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liver development

Aoife Parsons, Anke Lange, Thomas H Hutchinson, Shinichi Miyagawa, Taisen Iguchi, Tetsuhiro Kudoh, Charles R Tyler
Brominated flame retardants are known to disrupt thyroid hormone (TH) homeostasis in several vertebrate species, but the molecular mechanisms underlying this process and their effects on TH-sensitive tissues during the stages of early development are not well characterised. In this study, we exposed zebrafish (Danio rerio) embryo-larvae to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and tetrabromobisphenol A (TBBPA) via the water for 96 h from fertilisation and assessed for lethality, effects on development and on the expression of a suite of genes in the hypothalamic-pituitary-thyroid (HPT) axis via both real time quantitative PCR (qRT-PCR) on whole body extracts and whole mount in situ hybridisation (WISH) to identify tissue targets...
January 28, 2019: Aquatic Toxicology
Raquel Álvarez-Velilla, Maria Del Camino Gutiérrez-Corbo, Carmen Punzón, Maria Yolanda Pérez-Pertejo, Rafael Balaña-Fouce, Manuel Fresno, Rosa María Reguera
BACKGROUND: Visceral leishmaniasis is a neglected parasitic disease with no vaccine available and its pharmacological treatment is reduced to a limited number of unsafe drugs. The scarce readiness of new antileishmanial drugs is even more alarming when relapses appear or the occurrence of hard-to-treat resistant strains is detected. In addition, there is a gap between the initial and late stages of drug development, which greatly delays the selection of leads for subsequent studies. METHODOLOGY/PRINCIPAL FINDINGS: In order to address these issues, we have generated a red-shifted luminescent Leishmania infantum strain that enables long-term monitoring of parasite burden in individual animals with an in vivo limit of detection of 106 intracellular amastigotes 48 h postinfection...
February 14, 2019: PLoS Neglected Tropical Diseases
Peter J O'Shaughnessy, Jean Philippe Antignac, Bruno Le Bizec, Marie-Line Morvan, Konstantin Svechnikov, Olle Söder, Iuliia Savchuk, Ana Monteiro, Ugo Soffientini, Zoe C Johnston, Michelle Bellingham, Denise Hough, Natasha Walker, Panagiotis Filis, Paul A Fowler
Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone (DHT) through both the canonical androgenic pathway and an alternative (backdoor) pathway. The fetal testes are essential for canonical androgen production, but little is known about the synthesis of backdoor androgens, despite their known critical role in masculinization. In this study, we have measured plasma and tissue levels of endogenous steroids in second trimester human fetuses using multidimensional and high-resolution mass spectrometry...
February 2019: PLoS Biology
Mona Doshani, Mark Weng, Kelly L Moore, José R Romero, Noele P Nelson
Hepatitis A (HepA) vaccination is recommended routinely for children at age 12-23 months, for persons who are at increased risk for hepatitis A virus (HAV) infection, and for any person wishing to obtain immunity. Persons at increased risk for HAV infection include international travelers to areas with high or intermediate hepatitis A endemicity, men who have sex with men, users of injection and noninjection drugs, persons with chronic liver disease, person with clotting factor disorders, persons who work with HAV-infected primates or with HAV in a research laboratory setting, and persons who anticipate close contact with an international adoptee from a country of high or interme-diate endemicity (1-3)...
February 15, 2019: MMWR. Morbidity and Mortality Weekly Report
Jae-Won Eom, Tae-Youn Kim, Bo-Ra Seo, Hwangseo Park, Jae-Young Koh, Yang-Hee Kim
We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc neurotoxicity representing at least one mechanism of ischemic neuronal death. Inhibition of AMPK could be a viable therapeutic strategy to prevent ischemic brain injury following stroke. This prompted our search for novel inhibitors of AMPK activity and zinc-induced neuronal death using cultured mouse cortex and a rat model of brain injury after middle cerebral artery occlusion (MCAO)...
