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https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#1
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28412294/visualization-of-hepatitis-e-virus-rna-and-proteins-in-the-human-liver
#2
Daniela Lenggenhager, Jérôme Gouttenoire, Mohsen Malehmir, Marion Bawohl, Hanna Honcharova-Biletska, Susanne Kreutzer, David Semela, Jörg Neuweiler, Sandra Hürlimann, Patrick Aepli, Montserrat Fraga, Roland Sahli, Luigi Terracciano, Laura Rubbia-Brandt, Beat Müllhaupt, Christine Sempoux, Darius Moradpour, Achim Weber
BACKGROUND: / Aims: Although hepatitis E constitutes a substantial disease burden worldwide, surprisingly little is known about the localization of hepatitis E virus (HEV) in the human liver. We therefore aimed to visualize HEV RNA and proteins in situ. METHODS: A panel of 12 different antibodies against HEV open reading frame (ORF) 1-3 proteins was evaluated for immunohistochemistry (IHC) and two probes for in situ hybridization (ISH) in formalin-fixed, paraffin-embedded (FFPE) Huh-7 cells transfected with HEV ORF1-3 expression vectors...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28394798/sox10-and-dog1-expression-in-primary-adnexal-tumors-of-the-skin
#3
Cecilia Lezcano, Jonhan Ho, Raja R Seethala
Primary skin adnexal tumors can be challenging to classify and must be discerned from cutaneous adenocarcinoma metastases from various sites. We evaluated expression of Sox10 and DOG1 in normal cutaneous adnexa and in 194 primary skin adnexal tumors, and compared their performance in discriminating primary skin adnexal tumors from cutaneous metastatic adenocarcinomas with that of p40 and p63. In normal skin adnexa, we noted Sox10 expression in both the secretory and myoepithelial cells in eccrine glands, but only in myoepithelial cells in apocrine glands...
March 27, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28388864/clinical-and-histologic-features-of-azathioprine-induced-hepatotoxicity
#4
Sith Siramolpiwat, Dussadee Sakonlaya
BACKGROUND: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity. METHODS: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal...
April 7, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28385542/model-systems-for-studying-the-role-of-canalicular-efflux-transporters-in-drug-induced-cholestatic-liver-disease
#5
REVIEW
Bruno Stieger, Zainab M Mahdi
Bile formation is a key function of the liver. Disturbance of bile flow may lead to liver disease and is called cholestasis. Cholestasis may be inherited such as for example in progressive familial intrahepatic cholestasis or acquired, such as for example by drug-mediated inhibition of bile salt export from hepatocytes into the canaliculi. The key transport system for exporting bile salts into the canaliculi is the bile salt export pump. Inhibition of the bile salt export pump by drugs is a well-established cause of drug-induced cholestasis...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28377989/spatial-heterogeneity-in-the-canalicular-density-of-the-osteocyte-network-in-human-osteons
#6
Felix Repp, Philip Kollmannsberger, Andreas Roschger, Michael Kerschnitzki, Andrea Berzlanovich, Gerlinde M Gruber, Paul Roschger, Wolfgang Wagermaier, Richard Weinkamer
Osteocytes interconnect with each other forming an intricate cell network within the mineralized bone matrix. One important function of the osteocyte network is the mechano-regulation of bone remodeling, where a possible mechanism includes the fluid flow through the porosity housing the cell network - the osteocyte lacuno-canalicular network (OLCN). In our study the OLCN in human osteons was three-dimensionally imaged with the aim to obtain a quantitative description of the canalicular density and spatial variations of this quantity within osteons...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28345127/zoledronate-promotes-bone-formation-by-blocking-osteocyte-osteoblast-communication-during-bone-defect-healing
#7
Pingping Cui, Hongrui Liu, Jing Sun, Norio Amizuka, Qinfeng Sun, Minqi Li
Nitrogen-containing bisphosphonates (N-BPs) are potent antiresorptive drugs and their actions on osteoclasts have been studied extensively. Recent studies have suggested that N-BPs also target bone-forming cells. However, the precise mechanism of N-BPs in osteoblasts is paradoxical, and the specific role of osteocytes is worthy of in-depth study. Here, we investigated the cellular mechanisms of N-BPs regulating bone defect healing by zoledronate (ZA). Bone histomorphometry confirmed an increase in new bone formation by systemic ZA administration...
