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https://www.readbyqxmd.com/read/28223721/current-and-future-therapies-for-inherited-cholestatic-liver-diseases
#1
REVIEW
Wendy L van der Woerd, Roderick Hj Houwen, Stan Fj van de Graaf
Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2)...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28221291/ophthalmic-manifestations-of-facial-dog-bites-in-children
#2
Emily M Bratton, Liliya Golas, Leslie A Wei, Brett W Davies, Vikram D Durairaj
PURPOSE: To characterize ophthalmic manifestations and periocular injuries of pediatric facial dog bites. METHODS: A retrospective review of all children younger than 18 years who sought medical attention after a dog bite to the face between January 1, 2003 and May 22, 2014 was performed at a large tertiary pediatric hospital. Data on type and location of injury, surgical intervention, and complications were collected. RESULTS: A total of 1,989 children aged 0...
February 17, 2017: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28220208/abcb4-missense-mutations-d243a-k435t-g535d-i490t-r545c-and-s978p-significantly-impair-the-lipid-floppase-and-likely-predispose-to-secondary-pathologies-in-the-human-population
#3
Edward J Andress, Michael Nicolaou, Farrell McGeoghan, Kenneth J Linton
Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28216153/dynamic-modulation-of-cyp21a1-21-hydroxylase-expression-sites-in-the-mouse-developing-lung
#4
Catherine Gilbert, Pierre R Provost, Yves Tremblay
21-hydroxylase is expressed in the developing lung where it is proposed as a local source of glucocorticoids playing important roles in lung development. We have studied the precise sites of Cyp21a1 expression in the developing mouse lung from the pseudoglandular stage (gestation day (GD) 15.5) to the alveolar stage (postnatal day (PND) 15) by in situ hybridization. Cyp21a1-mRNA was found mainly in epithelial cells from GD 15.5 to PND 5, but the precise site of expression shifted from the distal epithelium during the pseudoglandular and the canalicular stages including the distal epithelium without lumina, to the proximal epithelium and the wall of developing saccules during the perinatal period (GD 19...
February 16, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28207432/spontaneous-canalicular-plug-erosion-after-punctal-plug-placement
#5
Xinxin Zhang, Maya Bitar, Richard M Davis
PURPOSE: To describe a case of keratoconjunctivitis sicca treated with punctal plug placement with the first reported complication of subsequent plug erosion through the canaliculus and extrusion through the lid. METHODS: Punctal plugs were placed in a patient with Sjogren syndrome for treatment of keratoconjunctivitis sicca. More than 12 years later, the plug was noted to have eroded through the canaliculus and extruded through the conjunctiva and lid. RESULTS: The extruded plug was removed, and punctal cautery was performed on 2 other puncta with improved symptom control...
February 15, 2017: Cornea
https://www.readbyqxmd.com/read/28180039/endoscopic-endonasal-optic-nerve-decompression-for-fibrous-dysplasia
#6
Timothy R DeKlotz, S Tonya Stefko, Juan C Fernandez-Miranda, Paul A Gardner, Carl H Snyderman, Eric W Wang
Objective To evaluate visual outcomes and potential complications for optic nerve decompression using an endoscopic endonasal approach (EEA) for fibrous dysplasia. Design Retrospective chart review of patients with fibrous dysplasia causing extrinsic compression of the canalicular segment of the optic nerve that underwent an endoscopic endonasal optic nerve decompression at the University of Pittsburgh Medical Center from 2010 to 2013. Main Outcome Measures The primary outcome measure assessed was best-corrected visual acuity (BCVA) with secondary outcomes, including visual field testing, color vision, and complications associated with the intervention...
