was the most abundant method for studying pharmacokinetics to predict parameters such as intestinal absorption. However, these methods are time consuming, and expensive as well as being ethically unfavourable. As a result, developing other methods to evaluate a drug’s pharmacokinetics is crucial. The aim of this work was to develop in vitro methods for estimation of human intestinal absorption (%HIA) to replace the use of the aforementioned, less favourable methods involving the use of animals. Among the developed methods in this thesis is a unique type of chromatography known as micellar liquid chromatography (MLC) using biosurfactants such as bile salts as a mobile phase. Furthermore, studies investigated the effect of a change in the stationary phase in addition to investigating the effect of the change in temperature on the elution of the analysed compounds. It was found that R2PRED for the developed MLC methods was in the range of 43.3 % - 91.12 %. Another developed method was a spectrophotometric method based on the use of the solubilising effects of bile salts, as well as their binding to compounds. Therefore, two spectrophotometric methods were developed, a solubilisation method and a double reciprocal method, and used in the prediction of %HIA. It was found that the solubilisation method had a better predictability for %HIA than that of the double reciprocal method where R2PRED was found to be 82.32 % and 61.90 % respectively. Finally, a permeation method was developed using the ability of NaDC to form a hydrogel under specific conditions and applying the investigated drugs in an infinite dose to the prepared hydrogels. This facilitated the determination of permeability coefficients (Kp) that were then used in the prediction of %HIA using the obtained model. The two developed permeation methods were found to have close values of R2PRED for % HIA where R2PRED of the permeation method using flow through cells was found to be 79.8 % while that of the permeation method using Franz cells was found to be 79.67 %. In summary, this work reports several unique models for the in vitro prediction of human intestinal absorption, potentially removing the need for animal testing to predict %HIA.

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13

Bramer, Steven L. "Absorption and toxicity of drugs in intestinal tract /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487779914824056.

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14

Roy, Isabelle. "Contribution à la mise en place d'un modèle "in vitro" prédictif de l'absorption et du métabolisme intestinal." Paris 5, 1994. http://www.theses.fr/1994PA05P159.

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15

Green, Alexander T. "An investigation into intestinal absorption of essential fatty acids." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259826.

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16

Khoo, Shui-Mei 1970. "An investigation of the factors which impact on the absorption and metabolism of halofantrine." Monash University, Dept. of Pharmaceutics, 2002. http://arrow.monash.edu.au/hdl/1959.1/8612.

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17

Ogawa, Eiichi. "The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice." Kyoto University, 2011. http://hdl.handle.net/2433/142540.

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18

Jackman, Mark Richard. "Endocytosis and transcytosis in the polarised epithelial cell line : caco-2." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283932.

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19

Sagor, Geoffrey Roland. "The hormonal mechanism of intestinal adaptation." Master's thesis, University of Cape Town, 1985. http://hdl.handle.net/11427/27274.

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The gastrointestinal tract has a large functional reserve. This is particularly true of the small intestine, and early studies by Flint in 1912, showed that dogs could withstand 50%-70% small intestinal resection, returning to normal health after an initial period of weight loss and malabsorption. No doubt, this reserve is in part due to the very high rate of epithelial proliferation in small bowel mucosa. Intestinal adaptation is the result of morphological and functional changes, and while these parameters can be accurately appreciated, the mechanisms by which these changes take place, are still under active investigation. This section summarises the changes, both structural and functional, in the adaptive process, and this is followed by a review of the background work done on the possible mechanism of adaptation. The normal anatomy of intestinal mucosa is however, considered first. Most of the work done to date in the field of intestinal adaptation, involves the small bowel, and this part of the gut will be discussed predominantly, but data available on colonic growth will be mentioned.

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20

Frazer, David Michael. "The molecular basis of intestinal iron absorption and its regulation /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17396.pdf.

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21

Matasconi, Manuela. "Pituitary regulation of plasma lipoprotein metabolism and intestinal cholesterol absorption /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-571-2/.

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22

Anderson, Paul. "Intestinal calcium absorption : the role of oestrogen and vitamin D /." Title page and abstract only, 1996. http://web4.library.adelaide.edu.au/theses/09SB/09sba548.pdf.

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23

Raja, K. "Studies on the mechanism and regulation of intestinal iron absorption." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383490.

