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Intestinal permeability

Harmanpreet Singh, Chateshwar Kumar, Narpinder Singh, Surinder Paul, Subheet Kumar Jain
Docosahexaenoic acid (DHA) is a vital structural component of neuronal tissue, which is critically required during pre- and post-natal brain development. Its liquid nature, fishy odor, poor bioavailability and oxidative stability are the major challenges in the development of a pharmaceutically elegant and stable formulation. In the present study, nanocapsules of DHA from microalgae oil were prepared using different combinations of wall materials (carbohydrates, polymers, gum and proteins). The encapsulation using spray drying was done to prepare a pharmaceutically stable DHA formulation...
March 16, 2018: Food & Function
Ji Hee Kim, Ju Sun Heo, Kyung Suk Baek, Soo-Yeon Kim, Jung Hyun Kim, Kwang-Hyun Baek, Ki Eun Kim, Youn Ho Sheen
BACKGROUND: Zonulin is acknowledged as the only physiological mediator established to reversibly regulate intestinal permeability through modulation of intercellular tight junctions. We aimed to determine whether there are differences in zonulin levels between 74 subjects with overweight or obesity and 76 with normal-weight and to assess correlations of circulating zonulin levels with anthropometric measures and obesity-related biomarkers. METHODS: We assessed anthropometric and laboratory measures, including body mass indes (BMI) z-score, blood pressure, liver enzymes, lipid profiles, and insulin resistance...
March 12, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Clizia Guccione, Maria Camilla Bergonzi, Khaled M Awada, Vieri Piazzini, Anna Rita Bilia
The aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17...
March 15, 2018: Planta Medica
Anita Ferraretto, Michela Bottani, Paola De Luca, Laura Cornaghi, Francesca Arnaboldi, Margherita Maggioni, Amelia Fiorilli, Elena Donetti
An intestinal 70/30 Caco2/HT-29 co-culture was set up starting from the parental populations of differentiated cells to mimic the human intestinal epithelium. Co-culture was harvested at confluence 0 (T0) and at 3, 6, 10 and 14 days of post-confluence after plating (T3, T6, T10 and T14, respectively) for morphological and functional analysis. Transmission electron microscopy revealed different features from T0 to T14: microvilli and a complete junctional apparatus from T6, mucus granules from T3, as also confirmed by PAS/Alcian Blue staining...
March 14, 2018: Bioscience Reports
Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Vida Abedi, Josep Bassaganya-Riera
Interactions among the gut microbiome, dysregulated immune responses, and genetic factors contribute to the pathogenesis of inflammatory bowel disease (IBD). Nlrx1 -/- mice have exacerbated disease severity, colonic lesions, and increased inflammatory markers. Global transcriptomic analyses demonstrate enhanced mucosal antimicrobial defense response, chemokine and cytokine expression, and epithelial cell metabolism in colitic Nlrx1 -/- mice compared to wild-type (WT) mice. Cell-specificity studies using cre-lox mice demonstrate that the loss of NLRX1 in intestinal epithelial cells (IEC) recapitulate the increased sensitivity to DSS colitis observed in whole body Nlrx1 -/- mice...
2018: Frontiers in Immunology
Zohaib Ahmed Bhutto, Fang He, Mire Zloh, Jing Yang, Jinhu Huang, Tingting Guo, Liping Wang
Modulation of P-glycoprotein (P-gp, encoded by Mdr1) by xenobiotics plays central role in pharmacokinetics of various drugs. Quercetin has a potential to modulate P-gp in rodents, however, its effects on P-gp modulation in chicken are still unclear. Herein, study reports role of quercetin in modulation of P-gp expression and subsequent effects on the pharmacokinetics of enrofloxacin in broilers. Results show that P-gp expression was increased in a dose-dependent manner following exposure to quercetin in Caco-2 cells and tissues of chicken...
March 13, 2018: Scientific Reports
Morgan K Hoke, Kimberly A McCabe, Aaron A Miller, Thomas W McDade
OBJECTIVE: To validate a method for measuring endotoxin-core antibodies (EndoCAb) from dried blood spots (DBS)-drops of capillary whole blood collected and dried on filter paper-as an indicator of environmental enteropathy (EE) in infancy and early childhood. METHODS: A commercially available enzyme immunoassay kit was adapted for use with DBS, with optimized steps for sample elution. Technical validation included analysis of linearity/recovery, precision and reliability, lower limit of detection, and correspondence between matched plasma and DBS samples...