February 2017: Journal of Neurological Surgery. Part B, Skull Base
https://www.readbyqxmd.com/read/28179894/vestibulo-ocular-reflex-stabilization-after-vestibular-schwannoma-surgery-a-story-told-by-saccades
#7
Angel Batuecas-Caletrio, Jorge Rey-Martinez, Gabriel Trinidad-Ruiz, Eusebi Matiño-Soler, Santiago Santa Cruz-Ruiz, Angel Muñoz-Herrera, Nicolas Perez-Fernandez
OBJECTIVE: To evaluate vestibular compensation via measurement of the vestibulo-ocular reflex (VOR) following vestibular schwannoma surgery and its relationship with changes in saccades strategy after surgery. PATIENTS: Thirty-six consecutive patients with vestibular schwannomas, without brainstem compression, underwent surgical resection. Patients were recruited from University Hospital of Salamanca, Spain. METHODS: We assessed the age, sex, tumor size, degree of canalicular weakness, and preoperative video head impulse test (gain and saccade organization measured with PR score)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28157235/possible-involvement-of-nitric-oxide-in-enhanced-liver-injury-and-fibrogenesis-during-cholestasis-in-cytoglobin-deficient-mice
#8
Tuong Thi Van Thuy, Le Thi Thanh Thuy, Katsutoshi Yoshizato, Norifumi Kawada
This study clarified the role of Cygb, the fourth globin in mammals originally discovered in rat hepatic stellate cells (HSCs), in cholestatic liver disease. Bile duct ligation (BDL) augmented inflammatory reactions as revealed by increased infiltrating neutrophils, CD68(+)-macrophages, and chemokine expression in Cygb(-/-) mice. In these mice, impairment of bile canalicular indicated by the loss of CD10 expression, down-regulation of bile salt transporters, increased total bile acid, and massive apoptotic and necrotic hepatocytes occurred with the release of cytochrome c, activation of caspase 3, resulting in reduced animal survival compared to wild-type mice...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155688/mathematically-modeling-fluid-flow-and-fluid-shear-stress-in-the-canaliculi-of-a-loaded-osteon
#9
Xiaogang Wu, Ningning Wang, Zhaowei Wang, Weilun Yu, Yanqin Wang, Yuan Guo, Weiyi Chen
BACKGROUND: Mechanical load-induced intraosseous pressure gradients may result in some fluid stimuli effects, such as fluid flow and fluid shear stress (FSS), which may enable bone cells to detect external mechanical signals. Interstitial bone fluid flow is known to occur in lacunar-canalicular porosity (PLC). METHODS: In order to characterize lacunar-canalicular fluid flow behavior, a hierarchical osteon system is developed. The osteon is modeled as a poroelastic annular cylinder with two types of impermeable boundary cases considered on its outer wall: one is elastic restrained (Case I), whereas the other is displacement confined (Case II)...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28145940/using-the-endoscopic-transconjunctival-and-transcaruncular-approach-to-repair-combined-orbital-floor-and-medial-wall-blowout-fractures
#10
Minwook Chang, Seong Won Yang, Jin-Hwan Park, Joonsik Lee, Hwa Lee, Min Soo Park, Sehyun Baek
PURPOSE: To demonstrate the effectiveness of the endoscopic transcaruncular and transconjunctival approach in the repair of combined medial and inferior orbital wall fractures. METHODS: A retrospective chart review was conducted on 160 patients with combined medial and inferior orbital wall fractures. All patients underwent surgery via an endoscopic transcaruncular and transconjunctival approach without lateral canthotomy, performed by a single surgeon. Porous polyethylene sheets (1...
January 31, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28144783/development-of-the-lung
#11
REVIEW
Johannes C Schittny
To fulfill the task of gas exchange, the lung possesses a huge inner surface and a tree-like system of conducting airways ventilating the gas exchange area. During lung development, the conducting airways are formed first, followed by the formation and enlargement of the gas exchange area. The latter (alveolarization) continues until young adulthood. During organogenesis, the left and right lungs have their own anlage, an outpouching of the foregut. Each lung bud starts a repetitive process of outgrowth and branching (branching morphogenesis) that forms all of the future airways mainly during the pseudoglandular stage...
March 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28139140/canalicular-lacerations-factors-predicting-outcome-at-a-tertiary-eye-care-centre
#12
Swati Singh, Anasua Ganguly, Apurva Hardas, Devjyoti Tripathy, Suryasnata Rath
To determine the factors predictive of outcome in canalicular laceration repair at a tertiary eye care centre. A retrospective review of the medical records of all primary canalicular laceration repairs managed at a tertiary eye care centre between the years 2006 and 2014 was done. Thirty-nine patients were included and majority were male (79.5%) with a mean age of 30.05 + 16.2 years (range 2-65). Most (n = 34) had monocanalicular laceration and 5 had bicanalicular laceration. All surgeries were done in the operating room setting...
January 31, 2017: Orbit
https://www.readbyqxmd.com/read/28134251/low-dose-acetaminophen-induces-early-disruption-of-cell-cell-tight-junctions-in-human-hepatic-cells-and-mouse-liver
#13
Wesam Gamal, Philipp Treskes, Kay Samuel, Gareth J Sullivan, Richard Siller, Vlastimil Srsen, Katie Morgan, Anna Bryans, Ada Kozlowska, Andreas Koulovasilopoulos, Ian Underwood, Stewart Smith, Jorge Del-Pozo, Sharon Moss, Alexandra Inés Thompson, Neil C Henderson, Peter C Hayes, John N Plevris, Pierre-Olivier Bagnaninchi, Leonard J Nelson
Dysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127842/hepatocarcinogenesis-in-multidrug-resistant-p-glycoprotein-3-deficiency
#14
Mukul Vij, Naresh P Shanmugam, Mettu Srinivas Reddy, Sanjay Govil, Mohamed Rela
MDR3 is a hepatocyte canalicular membrane protein encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine into bile. Severe MDR 3 deficiency typically presents during early childhood with chronic cholestasis evolving to cirrhosis and portal hypertension, requiring liver transplantation. Herein, we report a case of severe MDR3 deficiency in a male child diagnosed with negative MDR3 immunostaining in hepatic canaliculi who underwent LDLT at our centre. We also describe single incidentally detected early well-differentiated HCC in the explant liver...
