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https://www.readbyqxmd.com/read/28524363/donor-transmitted-mutation-of-the-abcb11-gene-and-ensuing-intra-hepatic-cholestasis-of-pregnancy-in-a-liver-transplant-recipient
#1
Tiong Yeng Lim, Iona Coltart, Pierre Foskett, Richard Thompson, Sandra Strautnieks, Leonie Penna, Catherine Williamson, Rosa Miquel, Michael A Heneghan
In liver transplant (LT) recipients, the cause of graft dysfunction in pregnancy is often difficult to ascertain. Moreover, a liver biopsy in late pregnancy is often avoided as a consequence of patient and physician factors. Management of graft dysfunction can be difficult in this setting. We report a 30-year-old female LT recipient who developed acutely deranged liver biochemistry during the third trimester of her first pregnancy. At 29 weeks gestation, her liver function test (LFT) became abnormal; AST peaked at 978 IU/L (normal range 10-50), GGT 25 IU/L (normal range 1-55), bilirubin 1...
May 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28523374/capturing-microscopic-features-of-bone-remodeling-into-a-macroscopic-model-based-on-biological-rationales-of-bone-adaptation
#2
Young Kwan Kim, Yoshitaka Kameo, Sakae Tanaka, Taiji Adachi
To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account...
May 18, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28516728/increased-heterogeneity-of-airway-calibre-in-adult-rats-after-hypoxia-induced-intrauterine-growth-restriction
#3
Kimberley C W Wang, Jude S Morton, Sandra T Davidge, Alexander N Larcombe, Alan L James, Graham M Donovan, Peter B Noble
BACKGROUND AND OBJECTIVE: Intrauterine growth restriction (IUGR) is associated with asthma development. We hypothesized that IUGR disrupts airway development leading to postnatal structural abnormalities of the airway that predispose to disease. This study therefore examined structural changes to the airway and lung in a rat model of maternal hypoxia-induced IUGR. METHODS: Pregnant rats were housed under hypoxic conditions (11.5% O2 ) from gestational days (GDs) 13 to 20 (pseudoglandular-canalicular stages, i...
May 17, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28513491/results-of-a-new-mirror-tuck-technique-for-fixation-of-lacrimal-bypass-tube-in-conjunctivodacryocystorhinostomy
#4
Ruchi Goel, Divya Kishore, Smriti Nagpal, Sushil Kumar, Neha Rathie
CONTEXT: Conjunctivodacryocystorhinostomy (CDCR) is the procedure of choice for proximal canalicular blocks. However, the complications of tube migration and extrusion limit its widespread practice. AIM: The aim of this study is to evaluate the efficacy and complications of the new "mirror tuck technique" for fixation of lacrimal bypass glass tube without holes in proximal canalicular blocks in laser CDCR. MATERIALS AND METHODS: A prospective interventional study was conducted in forty consecutive eyes of adult patients, undergoing 980 nm diode laser CDCR for proximal canalicular blocks...
April 2017: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/28492981/evidence-that-osteocytes-in-autogenous-bone-fragments-can-repair-disrupted-canalicular-networks-and-connect-with-osteocytes-in-de-novo-formed-bone-on-the-fragment-surface
#5
Furqan A Shah, Anders Palmquist
Autogenous bone fragments generated during surgery (e.g. implant site preparation) accelerate bone formation by the release of a large variety of growth factors from the extracellular matrix and the cells contained within. Osteocytes, whether viable or apoptotic, within such fragments are able to recruit osteoclasts to a site of bone remodelling. Here, using correlative scanning electron microscopy, we provide compelling evidence that at one week healing in the Sprague Dawley rat tibia, following surgery (and/or the placement of a bone-anchored implant), autogenous bone fragments support bone formation on their surface...
May 10, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28481222/hepatic-metal-ion-transporter-zip8-regulates-manganese-homeostasis-and-manganese-dependent-enzyme-activity
#6
Wen Lin, David R Vann, Paschalis-Thomas Doulias, Tao Wang, Gavin Landesberg, Xueli Li, Emanuela Ricciotti, Rosario Scalia, Miao He, Nicholas J Hand, Daniel J Rader
Genetic variants at the solute carrier family 39 member 8 (SLC39A8) gene locus are associated with the regulation of whole-blood manganese (Mn) and multiple physiological traits. SLC39A8 encodes ZIP8, a divalent metal ion transporter best known for zinc transport. Here, we hypothesized that ZIP8 regulates Mn homeostasis and Mn-dependent enzymes to influence metabolism. We generated Slc39a8-inducible global-knockout (ZIP8-iKO) and liver-specific-knockout (ZIP8-LSKO) mice and observed markedly decreased Mn levels in multiple organs and whole blood of both mouse models...
May 8, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28478831/hepatitis-c-virus-may-have-an-entero-hepatic-cycle-which-could-be-blocked-with-ezetimibe
#7
Hugo Monrroy, Marcelo López-Lastra, Alejandro Soza
Hepatitis C virus can lead to chronic infection, cirrhosis and hepatocellular carcinoma. With more than 170 million people infected worldwide, eradication remains a challenge even with the revolutionary current direct antiviral agents (DAAs). The risk of resistance, the safety profile in some populations, the genotype specificity and the high price of current DAAs explain why there is still interest in developing host targeting agents (HTA) that may help overcome some of these difficulties. Specifically, targeting the entry of HCV to the cell seems like a promising strategy...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28470757/osteocytes-acidify-their-microenvironment-in-response-to-pthrp-in-vitro-and-in-lactating-mice-in-vivo
#8
Katharina Jähn, Shilpa Kelkar, Hong Zhao, Yixia Xie, LeAnn M Tiede-Lewis, Vladimir Dusevich, Sarah L Dallas, Lynda F Bonewald
Osteocytes appear to mobilize calcium within minutes in response to PTH injections and we have previously shown that osteocytes remove their perilacunar matrix during lactation through activation of the PTH type 1 receptor. Mechanisms utilized by osteocytes to mobilize calcium are unknown but we hypothesized that the molecular components may be similar to those used by osteoclasts. Here we show, using IDG-SW3 cells that ATP6V0D2, an essential component of vacuolar ATPase in osteoclasts, and other genes associated with osteoclastic bone resorption increase with osteoblast to osteocyte differentiation...
May 4, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28456723/hepatobiliary-clearance-prediction-species-scaling-from-monkey-dog-and-rat-and-in-vitro-in-vivo-extrapolation-of-sandwich-cultured-human-hepatocytes-using-17-drugs
#9
Emi Kimoto, Yi-An Bi, Rachel E Kosa, Larry M Tremaine, Manthena V S Varma
Hepatobiliary elimination can be a major clearance pathway dictating the pharmacokinetics of drugs. Here, we first, compared the dose eliminated in bile in preclinical species (monkey, dog and rat) to that in human; and further evaluated single-species scaling (SSS) to predict human hepatobiliary clearance. Six compounds dosed in bile-duct cannulated monkeys showed biliary excretion comparable to human; and the SSS of hepatobiliary clearance with plasma fraction unbound correction yielded reasonable predictions (within 3-fold)...
April 26, 2017: Journal of Pharmaceutical Sciences
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
#10
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-DILI-concern and 55 of No-DILI-concern)...
May 4, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28412294/visualization-of-hepatitis-e-virus-rna-and-proteins-in-the-human-liver
#11
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
#12
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
#13
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
#14
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, for example, in progressive familial intrahepatic cholestasis or acquired, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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