March 27, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28337064/canalicular-pyocele-a-new-entity-and-literature-review
#8
Osama H Ababneh
Canaliculoceles are rare, and under-recognized lesions of the upper lacrimal drainage system that may present as medial canthal masses or swelling. The current case is that of an 85-year-old female patient presented with a painful right upper lid medial, cystic swelling of 10-day duration involving the punctum and the upper canaliculus. A literature review showed that this is the seventh reported case of a canaliculocele but the first case of acute onset that is associated with inflammatory signs and symptoms and accumulation of purulent material...
January 2017: Saudi Journal of Ophthalmology: Official Journal of the Saudi Ophthalmological Society
https://www.readbyqxmd.com/read/28330614/a-predictive-3d-multi-scale-model-of-biliary-fluid-dynamics-in-the-liver-lobule
#9
Kirstin Meyer, Oleksandr Ostrenko, Georgios Bourantas, Hernan Morales-Navarrete, Natalie Porat-Shliom, Fabian Segovia-Miranda, Hidenori Nonaka, Ali Ghaemi, Jean-Marc Verbavatz, Lutz Brusch, Ivo Sbalzarini, Yannis Kalaidzidis, Roberto Weigert, Marino Zerial
Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28327602/glucocorticoid-suppression-of-osteocyte-perilacunar-remodeling-is-associated-with-subchondral-bone-degeneration-in-osteonecrosis
#10
Tristan W Fowler, Claire Acevedo, Courtney M Mazur, Faith Hall-Glenn, Aaron J Fields, Hrishikesh A Bale, Robert O Ritchie, Jeffrey C Lotz, Thomas P Vail, Tamara Alliston
Through a process called perilacunar remodeling, bone-embedded osteocytes dynamically resorb and replace the surrounding perilacunar bone matrix to maintain mineral homeostasis. The vital canalicular networks required for osteocyte nourishment and communication, as well as the exquisitely organized bone extracellular matrix, also depend upon perilacunar remodeling. Nonetheless, many questions remain about the regulation of perilacunar remodeling and its role in skeletal disease. Here, we find that suppression of osteocyte-driven perilacunar remodeling, a fundamental cellular mechanism, plays a critical role in the glucocorticoid-induced osteonecrosis...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28273180/synthesis-in-vitro-and-in-vivo-evaluation-of-3%C3%AE-18f-fluorocholic-acid-for-the-detection-of-drug-induced-cholestasis-in-mice
#11
Stef De Lombaerde, Sara Neyt, Ken Kersemans, Jeroen Verhoeven, Lindsey Devisscher, Hans Van Vlierberghe, Christian Vanhove, Filip De Vos
INTRODUCTION: Drug-induced cholestasis is a liver disorder that might be caused by interference of drugs with the hepatobiliary bile acid transporters. It is important to identify this interference early on in drug development. In this work, Positron Emission Tomography (PET)-imaging with a 18F labeled bile acid analogue was introduced to detect disturbed hepatobiliary transport of bile acids. METHODS: 3β-[18F]fluorocholic acid ([18F]FCA) was prepared by nucleophilic substitution of a mesylated precursor with [18F]fluoride, followed by deprotection with sodium hydroxide...
2017: PloS One
https://www.readbyqxmd.com/read/28272174/endoscopic-features-of-a-lacrimal-sac-in-a-case-of-punctal-and-canalicular-agenesis
#12
Mohammad Javed Ali, Swati Singh, Milind N Naik
No abstract text is available yet for this article.
March 2017: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28261774/evaluation-of-anatomical-and-functional-outcomes-in-patients-undergoing-repair-of-traumatic-canalicular-laceration
#13
Hasan Aytoğan, Şeyda Karadeniz Uğurlu
BACKGROUND: The present study was designed to evaluate functional and anatomical success of traumatic canalicular laceration repair. METHODS: Consecutive patients who presented at Atatürk Training and Research Hospital Eye Clinic, İzmir Katip Çelebi University Faculty of Medicine and had canalicular laceration repair performed by the same surgeon between January 2009 and December 2014 were included in the study. Demographic data, length of time between injury and surgery, and cause of the trauma, surgical method employed, and duration of follow-up were recorded...
