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Intestinal permeability

Xiangming Ding, Dongxiao Li, Mengke Li, Han Wang, Qin He, Yunwu Wang, Hongbing Yu, Dean Tian, Qin Yu
SLC26A3 encodes a Cl-/HCO3- ion transporter that is also known as downregulated in adenoma (DRA) and is involved in HCO3-/mucus formation. The role of DRA in the epithelial barrier has not been previously established. In this study, we investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies reveal that DRA binds directly to tight junction (TJ) proteins and affects the expression of TJ proteins in polarized Caco-2BBe cells...
January 12, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
J Alex Pasternak, Vaishnavi Iyer Aka Aiyer, Glenn Hamonic, A Denise Beaulieu, Daniel A Columbus, Heather L Wilson
We intended to assess how exposure of piglets to deoxynivalenol (DON)-contaminated feed impacted their growth, immune response and gut development. Piglets were fed traditional Phase I, Phase II and Phase III diets with the control group receiving 0.20-0.40 ppm DON (referred to as the Control group) and treatment group receiving much higher level of DON-contaminated wheat (3.30-3.80 ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had no impact on average daily feed intake (ADFI) (p < 0...
January 12, 2018: Toxins
Eleonore Haltner-Ukomadu, Svitlana Gureyeva, Oleksii Burmaka, Andriy Goy, Lutz Mueller, Grygorii Kostyuk, Victor Margitich
An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility) of the antiviral compound enisamium iodide (4-(benzylcarbamoyl)-1-methylpyridinium iodide) were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp) of enisamium iodide was assessed using human colon carcinoma (Caco-2) cells at three concentrations. The solubility of enisamium iodide in four buffer solutions from pH 1...
January 11, 2018: Scientia Pharmaceutica
Jonas Franz, Jonas Grünebaum, Marcus Schäfer, Dennis Mulac, Florian Rehfeldt, Klaus Langer, Armin Kramer, Christoph Riethmüller
Symmetry is rarely found on cellular surfaces. An exception is the brush border of microvilli, which are essential for the proper function of transport epithelia. In a healthy intestine, they appear densely packed as a 2D-hexagonal lattice. For in vitro testing of intestinal transport the cell line Caco-2 has been established. As reported by electron microscopy, their microvilli arrange primarily in clusters developing secondly into a 2D-hexagonal lattice. Here, atomic force microscopy (AFM) was employed under aqueous buffer conditions on Caco-2 cells, which were cultivated on permeable filter membranes for optimum differentiation...
2018: PloS One
Martin Asama, Alex Hall, Yijun Qi, Branden Moreau, Heidi Walthier, Matthew Schaschwary, Blaine Bristow, Qun Wang
Approximately 907,000 Americans currently suffer from ulcerative colitis, a condition characterized by inflammation of the large intestine or rectum. Treatment of this disease often includes anti-inflammatory medication or immunosuppressants. Here foams are an attractive delivery platform, offering relatively high bioavailability, low systemic exposure, and improved patient comfort. However, the surfactants that generate these foams may adversely affect the diseased mucosa. Therefore, this project evaluated two alternative surfactants for use in topical drug delivery platforms: sodium caseinate and L-α-phosphatidylcholine...
January 3, 2018: Journal of Biomedical Materials Research. Part A
Ying Shi, Xi Zhao, Zhao Jianxin, Zhang Hao, Qixiao Zhai, Arjan Narbad, Wei Chen
AIMS: This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. METHODS AND RESULTS: Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia...
January 3, 2018: Journal of Applied Microbiology
Alexey A Tinkov, Viktor A Gritsenko, Margarita G Skalnaya, Sergey V Cherkasov, Jan Aaseth, Anatoly V Skalny
The primary objective of the present study was to review the impact of Cd exposure on gut microbiota and intestinal physiology, as well as to estimate whether gut may be considered as the target for Cd toxicity. The review is based on literature search in available databases. The existing data demonstrate that the impact of Cd on gut physiology is two-sided. First, Cd exposure induces a significant alteration of bacterial populations and their relative abundance in gut (increased Bacteroidetes-to-Firmicutes ratio), accompanied by increased lipopolysaccharide (LPS) production, reflecting changed metabolic activity of the intestinal microbiome...
