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https://www.readbyqxmd.com/read/27871064/benzopyrimido-pyrrolo-oxazine-dione-cftr-inhibitor-r-bpo-27-for-anti-secretory-therapy-of-diarrheas-caused-by-bacterial-enterotoxins
#1
Onur Cil, Puay-Wah Phuan, Anne Marie Gillespie, Sujin Lee, Lukmanee Tradtrantip, Jianyi Yin, Ming Tse, Nicholas C Zachos, Ruxian Lin, Mark Donowitz, Alan S Verkman
Secretory diarrheas caused by bacterial enterotoxins, including cholera and traveler's diarrhea, remain a major global health problem. Inappropriate activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel occurs in these diarrheas. We previously reported that the benzopyrimido-pyrrolo-oxazinedione (R)-BPO-27 inhibits CFTR chloride conductance with low-nanomolar potency. Here, we demonstrate using experimental mouse models and human enterocyte cultures the potential utility of (R)-BPO-27 for treatment of secretory diarrheas caused by cholera and Escherichia coli enterotoxins...
November 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27856110/role-of-gastrointestinal-motility-inhibition-and-antioxidant-properties-of-myrtle-berries-myrtus-communis-l-juice-in-diarrhea-treatment
#2
Mohamed-Amine Jabri, Kais Rtibi, Mohsen Sakly, Lamjed Marzouki, Hichem Sebai
INTRODUCTION: The myrtle (Myrtus communis) belongs to the Myrtaceae family; it is one of the central plants as part of the list of medicinal plants in the Tunisian Pharmacopoeia. Myrtle berry was used for its astringent, tonic, and antiseptic properties, to treat diarrhea, hemorrhoids, and gastrointestinal injury. METHODS: Adult male wistar rats were used to evaluate the normal gastro-intestinal transit and gastric emptying as well as castor oil-induced diarrhea, enteropooling tests, and small intestine oxidative stress...
November 14, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27523577/relative-distribution-of-gb3-isoforms-analogs-in-nod-scid-fabry-mice-tissues-determined-by-tandem-mass-spectrometry
#3
Philippe Provençal, Michel Boutin, Shaalee Dworski, Bryan Au, Jeffrey A Medin, Christiane Auray-Blais
AIM: Fabry disease is a lysosomal storage disorder leading to glycosphingolipid accumulation in different organs, tissues and biological fluids. The development of a Fabry disease gene therapy trial is underway in Canada. A tool to determine the distribution of Gb3 biomarkers in tissues of Fabry mice might be applicable to monitor the effect of gene therapy. Results & methodology: An ultra-performance LC-MS/MS (UPLC-MS/MS) method for the analysis of 22 Gb3 isoform/analogs in various Fabry mice tissues was developed and validated...
September 2016: Bioanalysis
https://www.readbyqxmd.com/read/27497746/the-zebrafish-goosepimples-myosin-vb-mutant-exhibits-cellular-attributes-of-human-microvillus-inclusion-disease
#4
Jaydeep Sidhaye, Clyde Savio Pinto, Shweta Dharap, Tressa Jacob, Shobha Bhargava, Mahendra Sonawane
Microvillus inclusion disease (MVID) is a life threatening enteropathy characterised by malabsorption and incapacitating fluid loss due to chronic diarrhoea. Histological analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy, whereas genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID.In order to understand the cellular basis of MVID and the associated formation of inclusion bodies, an animal model that develops ex-utero and is tractable genetically as well as by microscopy would be highly useful...
August 3, 2016: Mechanisms of Development
https://www.readbyqxmd.com/read/27072858/bioactive-anti-thrombotic-modification-of-decellularized-matrix-for-vascular-applications
#5
Jeremy J Glynn, Monica T Hinds
The decellularized matrix derived from porcine small intestinal submucosa (SIS) is a widely used biomaterial being investigated for numerous applications. Currently, thrombus deposition and neointimal hyperplasia have limited the use of SIS in some vascular applications. To limit these detrimental processes, this work applies bioactive, endothelial-inspired properties to the material. SIS is modified with the endothelial cell membrane protein thrombomodulin and the glycosaminoglycan heparin to facilitate protein C activation and anticoagulant activity, respectively...