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24

Moser, Sydney E. "Influence of dietary polyphenols on carbohydrate intestinal digestion and absorption." Thesis, Purdue University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10172872.

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Both epidemiological and clinical evidence support the notion that polyphenol rich foods and beverages may modify glycemic response, glucose homeostasis and subsequent risk of Type-2 diabetes. In vitro evidence typically derived from experiments with pure phenolics and phenolic rich extracts have pointed to this benefit being associated with two potential mechanisms: (1) the ability of specific polyphenolics to inhibit carbohydrate digestion (amylase and glucosidase) and (2) polyphenolic inhibition of intestinal glucose transport. While the high potential of these activities is evident, little is actually known regarding the extent to which these benefits are extendable to the actual food matrix these phenolics are naturally present in. Further, the extent to which co-consumption of polyphenol rich foods may actually result in decreased glycemic response from a mixed meal remains mostly unknown. Considering these limitations, additional insights are required in order to advance knowledge on the benefits of polyphenolics on glucomodulatory mechanisms and translation of these insights into meaningful recommendations and products for consumers. With this in mind, the objectives of these studies were to determine the extent to which phenolic-rich foods (grapes and potatoes) exert glucomodulatory properties in model food systems using in vitro and in vivo assessments. First, mechanisms associated with polyphenol rich extracts or model foods on carbohydrate intestinal digestion and glucose transport were investigated in vitro using a three-stage in vitro digestion model coupled to the Caco-2 human intestinal cell model. Components of this model used individually or in combination allowed for assessment of the two main mechanistic steps in phenolic modulation of glycemic response (starch digestion and glucose transport) in the context of interactions with bioaccessible phenolics. Additionally, the ability of the coupled in vitro digestion/Caco-2 model to predict in vivo outcomes was assessed.

The first study compared the ability of 100% Niagara or Concord grape juice (GJ) phenolics to modify carbohydrase activity and intestinal glucose transport relative to a sugar sweetened beverage. While grape juices remain a major dietary source of phenolics, they are also well recognized to be naturally high in sugar content. Insights into the ability of natural fruit phenolics to modify glycemic response of grape juice were investigated in vitro. Also, in consideration that 100% GJ is consumed with meals, the extent to which modulation of carbohydrate digestion and intestinal absorption by GJ phenolics can be extended to a carbohydrate rich meal was evaluated. In the first experiment, inhibition of α-amylase and α-glucosidase by GJ extracts (300 and 500 μM total phenolics) and ability of GJ extracts (10 to 100 μM total phenolics) to modulate labelled glucose and fructose transport across Caco-2 intestinal cell monolayers compared to a phenolic-free control were determined. GJ extracts decreased α-glucosidase, but not α-amylase activity at both concentrations tested. Further, glucose and fructose transport were significantly (p<0.05) decreased in a dose-dependent manner by Niagara and Concord GJ extracts. In a second experiment, GJs and phenolic-free control beverages were co-digested in vitro with a starch-rich model meal. Resulting aqueous digesta (AQ) from both experiments were used to assess impact of bioaccessible GJ phenolics on carbohydrate digestion and glucose transport. Concord and Niagara GJs significantly decreased in vitro gastrointestinal digestion of carbohydrate from model meal compared with a sugar-matched control. Further, d7-glucose transport from AQ fraction of GJ and co-digested GJ and carbohydrate-rich meal across Caco-2 human intestinal cell monolayers was significantly decreased compared to phenolic-free sugar-sweetened control.

The second study evaluated potential for phenolics from starch rich white, purple, or red potatoes to modulate carbohydrate digestion or glucose transport in a Caco-2 intestinal cell model. Potato phenolic extracts (300 μM) had no impact on α-amylase activity, and marginally decreased α-glucosidase activity. However, potato phenolic extracts (25-100μM) did decrease d7-glucose transport compared to phenolic-free control. Interestingly, whole potato phenolic extracts reduced glucose transport to a greater extent compared to those from potato peel. To determine if results from aforementioned in vitro assays are predictive of effects in vivo, a pilot clinical study (n=11) was completed to assess differences in acute blood glucose response and gastric emptying following consumption of phenolic-rich purple and red potato chips compared to white potato chips (50g available carbohydrate) containing lower level of total phenolics. Blood glucose levels were measured for up to two hours. Peak blood glucose levels were lower for pigmented chips, especially purple chips, compared to white chips without any significant changes in gastric emptying. These results suggest that potato phenolics may play a role in modulation of intestinal glucose transport and that these effects are translatable to consumer products such as potato chips.

