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Intestinal permeability

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https://www.readbyqxmd.com/read/29773368/mutlifunctional-nanoparticles-prepared-from-arginine-modified-chitosan-and-thiolated-fucoidan-for-oral-delivery-of-hydrophobic-and-hydrophilic-drugs
#1
Chien-Ho Chen, Yung-Song Lin, Shao-Jung Wu, Fwu-Long Mi
Self-assembled nanoparticles (NPs) from arginine-modified chitosan (CS-N-Arg) and thiolated fucoidan (THL-fucoidan) were synthesized to enhance the transport of dextran and curcumin across intestinal epithelial cell layer. CS-N-Arg/THL-fucoidan NPs exhibited a pH-sensitive assembly-disassembly and drug release property. Evaluations of the NPs in enhancing the transport of a hydrophilic macromolecule (FITC-dextran) and a hydrophobic drug (curcumin) were investigated in Caco-2 cell monolayers. The cationic CS-N-Arg in the NPs induced disruption of intestinal epithelial tight junctions as indicated by the decrease of transepithelial electrical resistance (TEER)...
August 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29770852/notch-inhibition-counteracts-paneth-cell-death-in-absence-of-caspase-8
#2
M K Jeon, E Kaemmerer, U Schneider, M Schiffer, C Klaus, J Hennings, T Clahsen, T Ackerstaff, M Niggemann, A Schippers, T Longerich, G Sellge, C Trautwein, N Wagner, C Liedtke, N Gassler
Opposing activities of Notch and Wnt signaling regulate mucosal barrier homeostasis and differentiation of intestinal epithelial cells. Specifically, Wnt activity is essential for differentiation of secretory cells including Wnt3-producing Paneth cells, whereas Notch signaling strongly promotes generation of absorptive cells. Loss of caspase-8 in intestinal epithelium (casp8∆int ) is associated with fulminant epithelial necroptosis, severe Paneth cell death, secondary intestinal inflammation, and an increase in Notch activity...
May 16, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29766204/adiponectin-administration-alleviates-dss-induced-colonic-inflammation-in-caco-2-cells-and-mice
#3
Qin Zhao, Yang Liu, Lei Tan, Liyong Yan, Xiuli Zuo
BACKGROUND: Adiponectin, a protein hormone produced by adipose tissues, exhibits anti-inflammatory functions in various models. This study was investigated the effects of adiponectin on dextran sodium sulfate (DSS)-colonic injury, inflammation, apoptosis, and intestinal barrier dysfunction in Caco-2 cell and mice. MATERIALS AND METHODS: The results showed that DSS caused inflammatory response and intestinal barrier dysfunction in vitro and in vivo. Adiponectin injection alleviated colonic injury and rectal bleeding in mice...
May 15, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/29763894/the-understanding-and-management-of-organism-toxicity-in-septic-shock
#4
Kelly Roveran Genga, Tadanaga Shimada, John H Boyd, Keith R Walley, James A Russell
The toxicity caused by different organisms in septic shock is substantially complex and characterized by an intricate pathogenicity that involves several systems and pathways. Immune cells' pattern recognition receptors initiate the host response to pathogens after the recognition of pathogen-associated molecular patterns. In essence, the subsequent activation of downstream pathways may progress to infection resolution or to a dysregulated host response that represents the hallmark of organ injury in septic shock...
May 15, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29760367/-pharmacological-action-and-clinical-outcome-of-newly-developed-nsaids-patch-loqoa-%C3%A2-tape
#5
Noboru Otsuka, Ikuko Yataba
Topical non-steroidal anti-inflammatory drugs (NSAIDs) patches are indispensable for the treatment of musculoskeletal diseases, while they are considered less effective than oral NSAIDs. LOQOA® tape is a tape-type patch containing esflurbiprofen (SFP) as a major active ingredient with potent cyclooxygenase inhibition and sufficient skin permeability. SFP patch (SFPP) showed higher percutaneous absorption rate, rapid pain relief, and potent anti-inflammatory efficacy comparing with existing NSAIDs patches in rat...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29758344/the-effects-of-three-absorption-modifying-critical-excipients-on-the-in-vivo-intestinal-absorption-of-six-model-compounds-in-rats-and-dogs
#6
Dahlgren David, Roos Carl, Johansson Pernilla, Tannergren Christer, Lundqvist Anders, Langguth Peter, Sjöblom Markus, Sjögren Erik, Lennernäs Hans
Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients (CPEs), or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system...
