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Gastrointestinal physiology

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https://www.readbyqxmd.com/read/28817288/in-silico-modeling-approach-for-the-evaluation-of-gastrointestinal-dissolution-supersaturation-and-precipitation-of-posaconazole
#1
Bart Hens, Shriram M Pathak, Amitava Mitra, Nikunjkumar Patel, Bo Liu, Sanjaykumar Patel, Masoud Jamei, Joachim Brouwers, Patrick Augustijns, David B Turner
The aim of this study was to evaluate gastrointestinal (GI) dissolution, supersaturation, and precipitation of posaconazole, formulated as an acidified (pH 1.6) and neutral (pH 7.1) suspension. A physiologically-based pharmacokinetic (PBPK) modeling and simulation tool was applied to simulate GI and systemic concentration-time profiles of posaconazole which were directly compared with intraluminal and systemic data measured in humans. The Advanced Dissolution Absorption and Metabolism (ADAM) model of the Simcyp® Simulator correctly simulated incomplete gastric dissolution and saturated duodenal concentrations of posaconazole in the duodenal fluids following administration of the neutral suspension...
August 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28815516/gastrointestinal-epithelial-organoid-cultures-from-postsurgical-tissues
#2
Soojung Hahn, Jongman Yoo
An organoid is a cellular structure three-dimensionally (3D) cultured from self-organizing stem cells in vitro, which has a cell population, architectures, and organ specific functions like the originating organs. Recent advances in the 3D culture of isolated intestinal crypts or gastric glands have enabled the generation of human gastrointestinal epithelial organoids. Gastrointestinal organoids recapitulate the human in vivo physiology because of all the intestinal epithelial cell types that differentiated and proliferated from tissue resident stem cells...
August 17, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28813664/intestinal-dysbiosis-and-biotin-deprivation-induce-alopecia-through-overgrowth-of-lactobacillus-murinus-in-mice
#3
Atsushi Hayashi, Yohei Mikami, Kentaro Miyamoto, Nobuhiko Kamada, Toshiro Sato, Shinta Mizuno, Makoto Naganuma, Toshiaki Teratani, Ryo Aoki, Shinji Fukuda, Wataru Suda, Masahira Hattori, Masayuki Amagai, Manabu Ohyama, Takanori Kanai
Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28809953/monitoring-health-and-reproductive-status-of-olms-proteus-anguinus-by-ultrasound
#4
Susanne Holtze, Maja Lukač, Ivan Cizelj, Frank Mutschmann, Claudia Anita Szentiks, Dušan Jelić, Robert Hermes, Frank Göritz, Stanton Braude, Thomas Bernd Hildebrandt
The olm (Proteus anguinus) is a troglomorphic, neotenous amphibian with extraordinary life expectancy and unique adaptations that deserve further investigation. A low reproductive rate and habitat decline render it threatened by extinction. Establishing captive populations for maintenance and artificial breeding may one day become crucial to the species. Longitudinal, in-vivo assessment of inner organs is invaluable to our understanding of reproductive physiology, health, and behavior. Using ultrasound, we measured heart rate and assessed health and reproductive status of 13 captive olms at Zagreb Zoo...
2017: PloS One
https://www.readbyqxmd.com/read/28806271/luminal-chemosensing-in-the-gastroduodenal-mucosa
#5
Izumi Kaji, Jonathan D Kaunitz
PURPOSE OF REVIEW: We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa. RECENT FINDINGS: Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation...
August 12, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28805195/-the-plasma-levels-and-diagnostic-utility-of-matrix-metalloproteinase-9-and-ca-125-in-cervical-cancer-patients
#6
Emilia Lubowicka, Ewa Gacuta, Monika Zajkowska, Edyta Katarzyna Głażewska, Andrzej Przylipiak, Lech Chrostek, Monika Zbucka-Krętowska, Sławomir Ławicki
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, involved in the degradation of extracellular matrix components. The physiological function of MMP-9 is associated with regulation of immune processes, embryogenesis, reproduction and wound healing. MMP-9 also plays a critical role in tumor invasion, degrading the basement membrane, what is observed in different types of cancers: breast, gastrointestinal, and gynecological. AIM: The aim of this study was to investigate the plasma levels and diagnostic utility of MMP-9 and CA 125 in cervical cancer patients...
July 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28803923/stress-induced-neural-reorganization-a-conceptual-framework-linking-depression-and-alzheimer-s-disease
#7
REVIEW
Jennifer A Ross, Gediminas Gliebus, Elisabeth J Van Bockstaele
Chronic stress is a risk factor for a number of physiological disorders including cardiovascular disease, obesity and gastrointestinal disorders, as well as psychiatric and neurodegenerative disorders. There are a number of underlying molecular and cellular mechanisms altered in the course of chronic stress, which may increase the vulnerability of individuals to develop psychiatric disorders such as depression, and neurodegenerative disorders such as Alzheimer's Disease (AD). This is evident in the influence of stress on large-scale brain networks, including the resting state Default Mode Network (DMN), the effects of stress on neuronal circuitry and architecture, and the cellular and molecular adaptations to stress, which may render individuals with stress related psychiatric disorders more vulnerable to neurodegenerative disease later in life...
