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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/28816705/microvascular-vasodilator-plasticity-following-acute-exercise
#2
Austin T Robinson, Ibra S Fancher, Abeer M Mahmoud, Shane A Phillips
Endothelium-dependent vasodilation is reduced following acute exercise, or following high intraluminal pressure in isolated arterioles from sedentary adults, but not in arterioles from regular exercisers. The preserved vasodilation in arterioles from exercisers is hydrogen peroxide (H2O2)-dependent, whereas resting dilation is nitric oxide (NO)-dependent. We hypothesize chronic exercise elicits adaptations allowing for maintained vasodilation when NO bioavailability is reduced.
August 14, 2017: Exercise and Sport Sciences Reviews
https://www.readbyqxmd.com/read/28815026/the-diagnostic-value-of-24-hour-ambulatory-intraesophageal-ph-impedance-in-patients-with-laryngopharyngeal-reflux-symptoms-comparable-with-typical-symptoms
#3
Yusuf S Sakin, Rukiye Vardar, Baha Sezgin, Zeynep Erdogan Cetin, Yasemin Alev, Esra Yildirim, Tayfun Kirazli, Serhat Bor
BACKGROUND: The diagnosis of laryngopharyngeal reflux is currently based on a combination of the patient history of multichannel intraluminal impedance and ambulatory pH (MII-pH); however, none of these findings alone is specific for the diagnosis of laryngopharyngeal reflux. We aimed to compare the baseline characteristics and esophageal baseline impedance values between patients with and without laryngopharyngeal reflux symptoms. METHODS: We retrospectively analyzed data from two groups of patients with laryngopharyngeal reflux according to their reflux finding score (RFS) as scored by ENTs...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28814500/mono-ubiquitination-of-syntaxin-3-leads-to-retrieval-from-the-basolateral-plasma-membrane-and-facilitates-cargo-recruitment-to-exosomes
#4
Adrian J Giovannone, Elena Reales, Pallavi Bhattaram, Alberto Fraile-Ramos, Thomas Weimbs
Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes though how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes mono-ubiquitination in a conserved polybasic domain. Stx3 present at the basolateral - but not the apical - plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs) and excreted in exosomes...
August 16, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28809582/iodixanol-versus-iopromide-at-coronary-ct-angiography-lumen-opacification-and-effect-on-heart-rhythm-the-randomized-isocor-trial
#5
Marisa M Lubbers, Marc Kock, André Niezen, Tjebbe Galema, Marcel Kofflard, Tobias Bruning, Henriette S Kooij, Hanneke van Valen, Marcel Dijkshoorn, Ronald Booij, Anthony Padmos, Alain Vogels, Ricardo P J Budde, Koen Nieman
Purpose To show that equal coronary lumen opacification can be achieved with iso- and low-osmolar contrast media when it is injected at the same iodine delivery rate with contemporary cardiac computed tomographic (CT) protocols and to investigate the cardiovascular effect of iso-osmolar contrast media and the image quality achieved. Materials and Methods Institutional review board approval and written informed consent were obtained for the Effect of Iso-osmolar Contrast Medium on Coronary Opacification and Heart Rhythm in Coronary CT Angiography, or IsoCOR, trial...
August 15, 2017: Radiology
https://www.readbyqxmd.com/read/28808763/characteristics-of-gastroesophageal-reflux-in-pediatric-patients-with-neurological-impairment
#6
Hisayoshi Kawahara, Yuko Tazuke, Hideki Soh, Noriaki Usui, Hiroomi Okuyama
PURPOSE: To clarify the characteristics of gastroesophageal reflux (GER) in pediatric patients with neurological impairment (NI). METHODS: Twenty-six patients with NI, 1-17-year-old, fed via a nasogastric tube were categorized based on the absence (group I) or presence (group II) of abnormal GER, defined with multichannel intraluminal impedance-pH monitoring as %time with an esophageal pH <4.0 being ≥5.0% or number of liquid/mixed bolus reflux events(RE) >70 in 24 h...
August 14, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28807884/escrt-and-autophagies-endosomal-functions-and-beyond
#7
REVIEW
Christophe Lefebvre, Renaud Legouis, Emmanuel Culetto
ESCRT (endosomal sorting complex required for transport) machinery has been initially identified for its role during endocytosis, which allows membrane proteins and lipids to be degraded in the lysosome. ESCRT function is required to form intraluminal vesicles permitting internalization of cytosolic components or membrane embedded cargoes and promoting endosome maturation. ESCRT machinery also contributes to multiple key cell mechanisms in which it reshapes membranes. In addition, ESCRT actively participates in different types of autophagy processes for degrading cytosolic components, such as endosomal microautophagy and macroautophagy...