January 5, 2018: Environmental Pollution
Yohan Lee, Hyun-Ro Lee, KyuHan Kim, Siyoung Q Choi
Because numerous drugs are administered through an oral route and primarily absorbed at the intestine by passive diffusion, the prediction of drug permeability across an intestinal epithelial cell membrane has been a crucial issue in drug discovery. Thus, various in vitro permeability assays have been developed such as the Caco-2 assay and the parallel artificial membrane permeability assay (PAMPA). However, due to the time-consuming and quite expensive process for culturing cells in the Caco-2 assays and the ambiguous membrane structures of the PAMPA, a simpler yet more accurate and versatile technique is still required...
January 8, 2018: Analytical Chemistry
Manal A Elsheikh, Yosra S R Elnaggar, Dina Y Otify, Ossama Y Abdallah
PURPOSE: To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS: Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model and Caco-2 cell model. Furthermore, Bioactive-chylomicrons' cellular uptake and distribution were examined by laser scanning confocal microscopy. Finally, a novel chylomicron flow-blockage assay on tissue and cellular levels were elaborated to assess the lymphatic targeting ability...
January 5, 2018: Pharmaceutical Research
Xin Zhang, Hongbo Cheng, Wei Dong, Meixia Zhang, Qiaoyu Liu, Xiuhua Wang, Jian Guan, Wu Haiyang, Shirui Mao
The objective of this study was to design intestinal mucus-penetrating core-shell nanocomplex by functionally mimicking the surface of virus, which can be used as the carrier for peroral delivery of macromolecules, and further understand the influence of nanocomplex surface properties on the mucosal permeation capacity. Taking insulin as a model drug, the core was formed by the self-assembly among positively charged chitosan, insulin and negatively charged sodium tripolyphosphate, different types of alginates were used as the shell forming material...
January 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Rachel C Anderson, Alastair K H MacGibbon, Neill Haggarty, Kelly M Armstrong, Nicole C Roy
Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600)...
2018: PloS One
Samarjit Jana, Jagannath Jana, Kartick Patra, Soma Mondal, Jyotsna Bhat, Arnab Sarkar, Pallabi Sengupta, Anindya Biswas, Meghomukta Mukherjee, Satya Prakash Tripathi, Rahul Gangwal, Joyita Hazra, Abhay T Sangamwar, Gopeswar Mukherjee, Shamee Bhattacharjee, Deba Prasad Mandal, Subhrangsu Chatterjee
Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion in vitro and in vivo. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC00273 as a novel molecular target of M2...
December 15, 2017: Oncotarget
Agnieszka Szymanska-Michalak, Dariusz Wawrzyniak, Grzegorz Framski, Jacek Stawinski, Jan Barciszewski, Adam Kraszewski
We have designed and synthesized new 5-fluoro-2'-deoxyuridine 5'-phosphate pronucleotides which can function as potential agents against the glioblastoma multiforme tumor. Their anti-malignant potency has been tested against T98G, U-118 MG, U-87 MG gliomas, HeLa, and Caco-2 cancer cell lines, using MRC-5 healthy cells as a reference. Five of the sixteen compounds (4c, 4f-i) exhibited significant anticancer potency and high selectivity indices (SI 12-66). It is likely that these zwitterionic pronucleotides may function in a similar manner to zwitterionic phospholipids, by inducing cell membrane charge disorder, making the cell permeable to bioactive agents...
December 21, 2017: European Journal of Medicinal Chemistry
Yanhua Liu, Tong Yang, Shijie Wei, Chengming Zhou, Yang Lan, Aichen Cao, Jianhong Yang, Wenping Wang
Low aqueous solubility and intestinal permeability limit the oral chemotherapy efficacy of paclitaxel (PTX). Traditional nanodrug delivery systems show excellent aqueous solubility improved ability of PTX. However, gastrointestinal (GI) mucus limits the improvement of intestinal permeability in traditional nanodrug delivery systems. A novel mucus adhesion- and penetration-functionalized chitosan-thioglycolic acid-Pluronic F127 (CS-TGA-PF) liposome system was developed for PTX oral delivery. The optimized formulation of PTX-loaded CS-TGA-PF liposomes showed particle size of 121...