May 11, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29746551/a-multi-chamber-microfluidic-intestinal-barrier-model-using-caco-2-cells-for-drug-transport-studies
#7
Hsih-Yin Tan, Sofie Trier, Ulrik L Rahbek, Martin Dufva, Jörg P Kutter, Thomas L Andresen
This paper presents the design and fabrication of a multi-layer and multi-chamber microchip system using thiol-ene 'click chemistry' aimed for drug transport studies across tissue barrier models. The fabrication process enables rapid prototyping of multi-layer microfluidic chips using different thiol-ene polymer mixtures, where porous Teflon membranes for cell monolayer growth were incorporated by masked sandwiching thiol-ene-based fluid layers. Electrodes for trans-epithelial electrical resistance (TEER) measurements were incorporated using low-melting soldering wires in combination with platinum wires, enabling parallel real-time monitoring of barrier integrity for the eight chambers...
2018: PloS One
https://www.readbyqxmd.com/read/29745333/alpha-lactalbumin-effect-on-myo-inositol-intestinal-absorption-in-vivo-and-in-vitro
#8
Giovanni Monastra, Simonetta Ferruzza, Yula Sambuy, Giulia Ranaldi, Daniela Ferrari
BACKGROUND: . Myo-inositol is a natural molecule with important therapeutic applications and an impaired oral absorption may result in a reduced clinical effect. Aim of this study was to determine if the combined oral administration of α-lactalbumin and myo-inositol in healthy subjects, could increase the plasma level of myo-inositol administered alone. In vitro studies on human differentiated intestinal Caco-2 cells were also conducted to identify the mechanisms involved in myo-inositol absorption...
May 8, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29744867/p-glycoprotein-mdr1-abcb1-restricts-brain-accumulation-and-cytochrome-p450-3a-cyp3a-limits-oral-availability-of-the-novel-alk-ros1-inhibitor-lorlatinib
#9
Wenlong Li, Rolf W Sparidans, Yaogeng Wang, Maria C Lebre, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Lorlatinib (PF-06463922) is a promising oral anaplastic lymphoma kinase (ALK) and ROS1 inhibitor currently in Phase III clinical trials for treatment of non-small cell lung cancer (NSCLC) containing an ALK rearrangement. With therapy-resistant brain metastases a major concern in NSCLC, lorlatinib was designed to have high membrane and blood-brain barrier permeability. We investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3A in plasma pharmacokinetics and tissue distribution of lorlatinib using genetically modified mouse strains...
May 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29744053/endoplasmic-reticulum-stress-induced-apoptosis-in-intestinal-epithelial-cells-a-feed-back-regulation-by-mechanistic-target-of-rapamycin-complex-1-mtorc1
#10
Yun Ji, Xuan Luo, Ying Yang, Zhaolai Dai, Guoyao Wu, Zhenlong Wu
Background: Endoplasmic reticulum (ER) stress is associated with multiple pathological processes of intestinal diseases. Despite a critical role of mechanistic target of rapamycin complex 1 (mTORC1) in regulating cellular stress response, the crosstalk between mTORC1 and ER stress signaling and its contribution to the intestinal barrier function is unknown. Results: In the present study, we showed that intestinal epithelial cells (IEC-6) incubated with tunicamycin led to caspase-3-dependent apoptotic cell death...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29740349/severe-burn-induced-intestinal-epithelial-barrier-dysfunction-is-associated-with-endoplasmic-reticulum-stress-and-autophagy-in-mice
#11
Yalan Huang, Yanhai Feng, Yu Wang, Pei Wang, Fengjun Wang, Hui Ren
The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29739809/application-of-physiologically-based-pharmacokinetic-modeling-in-understanding-bosutinib-drug-drug-interactions-importance-of-intestinal-p-glycoprotein
#12
Shinji Yamazaki, Cho-Ming Loi, Emi Kimoto, Chester Costales, Manthena V Varma
Bosutinib is an orally available Src/Abl tyrosine kinase inhibitor indicated for the treatment of patients with Ph+ chronic myelogenous leukemia at a clinically recommended dose of 500 mg once daily. Clinical results indicated that increases in bosutinib oral exposures were supra-proportional at the lower doses (50 to 200 mg) and approximately dose-proportional at the higher doses (200 to 600 mg). Bosutinib is a substrate of CYP3A4 and P-glycoprotein and exhibits pH-dependent solubility with moderate intestinal permeability...