August 11, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28803639/atrial-fibrillation-and-stroke-as-initial-manifestations-of-painless-type-a-aortic-dissection
#8
Claudia Stöllberger, Lilian Schäffl-Doweik, Maria Korn, Josef Finsterer
Aortic dissection is diagnostically challenging, especially in pain-free patients. Detection of acute ischemic stroke secondary to painless aortic dissection is a challenge for emergency physicians and neurologists. We report a previously healthy 58-years old female, admitted because of nausea, dizziness, somnolence, a left-sided hemiparesis and arterial hypotension. The electrocardiogram showed atrial fibrillation with ST-elevations and ST-depressions. Perfusion CT-imaging showed a dilatation of the aortic arch and intraluminal structures indicating an intima flap of aortic dissection...
July 21, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28802163/obstructive-mobile-small-intestinal-tumor-without-radiographic-stigmata-of-bezoar
#9
Elif Onursal, Merilyn Baby, Ali Chaudhri, Gerard A Baltazar
INTRODUCTION: Gastrointestinal leiomyomas are often clinically silent until they bleed or grow large enough to cause local mass effect. PRESENTATION OF CASE: We report the unique case of an otherwise healthy 69-year-old male who developed a small bowel obstruction secondary to a mobile small intestinal leiomyoma. During initial evaluation, computed tomography did not demonstrate the cause of obstruction. Because of worsening clinical status with conservative management, the patient required emergency laparotomy...
July 19, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28801072/irinotecan-chemotherapy-induced-intestinal-oxidative-stress-underlying-causes-of-disturbed-mucosal-water-and-electrolyte-transport
#10
Kaïs Rtibi, Slimen Selmi, Dhekra Grami, Hichem Sebai, Mohamed Amri, Lamjed Marzouki
Irinotecan, a chemotherapy drug, can cause acute diarrhea immediately after administration. Hence, the present study was designed to investigate the gastrointestinal (GI) disturbances after an intraperitoneal (IP) administration of irinotecan in rats.Twenty Wistar rats were separated into two groups of ten. Group A was considered as a control group (NaCl, 0.9%). Group B was treated with irinotecan at a single dose of 200mgkg(-1). The rats were observed for defecation. For the enteropooling test, the animals were sacrificed by decapitation 1h post-treatment...
July 23, 2017: Pathophysiology: the Official Journal of the International Society for Pathophysiology
https://www.readbyqxmd.com/read/28800989/a-prospective-comparison-of-intraluminal-and-extraluminal-placement-of-the-9-french-arndt-bronchial-blocker-in-adult-thoracic-surgery-patients
#11
T Wesley Templeton, Benjamin N Morris, Eduardo J Goenaga-Diaz, Daniel J Forest, Rhett Hadley, Blake A Moore, Yvon F Bryan, Roger L Royster
OBJECTIVE: To compare the standard intraluminal approach with the placement of the 9-French Arndt endobronchial blocker with an extraluminal approach by measuring the time to positioning and other relevant intraoperative and postoperative parameters. DESIGN: A prospective, randomized, controlled trial. SETTING: University hospital. PARTICIPANTS: The study comprised 41 patients (20 intraluminal, 21 extraluminal) undergoing thoracic surgery...
August 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/28797837/endosomal-sort-of-signaling-control-the-role-of-escrt-machinery-in-regulation-of-receptor-mediated-signaling-pathways
#12
REVIEW
Ewelina Szymanska, Noga Budick-Harmelin, Marta Miaczynska
The endosomal sorting complexes required for transport (ESCRTs) machinery consists of four protein assemblies (ESCRT-0 to -III subcomplexes) which mediate various processes of membrane remodeling in the cell. In the endocytic pathway, ESCRTs sort cargo destined for degradation into intraluminal vesicles (ILVs) of endosomes. Cargos targeted by ESCRTs include various signaling molecules, mainly internalized cell-surface receptors but also some cytosolic proteins. It is therefore expected that aberrant trafficking caused by ESCRT dysfunction affects different signaling pathways...
August 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28795840/a-complete-histologic-approach-to-gastrointestinal-biopsy-from-hematopoietic-stem-cell-transplant-patients-with-evidence-of-transplant-associated-gastrointestinal-thrombotic-microangiopathy
#13
Mikako Warren, Sonata Jodele, Christopher Dandoy, Kasiani C Myers, Gregory Wallace, Adam Nelson, Javier El-Bietar
CONTEXT: - Transplant-associated thrombotic microangiopathy is a serious complication of hematopoietic stem cell transplant that may progress to multi-organ dysfunction. Transplant-associated thrombotic microangiopathy may involve the intestinal vasculature (intestinal transplant-associated thrombotic microangiopathy [iTMA]), causing patients to experience debilitating symptoms of ischemic colitis, including disproportionately severe abdominal pain and gastrointestinal bleeding, requiring heavy narcotic use and frequent transfusion support...