August 10, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28803922/studying-furosemide-solubilization-using-an-in-vitro-model-simulating-gastrointestinal-digestion-and-drug-solubilization-in-neonates-and-young-infants
#8
Mette Klitgaard, Philip Jonas Sassene, Arzu Selen, Anette Müllertz, Ragna Berthelsen
OBJECTIVE: The aim of the present study was to study the oral performance of furosemide in neonates and young infants using a newly developed in vitro model simulating digestion and drug solubilization in the gastrointestinal (GI) tract of the human neonate and young infant population (age 0-2months). METHODS: The utilized in vitro model was designed to mimic the digestion and drug solubilization processes occurring in the stomach, and the small intestine of the neonate and young infant population, using physiologically relevant media, volumes and digestive enzymes...
August 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28802247/effect-of-lead-speciation-on-its-oral-bioaccessibility-in-surface-dust-and-soil-of-electronic-wastes-recycling-sites
#9
Takashi Fujimori, Masaya Taniguchi, Tetsuro Agusa, Kenji Shiota, Masaki Takaoka, Aya Yoshida, Atsushi Terazono, Florencio C Ballesteros, Hidetaka Takigami
We measured bioaccessible lead (Pb) in simulated gastrointestinal fluids containing Pb-contaminated soil or dust from electronic waste (e-waste) recycling sites to assess the risk of Pb ingestion. The physiologically based extraction test (PBET) was used as in vitro bioaccessibility assay. Pb speciation was determined using X-ray absorption spectroscopy. The total Pb concentrations in dusts (n=8) and soils (n=4) were in the range of 1630-131,000 and 239-7800mg/kg, respectively. Metallic Pb, a common component of e-waste, was ubiquitous in the samples...
August 4, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28802231/phytochemical-properties-and-pharmacological-effects-of-quercus-ilex-l-aqueous-extract-on-gastrointestinal-physiological-parameters-in-vitro-and-in-vivo
#10
Kaïs Rtibi, Imen Hammami, Slimen Selmi, Dhekra Grami, Hichem Sebai, Mohamed Amri, Lamjed Marzouki
INTRODUCTION: Several research studies have reported on the pharmacological relevance of the medicinal plants used for treating various gastrointestinal disorders and controlling the dietary glucose uptake in the intestinal tract. METHODS: Male rats were used to investigate the pharmacological effects of green oak acorn aqueous extract (GOAE) on gastrointestinal physiological parameters in vivo and in vitro. In this respect, the gastro-intestinal motility and hypersecretion essays were evaluated using a simple test meal (10% charcoal in 5% gum arabic) and castor oil induced diarrhea...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28801825/intractable-constipation-in-the-elderly
#11
REVIEW
Noemi Baffy, Amy E Foxx-Orenstein, Lucinda A Harris, Susan Sterler
Chronic constipation is a common gastrointestinal disorder disproportionately affecting the elderly. Immobility, polypharmacy, and physiologic changes contribute to its increased prevalence in this population. Unidentified and undertreated constipation leads to a significant negative impact on quality of life and an increase in healthcare spending. Careful physical examination and exploration of the clinical history can unmask primary and secondary forms of constipation, guiding diagnostic and therapeutic considerations...
August 11, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28801754/expression-profiling-of-tas2r-genes-reveals-a-complex-pattern-along-the-mouse-gi-tract-and-the-presence-of-tas2r131-in-a-subset-of-intestinal-paneth-cells
#12
Simone Prandi, Anja Voigt, Wolfgang Meyerhof, Maik Behrens
The chemical variability of the intestinal lumen requires the presence of molecular receptors detecting the various substances naturally occurring in the diet and as a result of the activity of the microbiota. Despite their early discovery, intestinal bitter taste receptors (Tas2r) have not yet been assigned an unambiguous physiological function. Recently, using a CRE-recombinant approach we showed that the Tas2r131 gene is expressed in a subset of mucin-producing goblet cells in the colon of mice. Moreover, we also demonstrated that the expression of the Tas2r131 locus is not restricted to this region...