June 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27047743/intestinal-removal-of-free-fatty-acids-from-hosts-by-lactobacilli-for-the-treatment-of-obesity
#6
Hea-Jong Chung, Jae G Yu, In-Ah Lee, Ming-Jie Liu, Yan-Fei Shen, Satya P Sharma, Mohammad A H M Jamal, Jun-Hyun Yoo, Hyeon-Jin Kim, Seong-Tshool Hong
Recent findings on the association of gut microbiota with various diseases, including obesity, prompted us to investigate the possibility of using a certain type of gut bacteria as a safe therapeutic for obesity. Lactobacillus mutants with enhanced capacity in absorption of free fatty acids (FFAs) were isolated to show reduced absorption of FFAs by the administered host, attributing to inhibition of body weight gain and body fat accumulation as well as amelioration of blood profiles. Consequently, high throughput screening of natural FFAs-absorbing intestinal microbes led to the isolation of Lactobacillus reuteri JBD30 l...
January 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/26649803/short-article-relapsing-whipple-s-disease-a-case-report-and-literature-review
#7
Elena Ruggiero, Anna Zurlo, Valter Giantin, Francesca Galeazzi, Claudia Mescoli, Giovanni Nante, Florinda Petruzzellis, Enzo Manzato
Whipple's disease is a rare infection caused by Tropheryma whipplei, a Gram-negative Bacillus usually found in macrophages of the lamina propria of the small intestine. The typical clinical manifestations of classic Whipple's disease are diarrhea, weight loss, malabsorption, abdominal pain, and arthralgia. The disease's laboratory diagnosis is currently based on duodenal biopsy. Treatment generally includes primary therapy for 2 weeks with intravenous antibiotics capable of reaching high levels in the cerebrospinal fluid, such as ceftriaxone, usually followed by treatment with oral cotrimoxazole for 1 year...
March 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/26564721/ex-vivo-perfusion-of-the-isolated-rat-small-intestine-as-a-novel-model-of-salmonella-enteritis
#8
Erin C Boyle, Heike Dombrowsky, Jürgen Sarau, Janin Braun, Martin Aepfelbacher, Ingmar Lautenschläger, Guntram A Grassl
Using an ex vivo perfused rat small intestinal model, we examined pathological changes to the tissue, inflammation induction, as well as dynamic changes to smooth muscle activity, metabolic competence, and luminal fluid accumulation during short-term infection with the enteropathogenic bacteria Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. Although few effects were seen upon Yersinia infection, this system accurately modeled key aspects associated with Salmonella enteritis. Our results confirmed the importance of the Salmonella Pathogenicity Island 1 (SPI1)-encoded type 3 secretion system (T3SS) in pathology, tissue invasion, inflammation induction, and fluid secretion...
January 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/26269243/the-intestinal-transport-of-bovine-milk-exosomes-is-mediated-by-endocytosis-in-human-colon-carcinoma-caco-2-cells-and-rat-small-intestinal-iec-6-cells
#9
Tovah Wolf, Scott R Baier, Janos Zempleni
BACKGROUND: MicroRNAs play essential roles in gene regulation. A substantial fraction of microRNAs in tissues and body fluids is encapsulated in exosomes, thereby conferring protection against degradation and a pathway for intestinal transport. MicroRNAs in cow milk are bioavailable in humans. OBJECTIVE: This research assessed the transport mechanism of bovine milk exosomes, and therefore microRNAs, in human and rodent intestinal cells. METHODS: The intestinal transport of bovine milk exosomes and microRNAs was assessed using fluorophore-labeled bovine milk exosomes in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells...
October 2015: Journal of Nutrition
https://www.readbyqxmd.com/read/26059375/lactobacillus-casei-crl-431-administration-decreases-inflammatory-cytokines-in-a-diet-induced-obese-mouse-model
#10
Ivanna Novotny Núñez, Carolina Maldonado Galdeano, Alejandra de Moreno de LeBlanc, Gabriela Perdigón
OBJECTIVES: Obesity is a chronic disease associated with an inflammatory process in which cytokines play an important role. Probiotic microorganisms have been associated with modulation of the host immune system. The aim of this study was to evaluate the influence of the probiotic bacterium Lactobacillus casei CRL 431 on the cytokine response in a model of mice under high-fat diet (HFD) conditions. METHODS: BALB/c mice received a conventional balanced diet or an HFD...
