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Intestinal permeability

Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Deju Peng, Huiqin Ma, Shangwu Chen
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, is an excellent therapeutic peptide drug for type 2 diabetes due to longer lasting biological activity compared to GLP-1. This study explored the feasibility of using probiotic Lactobacillus paracasei as an oral vector for recombinant exendin-4 peptide delivery, an alternative to costly chemical synthesis and inconvenient administration by injection. L. paracasei transformed with a plasmid encoding the exendin-4 gene (L. paracasei L14/pMG76e-exendin-4) with a constitutive promotor was successfully constructed and showed efficient secretion of exendin-4...
2016: PloS One
Julia König, Jerry Wells, Patrice D Cani, Clara L García-Ródenas, Tom MacDonald, Annick Mercenier, Jacqueline Whyte, Freddy Troost, Robert-Jan Brummer
The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed...
October 20, 2016: Clinical and Translational Gastroenterology
Im-Sook Song, Jin-Sun Cha, Min-Koo Choi
The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol...
October 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
T Titma, R Shimmo, J Siigur, A Kahru
Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 μg/mL of Sb2O3, Mn3O4 and TiO2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co3O4 and ZnO NPs had moderate effects and CuO NPs were toxic below 100 μg/mL (24 h EC25 = 11 for A549 and 71 μg/mL for Caco2)...
October 19, 2016: Cytotechnology
Younggeon Jin, Anthony T Blikslager
Intestinal anoxia/reoxygenation (A/R) injury induces loss of barrier function followed by epithelial repair. Myosin light chain kinase (MLCK) has been shown to alter barrier function via regulation of interepithelial tight junctions (TJ), but has not been studied in intestinal A/R injury. We hypothesized that A/R injury would disrupt TJ barrier function via MLCK activation and MLC phosphorylation. Caco-2BBe1 monolayers were subjected to anoxia for 2 hours followed by reoxygenation in 21% O2, after which barrier function was determined by measuring transepithelial resistance (TER) and FITC-dextran flux...
October 19, 2016: American Journal of Physiology. Cell Physiology
Aziz Homayouni Rad, Farnaz Sahhaf, Tohid Hassanalilou, Hanieh-Sadat Ejtahed, Negar Motayagheni, Ahmad-Reza Soroush, Mina Javadi, Amir Mohammad Mortazavian, Leila Khalili
BACKGROUND: Diabetes mellitus, a condition of multifactorial origin, is related to the intestinal microbiota by numerous molecular mechanisms. Controlling the vast increase in the prevalence of diabetes needs a natural and safe solution. Probiotics, known as live microorganisms that exert health benefits to the host, have anti-diabetic property. OBJECTIVE: This review will highlight the current evidences in probiotic effectiveness and future prospects for exploring probiotic therapy in the prevention and control of diabetes...
October 14, 2016: Current Diabetes Reviews
Panfeng Zhao, Xiangshu Piao, Zhikai Zeng, Ping Li, Xiao Xu, Hongliang Wang
We investigated the effects of Forsythia suspensa extract (FSE) and chito-oligosaccharide (COS), alone or together, on performance and health status of weaned piglets. The treatments included a basal diet and three diets with 160 mg/kg COS, 100 mg/kg FSE, or 100 mg/kg FSE and 160 mg/kg COS. Supplementation with COS or FSE alone improved (P < 0.01) average daily gain and feed conversion ratio compared with the basal diet in the first 2 weeks. On day 14, COS or FSE supplementation separately produced stronger (P < 0...
October 18, 2016: Animal Science Journal, Nihon Chikusan Gakkaihō
Mahalingam Balakumar, Durai Prabhu, Chandrakumar Sathishkumar, Paramasivam Prabu, Namita Rokana, Ramesh Kumar, Srividhya Raghavan, Avinash Soundarajan, Sunita Grover, Virender Kumar Batish, Viswanathan Mohan, Muthuswamy Balasubramanyam
PURPOSE: Diabetes and obesity are characterized by glucose intolerance, fat deposition, inflammation, and dyslipidemia. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects and modulating gut microbiota beneficially through specific probiotics could be a potential therapeutic option for type 2 diabetes/obesity. Therefore, we attempted to study the efficacy of probiotics of Indian gut origin (Lactobacillus plantarum MTCC5690 and Lactobacillus fermentum MTCC5689) along with a positive control, Lactobacillus rhamnosus (LGG) on glucose/lipid homeostasis in high-fat-diet-induced diabetic animal model...