January 27, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28124283/a-critical-evaluation-of-liver-pathology-in-humans-with-danon-disease-and-experimental-correlates-in-a-rat-model-of-lamp-2-deficiency
#15
Lu Wang, Jingbo Wang, Weile Cai, Yongquan Shi, Xinmin Zhou, Guanya Guo, Changcun Guo, Xiaofeng Huang, Zheyi Han, Shuai Zhang, Shuoyi Ma, Xia Zhou, Daiming Fan, M Eric Gershwin, Ying Han
Danon disease is a genetic deficiency in lysosome-associated membrane protein 2 (LAMP-2), a highly glycosylated constituent of the lysosomal membrane and characterized by a cardiomyopathy, skeletal muscle myopathy, and cognitive impairment. Patients, however, often manifest hepatic abnormalities, but liver function has not been well evaluated and the syndrome is relatively uncommon. Hence, we have taken advantage of a rat that has been deleted of LAMP-2 to study the relative role of LAMP-2 on liver function...
January 26, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28108666/antibiotic-induced-elevations-of-plasma-bile-acids-in-rats-independent-of-bsep-inhibition
#16
Yutai Li, Michael J Hafey, Hong Duong, Raymond Evers, Kyeongmi Cheon, Daniel J Holder, Alema Galijatovic-Idrizbegovic, Frank D Sistare, Warren E Glaab
Drug-induced liver injury (DILI) is a common toxicity observed in drug development and can lead to withdrawal of approved drugs from the market. To better understand the numerous mechanisms of DILI, recent efforts have focused on transporter inhibition, specifically liver canalicular bile salt export pump (Bsep) as one mechanism of DILI, and on the potential use of plasma bile acids as monitorable mechanism-based biomarkers of Bsep inhibition. To explore alternative mechanisms of bile acid increases in plasma, six antibiotic and two non-antibiotic drugs unlikely to be Bsep inhibitors were evaluated in rat studies...
January 20, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28061633/mechanisms-of-bone-response-to-injury
#17
Keren E Dittmer, Elwyn C Firth
Bone, despite its relatively inert appearance, is a tissue that is capable of adapting to its environment. Wolff's law, first described in the 19th century, describes the ability of bone to change structure depending on the mechanical forces applied to it. The mechanostat model extended this principle and suggested that the amount of strain a bone detects depends on bone strength and the amount of muscle force applied to the bone. Experimental studies have found that low-magnitude, high-frequency mechanical loading is considered to be the most effective at increasing bone formation...
January 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28036031/drug-transporter-expression-and-activity-in-human-hepatoma-huh-7-cells
#18
Elodie Jouan, Marc Le Vée, Claire Denizot, Yannick Parmentier, Olivier Fardel
Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2...
December 28, 2016: Pharmaceutics
https://www.readbyqxmd.com/read/28029505/parenteral-nutrition-dysregulates-bile-salt-homeostasis-in-a-rat-model-of-parenteral-nutrition-associated-liver-disease
#19
Kiran V K Koelfat, Frank G Schaap, Caroline M J M Hodin, Ruben G J Visschers, Björn I Svavarsson, Martin Lenicek, Ronit Shiri-Sverdlov, Kaatje Lenaerts, Steven W M Olde Damink
BACKGROUND & AIMS: Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis...
September 24, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28027573/defects-in-myo5b-are-associated-with-a-spectrum-of-previously-undiagnosed-low-%C3%AE-glutamyltransferase-cholestasis
#20
Yi-Ling Qiu, Jing-Yu Gong, Jia-Yan Feng, Ren-Xue Wang, Jun Han, Teng Liu, Yi Lu, Li-Ting Li, Mei-Hong Zhang, Jonathan A Sheps, Neng-Li Wang, Yan-Yan Yan, Jia-Qi Li, Lian Chen, Christoph H Borchers, Bence Sipos, A S Knisely, Victor Ling, Qing-He Xing, Jian-She Wang
: Hereditary cholestasis in childhood and infancy with normal serum gamma-glutamyltransferase activity (GGT) is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin 5B (MYO5B) cause microvillus inclusion disease (MVID, MIM251850) with recurrent watery diarrhea. Cholestasis reported as an atypical presentation in MVID has been considered a side effect of parenteral alimentation. Here, however, we report ten patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who neither had recurrent diarrhea nor received parenteral alimentation...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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