July 2015: Nutrition
https://www.readbyqxmd.com/read/25971245/mucopolysaccharidosis-like-phenotype-in-feline-sandhoff-disease-and-partial-correction-after-aav-gene-therapy
#11
Heather L Gray-Edwards, Brandon L Brunson, Merrilee Holland, Adrien-Maxence Hespel, Allison M Bradbury, Victoria J McCurdy, Patricia M Beadlescomb, Ashley N Randle, Nouha Salibi, Thomas S Denney, Ronald J Beyers, Aime K Johnson, Meredith L Voyles, Ronald D Montgomery, Diane U Wilson, Judith A Hudson, Nancy R Cox, Henry J Baker, Miguel Sena-Esteves, Douglas R Martin
Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme β-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids...
September 2015: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/25854323/impaired-aquaporins-expression-in-the-gastrointestinal-tract-of-rat-after-mercury-exposure
#12
Cinzia Bottino, Marta Vázquez, Vicenta Devesa, Umberto Laforenza
The main route of exposure to mercury in humans is through the diet. Consequently, the gastrointestinal mucosa is exposed to the mercurial forms, where they cause intestinal fluid accumulation, mucosal injuries and diarrhea. The relationship between inorganic mercury (HgCl2 ) and methylmercury (CH3 HgCl) exposure and water movement in the gastrointestinal tract is still unexplored. The leading role of aquaporins (AQPs) in the rapid bidirectional movement of fluid in the gastrointestinal tract of mammals is well established...
January 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/25799493/hydroxyethyl-starch-hes-130-0-4-impairs-intestinal-barrier-integrity-and-metabolic-function-findings-from-a-mouse-model-of-the-isolated-perfused-small-intestine
#13
Yuk Lung Wong, Ingmar Lautenschläger, Heike Dombrowsky, Karina Zitta, Berthold Bein, Thorsten Krause, Torsten Goldmann, Inez Frerichs, Markus Steinfath, Norbert Weiler, Martin Albrecht
BACKGROUND: The application of hydroxyethyl starch (HES) for volume resuscitation is controversially discussed and clinical studies have suggested adverse effects of HES substitution, leading to increased patient mortality. Although, the intestine is of high clinical relevance and plays a crucial role in sepsis and inflammation, information about the effects of HES on intestinal function and barrier integrity is very scarce. We therefore evaluated the effects of clinically relevant concentrations of HES on intestinal function and barrier integrity employing an isolated perfused model of the mouse small intestine...
2015: PloS One
https://www.readbyqxmd.com/read/25770894/animal-models-to-study-the-pathogenesis-of-human-and-animal-clostridium-perfringens-infections
#14
REVIEW
Francisco A Uzal, Bruce A McClane, Jackie K Cheung, James Theoret, Jorge P Garcia, Robert J Moore, Julian I Rood
The most common animal models used to study Clostridium perfringens infections in humans and animals are reviewed here. The classical C. perfringens-mediated histotoxic disease of humans is clostridial myonecrosis or gas gangrene and the use of a mouse myonecrosis model coupled with genetic studies has contributed greatly to our understanding of disease pathogenesis. Similarly, the use of a chicken model has enhanced our understanding of type A-mediated necrotic enteritis in poultry and has led to the identification of NetB as the primary toxin involved in disease...
August 31, 2015: Veterinary Microbiology
https://www.readbyqxmd.com/read/25731562/-no-recurrent-case-of-the-combination-of-surgical-management-with-chemotherapy
#15
Hirofumi Hasegawa, Akira Harada, Dai Kitagawa, Toshihiko Nakamura, Naoko Kondo, Fumihiro Shoji, Akira Kabashima, Seiichi Teramoto, Wataru Funahashi, Youichi Ikeda
A 61-year-old man consulted a nearby doctor with the chief complaint of lassitude in June 2010. Blood tests revealed a hemoglobin level of 3.7 g/dL. The observation of significant anemia resulted in a full medical workup. On computed tomography (CT) findings, a large mass (17 × 10 cm in diameter) was found in the abdominal region. The lumen was distended with accumulation of air and fluid. In addition, I continued with a bladder wall, but did not recognize the abnormality that was apparent to a bladder lumen...