Taken together, these data support the notion that phenolics intrinsic to select foods have the ability to modify glycemic response through alteration of glucose transport and to a certain extent starch digestion. Therefore, it is likely that observed benefits associated with consumption of phenolic-rich foods and 100% fruit juices, as a part of an overall healthy diet, may be associated with the ability of intrinsic and bioaccessible phenolics to modify glycemic response. Future research that focuses on hypoglycemic effects of phenolic-rich foods should be larger scale and should evaluate a greater variety of phenolic-rich foods in order to better understand the extent to which phenolic class and food matrix impact hypoglycemic effects. Regarding meal-effects, a pilot clinical study should be completed to validate in vitro results and to provide information as to what degree various types of meal patterns alter glycemic effects of phenolic-rich foods. Such information can be leveraged in the development of phenolic-rich food products that have post-prandial glycemic effects and for making recommendations of dietary choices which may result in improved glucose homeostasis.

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25

Holt, Adrian C. "The intestinal absorption of lead: the importance of lead speciation." Thesis, Aston University, 1988. http://publications.aston.ac.uk/14519/.

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26

Cong, Diem Huyen Ton Nu Quy. "Intestinal absorption and availability, a vascular perfusion study of the rat small intestine with benzoic acid." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0016/MQ54173.pdf.

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27

Betts, Andrea M. "An investigation into the intestinal absorption of melphalan in vivo and in vitro." Thesis, University of Aberdeen, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235651.

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Melphalan (the synthetic product of nitrogen mustard and L-phenylalanine) is an alkylating agent and is the drug of choice in the treatment of multiple myeloma. The bioavailability of melphalan is variable but factors affecting its absorption and the mechanism(s) by which the drug crosses the intestinal epithelium are not known. A sensitive assay for melphalan in plasma (down to a concentration of 2ng.ml^-1) has been developed. The method, involving solid phase extraction and derivatisation with o-phthalaldehyde followed by reversed-phase high-performance liquid chromatography, was applied to the study of melphalan pharmacokinetics in multiple myeloma patients. Bioavailability ranged from 0.16 to 1.37 in nine fasting patients and peak plasma concentrations of melphalan ranged from 8.0 to 170 ng.ml^-1 and occurred 0.5 to 2.0 hours after an oral dose of 10mg. When melphalan was taken with food (three patients) a mean reduction of 40% in bioavailability was observed. Significant correlations (P< 0.05) were observed between bioavailability and melphalan plasma concentrations in single samples drawn at 0.5, 1.0 and 2.0 hours. There was no significant correlation between renal function and melphalan absorption, distribution or elimination. A second peak was observed in the distribution phase of six of the eleven plasma concentration-time curves when melphalan was administered intravenously. The secondary peak may be attributed to either melphalan redistribution or enterohepatic circulation. An in vitro method (modified Ussing technique) was developed to investigate melphalan transport across rat and human small intestine. There was no evidence for the Na⁺-coupled (active) transport of melphalan in these tissues. The rate of melphalan transfer was non-saturable and values of apparent mass transfer coefficients were comparable with the diffusional contribution to the intestinal transport of amino acids The results indicate that passive diffusion is the major process responsible for the transfer of melphalan across intestinal epithelium.

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28

Davie, R. J. "The uptake and transport of zinc in isolated intestinal mucosa." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234707.

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29

Alvarenga, Mariana Lindenberg. "Cinética na absorção intestinal de [14C]-glutamina em camundongos saudáveis e submetidos à endotoxemia." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-02092013-110000/.