March 13, 2018: American Journal of Human Biology: the Official Journal of the Human Biology Council
Sanyog Jain, Pooja Yadav, Rajan Swami, Nitin Kumar Swarnakar, Varun Kushwah, Sameer S Katiyar
Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (< 210 nm) with a narrow distribution (~ 0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity...
March 12, 2018: AAPS PharmSciTech
Claudia Miranda, Zenia Pérez-Rodríguez, Rosario Hernández-Armengol, Yaidel Quiñones-García, Tania Betancourt-Purón, Miguel Ángel Cabrera-Pérez
The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1...
March 12, 2018: AAPS PharmSciTech
Yan Liu, Dongyang Zhao, Mengchi Sun, Wei Wei, Yingli Wang, Jiahua Zhou, Ruoshi Zhang, Jian Wang, Haotian Zhang, Zhonggui He, Qiming Kan, Jin Sun
5-Fluorouracil (5-FU) is one of the important antitumor drugs and is widely used to treat various types of cancers. However, its administration is limited to intravenous route due to poor oral bioavailability. Herein, we hypothesized that the maleimide group-containing 5-FU prodrug (EMC-5-FU) could improve the intestinal mucoadhesion because the maleimide end group can covalently target thiol residues of mucin glycoprotein covering the intestinal enterocytes. In vitro bioadhesion results showed that EMC-5-FU exhibited good affinity to the cysteine-rich subdomains of mucin and NMR studies successfully verified the covalent attachment of EMC-5-FU to mucin...
March 12, 2018: Drug Delivery and Translational Research
Lora J Kasselman, Nicholas A Vernice, Joshua DeLeon, Allison B Reiss
Cardiovascular disease associated with obesity and autoimmunity is the leading cause of death in these populations and significant residual risk remains despite current treatment approaches. Obesity, type 1 diabetes mellitus (T1DM), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) are linked to chronic inflammation, and subjects with these disorders have characteristic shifts in their gut microbiome composition. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting cardiovascular disease...
March 2, 2018: Atherosclerosis
Ditlev Birch, Ragna G Diedrichsen, Philip C Christophersen, Huiling Mu, Hanne M Nielsen
The absence of a surface-lining mucus layer is a major pitfall for the Caco-2 epithelial model. However, this can be alleviated by applying biosimilar mucus (BM) to the apical surface of the cell monolayer, thereby constructing a mucosa mimicking in vivo conditions. This study aims to elucidate the influence of BM as a barrier towards exogenic compounds such as permeation enhancers, and components of fed state simulated intestinal fluid (FeSSIF). Caco-2 cell monolayers surface-lined with BM were exposed to several compounds with distinct physicochemical properties, and the cell viability and permeability of the cell monolayer was compared to that of cell monolayers without BM and well-established mucus-secreting epithelial models (HT29 monolayers and HT29/Caco-2 co-culture monolayers)...
March 7, 2018: European Journal of Pharmaceutical Sciences
Christoph A Thaiss, Maayan Levy, Inna Grosheva, Danping Zheng, Eliran Soffer, Eran Blacher, Sofia Braverman, Anouk C Tengeler, Oren Barak, Maya Elazar, Rotem Ben-Zeev, Dana Lehavi-Regev, Meirav N Katz, Meirav Pevsner-Fischer, Arieh Gertler, Zamir Halpern, Alon Harmelin, Suhail Aamar, Patricia Serradas, Alexandra Grosfeld, Hagit Shapiro, Benjamin Geiger, Eran Elinav
Obesity, diabetes and related manifestations are associated with an enhanced, but poorly understood risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection...
