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Jean-Luc Daire, Benjamin Leporq, Valérie Vilgrain, Bernard E Van Beers, Sabine Schmidt, Catherine M Pastor
BACKGROUND AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) is a commercialised hepatobiliary contrast agent used during liver magnetic resonance imaging (MRI) to detect liver diseases. It enters into human hepatocytes through organic anion transporting polypeptides (OATP1B1/B3) and crosses the canalicular transporter multiple resistance-associated protein 2 (MRP2) to be excreted into bile canaliculi. Gd-BOPTA can return to sinusoids via the sinusoidal transporters MRP3/MRP4. Hepatocyte concentrations of Gd-BOPTA depend on three clearances: the sinusoidal clearance or volume of sinusoidal blood cleared of drugs per unit of time and two hepatocyte clearances (into bile canaliculi or back to sinusoids) or volume of hepatocytes cleared of drugs per unit of time in the respective liver compartments...
October 24, 2016: European Journal of Drug Metabolism and Pharmacokinetics
Ruchi Goel, Smriti Nagpal, Sushil Kumar, Ravi Meher, Saurabh Kamal, Sonam Garg
PURPOSE: To evaluate and compare the success rate of transcanalicular laser-assisted dacryocystorhinostomy with endonasal augmentation, with and without intubation, in patients suffering from primary acquired nasolacrimal duct obstruction, at 1 year of follow up. METHODS: A prospective, randomized interventional pilot study was conducted at a tertiary care center, in accordance with the guidelines of Declaration of Helsinki. Sixty eyes of 60 adult patients with primary acquired nasolacrimal duct obstruction were included...
October 20, 2016: Ophthalmic Plastic and Reconstructive Surgery
Guigang Li, Jingmin Guo, Rong Liu, Weikun Hu, Lingjuan Xu, Juan Wang, Subo Cai, Hong Zhang, Yingting Zhu
Background: To explore the prevalence of lacrimal duct obstruction in patients with infectious keratitis, and the necessity of lacrimal duct dredge in the treatment of human infectious keratitis. Methodology/Principle Findings: The design is prospective, non-control case series. Thirty-one eyes from twenty-eight continuous patients with infectious keratitis were included in this study. The presence/absence of lacrimal duct obstruction was determined by the lacrimal duct irrigation test. The diagnosis of infectious keratitis was made based on clinical manifestations, cornea scraping microscopic examination and bacterial/fungus culture...
2016: International Journal of Medical Sciences
Soo Won Ko, Jong Seok Lee, Han Sung Choi, Young Gwan Ko, Hoon Pyo Hong
The use of high-pressure air instruments has become more common. Consequently, there have been a number of cases of orbital emphysema caused by contact with high-pressure air. In this case, a 62-year-old male patient visited an emergency medical center after his left eye was shot by an air compressor gun that was used to wash cars. Lacerations were observed in the upper and lower eyelids of his left eye. Radiological examinations revealed orbital emphysema, optic nerve transection, pneumocephalus, and subcutaneous emphysema in the face, neck, shoulder, and mediastinum...
September 2016: Clin Exp Emerg Med
Hitomi Hoshino, Makoto Ohta, Makoto Ito, Kenji Uchimura, Yasuhiro Sakai, Takeshi Uehara, Shulin Low, Mana Fukushima, Motohiro Kobayashi
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver neoplasm, followed by hepatocellular carcinoma. ICC can be further subclassified as (i) perihilar and (ii) peripheral types, the latter histologically resembling small-sized intrahepatic bile ducts, such as interlobular bile ducts, cholangioles/ductules and the canals of Hering. Cholangiolocellular carcinoma (CoCC), now classified by the World Health Organization as a subtype of combined hepatocellular-cholangiocarcinoma, is currently regarded as a subtype of peripheral-type ICC...
October 17, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Harriet Gaskell, Parveen Sharma, Helen E Colley, Craig Murdoch, Dominic P Williams, Steven D Webb
More predictive in vitro liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells...
June 1, 2016: Toxicology Research
Lixia Fan, Shaopeng Pei, X Lucas Lu, Liyun Wang
The transport of fluid, nutrients, and signaling molecules in the bone lacunar-canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30-50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach...
2016: Bone Research
Katalin Jemnitz, Attila Bátai-Konczos, Mónika Szabó, Enikő Ioja, Orsolya Kolacsek, Tamás I Orbán, György Török, László Homolya, Eszter Kovács, István Jablonkai, Zsuzsa Veres
Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Furthermore, elevated intracellular Ca(2+) level of hepatocytes is considered as a common marker of DILI. Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co-cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2 fluorescent Ca(2+) sensor protein to investigate the effects of polycationic (G5), polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers known to accumulate in the liver, primarily in KCs...
