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https://www.readbyqxmd.com/read/28214380/application-of-the-mechpeff-model-to-predict-passive-effective-intestinal-permeability-in-the-different-regions-of-the-rodent-small-intestine-and-colon
#1
D Pade, M Jamei, A Rostami-Hodjegan, D B Turner
A major component of Physiologically-Based Pharmacokinetic (PBPK) models is prediction of the rate and extent of absorption of orally dosed drugs for which knowledge of effective passive intestinal permeability (Peff ) is essential. Single pass intestinal perfusion (SPIP) studies are used to establish effective permeability in vivo but are difficult to perform in rodents while mechanistic models to predict drug Peff in rat and mouse have not been published. This work evaluates the predictive performance of the 'MechPeff' model to predict Peff in the rodent intestine based upon knowledge of regional gut physiology and drug-specific physicochemical parameters...
February 18, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28214100/nlrp6-a-multifaceted-innate-immune-sensor
#2
REVIEW
Maayan Levy, Hagit Shapiro, Christoph A Thaiss, Eran Elinav
NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling regulation and facilitation of gastrointestinal antiviral effector functions. Additionally, NLRP6 contributes to the regulation of mucus secretion and antimicrobial peptide production, thereby impacting intestinal microbial colonization and associated microbiome-related infectious, autoinflammatory, metabolic, and neoplastic diseases...
February 14, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28212861/accumulation-of-phosphatidylcholine-on-gut-mucosal-surface-is-not-dominated-by-electrostatic-interactions
#3
Agatha Korytowski, Wasim Abuillan, Federico Amadei, Ali Makky, Andrea Gumiero, Irmgard Sinning, Annika Gauss, Wolfgang Stremmel, Motomu Tanaka
The accumulation of phosphatidylcholine (PC) in the intestinal mucus layer is crucial for the protection of colon epithelia from the bacterial attack. It has been reported that the depletion of PC is a distinct feature of ulcerative colitis. Here we addressed the question how PC interacts with its binding proteins, the mucins, which may establish the hydrophobic barrier against colonic microbiota. In the first step, the interactions of dioleoylphosphatidylcholine (DOPC) with two mucin preparations from porcine stomach, have been studied using dynamic light scattering, zeta potential measurement, and Langmuir isotherms, suggesting that mucin binds to the surface of DOPC vesicles...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212382/de-novo-assembly-of-the-sea-trout-salmo-trutta-m-trutta-skin-transcriptome-to-identify-putative-genes-involved-in-the-immune-response-and-epidermal-mucus-secretion
#4
Magdalena Malachowicz, Roman Wenne, Artur Burzynski
In fish, the skin is a multifunctional organ and the first barrier against pathogens. Salmonids differ in their susceptibility to microorganisms due to varied skin morphology and gene expression patterns. The brown trout is a salmonid species with important commercial and ecological value in Europe. However, there is a lack of knowledge regarding the genes involved in the immune response and mucus secretion in the skin of this fish. Thus, we characterized the skin transcriptome of anadromous brown trout using next-generation sequencing (NGS)...
2017: PloS One
https://www.readbyqxmd.com/read/28210224/skin-mucus-of-gilthead-sea-bream-sparus-aurata-l-protein-mapping-and-regulation-in-chronically-stressed-fish
#5
Jaume Pérez-Sánchez, Genciana Terova, Paula Simó-Mirabet, Simona Rimoldi, Ole Folkedal, Josep A Calduch-Giner, Rolf E Olsen, Ariadna Sitjà-Bobadilla
The skin mucus of gilthead sea bream was mapped by one-dimensional gel electrophoresis followed by liquid chromatography coupled to high resolution mass spectrometry using a quadrupole time-of-flight mass analyzer. More than 2,000 proteins were identified with a protein score filter of 30. The identified proteins were represented in 418 canonical pathways of the Ingenuity Pathway software. After filtering by canonical pathway overlapping, the retained proteins were clustered in three groups. The mitochondrial cluster contained 59 proteins related to oxidative phosphorylation and mitochondrial dysfunction...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28210078/sex-differences-and-effects-of-oestrogen-in-rat-gastric-mucosal-defence
#6
Richard Shore, Håkan Björne, Yoko Omoto, Anna Siemiatkowska, Jan-Åke Gustafsson, Mats Lindblad, Lena Holm
AIM: To evaluate sex differences and the effects of oestrogen administration in rat gastric mucosal defence. METHODS: Sex differences in gastric mucus thickness and accumulation rate, absolute gastric mucosal blood flow using microspheres, the integrity of the gastric mucosal epithelium in response to a chemical irritant and the effects of oestrogen administration on relative gastric mucosal blood flow in an acute setting was assessed in an in vivo rat experimental model...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209206/rethinking-the-role-of-alpha-toxin-in-clostridium-perfringens-associated-enteric-diseases-a-review-on-bovine-necro-haemorrhagic-enteritis
#7
REVIEW
Evy Goossens, Bonnie R Valgaeren, Bart Pardon, Freddy Haesebrouck, Richard Ducatelle, Piet R Deprez, Filip Van Immerseel
Bovine necro-haemorrhagic enteritis is an economically important disease caused by Clostridium perfringens type A strains. The disease mainly affects calves under intensive rearing conditions and is characterized by sudden death associated with small intestinal haemorrhage, necrosis and mucosal neutrophil infiltration. The common assumption that, when causing intestinal disease, C. perfringens relies upon specific, plasmid-encoded toxins, was recently challenged by the finding that alpha toxin, which is produced by all C...