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Os diversos estudos com a suplementação de glutamina em situações de estresse fisiológico demonstram o essencial papel deste aminoácido no metabolismo. Agudamente, a suplementação com glutamina aumenta a glutaminemia. Cronicamente, verifica-se maior concentração de glutamina em tecidos, tais como o muscular e o hepático. Entretanto, não é conhecido se esses efeitos são decorrentes diretos da suplementação oral com glutamina ou da redução de sua captação a partir da membrana basolateral de enterócitos. O estudo da cinética na absorção de glutamina traz informações relacionadas à proporção da concentração de glutamina absorvida e a retida no tecido intestinal, de acordo com as doses utilizadas, e aponta quais são as alterações decorrentes da sepse induzida pela endotoxemia. O objetivo deste trabalho foi investigar a cinética de absorção de glutamina em camundongos submetidos à endotoxemia, o que não fora previamente investigado em outros trabalhos. Para avaliar a cinética da absorção intestinal de glutamina foi realizada eversão intestinal em camundongos machos, o que permite a coleta dos líquidos das camadas mucosa e serosa com maior precisão. Foram utilizadas doses de 10, 20, 40 e 50 mM de L-glutamina associada a [14C]-glutamina, nos tempos 0, 5, 10, 20, 30, 40, 60, 90 e 120 minutos. Os resultados obtidos demonstraram que em alta concentração de glutamina (50 mM) ocorre maior absorção em relação à retenção tecidual e esta é realizada por transporte ativo de aminoácidos. Os animais que foram submetidos à endotoxemia por LPS (5mg/kg) apresentaram alterações estruturais no tecido intestinal, detectadas pela histologia. Neste grupo, a retenção tecidual de glutamina foi significativamente maior do que no grupo controle, sobretudo na presença de glicose. Conclui-se que a cinética na absorção de glutamina é dose e tempo dependente em animais saudáveis e que, em condições de endotoxemia, ocorre maior retenção de glutamina no tecido intestinal na presença de glicose. Sugere-se que a via da hexosamina está envolvida; no entanto, mais estudos são necessários para esclarecer tais mecanismos.
The various studies of glutamine supplementation in stressful situations demonstrate the physiological role of this essential amino acid in metabolism. Acutely, supplementation with glutamine improves glutaminemia. Chronically, there is a greater concentration of glutamine in tissues such as muscle and liver. However, it is not known whether these effects are direct result of glutamine oral supplementation or reduced uptake within the basolateral membrane of enterocytes. The kinetic study of the absorption of glutamine provides information related to the ratio of concentration of glutamine absorbed and retained in the intestinal tissue, according to the doses used, and points out the changes resulting from sepsis induced by endotoxemia. The objective of this study was to investigate the kinetics of glutamine uptake in mice subjected to endotoxemia. To evaluate the kinetics of intestinal absorption of glutamine intestinal eversion was performed in male mice, allowing to collect the liquid layers of mucosa and serosa with greater precision. The doses used were 10, 20, 40 and 50 mM L-glutamine associated with [14C]-glutamine at 0, 5, 10, 20, 30, 40, 60, 90 and 120 minutes. The results showed that high concentrations of glutamine (50 mM) a higher absorption occurs in relation to tissue retention and this is accomplished by active transport of amino acids. The animals subjected to endotoxemia by LPS (5mg/kg) showed structural changes in the intestinal tissue, detected by histology. In this group, the tissue retention of glutamine was significantly higher than in the control group, especially in the presence of glucose. It is concluded that the kinetics of glutamine uptake is dose and time dependent in healthy animals, and in conditions of endotoxemia, there is greater retention of glutamine in intestinal tissue in the presence of glucose. It is suggested that the hexosamine pathway is involved; however, more studies are needed to clarify these mechanisms.

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30

Chan, Lauretta Man Sum. "Interactions between intestinal metabolic and secretory efflux systems." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366781.

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31

Monaghan, Alan S. "Chloride and potassium channels of enterocytes isolated from guinea-pig small intestinal villi." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338067.

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32

Høst, Jan. "In silico predicition of intestinal transport /." Cph. : The Danish University of Pharmaceutical Sciences, 2006. http://www.dfuni.dk/index.php/Jan_Hoest/3066/0/.

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33

Voght, Stephen P. "Establishment of a Drosophila model of intestinal sterol absorption and trafficking /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10303.

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34

Laftah, Abas Humood. "Role of haem biosynthesis in the regulation of intestinal iron absorption." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249734.

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35

Estes, Kari Ann. "Assessing Intestinal Absorption of Amino Acids Utilizing an Isotope Based Approach." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/84352.

