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Intestinal absorption

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https://www.readbyqxmd.com/read/29674332/potent-sglt1-2-dual-inhibition-improves-glycemic-control-without-marked-gastrointestinal-adaptation-or-colonic-microbiota-changes-in-rodents
#1
Fuyong Du, Simon Hinke, Cassandre Cavanaugh, David Polidori, Nathanial Wallace, Thomas Kirchner, Matthew Jennis, Wensheng Lang, Gee-Hong Kuo, Micheal Gaul, James Lenhard, Keith Demarest, Nadim J Ajami, Yin Liang, Pamela J Hornby
The sodium/glucose cotransporters (SGLT1 and SGLT2) transport glucose across the intestinal brush border and kidney tubule. Dual SGLT1/2 inhibition could reduce hyperglycemia more than SGLT2-selective in patients with Type 2 Diabetes; however, questions remain about altered gastrointestinal (GI) luminal glucose and tolerability. Therefore, this was evaluated in slc5a1-/- mice or using a potent dual inhibitor (cmpd 8; SGLT1 Ki = 1.5±0.5nM 100 fold > potency than phlorizin; SGLT2 Ki = 0.4±0.2 nM). 13C6-glucose uptake was quantified in slc5a1 -/- mice and in isolated rat jejunum...
April 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29673144/serum-hepcidin-concentration-in-individuals-with-sickle-cell-anemia-basis-for-the-dietary-recommendation-of-iron
#2
Juliana Omena, Cláudia Dos Santos Cople-Rodrigues, Jessyca Dias do Amaral Cardoso, Andrea Ribeiro Soares, Marcos Kneip Fleury, Flávia Dos Santos Barbosa Brito, Josely Correa Koury, Marta Citelli
Dietary iron requirements in patients with sickle cell disease (SCD) remain unclear. SCD is a neglected hemoglobinopathy characterized by intense erythropoietic activity and anemia. Hepcidin is the hormone mainly responsible for iron homeostasis and intestinal absorption. Intense erythropoietic activity and anemia may reduce hepcidin transcription. By contrast, iron overload and inflammation may induce it. Studies on SCD have not evaluated the role of hepcidin in the presence and absence of iron overload. We aimed to compare serum hepcidin concentrations among individuals with sickle cell anemia, with or without iron overload, and those without the disease...
April 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29672039/discovery-of-allosteric-potent-subtype-selective-and-peripherally-restricted-trka-kinase-inhibitors
#3
Sharan K Bagal, Kiyoyuki Omoto, David C Blakemore, Peter J Bungay, James G Bilsland, Philip J Clarke, Matthew S Corbett, Ciarán N Cronin, Jingrong Jean Cui, Rebecca Dias, Neil J Flanagan, Samantha E Greasley, Rachel Grimley, Eric Johnson, David Fengas, Linda Kitching, Michelle L Kraus, Indrawan McAlpine, Asako Nagata, Gareth J Waldron, Joseph S Warmus
Tropomyosin receptor kinases are a family of three tyrosine kinases (TrkA, TrkB, TrkC) activated by peptide hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and neurotrophin 4 (NT4). The NGF antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA kinase pathway in pain. In turn, this has led to significant interest in the development of small molecule inhibitors of TrkA as an alternative intervention point on the NGF pathway...
April 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29671906/the-particulate-passage-rate-nutrient-composition-and-fermentation-characteristics-across-gastrointestinal-tracts-in-lactating-dairy-cows-fed-three-different-forage-source-diets
#4
B Wang, F F Gu, X B Huang, J X Liu
This study was conducted to investigate the particulate passage rate, nutrient characteristics and fermentation parameters across the gastrointestinal tract (GIT) in lactating dairy cows fed cereal straws in comparison with alfalfa hay. Eighteen multiparous Holstein cows were randomly assigned to one of three experimental diets consisting of 55% concentrate, 15% corn silage and 30% different forage sources as follows (% of dry matter [DM]): (i) 23% alfalfa hay and 7% Chinese wild rye hay (AH); (ii) 30% corn stover (CS); and (iii) 30% rice straw (RS)...