February 16, 2017: Veterinary Research
https://www.readbyqxmd.com/read/28207927/attenuated-airway-hyperresponsiveness-and-mucus-secretion-in-hdm-exposed-igf1r-deficient-mice
#8
S Piñeiro-Hermida, J A Gregory, I P López, R Torrens, C Ruíz-Martínez, M Adner, J G Pichel
BACKGROUND: Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR) and inflammation. IGFs have been reported to play a role in asthma but little is known about how the Insulin-like Growth Factor 1 Receptor (IGF1R) affects asthma pathobiology. METHODS: Female Igf1r-deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchioalveolar lavage fluid (BALF), serum and lungs were collected on day 28 for further cellular, histological and molecular analysis...
February 16, 2017: Allergy
https://www.readbyqxmd.com/read/28206729/gut-microbiota-and-gastric-disease
#9
Dolores Sgambato, Agnese Miranda, Lorenzo Romano, Marco Romano
The gut microbiota may be considered a crucial "organ" of human body because of its role in the maintenance of the balance between health as well as disease. It is mainly located in the small bowel and colon, while, the stomach was long thought to be sterile in particular for its high acid production. In particular, stomach was considered "an hostile place" for bacterial growth until the identification of Helicobacter pylori (HP). Now, the stomach and its microbiota can be considered as two different "organs" that share the same place and they have an impact on each other...
15, 2017: Minerva Gastroenterologica e Dietologica
https://www.readbyqxmd.com/read/28205598/lyn-regulates-mucus-secretion-and-muc5ac-via-the-stat6-signaling-pathway-during-allergic-airway-inflammation
#10
Xiaoyun Wang, Yin Li, Deyu Luo, Xing Wang, Yun Zhang, Zhigang Liu, Nanshan Zhong, Min Wu, Guoping Li
Hypersecretion of mucus is an important component of airway remodeling and contributes to the mucus plugs and airflow obstruction associated with severe asthma phenotypes. Lyn has been shown to down-regulate allergen-induced airway inflammation. However, the role of Lyn in mucin gene expression remains unresolved. In this study, we first demonstrate that Lyn overexpression decreased the mucus hypersecretion and levels of the muc5ac transcript in mice exposed to ovalbumin (OVA). Lyn overexpression also decreased the infiltration of inflammatory cells and the levels of IL-13 and IL-4 in OVA-challenged airways...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197867/ultramorphological-changes-in-gill-rakers-of-astyanax-altiparanae-characidae-kept-in-contaminated-environments
#11
F P Lopes, B F Pereira, R M S Alves, J R T Valim, F A T Figueiredo, D L Pitol, F H Caetano
Most water bodies in Brazil, and in the world, are contaminated by some types of pollutants, ranging from sewage to metal/chemicals, carcinogenic products, and biodegradable detergents. Despite the extensive knowledge on their effects on fish biology and especially on gill morphology, research that concerns their impacts on gill rakers and implications in parameters such as food consumption cannot be found in the literature. Gill rakers are vital because, together with gills, they are responsible for the defense and protection of the organism and for selecting appropriate food for survival...
February 14, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28196385/-comparison-of-different-mechanical-insufflator-exsufflator-systems-by-measurement-of-the-peak-exspiratory-flow-pef
#12
Ansgar Schütz, Janine Wagner, Anne Conrad, Andreas Funke
Background The management of pulmonary secretion in patients with respiratory muscle weakness using mechanical insufflator-exsufflator systems (MIE) is an established treatment option. There are significant differences in the efficiency of different devices in practical use. The intention of this study was to evaluate the peak exspiratory flow (PEF) values of different devices with and without use of equipment. Methods PEFs of ten MIE were investigated in vitro using different equipment. Results The efficiency of the devices showed significant differences...
February 14, 2017: Pneumologie
https://www.readbyqxmd.com/read/28195642/functional-mucous-layer-and-healing-of-proximal-colonic-anastomoses-in-an-experimental-model
#13
J W A M Bosmans, A C H M Jongen, G M H Birchenough, E E L Nyström, M J J Gijbels, J P M Derikx, N D Bouvy, G C Hansson
BACKGROUND: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. METHODS: Mice of different Muc2 genotypes were used in a proximal colonic AL model...