January 2017: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/28250999/a-rare-case-of-rivaroxaban-causing-delayed-symptomatic-hepatocellular-injury-and-hyperbilirubinemia
#14
Keith Glenn, Patrick Chen, Mustafa Musleh, Rao Pallivi, Melissa Grilliot
Importance. As Rivaroxaban has increased in popularity, it has been accompanied with a growing body of evidence displaying its ability to cause drug induced liver injury (DILI). Observation. A 74-year-old Caucasian female developed Rivaroxaban DILI two weeks after finishing a 14-day course. The patient was symptomatic and jaundiced with elevated transaminases and hyperbilirubinemia with normal lab values two months priorly. Liver biopsies showed mixed inflammatory infiltrate of lymphocytes, neutrophils and eosinophils, rare necrotic hepatocytes, and canalicular and intrahepatocellular cholestasis, all of which are consistent with DILI...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/28249699/detection-of-high-biliary-and-fecal-viral-loads-in-patients-with-chronic-hepatitis-c-virus-infection
#15
Hugo Monrroy, Jenniffer Angulo, Karla Pino, Pilar Labbé, Juan Francisco Miquel, Marcelo López-Lastra, Alejandro Soza
BACKGROUND: The life cycle of the hepatitis C virus (HCV) is closely associated with lipid metabolism. Recently, NPC1L1 (a cholesterol transporter) has been reported to function as an HCV receptor. This receptor is expressed in the hepatocyte canalicular membrane and in the intestine; serving as a key transporter for the cholesterol enterohepatic cycle. OBJECTIVES: We hypothesized that HCV might have a similar cycle, so we aimed to study the presence of HCV in bile and stools of infected patients...
February 26, 2017: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/28249282/progress-in-the-molecular-characterization-of-hepatobiliary-transporters
#16
Dietrich Keppler
Over the last 25 years, our understanding of the driving forces for hepatobiliary elimination and knowledge of the molecular basis of uptake and efflux transport in hepatocytes have undergone fundamental changes. This refers to bile acids and many other endogenous substances as well as to drugs that are eliminated on the hepatobiliary route. In this development, not only molecular cloning, functional characterization, and localization of transporters were decisive, but also the discovery of hereditary mutations in genes encoding sinusoidal uptake transporters and canalicular export pumps in humans and rodents...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249278/mechanisms-of-tauroursodeoxycholate-mediated-hepatoprotection
#17
Dieter Häussinger, Claus Kordes
Ursodeoxycholate and its taurine conjugate tauroursodeoxycholate (TUDC) promote choleresis by triggering the insertion of transport proteins for bile acids into the canalicular and basolateral membranes of hepatocytes. In addition, TUDC exerts hepatoprotective and anti-apoptotic effects, can counteract the action of toxic bile acids and reduce endoplasmic reticulum stress. TUDC can also initiate the differentiation of multipotent mesenchymal stem cells (MSC) including hepatic stellate cells and promote their development into hepatocyte-like cells...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249274/the-emerging-role-of-soluble-adenylyl-cyclase-in-primary-biliary-cholangitis
#18
Jung-Chin Chang, Ulrich Beuers, Ronald P J Oude Elferink
BACKGROUND: Primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis) is a chronic fibrosing cholangiopathy with the signature of an autoimmune disease and features of intrahepatic cholestasis. Immunosuppressing treatments are largely unsuccessful. Responsiveness to ursodeoxycholic acid and reduced expression of anion exchanger 2 (AE2) on canalicular membranes and small bile ducts underline the importance of bicarbonate transportation in its disease mechanism...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28248874/clinical-features-and-surgical-outcomes-of-primary-canaliculitis-with-concretions
#19
Shengjin Xiang, Bin Lin, Qintuo Pan, Meiqin Zheng, Xiaoyi Qin, Youpei Wang, Zongduan Zhang
The purpose of our study is to analyze the clinical, ultrasonic, microbiologic, and histopathologic characteristics, management, and outcomes in a series of primary canaliculitis with concretions patients who underwent canaliculotomy with curettage.Thirty-six patients were reviewed for age, sex, location and laterality, duration of symptoms, clinical symptoms, ultrasonic signs, result of microbiologic culture and histopathologic examination, treatment, and outcomes. Main outcomes were the clinical, ultrasonic, and microbiological characteristics of the canalicular concretions; the histopathologic profiles; and the treatment effect...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28245962/targeted-pharmacotherapies-for-defective-abc-transporters
#20
REVIEW
Virginie Vauthier, Chantal Housset, Thomas Falguières
Human ABC (ATP Binding Cassette) transporters form a superfamily of forty-eight transmembrane proteins, which transport their substrates across biological membranes against important concentration gradients, in an energy-dependent manner. Gene variations in approximately half of these transporters have been identified in subjects with rare and often severe genetic diseases, highlighting the importance of their biological function. For missense variations leading to defects in ABC transporters, the current challenge is to identify new molecules with therapeutic potential able to rescue the induced molecular deficiency...
February 27, 2017: Biochemical Pharmacology
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