April 19, 2018: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/29669985/dynamics-of-basal-lamina-fenestrations-in-the-rat-intestinal-villous-epithelium-in-response-to-dietary-conditions
#5
Rie Azumi, Keisuke Morita, Yusuke Mizutani, Manabu Hayatsu, Shuji Terai, Tatsuo Ushiki
The epithelial basal lamina of the small intestine forms a felt-like sheet at the base of the epithelium. Previous studies have shown that the basal lamina has numerous fenestrations, which are produced by leukocytes penetrating through the basal lamina. In this study, we aimed to directly visualize fenestrations of the rat basal lamina in intestinal villi by scanning electron microscopy (SEM) after removal of the villous epithelium by osmium maceration and ultrasonic treatment. Structural changes in fenestrations were then investigated in relation to dietary conditions...
2018: Biomedical Research
https://www.readbyqxmd.com/read/29669261/chrebp-deficiency-leads-to-diarrhea-predominant-irritable-bowel-syndrome
#6
Ah-Reum Oh, Seonyong Sohn, Junghoon Lee, Jong-Min Park, Ki Taek Nam, Ki-Baik Hahm, Young-Bum Kim, Ho-Jae Lee, Ji-Young Cha
OBJECTIVE: Fructose malabsorption is a common digestive disorder in which absorption of fructose in the small intestine is impaired. An abnormality of the main intestinal fructose transporter proteins has been proposed as a cause for fructose malabsorption. However the underlying molecular mechanism for this remains unclear. In this study, we investigated whether carbohydrate response element-binding protein (ChREBP) plays a role in intestinal fructose absorption through the regulation of genes involved in fructose transport and metabolism and ion transport...
April 15, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29669219/biotin-and-pantothenic-acid-over-supplementation-to-conditional-slc5a6-ko-mice-prevents-the-development-of-intestinal-mucosal-abnormalities-and-growth-defects
#7
Subrata Sabui, Rubina Kapadia, Abhisek Ghosal, Michael Schneider, Nils Lambrecht, Hamid M Said
Intestinal absorption of the water-soluble vitamins, biotin and pantothenic acid is carrier-mediated and involves the sodium-dependent multivitamin transporter (SMVT; product of the SLC5A6 gene). We recently observed that intestinal-specific (conditional) knockout of the mouse Slc5a6 gene (SMVT-cKO) is associated with growth retardation, the development of spontaneous and severe inflammation, abnormal histology in the large intestine, altered gut permeability, and early death. Our aim in this study was to examine the possibility that biotin and pantothenic acid over-supplementation (BPS) of the SMVT-cKO mice could reverse the above-described abnormalities...
April 18, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29668341/silicon-dioxide-nanoparticle-exposure-affects-small-intestine-function-in-an-in-vitro-model
#8
Zhongyuan Guo, Nicole J Martucci, Yizhong Liu, Eusoo Yoo, Elad Tako, Gretchen J Mahler
The use of nanomaterials to enhance properties of food and improve delivery of orally administered drugs has become common, but the potential health effects of these ingested nanomaterials remain unknown. The goal of this study is to characterize the properties of silicon dioxide (SiO2 ) nanoparticles (NP) that are commonly used in food and food packaging, and to investigate the effects of physiologically realistic doses of SiO2 NP on gastrointestinal (GI) health and function. In this work, an in vitro model composed of Caco-2 and HT29-MTX co-cultures, which represent absorptive and goblet cells, was used...
April 18, 2018: Nanotoxicology
https://www.readbyqxmd.com/read/29667422/intestinal-permeability-of-mitragynine-in-rats-using-in-situ-absorption-model
#9
J D Yuvenesan Jagabalan, Vikneswaran Murugaiyah, Hadzliana Zainal, Sharif Mahsufi Mansor, Surash Ramanathan
The intestinal permeability of mitragynine was investigated in situ using a single pass intestinal perfusion (SPIP) absorption model, in small intestine of rat using mitragynine in the absence/presence of the permeability markers, P-gp and/or CYP3A4 inhibitors. Mitragynine demonstrated high intestinal permeability (Peff of 1.11 × 10-4  cm/s) that is in the range of highly permeable drugs such as propranolol (Peff of 1.27 × 10-4  cm/s) indicating that it readily crosses the intestine. The addition of azithromycin (P-glycoprotein inhibitor) and ciprofloxacin (CYP3A4 inhibitor) or combination of both has no effect on intestinal permeability of mitragynine across the rat small intestine...