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The purpose of this research was to further test a stable isotope based approach as a more reliable in vivo method to determine amino acid bioavailability from a variety of ingredients. The method was used to assess feather meal (FM), blood meal (BM), soybean meal (SBM), and a rumen protected amino acid (RPAA). An abomasal infusion of raw EAAs (isoleucine, leucine and methionine) and an abomasal infusion of sodium caseinate were used as control treatments to test the accuracy of the technique. The isotope-based results were then compared to in situ, in vitro and in vivo test results. The isotope-based technique provided AA bioavailability values for five non-essential AA and seven essential AA. The raw EAA infusion had the greatest AA recovery in plasma with an estimated absorbed RUP value of 93.4± 7.35% followed by the casein infusion (86.7 ± 4.81%), SBM (54.8 ± 5.19%), FM (52.7 ± 4.81%) and BM (47.5 ± 4.81%). The RPAA treatment had the lowest bioavailability at 9.9 ± 12.73%. Numerically, SBM supplied the most absorbable EAA of the 4 feed ingredients, but was not significantly different from that of BM and FM. Simply based on the control treatments in this research (raw EAA and casein), this isotope method was a more accurate method in determining AA bioavailability values with relatively low standard errors. Ingredients are exposed to all aspects of natural digestive processes and the method is able to determine AA appearance in the blood with no use of in situ or in vitro measurements.
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36

Newby, Danielle Anne. "Data mining methods for the prediction of intestinal absorption using QSAR." Thesis, University of Kent, 2014. https://kar.kent.ac.uk/47600/.

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Oral administration is the most common route for administration of drugs. With the growing cost of drug discovery, the development of Quantitative Structure-Activity Relationships (QSAR) as computational methods to predict oral absorption is highly desirable for cost effective reasons. The aim of this research was to develop QSAR models that are highly accurate and interpretable for the prediction of oral absorption. In this investigation the problems addressed were datasets with unbalanced class distributions, feature selection and the effects of solubility and permeability towards oral absorption prediction. Firstly, oral absorption models were obtained by overcoming the problem of unbalanced class distributions in datasets using two techniques, under-sampling of compounds belonging to the majority class and the use of different misclassification costs for different types of misclassifications. Using these methods, models with higher accuracy were produced using regression and linear/non-linear classification techniques. Secondly, the use of several pre-processing feature selection methods in tandem with decision tree classification analysis – including misclassification costs – were found to produce models with better interpretability and higher predictive accuracy. These methods were successful to select the most important molecular descriptors and to overcome the problem of unbalanced classes. Thirdly, the roles of solubility and permeability in oral absorption were also investigated. This involved expansion of oral absorption datasets and collection of in vitro and aqueous solubility data. This work found that the inclusion of predicted and experimental solubility in permeability models can improve model accuracy. However, the impact of solubility on oral absorption prediction was not as influential as expected. Finally, predictive models of permeability and solubility were built to predict a provisional Biopharmaceutic Classification System (BCS) class using two multi-label classification techniques, binary relevance and classifier chain. The classifier chain method was shown to have higher predictive accuracy by using predicted solubility as a molecular descriptor for permeability models, and hence better final provisional BCS prediction. Overall, this research has resulted in predictive and interpretable models that could be useful in a drug discovery context.

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37

Postal, Bárbara Graziela. "Role of environmental factors on intestinal barrier dysfunctions reported in obesity." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS310.pdf.