October 18, 2016: European Journal of Nutrition
R Onnainty, E M Schenfeld, J P Petiti, M R Longhi, A Torres, M A Quevedo, G E Granero
Here, a novel drug delivery system was developed for the hydrochlorothiazide (HCT):ß-cyclodextrin (ßCD) inclusion complex loaded into chitosan (CS) nanoparticles (NPs)[CS/HCT:ßCD NPs]. It was found, for the first time, that exposure of the intestinal mucosa to free HCT resulted in an increased and abnormal intestinal permeability associated with several injuries to the intestinal epithelium. Nevertheless, the HCT delivery system obtained ameliorated the damage of the intestinal epithelium induced by HCT...
October 18, 2016: Molecular Pharmaceutics
V V Muthusamy
Cardiovascular disease burden is increasing all over the world. The diagnosis of hypertension is considered when a person has persistently elevated BP (Systolic BP more than 140 mmHg and/or Diastolic BP more than 90 mmHg). Dyslipidemia denotes abnormal levels of lipids in the blood (Total Cholesterol >200 mg%, Low density lipoprotein (LDL) >100 mg%, Triglycerides (TGL) >150 mg% and High density lipoprotein (HDL) <40 mg in men and < 50 mg in women. Hypertension and Dyslipidemia constitute the important components of metabolic syndrome as per the definition of NCEP Guidelines-Adult Treatment Panel III (ATP III)...
September 2016: Journal of Hypertension
Francesco Russo, Guglielmina Chimienti, Michele Linsalata, Caterina Clemente, Antonella Orlando, Giuseppe Riezzo
BACKGROUND: Ghrelin levels and obestatin/ghrelin ratio have been proposed as activity markers in ulcerative colitis, but no data are available in celiac disease (CD) and irritable bowel syndrome (IBS). Our aims were as follows: (a) to assess obestatin and ghrelin concentrations in adult active CD patients, diarrhea-predominant IBS (IBS-d), and healthy controls (HC) in relation to intestinal permeability; (b) to evaluate the ghrelin-obestatin profile in CD patients after a 1-year gluten-free diet (GFD); and (c) to establish the impact of ghrelin genetics...
October 12, 2016: European Journal of Gastroenterology & Hepatology
Najate Achamrah, Pierre Déchelotte, Moïse Coëffier
PURPOSE OF REVIEW: Glutamine is the most abundant amino acid in plasma and plays a key role in maintaining the integrity of intestinal barrier. RECENT FINDINGS: Experimental studies showed that glutamine is able to modulate intestinal permeability and tight junction protein expression in several conditions. Recent articles underlined its putative beneficial role in gastrointestinal disorders such as irritable bowel syndrome. SUMMARY: Glutamine is a major nutrient to maintain intestinal barrier function in animals and humans...
October 5, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
Mare Oja, Uko Maran
Human intestinal absorption is a key property for orally administered drugs and is dependent on pH. This study focuses on neutral and amphoteric compounds and their membrane permeabilities across the range of pH values found in the human intestine. The membrane permeability values for 15 neutral and 60 amphoteric compounds at pH 3, 5, 7.4 and 9 were measured using the parallel artificial membrane permeability assay (PAMPA). For each data series the quantitative structure-permeability relationships were developed and analysed...
October 17, 2016: SAR and QSAR in Environmental Research
Lijun Du, John J Kim, Jinhua Shen, Ning Dai
The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn's disease (CD), ulcerative colitis (UC), celiac disease, and irritable bowel syndrome (IBS). Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK-) and myosin light chain kinase- (MLCK-) mediated pathways are involved in the regulation of intestinal permeability...