October 4, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Angélica Morales, Sumiko Morimoto, Felipe Vilchis, Natsuko Taniyama, Claudia J Bautista, Carlos Robles, Enrique Bargalló
Vascular endothelial growth factor (VEGF) is important in the growth and metastasis of cancer cells. In 2001, another angiogenic factor, endocrine gland-derived VEGF (EG-VEGF), was characterized and sequenced. EG-VEGF activity appears to be restricted to endothelial cells derived from endocrine glands. At the molecular level, its expression is regulated by hypoxia and steroid hormones. Although VEGF and EG-VEGF are structurally different, they function in a coordinated fashion. Since the majority of mammary tumors are hormone-dependent, it was hypothesized that EG-VEGF would be expressed in these tumors, and therefore, represent a potential target for anti-angiogenic therapy...
October 2016: Oncology Letters
Xiaojiaoyang Li, Runping Liu, Linxi Yu, Zihang Yuan, Rong Sun, Hang Yang, Luyong Zhang, Zhenzhou Jiang
Alpha-naphthylisothiocyanate (ANIT) is widely used to induce cholestasis in basic researches. Although direct damage induced by ANIT to bile duct epithelial cells has been documented in previous studies, few works investigated ANIT-induced effects on hepatocytes. Our previous study indicated that activated AMP-activated protein kinase (AMPK) inhibited farnesoid X receptor (FXR) expression and further participated in the pathogenesis of estrogen-induced cholestasis. However, whether ANIT has effects on bile acid homeostasis in hepatocytes, and the role of AMPK-FXR pathway played in these effects remain unclear...
October 1, 2016: Toxicology
Mohsen Bahmani Kashkouli, Mohammad Bagher Abtahi, Hamed Sianati, Nina Mahvidizadeh, Farzad Pakdel, Pedram Bahmani Kashkouli, Parya Abdolalizadeh
PURPOSE: To report 10-year results of a 1-stage, obstruction-based, endoscopic approach in children with congenital nasolacrimal duct obstruction (CNLDO) with and without prior failed probing/intubation. METHODS: In a retrospective study, children with primary CNLDO of >6 months old previously failed probing/intubation, acute dacryocystitis or dacryocele at any age, and at least 6 months follow up. Diagnosis was based on history of tearing and dye disappearance test...
September 15, 2016: Ophthalmic Plastic and Reconstructive Surgery
Kaori Oya, Ken Ishida, Tomoki Nishida, Sunao Sato, Mitsunobu Kishino, Katsutoshi Hirose, Yuzo Ogawa, Kazunori Ikebe, Fumio Takeshige, Hidehiro Yasuda, Toshihisa Komori, Satoru Toyosawa
Dmp1 is an acidic phosphoprotein that is specifically expressed in osteocytes. During the secretory process, the full-length, precursor Dmp1 is cleaved into N- and C-terminal fragments. C-terminal Dmp1 is phosphorylated, becoming a highly negatively charged domain that may assist in bone mineralization by recruiting calcium ions and influencing subsequent mineral deposition. It has been recently reported that the Golgi-localized protein kinase Fam20C phosphorylates Dmp1 in vitro. To investigate this phosphorylation in situ, we determined the locations of phosphorylated Dmp1 and Fam20C in rat bones using immunohistochemistry...
September 10, 2016: Histochemistry and Cell Biology
C Guth, U Beuers, K Beckh
Intermittent cholestatic liver disease may indicate an inherited deficiency of bile salt transport proteins. Episodes of cholestasis may start during pregnancy or during use of oral contraceptives or other medication. We describe the case of a 22-year-old mother with increasing jaundice and severe pruritus two weeks after starting hormonal contraception. A few months before she was suffering from intrahepatic cholestasis of pregnancy (ICP). Liver biopsy showed bland cholestasis with canalicular bile plugs...
September 2016: Zeitschrift Für Gastroenterologie
A L Dzierlenga, J D Clarke, N J Cherrington
Interindividual variability in drug response in nonalcoholic steatohepatitis (NASH) can be mediated by altered regulation of drug metabolizing enzymes and transporters. Among these is the mislocalization of multidrug resistance-associated protein (MRP2)/Mrp2 away from the canalicular membrane, which results in decreased transport of MRP2/Mrp2 substrates. The exact mechanism of this mislocalization is unknown, although increased activation of membrane retrieval processes may be one possibility. The current study measures the activation status of various mediators implicated in the active membrane retrieval or insertion of membrane proteins to identify which processes may be important in rodent methionine and choline deficient diet-induced NASH...