April 18, 2018: Journal of Asian Natural Products Research
https://www.readbyqxmd.com/read/29667316/opposite-effects-of-the-spinach-food-matrix-on-lutein-bioaccessibility-and-intestinal-uptake-lead-to-unchanged-bioavailability-compared-to-pure-lutein
#10
Marielle Margier, Caroline Buffière, Pascale Goupy, Didier Remond, Charlotte Halimi, Catherine Caris, Patrick Borel, Emmanuelle Reboul
SCOPE: Food matrix is generally believed to alter carotenoid bioavailability, but its effect on xanthophylls is usually limited. We thus aimed to decipher the digestion-absorption process of lutein in the presence or not of a food matrix. METHODS: We assessed lutein transfer to gastric-like lipid droplets or artificial mixed micelles when lutein was added to test meals either as a pure molecule ((all-E)-lutein) or in canned spinach ((Z) + (all-E)-lutein). The obtained mixed micelles were delivered to Caco-2 cells to evaluate lutein uptake...
April 17, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29666202/nutritional-role-of-amniotic-fluid-clues-from-infants-with-congenital-obstruction-of-the-digestive-tract
#11
Nigel J Hall, Melanie Drewett, David Burge
AIMS: To investigate the role played by amniotic fluid in late fetal nutrition by analysis of infants born with digestive tract atresia. METHODS: Birth weight (BW), gestational age and gender of infants born with oesophageal (OA), duodenal (DA), jejunal (JA) and ileal atresia (IA) were recorded and BW Z-scores compared. Infants with incomplete obstruction (stenosis), chromosomal or syndromic conditions and multiple congenital malformations were excluded. Term infants admitted with suspected postnatal intestinal obstruction in whom no congenital malformation was found were used as a control group...
April 17, 2018: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/29665864/recurrent-pregnancy-loss-is-associated-to-leaky-gut-a-novel-pathogenic-model-of-endometrium-inflammation
#12
C Tersigni, S D'Ippolito, F Di Nicuolo, R Marana, V Valenza, V Masciullo, F Scaldaferri, F Malatacca, C de Waure, A Gasbarrini, G Scambia, N Di Simone
BACKGROUND: Recurrent pregnancy loss (RPL) occurs in 3-5% in about 30% of cases no cause can be found. Women with RPL show higher prevalence of undiagnosed gut disorders. Furthermore, in endometrial tissues of RPL women, higher expression of pro-inflammatory cytokines and Nalp-3 inflammasome has been observed. Aim of this study was to investigate whether an abnormal gut permeability might occur in RPL women and allow passage into systemic circulation of pro-inflammatory molecules able to induce endometrial inflammation...
April 17, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29665381/a-refined-developability-classification-system-rdcs
#13
J Rosenberger, J Butler, J Dressman
In 2010, the Developability Classification System (DCS) was proposed. The DCS was deigned to close the gap between the BCS, which is aimed at guiding regulatory decisions about well-characterized drugs, and the need for early evaluation of drug candidates with respect to their suitability for oral delivery. The DCS applied solubility in FaSSIF to estimate intestinal solubility, assessed the compensatory nature of permeability and solubility during oral absorption and provided a way of estimating the critical the particle size at which dissolution becomes rate-limiting to absorption...
April 14, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29664912/metatranscriptome-analysis-of-the-microbial-fermentation-of-dietary-milk-proteins-in-the-murine-gut
#14
Floor Hugenholtz, Mark Davids, Jessica Schwarz, Michael Müller, Daniel Tomé, Peter Schaap, Guido J E J Hooiveld, Hauke Smidt, Michiel Kleerebezem
Undigestible food ingredients are converted by the microbiota into a large range of metabolites, predominated by short chain fatty acids (SCFA). These microbial metabolites are subsequently available for absorption by the host mucosa and can serve as an energy source. Amino acids fermentation by the microbiota expands the spectrum of fermentation end-products beyond acetate, propionate and butyrate, to include in particular branched-SCFA. Here the long-term effects of high protein-diets on microbial community composition and functionality in mice were analyzed...