2016: Gastroenterology Research and Practice
A J Cox, P Zhang, D W Bowden, B Devereaux, P M Davoren, A W Cripps, N P West
AIM: Relationships between the intestinal microbiota, intestinal permeability and inflammation in the context of risk for obesity-associated disease continue to be of interest. The aim of the study was to examine the associations between intestinal permeability and type 2 diabetes (T2D). METHODS: A total of 130 individuals with T2D (age: 57.5±6.2 years (mean±SD); BMI: 30.4±3.2; 45% female) and 161 individuals without T2D (age: 37.4±12.5 years; BMI: 25.1±3.9; 65% female) were included in the study...
October 10, 2016: Diabetes & Metabolism
Ludmila Khailova, Christine H Baird, Aubri A Rush, Christopher Barnes, Paul E Wischmeyer
BACKGROUND & AIMS: Recent clinical trials and in vivo models demonstrate probiotic administration can reduce occurrence and improve outcome of pneumonia and sepsis, both major clinical challenges worldwide. Potential probiotic benefits include maintenance of gut epithelial barrier homeostasis and prevention of downstream organ dysfunction due to systemic inflammation. However, mechanism(s) of probiotic-mediated protection against pneumonia remain poorly understood. This study evaluated potential mechanistic targets in the maintenance of gut barrier homeostasis following Lactobacillus rhamnosus GG (LGG) treatment in a mouse model of pneumonia...
October 1, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Xiawen Liu, Lijun Zhu, Biyun Huang, Junjun Huang, Yi Cai, Liu Zhu, Bo Wu, Xiaojing Fu, Xingfei Zhang, Yi Rong, Qing Xiao, Jiewen Guo, Arong Li, Yifei Guo, Mu Yuan
Racemic naftopidil (NAF) is used to treat benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). It exhibits greater efficacy but requires higher dose than other ɑ1-adrenoceptor blockers because of its poor bioavailability. It was previously shown that bioavailability of S(-)-NAF (14.5%) was twice that of R(+)-NAF (6.8%). The present study aimed to elucidate the major factors contributing to the poor and enantioselective bioavailability of NAF. First, absorption of NAF enantiomers was examined using a perfusated intestinal model...
September 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
Maurizio Koch
Microbes are mostly important for the digestion of food, the absorption of some micronutrients, and the production of vitamins. The microbiota stimulates lymphoid structures in the gastrointestinal mucosa and decrease pathogens by competing for nutrients and space. Bacterial translocation is defined as the escape of gut bacteria and their products through the intestinal mucosa to the outside of the intestine as portovenous or systemic circulation. This is induced by a leaky gut barrier. There is evidence for a role of intestinal permeability in the pathogenesis of nonalcoholic fatty liver disease...
November 2016: Journal of Clinical Gastroenterology
Sam Maher, Mekki Medani, Nestor N Carballeira, Desmond C Winter, Alan W Baird, David J Brayden
Intestinal permeation enhancers (PEs) offer an attractive strategy to enable oral peptide administration. However, optimal presentation of peptide and PE from solid-dosage forms is offset by slow dissolution rates in the small intestine, which reduces the likelihood that the PE can reach the threshold concentration for sufficient permeability enhancement. The purpose of this study was to design a PE-based liquid dispersion that can improve intestinal permeation of macromolecules across Caco-2 monolayers and isolated rat/human intestinal mucosae mounted in Ussing chambers...
October 13, 2016: AAPS Journal
Regina Irwin, Sandi Raehtz, Narayanan Parameswaran, Laura R McCabe
Increasing evidence indicates a strong link between intestinal health and bone health. For example, inflammatory bowel disease can cause systemic inflammation, weight loss and extra-intestinal manifestations such as decreased bone growth and density.  However, the effects of moderate intestinal inflammation without weight loss on bone health have never been directly examined; yet this condition is relevant not only to IBD but to conditions of increased intestinal permeability and inflammation as seen with ingestion of high fat diets, intestinal dysbiosis, irritable bowel syndrome, metabolic syndrome and food allergies...
October 12, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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