November 2014: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/25553976/%C3%AE-galactosidase-a-knockout-mice-progressive-organ-pathology-resembles-the-type-2-later-onset-phenotype-of-fabry-disease
#16
Dinesh S Bangari, Karen M Ashe, Robert J Desnick, Colleen Maloney, John Lydon, Peter Piepenhagen, Eva Budman, John P Leonard, Seng H Cheng, John Marshall, Beth L Thurberg
Fabry disease is an X-linked lysosomal storage disease caused by deficient activity of α-galactosidase A and the resultant systemic accumulation of globotrioasylceramide (GL-3) and related glycolipids. α-Galactosidase A gene knockout (Gla KO) mice have no α-galactosidase A activity and progressively accumulate GL-3 in tissues and fluids, similarly to FD patients. The nature and temporal effects of the progressive substrate accumulation on tissue histology in these mice have not previously been characterized...
March 2015: American Journal of Pathology
https://www.readbyqxmd.com/read/25480797/essential-amino-acid-transporter-lat4-slc43a2-is-required-for-mouse-development
#17
Adriano Guetg, Luca Mariotta, Lukas Bock, Brigitte Herzog, Ralph Fingerhut, Simone M R Camargo, François Verrey
Amino acid (AA) uniporter Lat4 (Slc43a2) mediates facilitated diffusion of branched-chain AAs, methionine and phenylalanine, although its physiological role and subcellular localization are not known. We report that Slc43a2 knockout mice were born at expected Mendelian frequency but displayed an ∼10% intrauterine growth retardation and low amniotic fluid AAs, suggesting defective transplacental transport. Postnatal growth was strongly reduced, with premature death occurring within 9 days such that further investigations were made within 3 days of birth...
March 1, 2015: Journal of Physiology
https://www.readbyqxmd.com/read/25327386/the-application-of-1-8-cineole-a-terpenoid-oxide-present-in-medicinal-plants-inhibits-castor-oil-induced-diarrhea-in-rats
#18
Ghader Jalilzadeh-Amin, Massoud Maham
CONTEXT: 1,8-Cineole, a terpene, characterized as a major constituent occurring in the essential oils of several aromatic plants. It is widely used in pharmaceutical industry, as a food additive and for culinary purposes. OBJECTIVE: This study investigates the inhibitory effect of 1,8-cineole on transit time and diarrhea in animal models. MATERIALS AND METHODS: Acute toxicity and lethality of 1-8-cineole was determined by Lork's guidelines...
April 2015: Pharmaceutical Biology
https://www.readbyqxmd.com/read/25271767/abnormal-accumulation-of-intestinal-fluid-following-ingestion-of-an-unabsorbable-carbohydrate-in-patients-with-irritable-bowel-syndrome-an-mri-study
#19
R Undseth, A Berstad, N-E Kløw, K Arnljot, K S Moi, J Valeur
BACKGROUND: Postprandial discomfort following intake of poorly absorbable, but fermentable carbohydrates is a common complaint in patients with irritable bowel syndrome (IBS). We used lactulose as a model substance for this group of symptom triggering carbohydrates, aiming to visualize the intestinal response in IBS patients compared to healthy controls. METHODS: Patients with IBS according to Rome III criteria (n = 52) and healthy controls (n = 16) underwent a lactulose challenge test...
December 2014: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/25156725/a-synthetic-peptide-corresponding-to-the-extracellular-loop-2-region-of-claudin-4-protects-against-clostridium-perfringens-enterotoxin-in-vitro-and-in-vivo
#20
Archana Shrestha, Susan L Robertson, Jorge Garcia, Juliann Beingasser, Bruce A McClane, Francisco A Uzal
Clostridium perfringens enterotoxin (CPE) action starts when the toxin binds to claudin receptors. Claudins contain two extracellular loop domains, with the second loop (ECL-2) being slightly smaller than the first. CPE has been shown to bind to ECL-2 in receptor claudins. We recently demonstrated that Caco-2 cells (a naturally CPE-sensitive enterocyte-like cell line) can be protected from CPE-induced cytotoxicity by preincubating the enterotoxin with soluble full-length recombinant claudin-4 (rclaudin-4), which is a CPE receptor, but not with recombinant nonreceptor claudins, such as rclaudin-1...
November 2014: Infection and Immunity
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