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L’obésité est associée à une inflammation intestinale. Une altération de la barrière intestinale par des facteurs environnementaux et nutritionnels, pourrait être impliquée dans l’initiation ou la modulation de cette inflammation. Dans ce contexte, j’ai étudié le rôle d’un lipide alimentaire et du facteur de transcription Aryl Hydrocarbon (AhR). J’ai montré qu’un apport à court-terme d’huile de palme provoque dans l’intestin une altération de la barrière et une inflammation modérée chez la souris. Dans la lignée Caco-2/TC7, l’acide palmitique augmente la perméabilité intestinale, la sécrétion de la cytokine IL-8 via des mécanismes impliquant la synthèse des céramides. L’évaluation du rôle d’AhR sur l’inflammation intestinale de patients obèses a montré qu’elle est négativement corrélée avec le taux d’ARNm d’AhR et de ses gènes cibles. L'activation d’AhR empêche l'altération des jonctions cellule-cellule induite par l'huile de palme chez la souris; limite les altérations de la barrière et la sécrétion de cytokines pro-inflammatoires via l’implication de protéines kinases dans les cellules Caco-2/TC7. Ainsi la détérioration de l’intégrité de la barrière intestinale contribue à l’inflammation dans l’épithélium intestinal. Un effet protecteur contre les atteintes intestinales dans l’obésité pourrait être obtenus par l’activation d’AhR qui deviendrait ainsi une cible thérapeutique
Obesity is associated with low-grade intestinal inflammation. The intestinal barrier disruption by nutrients and environmental factors may be implicated on the onset or modulation of this inflammation. Then, my aim was investigating the role of diet lipid and the transcription factor sensitive to environmental changes, Aryl Hydrocarbon receptor (AhR) on intestinal dysfunctions in obesity. I showed that a short-term intake of palm oil altered the intestinal barrier and a moderated the intestinal inflammation in mice. In Caco-2/TC7 cells, palmitic acid increased the paracellular permeability and IL-8 expression and secretion via the ceramides synthesis pathway. The evaluation of the role of AhR on the intestinal inflammation of obese patients has shown that it is negatively correlated with the level of AhR mRNA and its target genes. AhR activation prevents the alteration of cell-cell junctions induced by palm oil in mice; limits the alterations of the barrier and the secretion of pro-inflammatory cytokines via the involvement of protein kinases in Caco-2/TC7 cells. Thus, these data demonstrated that alteration of the intestinal epithelial barrier integrity is an important contributor of gut inflammation. A protective effect against intestinal inflammatory responses and barrier function damage in obesity could be achieved by AhR activation, which would become a therapeutic target

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38

Abgueguen, Emmanuelle. "Etude du rôle d'HFE dans l'épithélium intestinal de souris." Rennes 1, 2004. http://www.theses.fr/2004REN10110.

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Le gène HFE, muté dans l'Hémochromatose Héréditaire HFE1, interviendrait dans la régulation de l'absorption intestinale du fer mais son rôle dans les cellules des cryptes est inconnu. Afin de le préciser, nous avons étudié sur des puces à ADN les variations du transcriptome du duodénum de souris Hfe-/- et de souris surchargées en fer secondairement. L'analyse a révélé que 19 gènes étaient différentiels dans les souris Hfe-/-. Leur annotation fonctionnelle indique une sous expression des molécules du cytosquelette. Nous avons également recherché si l'expression de gènes du métabolisme du fer pouvait être modulée dans les cellules immortalisées des cryptes par un signal systémique. Le sérum de souris Hfe-/- appliqué aux cellules Hfe+/+ entraîne l'augmentation de l'expression de la ferroportine et de Dmt1 indiquant qu'un facteur sérique agirait au niveau des cellules des cryptes par l'intermédiaire d'Hfe pour moduler l'absorption du fer.

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Oti-Boateng, Peggy. "Effects of dietary calcium on intestinal non-haem iron absorption during weaning." Title page, contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09pho881.pdf.

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Corrigenda tipped to title page. Bibliography: leaves 313-353. This study investigated the iron status and dietary intakes in 6-24 month old children in Australia and Ghana and assessed the effects of dietary calcium on intestinal iron absorption. The true prevalence of non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA) and dietary intakes in infants and toddlers from a broad socio-economic background were assessed by haematological and biochemical parameters, semi-quantitative diet recall and anthropometric measurements. The high prevalence of iron deficiency and anaemia found in Australian and Ghanaian children can be attributed to the low intake of bioavailable iron in weaning diets which are often ingested with large amounts of calcium. While calcium has been shown to inhibit the absorption of iron, its mechanism of interaction with iron absorption at the intestinal level is not known. The rat was used as an experimental model to investigate the effects of dietary calcium on duodenal iron uptake. The results indicate there is a critical period during weaning when the consumption of high dietary calcium with low iron can retard growth potential. Dietary calcium significantly inhibits non-haem iron absorption at the intracellular level by up-regulating villus enterocyte ferritin concentrations under iron deficiency conditions.

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Tippin, Timothy Kent Thakker Dhiren R. "Novel approaches to assess the efficacy and toxicity of intestinal absorption enhancers." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,691.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.
Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Pharmacy." Discipline: Pharmacy; Department/School: Pharmacy.

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Barrow, Dalna Michelle. "The characterization of two novel genes involved in mammalian intestinal iron absorption." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409577.