March 8, 2018: Science
Tasha Barr, Suhas Sureshchandra, Paul Ruegger, Jingfei Zhang, Wenxiu Ma, James Borneman, Kathleen Grant, Ilhem Messaoudi
Alcohol use disorder (AUD) results in increased intestinal permeability, nutrient malabsorption, and increased risk of colorectal cancer (CRC). Our understanding of the mechanisms underlying these morbidities remains limited because studies to date have relied almost exclusively on short-term heavy/binge drinking rodent models and colonic biopsies/fecal samples collected from AUD subjects with alcoholic liver disease (ALD). Consequently, the dose- and site-dependent impact of chronic alcohol consumption in the absence of overt liver disease remains poorly understood...
March 8, 2018: Gut Microbes
Bhargavi Manda, Hina Mir, Ruchika Gangwar, Avtar S Meena, Shrunali Amin, Pradeep K Shukla, Kesha Dalal, Takuya Suzuki, Radha Krishna Rao
The apical junctional complex (AJC), which includes tight junction (TJ) and adherens junction (AJ) determine the epithelial polarity, cell-cell adhesion and permeability barrier. An intriguing characteristic of TJ is the dynamic nature of its multiprotein complex. Occludin is the most mobile TJ protein, but its significance in TJ dynamics is poorly understood. On the basis of phosphorylation sites we distinguished a sequence in the C-terminal domain of occludin as a regulatory motif (ORM). Deletion of ORM and expression of deletion mutant occludin in renal and intestinal epithelia reduced the mobility of occludin at the TJ...
March 5, 2018: Journal of Cell Science
Seungbum Kim, Ruby Goel, Ashok Kumar, Yanfei Qi, Gil Lobaton, Koji Hosaka, Mohammed Mohammed, Eileen M Handberg, Elaine M Richards, Carl J Pepine, Mohan K Raizada
Recent evidence indicates a link between gut pathology and microbiome with hypertension in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in this study were to test the hypotheses that high blood pressure patients have distinct gut microbiomes and that gut epithelial barrier function markers and microbiome composition could predict systolic blood pressure. Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high blood pressure and reference subjects...
March 5, 2018: Clinical Science (1979-)
Shuofei Yang, Jiaquan Chen, Qihong Ni, Haozhe Qi, Xiangjiang Guo, Lan Zhang, Guanhua Xue
BACKGROUND: Acute superior mesenteric venous thrombosis (ASMVT) is an abdominal vascular condition. Early recanalization is essential to successful treatment. The aim of the study was to establish rabbit models of ASMVT and assess the time course of intestinal epithelial barrier disruption. METHODS: After surgical exposure of superior mesenteric vein (Sham group), large-vessel (L-group) and small-vessel (S-group) models were established by endothelium damage, stenosis creation, and thrombin injection...
April 2018: Journal of Surgical Research
Li-Yu Luo, Miao-Xuan Fan, Hai-Yu Zhao, Mingxing Li, Xu Wu, Wenyuan Gao
Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability and the in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account...
March 5, 2018: Journal of Agricultural and Food Chemistry
Shixiang Wang, Nan Tan, Cuicui Ma, Jie Wang, Pu Jia, Jianghong Liu, Yang Yang, Zhanxiong Xie, Kun Zhao, Xiaohui Zheng
AIMS: In clinical practice, herbal medicines have played an important role in the modulation of drug transporters through the combination of conventional prescription drugs, which necessitates the elucidation of herb-drug interactions. The present study was designed to investigate the inhibitory effects and mechanisms of benzaldehyde, vanillin, muscone, and borneol on P-glycoprotein (P-gp). METHODS: The effects of the 4 compounds on the intracellular accumulation of rhodamine-123 (Rho-123) in vinblastine-treated Caco-2 (VB-Caco-2) cells were studied by monitoring fluorescence intensity through a flow cytometry assay, and the effects of these compounds on Rho-123 transport through VB-Caco-2 monolayers and Rho-123 intestinal absorption in the rat everted gut sac were investigated by high-performance liquid chromatography...
March 2, 2018: Pharmacology
Marta Farràs, Kanta Chandwe, Jordi Mayneris-Perxachs, Beatrice Amadi, John Louis-Auguste, Ellen Besa, Kanekwa Zyambo, Richard Guerrant, Paul Kelly, Jonathan Richard Swann
BACKGROUND: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia...
2018: PloS One
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