February 13, 2017: British Journal of Surgery
https://www.readbyqxmd.com/read/28194802/safe-treatment-of-ethmoid-sinusitis-utilizing-minimally-invasive-ethmoid-punch-sinusotomy-eps-in-chronic-rhinosinusitis-without-polyposis-crssnp-patients
#14
Nathalia Velasquez, Andrew Thamboo, Waleed M Abuzeid, Jayakar V Nayak
OBJECTIVES/HYPOTHESIS: Current rhinologic practice is devoid of minimally invasive procedures dedicated to the treatment of ethmoid sinusitis to improve ventilation and topical drug delivery. We have recently described a handheld spiral punch to create minimally invasive ethmoid punch sinusotomy (EPS) sites into the ethmoid bulla and basal lamella, which significantly increased irrigant access to the ethmoid sinuses in cadaver models. Here, we conducted a clinical feasibility study to determine the initial safety evaluation of EPS in chronic rhinosinusitis without polyposis (CRSsNP) patients with active ethmoid disease...
February 14, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28194635/using-the-slug-mucosal-irritation-assay-to-investigate-the-tolerability-of-tablet-excipients-on-human-skin-in-the-context-of-the-use-of-a-nipple-shield-delivery-system
#15
Richard Kendall, Joke Lenoir, Stephen Gerrard, Rebekah L Scheuerle, Nigel K H Slater, Catherine Tuleu
PURPOSE: Neonates are particularly challenging to treat. A novel patented drug delivery device containing a rapidly disintegrating tablet held within a modified nipple shield (NSDS) was designed to deliver medication to infants during breastfeeding. However concerns exist around dermatological nipple tolerability with no pharmaceutical safety assessment guidance to study local tissue tolerance of the nipple and the areola. This is the first Slug Mucosal Irritation (SMI) study to evaluate irritancy potential of GRAS excipients commonly used to manufacture rapidly disintegrating immediate release solid oral dosage form METHODS: Zinc sulphate selected as the antidiarrheal model drug that reduces infant mortality, was blended with functional excipients at traditional levels [microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium, magnesium stearate]...
February 13, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28192541/immune-driven-alterations-in-mucin-sulphation-is-an-important-mediator-of-trichuris-muris-helminth-expulsion
#16
Sumaira Z Hasnain, Paul A Dawson, Rohan Lourie, Peter Hutson, Hui Tong, Richard K Grencis, Michael A McGuckin, David J Thornton
Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T...
February 13, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28191818/changes-in-protein-expression-after-treatment-with-ancylostoma-caninum-excretory-secretory-products-in-a-mouse-model-of-colitis
#17
Javier Sotillo, Ivana Ferreira, Jeremy Potriquet, Thewarach Laha, Severine Navarro, Alex Loukas, Jason Mulvenna
Different reports have highlighted the potential use of helminths and their secretions in the treatment of inflammatory bowel disease (IBD) conditions; however, no reports have investigated their effects at a proteome level. Herein, we characterise the protein expression changes that occur in lamina propria (LP) and the intestinal epithelial cells (IEC) of mice with dextran sulfate sodium (DSS)-induced colitis treated with Ancylostoma caninum excretory/secretory (ES) products using a quantitative proteomic approach...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28188751/r1-immunohistochemical-study-of-mucins-in-human-intestinal-spirochetosis
#18
Sho Ogata, Ken Shimizu, Susumu Tominaga, Kuniaki Nakanishi
Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?". Using antibodies for MUCs 1, 2, 4, 5 AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)"...
February 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28188658/in-vivo-adherence-of-flavobacterium-psychrophilum-to-mucosal-external-surfaces-of-rainbow-trout-oncorhynchus-mykiss-fry
#19
A Papadopoulou, I Dalsgaard, A Lindén, T Wiklund
The adherence of Flavobacterium psychrophilum to surfaces of epithelial tissues has been inconclusively suggested as a mechanism, which enables the bacterium to invade the host. Hence, the present study aimed to examine the adherence of the cells of two colony phenotypes, smooth and rough, of F. psychrophilum to mucosal tissues of rainbow trout fry and to test the skin mucus as a nutrient for the growth of F. psychrophilum. Fish were immersed in water containing 10(6 ) CFU( ) mL(-1) F. psychrophilum for each colony phenotype...
February 11, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/28187947/partial-restoration-of-cftr-function-in-cftr-null-mice-following-targeted-cell-replacement-therapy
#20
Pascal Duchesneau, Rickvinder Besla, Mathieu F Derouet, Li Guo, Golnaz Karoubi, Amanda Silberberg, Amy P Wong, Thomas K Waddell
Cystic fibrosis (CF) is a fatal recessive genetic disorder caused by a mutation in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Alteration in CFTR leads to thick airway mucus and bacterial infection. Cell therapy has been proposed for CFTR restoration, but efficacy has been limited by low engraftment levels. In our previous studies, we have shown that using a pre-conditioning regimen in combination with optimization of cell number and time of delivery, we could obtain greater bone marrow cell (BMC) retention in the lung...
February 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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