May 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29729479/palmitate-lipotoxicity-in-enteric-glial-cells-lipid-remodeling-and-mitochondrial-ros-are-responsible-for-cyt-c-release-outside-mitochondria
#13
Lara Macchioni, Maya Petricciuolo, Magdalena Davidescu, Katia Fettucciari, Paolo Scarpelli, Rita Vitale, Leonardo Gatticchi, Pierluigi Orvietani, Andrea Marchegiani, Pierfrancesco Marconi, Gabrio Bassotti, Angela Corcelli, Lanfranco Corazzi
Enteric glial cells (EGCs) are components of the enteric nervous system, an organized structure that controls gut functions. EGCs may be vulnerable to different agents, such as bacterial infections that could alter the intestinal epithelial barrier, allowing bacterial toxins and/or other agents possessing intrinsic toxic effect to access cells. Palmitate, known to exhibit lipotoxicity, is released in the gut during the digestion process. In this study, we investigated the lipotoxic effect of palmitate in cultured EGCs, with particular emphasis on palmitate-dependent intracellular lipid remodeling...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29725271/the-protective-mechanism-of-cay10683-on-intestinal-mucosal-barrier-in-acute-liver-failure-through-lps-tlr4-myd88-pathway
#14
Yao Wang, Hui Chen, Qian Chen, Fang-Zhou Jiao, Wen-Bin Zhang, Zuo-Jiong Gong
The purpose of this study was to investigate the protective mechanism of HDAC2 inhibitor CAY10683 on intestinal mucosal barrier in acute liver failure (ALF). In order to establish ALF-induced intestinal epithelial barrier disruption models, D-galactosamine/LPS and LPS were, respectively, used with rats and NCM460 cell and then administrated with CAY10683. Transepithelial electrical resistance (TEER) was measured to detect the permeability of cells. Real-time PCR and Western blotting were employed to detect the key mRNA and protein levels...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29722014/il-23-promotes-intestinal-th17-immunity-and-ameliorates-obesity-associated-metabolic-syndrome-in-a-murine-high-fat-diet-model
#15
Larissa M S Martins, Malena M Perez, Camila A Pereira, Frederico R C Costa, Murilo S Dias, Rita C Tostes, Simone G Ramos, Marcel R de Zoete, Bernhard Ryffel, João S Silva, Daniela Carlos
We addressed the role of IL-23 in driving the intestinal Th17 response during obesity and metabolic syndrome progression induced by a high-fat diet (HFD). Diet-induced obese (DIO) and lean mice received HFD or control diet (CTD), respectively, for 20 weeks. The nutritional, metabolic and immune parameters were examined at weeks 9 and 20. Gene and protein IL-23p19 and IL-23R expression was increased in the ileum of obese wild-type mice (WT) fed the HFD for nine weeks. Mice lacking IL-23 and fed the HFD exhibited greater weight gain, higher fat accumulation, adipocyte hypertrophy and hepatic steatosis...
May 2, 2018: Immunology
https://www.readbyqxmd.com/read/29719776/designing-the-new-generation-of-intelligent-biocompatible-carriers-for-protein-and-peptide-delivery
#16
REVIEW
Angela M Wagner, Margaret P Gran, Nicholas A Peppas
Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties, therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available...
March 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29719601/increased-gut-permeability-in-cancer-cachexia-mechanisms-and-clinical-relevance
#17
Laure B Bindels, Audrey M Neyrinck, Audrey Loumaye, Emilie Catry, Hannah Walgrave, Claire Cherbuy, Sophie Leclercq, Matthias Van Hul, Hubert Plovier, Barbara Pachikian, Luis G Bermúdez-Humarán, Philippe Langella, Patrice D Cani, Jean-Paul Thissen, Nathalie M Delzenne
Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue)...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719415/plasma-concentrations-of-zonulin-are-elevated-in-obese-men-with-fatty-liver-disease
#18
A-Sol Kim, Hae-Jin Ko
Purpose: Zonulin is considered as a biomarker of increased intestinal permeability. The relationship between intestinal permeability and obesity is known, and many studies have investigated the relationship between intestinal permeability and liver disease. Thus, we aimed to investigate the potential association between plasma zonulin concentrations and fatty liver in obese men. Patients and methods: A total of 140 obese men without inflammatory bowel diseases, autoimmune diseases, and severe liver diseases were included...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29719231/hold-the-door-role-of-the-gut-barrier-in-diabetes
#19
Anthony Martin, Suzanne Devkota
While metabolic tissues such as adipose, liver, muscle, and pancreas have been extensively studied in dysmetabolism, the contribution of the gut remains poorly understood. In a recent Science article, Thaiss et al. (2018) unravel mechanisms underlying intestinal permeability observed in obesity and link barrier dysfunction and risk for infection with hyperglycemia.
May 1, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29718342/increased-systemic-inflammation-and-gut-permeability-among-women-with-treated-hiv-infection-in-rural-uganda
#20
Mark J Siedner, Markella Zanni, Russell P Tracy, Douglas S Kwon, Alexander C Tsai, Bernard Kakuhire, Peter W Hunt, Samson Okello
In a cohort of HIV-infected individuals and age and sex-matched HIV-uninfected comparators, we assessed soluble (s)CD14, sCD163, interleukin (IL)-6, intestinal fatty acid binding protein (IFAPB) and high-sensitivity C-reactive protein (hs-CRP). The median age was 51 years; and among HIV+, median ART duration was 7 years, median CD4 T-cell count was 433, and 86% had an undetectable viral load. Although HIV+ had higher sCD14, IFABP and hs-CRP, we found evidence of interaction by sex, such that HIV+ women had greater differences versus HIV- compared to men...
April 28, 2018: Journal of Infectious Diseases
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