August 11, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28799907/salmonella-spi-2-type-iii-secretion-system-effectors-molecular-mechanisms-and-physiological-consequences
#13
REVIEW
Elliott Jennings, Teresa L M Thurston, David W Holden
Serovars of Salmonella enterica cause both gastrointestinal and systemic diseases in a broad range of mammalian hosts, including humans. Salmonella virulence depends in part on its pathogenicity island 2 type III secretion system (SPI-2 T3SS), which is required to translocate at least 28 effector proteins from vacuolar-resident bacteria into host cells. Comparative genomic analysis reveals that all serovars encode a subset of "core" effectors, suggesting that they are critical for virulence in different hosts...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28792489/l-phenylalanine-modulates-gut-hormone-release-and-glucose-tolerance-and-suppresses-food-intake-through-the-calcium-sensing-receptor-in-rodents
#14
A Alamshah, E Spreckley, M Norton, J S Kinsey-Jones, A Amin, A Ramgulam, Y Cao, R Johnson, K Saleh, E Akalestou, Z Malik, N Gonzalez-Abuin, A Jomard, R Amarsi, A Moolla, P R Sargent, G W Gray, S R Bloom, K G Murphy
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo...
July 13, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28789870/relevance-of-the-nucleus-of-the-solitary-tract-gelatinous-part-in-learned-preferences-induced-by-intragastric-nutrient-administration
#15
María A Zafra, Antonio D Agüera, Filomena Molina, Amadeo Puerto
Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task...
August 5, 2017: Appetite
https://www.readbyqxmd.com/read/28774868/role-of-g-protein-coupled-receptors-microrna-interactions-in-gastrointestinal-pathophysiology
#16
Ivy Ka Man Law, David Miguel Padua, Dimitrios Ilopoulos, Charalabos Pothoulakis
G protein-coupled receptors (GPCRs) make up the largest transmembrane receptor superfamily in the human genome and are expressed in nearly all gastrointestinal (GI) cell types. Coupling of GPCRs and their respective ligands activates various phosphotransferase in the cytoplasm, and thus, activation of GPCR signaling in intestine regulates many cellular and physiological processes. Studies in microRNAs (miRNAs) demonstrate that they represent critical epigenetic regulators of different pathophysiologic responses in different organs and cell types in humans and animals...
August 3, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28772020/interplay-between-lactobacillus-rhamnosus-gg-and-candida-and-the-involvement-of-exopolysaccharides
#17
Camille N Allonsius, Marianne F L van den Broek, Ilke De Boeck, Shari Kiekens, Eline F M Oerlemans, Filip Kiekens, Kenn Foubert, Dieter Vandenheuvel, Paul Cos, Peter Delputte, Sarah Lebeer
A number of clinical studies have shown protective effects of lactobacilli against Candida species in the gastrointestinal tract, the urogenital tract and the oral cavity, while others did not show clear effects. Evidence on the mode of action of lactobacilli against Candida is also still lacking. In this study, the anti-Candida activity of the model probiotic strain Lactobacillus rhamnosus GG was explored in different assays to determine molecular interactions. We found that L. rhamnosus GG was able to interfere with Candida growth, morphogenesis and adhesion...
August 3, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28771924/less-is-more-caloric-regulation-of-neurogenesis-and-adult-brain-function
#18
REVIEW
Alwena H Morgan, Zane B Andrews, Jeffrey S Davies
Calorie intake is essential for regulating normal physiological processes and is fundamental to maintaining life. Indeed, both extremes of calorie intake result in increased morbidity and mortality. In this review, we discuss the effect of calorie intake on adult brain function, with emphasis on the beneficial effects of mild calorie restriction. Recent findings relating to the regenerative and protective effect of the gastrointestinal hormone, ghrelin, suggest that it may underlie the beneficial effects of calorie restriction...
August 3, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28771242/pancreatic-and-intestinal-function-post-roux-en-y-gastric-bypass-surgery-for-obesity
#19
Stephen J D O'Keefe, Tina Rakitt, Junhai Ou, Ihab I El Hajj, Elizabeth Blaney, Kishore Vipperla, Jens-Jules Holst, Jens Rehlfeld
OBJECTIVES: Despite the fact that the most effective treatment for morbid obesity today is gastric bypass surgery, some patients develop life-threatening nutritional complications associated with their weight loss. METHODS: Here we examine the influence of the altered anatomy and digestive physiology on pancreatic secretion and fat absorption. Thirteen post Roux-en-Y gastric bypass (RYGB) patients who had lost >100 lbs in the first year following surgery and who gave variable histories of gastrointestinal (GI) dysfunction, were selected for study...
August 3, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28771235/systemic-gene-delivery-transduces-the-enteric-nervous-system-of-guinea-pigs-and-cynomolgus-macaques
#20
S E Gombash, C J Cowley, J A Fitzgerald, C A Lepak, M G Neides, K Hook, L J Todd, G-D Wang, C Mueller, B K Kaspar, E C Bielefeld, A J Fischer, J D Wood, K D Foust
Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or PBS. Piglets were euthanized three weeks post-injection and tissues were harvested for immunofluorescent analysis...
August 3, 2017: Gene Therapy
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