December 27, 2017: International Journal of Pharmaceutics
Isabel Lozoya-Agullo, Isabel Gonzalez-Alvarez, Moran Zur, Noa Fine-Shamir, Yael Cohen, Milica Markovic, Teresa M Garrigues, Arik Dahan, Marta Gonzalez-Alvarez, Matilde Merino-Sanjuán, Marival Bermejo, Alex Avdeef
PURPOSE: The effective rat intestinal permeability (P eff ) was deconvolved using a biophysical model based on parameterized paracellular, aqueous boundary layer, transcellular permeabilities, and the villus-fold surface area expansion factor. METHODS: Four types of rat intestinal perfusion data were considered: single-pass intestinal perfusion (SPIP) in the jejunum (n = 40), and colon (n = 15), closed-loop (Doluisio type) in the small intestine (n = 78), and colon (n = 74)...
December 29, 2017: Pharmaceutical Research
David R Hill, Sha Huang, Yu-Hwai Tsai, Jason R Spence, Vincent B Young
Advances in 3D culture of intestinal tissues obtained through biopsy or generated from pluripotent stem cells via directed differentiation, have resulted in sophisticated in vitro models of the intestinal mucosa. Leveraging these emerging model systems will require adaptation of tools and techniques developed for 2D culture systems and animals. Here, we describe a technique for measuring epithelial barrier permeability in human intestinal organoids in real-time. This is accomplished by microinjection of fluorescently-labeled dextran and imaging on an inverted microscope fitted with epifluorescent filters...
December 18, 2017: Journal of Visualized Experiments: JoVE
Silke Crommen, Marie-Christine Simon
Type 2 diabetes is a combined disease, resulting from a hyperglycemia and peripheral and hepatic insulin resistance. Recent data suggest that the gut microbiota is involved in diabetes development, altering metabolic processes including glucose and fatty acid metabolism. Thus, type 2 diabetes patients show a microbial dysbiosis, with reduced butyrate-producing bacteria and elevated potential pathogens compared to metabolically healthy individuals. Furthermore, probiotics are a known tool to modulate the microbiota, having a therapeutic potential...
December 29, 2017: Genes
Zhongze Liu, Liangzi Li, Weigang Chen, Qimeng Wang, Weidong Xiao, Yuanhang Ma, Baifa Sheng, Xiang Li, Lihua Sun, Min Yu, Hua Yang
Intestinal ischemia/reperfusion (I/R) induces disruption of the intestinal barrier function. Aryl hydrocarbon receptor (AhR) has a vital role in maintaining the intestinal barrier function. However, the precise mechanism by which AhR maintains intestinal barrier function remains unclear. Notch1 signaling is downstream of AhR, and has also been reported to have a role in the development of tight junctions (TJs) and maintenance of intestinal homeostasis. Therefore, we hypothesized that AhR activation may attenuate the intestinal barrier dysfunction through increased activation of Notch1 signaling...
December 22, 2017: International Journal of Molecular Medicine
Agata Binienda, Martin Storr, Jakub Fichna, Maciej Salaga
Irritable bowel syndrome (IBS) is a chronic, recurrent bowel disorder with an unknown etiology, which is most likely multifactorial. Increased mucosal permeability, visceral hypersensitivity and activation status of intestinal mucosal immune cells cause changes in gastrointestinal (GI) motility, secretion and sensation observed in the course of IBS. Permanent, cumbersome symptoms, such as diarrhea, constipation and abdominal pain greatly lower quality of life of IBS patients. On this basis, according to the Rome IV criteria, different forms of IBS can be distinguished...
December 27, 2017: Current Drug Targets
Innocent Mwape, Samuel Bosomprah, John Mwaba, Katayi Mwila-Kazimbaya, Natasha Makabilo Laban, Caroline Cleopatra Chisenga, Gibson Sijumbila, Michelo Simuyandi, Roma Chilengi
INTRODUCTION: Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity and mortality globally. Unfortunately, vaccine performance in low-middle income countries (LMICs) is generally lower than in developed countries. The cause for this has been associated with several host and maternal factors including poor water sanitation and hygiene (WASH) status, which are predominant in LMICs. More recently, environmental enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine uptake and response...
2017: PloS One
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