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Ming, Xin Thakker Dhiren R. "Role of basolateral efflux transporters in intestinal absorption of drugs and prodrugs." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1825.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.
Title from electronic title page (viewed Dec. 11, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the School of Pharmacy." Discipline: Pharmacy; Department/School: Pharmacy.

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Ferrer, i. Roig Ruth. "Estudi histològic i del transport de manosacàrids dels segments cecals del pollastre." Doctoral thesis, Universitat de Barcelona, 1985. http://hdl.handle.net/10803/672986.

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L'intestí gruixut del pollastre està format pel recte, la cloaca i els cecs. Aquests darrers són un parell de ben desenvolupats diverticles que es troben connectats a la resta del tracte digestiu en el punt d'unió de l'ili amb el recte. Malgrat que no es coneix la significació fisiològica real dels segments cecals, se'ls ha atribuït nombroses funcions. Així, hi ha evidència que s'hi produeixen grans quantitats d'àcids grassos volàtils, vitamines i la hidròlisi de carbohidrats i proteïnes (McNAB, 1973). Els cecs també tenen un paper important en l'osmoregulació de l'organisme, ja que s'hi produeix l'absorció d'aigua i electròlits, tant de procedència urinària com intestinal (SKADHAUGE, 1981). Quant a l'absorció de no electròlits, les dades que fins ara es tenen són bastant limitades. HOLDSWORTH i WILSON (1967) trobaren que el transport actiu de sucres i aminoàcids en el cec de pollastre, hi era present només durant els tres primers dies després de l'eclosió de l'ou, desapareixent posteriorment. En el 1975, LERNER et al. confirmaren les dades anteriors utilitzant metionina com a substrat. Tanmateix, aquests resultats són diferents dels obtinguts en el nostre Laboratori, en els quals es demostra l'existència d'un mecanisme de transport mitjançat concentratiu per a monosacàrids en aquests segments intestinals i en animals de 4 a 7 setmanes. Atesa la manca d'informació i les discrepàncies amb la bibliografia, ens proposàrem realitzar un estudi dels sistemes de transport presents en aquests segments, complementat per un estudi histològic per si fos oportú correlacionar l'estructura amb la capacitat d'acumulació de monosacàrids. El que hom pretén és avaluar els diferents mecanismes existents a l'enteròcit, implicats en l'absorció intestinal de sucres. És a dir, el transport mitjançat concentratiu de la membrana luminal, el transport mitjançat equilibratiu de la membrana basolateral i la difusió simple existent a ambdues membranes. L'existència d'un mecanisme de transport actiu per a monosacàrids en el cec suposaria la recuperació dels nutrients que escapen de l'absorció a l'intestí prim a més de significar una modificació important en el concepte del paper que juguen els cecs en la nutrició del pollastre.

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Nauli, Andromeda Margono. "Intestinal Lipid Uptake and Secretion of VLDL and Chylomicron." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123866425.

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Margier, Marielle. "Absorption intestinale des vitamines D et K : mécanismes moléculaires et interactions avec les composés des légumineuses." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0623/document.