2018: PloS One
https://www.readbyqxmd.com/read/29664632/ph-and-amylase-responsive-carboxymethyl-starch-poly-2-isobutyl-acrylic-acid-hybrid-microgels-as-effective-enteric-carriers-for-oral-insulin-delivery
#15
Liang Liu, Ying Zhang, Shuangjiang Yu, Zhen Zhang, Chaoliang He, Xuesi Chen
Oral delivery of insulin has the potential to revolutionize diabetes care since it is regarded as a non-invasive therapeutic approach without the side effects caused by frequent subcutaneous injection. However, the insulin delivery efficiency through oral route was still limited, likely due to the chemical, enzymatic and absorption barriers. In this study, a novel type of pH- and amylase-responsive microgels as an insulin drug carrier for oral administration was developed to improve the drug delivery efficiency...
April 17, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29663812/effect-of-foods-and-%C3%AE-cyclodextrin-on-the-bioaccessibility-and-the-uptake-by-caco-2-cells-of-hydroxytyrosol-from-either-a-pure-standard-or-alperujo
#16
Aurélia Malapert, Valerie Tomao, Olivier Dangles, Emmanuelle Reboul
Hydroxytyrosol bioaccessibility and absorption by the intestinal cells have been studied using an in vitro digestion model and Caco-2 TC7 monolayers cells in culture, in the presence or absence of β-cyclodextrin and foods. Hydroxytyrosol was either provided as a pure standard or in an alperujo powder. The presence of foods significantly decreased hydroxytyrosol bioaccessibility and absorption (-20% and -10%, respectively), while β-cyclodextrin had no effect. Moreover, the presence of other compounds from alperujo in the intestine compartment reduced hydroxytyrosol absorption by Caco-2 cells compared to pure standard (-60%)...
April 17, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29663515/determining-optimal-therapy-of-dogs-with-chronic-enteropathy-by-measurement-of-serum-citrulline
#17
Magda Gerou-Ferriani, Rhiannon Allen, Peter-John M Noble, Alexander J German, Marco Caldin, Daniel J Batchelor
BACKGROUND: Serum concentration of citrulline is a useful biomarker in human intestinal disease and indicates globally reduced enterocyte mass and absorptive function in various disease states. OBJECTIVES: To determine whether serum citrulline concentration is a biomarker in chronic enteropathy (CE) in dogs, to provide useful information regarding optimal treatment or to predict outcome. ANIMALS: Seventy-four dogs with CE and 83 breed- and age-matched hospital controls with no clinical signs of intestinal disease...
April 16, 2018: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29663288/in-vitro-in-vivo-predictive-dissolution-permeation-absorption-dynamics-of-highly-permeable-drug-extended-release-tablets-via-drug-dissolution-absorption-simulating-system-and-ph-alteration
#18
Zi-Qiang Li, Shuang Tian, Hui Gu, Zeng-Guang Wu, Makafui Nyagblordzro, Guo Feng, Xin He
Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form...
April 16, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29660464/drug-permeability-profiling-using-cell-free-permeation-tools-overview-and-applications
#19
REVIEW
Philippe Berben, Annette Bauer-Brandl, Martin Brandl, Bernard Faller, Gøril Eide Flaten, Ann-Christin Jacobsen, Joachim Brouwers, Patrick Augustijns
Cell-free permeation systems are gaining interest in drug discovery and development as tools to obtain a reliable prediction of passive intestinal absorption without the disadvantages associated with cell- or tissue-based permeability profiling. Depending on the composition of the barrier, cell-free permeation systems are classified into two classes including (i) biomimetic barriers which are constructed from (phospho)lipids and (ii) non-biomimetic barriers containing dialysis membranes. This review provides an overview of the currently available cell-free permeation systems including Parallel Artificial Membrane Permeability Assay (PAMPA), Phospholipid Vesicle-based Permeation Assay (PVPA), Permeapad®, and artificial membrane based systems (e...
April 13, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29660405/microbiome-mediated-bile-acid-modification-role-in-intestinal-drug-absorption-and-metabolism
#20
REVIEW
Elaine F Enright, Brendan T Griffin, Cormac G M Gahan, Susan A Joyce
Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research...
April 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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