November 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Kyle J Beauchemin, Julie M Wells, Alvin T Kho, Vivek M Philip, Daniela Kamir, Isaac S Kohane, Joel H Graber, Carol J Bult
To characterize temporal patterns of transcriptional activity during normal lung development, we generated genome wide gene expression data for 26 pre- and post-natal time points in three common inbred strains of laboratory mice (C57BL/6J, A/J, and C3H/HeJ). Using Principal Component Analysis and least squares regression modeling, we identified both strain-independent and strain-dependent patterns of gene expression. The 4,683 genes contributing to the strain-independent expression patterns were used to define a murine Developing Lung Characteristic Subtranscriptome (mDLCS)...
2016: PeerJ
Claudia D Fuchs, Gustav Paumgartner, Annika Wahlström, Philipp Schwabl, Thomas Reiberger, Nadja Leditznig, Tatjana Stojakovic, Nataliya Rohr-Udilova, Peter Chiba, Hanns-Ulrich Marschall, Michael Trauner
BACKGROUND & AIMS: Cholestasis is characterized by intrahepatic accumulation of potentially cytotoxic bile acids (BAs) subsequently leading to liver injury with disruption of hepatocellular integrity, inflammation, fibrosis and ultimately liver cirrhosis. Bile salt export pump (BSEP/ABCB11) is the main canalicular BA transporter and therefore the rate limiting step for hepatobiliary BA excretion. In this study we aimed to investigate the role of BSEP/ABCB11 in the development of acquired cholestatic liver and bile duct injury...
September 1, 2016: Journal of Hepatology
Abhishek Kumar Tiwari, Jitendra Prasad
Bone loss is a serious health problem. In vivo studies have found that mechanical stimulation may inhibit bone loss as elevated strain in bone induces osteogenesis, i.e. new bone formation. However, the exact relationship between mechanical environment and osteogenesis is less clear. Normal strain is considered as a prime stimulus of osteogenic activity; however, there are some instances in the literature where osteogenesis is observed in the vicinity of minimal normal strain, specifically near the neutral axis of bending in long bones...
September 1, 2016: Biomechanics and Modeling in Mechanobiology
Jasmin Svinka, Sandra Pflügler, Markus Mair, Hanns-Ulrich Marschall, Jan G Hengstler, Patricia Stiedl, Valeria Poli, Emilio Casanova, Gerald Timelthaler, Maria Sibilia, Robert Eferl
: We have demonstrated that the signal transducer and activator of transcription 3 (STAT3) protects from cholestatic liver injury. Specific ablation of STAT3 in hepatocytes and cholangiocytes (STAT3(∆hc)) aggravated liver damage and fibrosis in the Mdr2(-/-) (multidrug resistance 2) mouse model for cholestatic disease. Upregulation of bile acid biosynthesis genes and downregulation of epidermal growth factor receptor (EGFR) expression were observed in STAT3(∆hc) Mdr2(-/-) mice but the functional consequences of these processes in cholestatic liver injury remained unclear...
August 27, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Khami Satchi, Alan A McNab
Patients with conjunctival cicatrizing disease may develop lacrimal obstruction. Little is published on lacrimal obstruction as the presenting feature of otherwise asymptomatic cicatrizing conjunctival disease. The records of all patients presenting between 1994 and 2015 with lacrimal obstruction found to have cicatrizing conjunctival disease were reviewed. Demographic details, clinical findings, disease progression and treatment were analyzed. Thirty-five patients (25 female), aged 43-91 years (median 74, mean 71...
August 25, 2016: Orbit
Michele Casanova, Janelle Herelle, Marcel Thomas, Rowan Softley, Aaron Schindeler, David Little, Philipp Schneider, Ralph Müller
In recent years, great interest in combined treatment of parathyroid hormone (PTH) with anti-resorptive therapy has emerged. PTH has been suggested to aid bridging of atrophic fractures and improve strength in closed fracture models. Bisphosphonate treatments typically result in a larger woven bone callus that is slower to remodel. The combination of both drugs has been demonstrated to be effective for the treatment of osteoporotic bone loss in many preclinical studies. However, the effect of combined treatment on fracture repair is still largely unexplored...
November 2016: Bone
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