August 10, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28795477/exogenous-serotonin-regulates-colorectal-motility-via-the-5-ht2-and-5-ht3-receptors-in-the-spinal-cord-of-rats
#14
H Nakamori, K Naitou, Y Sano, H Shimaoka, T Shiina, Y Shimizu
BACKGROUND: We previously reported that intrathecal injection of noradrenaline or dopamine causes enhancement of colorectal motility. As these monoamines are neurotransmitters of descending pain inhibitory pathways in the spinal cord, we hypothesized that serotonin, which is one of the neurotransmitters involved in descending pain inhibition, also influences the lumbosacral defecation center. Therefore, we examined whether serotonin acting on the spinal defecation center enhances colorectal motility...
August 10, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28781024/intraluminal-intensity-of-blood-speckle-on-intravascular-ultrasound-a-novel-predictor-of-periprocedural-myocardial-injury-after-coronary-stenting
#15
Yoshiyuki Okuya, Yuichi Saito, Hideki Kitahara, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
The difference in the intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across a coronary artery stenosis (i.e., ΔIBS) has previously shown a negative correlation with fractional flow reserve, reflecting an impaired coronary blood flow. Periprocedural myocardial injury (PMI) after coronary stenting has also been associated with coronary circulatory dysfunction. The aim of this study was to investigate the relation between ΔIBS after coronary stenting and PMI...
July 14, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28780148/intra-abdominal-hypertension-abdominal-compartment-syndrome-and-the-open-abdomen
#16
REVIEW
William Kirke Rogers, Luis Garcia
Abdominal Compartment Syndrome (ACS) is the endpoint of a process whereby massive interstitial swelling in the abdomen or rapid development of a space-filling lesion within the abdomen (such as ascites or a hematoma) leads to a pathologically increased pressure. This results in so-called Intra-Abdominal Hypertension (IAH), causing decreased perfusion of the kidneys and abdominal viscera and possible difficulties with ventilation and maintenance of cardiac output. These effects contribute to a cascade of ischemia and multiple organ dysfunction with high mortality...
August 2, 2017: Chest
https://www.readbyqxmd.com/read/28777538/microinjection-for-the-ex-vivo-modification-of-cells-with-artificial-organelles
#17
Peter Tiefenboeck, Jong Ah Kim, Ferdinand Trunk, Tamara Eicher, Erica Russo, Alvaro Teijeira, Cornelia Halin, Jean-Christophe Leroux
Microinjection is extensively used across fields to deliver material intracellularly. Here we address the fundamental aspects of introducing exogenous organelles into cells to endow them with artificial functions. Nanocarriers encapsulating biologically active cargo or extreme intraluminal pH were injected directly into the cytosol of cells, where they bypassed subcellular processing pathways and persisted intact for several days. Nanocarriers' size was found to dictate their intracellular distribution pattern upon injection, with larger vesicles adopting polarized agglomerated distributions and smaller colloids spreading evenly in the cytosol...
August 4, 2017: ACS Nano
https://www.readbyqxmd.com/read/28775003/interference-with-gs%C3%AE-coupled-receptor-signaling-in-renin-producing-cells-leads-to-renal-endothelial-damage
#18
Peter Lachmann, Linda Hickmann, Anne Steglich, Moath Al-Mekhlafi, Michael Gerlach, Niels Jetschin, Steffen Jahn, Brigitte Hamann, Monika Wnuk, Kirsten Madsen, Valentin Djonov, Min Chen, Lee S Weinstein, Bernd Hohenstein, Christian P M Hugo, Vladimir T Todorov
Intracellular cAMP, the production of which is catalyzed by the α-subunit of the stimulatory G protein (Gsα), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gsα in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gsα-deficient animals. Progressive albuminuria occurred in Gsα-deficient mice...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28771009/model-based-analysis-of-biopharmaceutical-experiments-to-improve-mechanistic-oral-absorption-modelling-an-integrated-in-vitro-in-vivo-extrapolation-iviv_e-perspective-using-ketoconazole-as-a-model-drug
#19
Shriram M Pathak, Aaron Ruff, Edmund Kostewicz, Nikunjkumar Patel, David B Turner, Masoud Jamei
Mechanistic modelling of in vitro data generated from metabolic enzyme systems (viz. liver microsomes, hepatocytes, rCYP enzymes etc.) facilitates in vitro-in vivo extrapolation (IVIV_E) of metabolic clearance which plays a key role in the successful prediction of clearance in vivo within Physiologically-Based Pharmacokinetic (PBPK) modelling. A similar concept can be applied to solubility and dissolution experiments whereby mechanistic modelling can be used to estimate intrinsic parameters required for mechanistic oral absorption simulation in vivo...
August 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28761578/esophageal-motility-and-rikkunshito-treatment-for-proton-pump-inhibitor-refractory-nonerosive-reflux-disease-a-prospective-uncontrolled-open-label-pilot-study-trial
#20
Takeo Odaka, Shigeru Yamato, Osamu Yokosuka
BACKGROUND: Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. OBJECTIVE: To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent...
2017: Current Therapeutic Research, Clinical and Experimental
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