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Les vitamines D et K sont des micronutriments liposolubles qui participent au bon fonctionnement de l’organisme. Elles jouent des rôles clés dans la prévention de trouble de l'hémostase et de la coagulation, des pathologies osseuses, métaboliques et cardiovasculaires. Cependant, même si ces vitamines sont apportées en quantités suffisantes par notre alimentation, leurs effets bénéfiques sont étroitement conditionnés par leur biodisponibilité. Or, mieux connaitre les mécanismes d’absorption permettrait d’appréhender leur biodisponibilité. Nous avons tout d’abord montré que l’absorption de la vitamine K implique des transporteurs du cholestérol, SR-B1 et CD36. Nous avons également montré que l’entérocyte est non seulement capable d’effluer les vitamines D et K néo-absorbées mais également d’excréter ces vitamines du compartiment sanguin vers la lumière intestinale. Ce phénomène bien connu pour le cholestérol (excrétion transintestinale du cholestérol) implique des transporteurs communs, dont ABCB1 et ABCG5/G8. Dans un second temps, dans le cadre de la relance de la consommation des légumineuses, nous avons mis en évidence que la présence de légumineuses dans un repas limite la biodisponibilité de ces vitamines. En effet, les fibres, phytates, saponines et tanins diminuent leur bioaccessibilité et/ou leur captage. La méthode de cuisson des légumineuses, en affectant leur composition nutritionnelle, peut moduler l’incorporation des vitamines D et K au sein des micelles mixtes et donc affecter leur biodisponibilité. Ces données soulignent ainsi le fait que les légumineuses doivent être cuites de manière appropriée et consommés dans des repas riches en micronutriments
Vitamin D and K are fat-soluble micronutrients that participate to the proper functioning of the organism. They are essential to prevent bleeding, bone, metabolic and cardiovascular disorders. However, even if those vitamins are provided in sufficient quantities in our diet, their health effects are closely linked to their bioavailability. A better knowledge of their absorption mechanisms would help to optimize their bioavailability.Firstly, we showed that vitamin K absorption involves the cholesterol transporters SR-B1 and CD36. We also showed that enterocytes can not only efflux newly absorbed vitamins D and K but also excrete vitamin D and K from the blood compartment to the intestinal lumen. This phenomenon of transintestinal excretioninvolves the cholesterol membrane transporters ABCB1 and ABCG5/G8.Secondly, we showed that the presence of pulses within a meal limits vitamin D and K bioavailability. Indeed, fibers, phytates, saponins and tannins can decrease bioaccessibility and/or uptake of vitamin K. By modulating the nutritional profile of pulses, the cooking method can impact on fat-soluble vitamin transfer to mixed micelles, and in turn affect their bioavailability. These data suggest that pulses must be cooked in an appropriate manner and consumed in micronutrient-rich meals.Keywords: vitamin D, vitamin K, bioaccessibility, intestinal absorption, pulses

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Bergström, Christel A. S. "Computational and Experimental Models for the Prediction of Intestinal Drug Solubility and Absorption." Doctoral thesis, Uppsala University, Department of Pharmacy, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3593.

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New effective experimental techniques in medicinal chemistry and pharmacology have resulted in a vast increase in the number of pharmacologically interesting compounds. However, the number of new drugs undergoing clinical trial has not augmented at the same pace, which in part has been attributed to poor absorption of the compounds.

The main objective of this thesis was to investigate whether computer-based models devised from calculated molecular descriptors can be used to predict aqueous drug solubility, an important property influencing the absorption process. For this purpose, both experimental and computational studies were performed. A new small-scale shake flask method for experimental solubility determination of crystalline compounds was devised. This method was used to experimentally determine solubility values used for the computational model development and to investigate the pH-dependent solubility of drugs. In the computer-based studies, rapidly calculated molecular descriptors were used to predict aqueous solubility and the melting point, a solid state characteristic of importance for the solubility. To predict the absorption process, drug permeability across the intestinal epithelium was also modeled.

The results show that high quality solubility data of crystalline compounds can be obtained by the small-scale shake flask method in a microtiter plate format. The experimentally determined pH-dependent solubility profiles deviated largely from the profiles predicted by a traditionally used relationship, highlighting the risk of data extrapolation. The in silico solubility models identified the non-polar surface area and partitioned total surface areas as potential new molecular descriptors for solubility. General solubility models of high accuracy were obtained when combining the surface area descriptors with descriptors for electron distribution, connectivity, flexibility and polarity. The used descriptors proved to be related to the solvation of the molecule rather than to solid state properties. The surface area descriptors were also valid for permeability predictions, and the use of the solubility and permeability models in concert resulted in an excellent theoretical absorption classification. To summarize, the experimental and computational models devised in this thesis are improved absorption screening tools applicable to the lead optimization in the drug discovery process.

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Ao, Hei Sio. "In-vitro studies on the intestinal absorption mechanisms of flavonoids in Herba Epimedii." Thesis, University of Macau, 2008. http://umaclib3.umac.mo/record=b2158667.

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Engman, Helena. "Intestinal barriers to oral drug absorption : cytochrome P450 3A and ABC-transport proteins /." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3599.

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Yaakob, Harisun. "Understanding the effects of lipid and surfactants on the intestinal absorption of flavonoids." Thesis, University of East Anglia, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.533703.

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Foster, Russell. "Modulation of intestinal permeability with special reference to the absorption of bioactive peptides." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281711.

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Dissertations / Theses on the topic 'Intestinal absorption'

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