February 14, 2019: ACS Chemical Neuroscience
Wen Wen, Robert F Schwabe
Nearly 25% of the world's population is suffering from non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity and type 2 diabetes. NAFLD may progress to the development of non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). With efficient medical therapies lacking, modifications of life style and diet are considered the best options for the prevention and treatment of NAFLD. For the latter, it is thought that besides reducing fat, sugar and caloric intake, increasing fiber may exert beneficial effects on NAFLD, e...
February 14, 2019: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Stella Chin-Shaw Tsai, Jing-Yang Huang, Chuck Lin, Yung-Po Liaw, Frank Cheau-Feng Lin
Human papillomavirus (HPV) has been linked with development of oropharyngeal squamous cell carcinoma, a subset of head and neck cancer (HNC). This study aimed to evaluate the association between HPV infection and subsequent development of HNC and to report epidemiological information in Taiwan.This population-based cohort study retrieved patient data from the longitudinal health insurance database (LHID) of Taiwan's National Health Insurance Research Database (NHIRD) from 2005 to 2010 and analyzed it retrospectively...
February 2019: Medicine (Baltimore)
Li-Li Lou, Ying Zhang, Xu Huang, Li-Xia Zhang, Hui-Fan Ji, Xu Li, Xiao-Lin Guo
RATIONALE: Hepatocellular carcinoma (HCC) is the fifth most common cancer and third leading cause of cancer-related deaths worldwide. Nasopharyngeal metastasis of hepatocellular carcinoma is very rare. This is the first report of posttransplantation nasopharyngeal metastasis. PATIENT CONCERNS: A 45-year-old man with a history of hepatitis B related hepatocellular carcinoma (HCC) in the right segment of the liver received an orthotopic liver transplant. Two year after the transplantation, he suffered from severe headache, and head contrast enhanced CT scans did not show clues for brain or skull metastasis...
February 2019: Medicine (Baltimore)
Joel Lim, Alexandra Oschman, Kayla Curiel
PURPOSE OF REVIEW: The current review provides a summary of available lipid products and discusses current literature and the limitations to the use of various lipid products for treatment and prevention of intestinal failure-associated liver disease (IFALD) in pediatric patients dependent on parenteral nutrition. RECENT FINDINGS: Improvements in markers of cholestasis and liver function have been seen with minimizing soybean lipid, fish oil lipid, and mixed fish oil-containing lipid emulsions...
February 11, 2019: Current Opinion in Organ Transplantation
Lauren Pavlik, Arie Regev, Paul A Ardayfio, Naga P Chalasani
Drug-induced steatosis (DIS) and drug-induced steatohepatitis (DISH) are two of several types of drug-induced liver injury (DILI). They can be caused by various drugs and may present as acute, potentially lethal disorders or as chronic slowly progressive liver injury. Despite the fact that they are distinct disorders, the slow progressive forms of DIS and DISH are often confused with or misdiagnosed as non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), which are much more common and, by definition, not caused by drugs...
February 14, 2019: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Yung-Luen Shih, Hung-Sheng Shang, Yung-Liang Chen, Shu-Ching Hsueh, Hsiao-Min Chou, Hsu-Feng Lu, Ming-Zhe Lee, Hsin-Tu Hou, Ying-Ying Chuang, Mei-Hui Lee, Kuo-Wei Chen, Jing-Gung Chung
Ouabain, a cardiotonic steroid, was used for the treatment of heart failure and atrial fibrillation and induces cancer cell apoptosis in many human cancer cells including human leukemia cells. However, there are no reports to show the effects on immune responses in a leukemia mouse model. In this study, WEHI-3 cell generated leukemia mice were developed and treated by oral ouabain at 0, 0.75, 1.5, and 3 mg/kg for 15 days. Results indicated that ouabain did not affect body appearance, but decreased liver and spleen weights, B- and T-cell proliferation at all three doses treatment and increased CD19 cells at 3...
February 13, 2019: Environmental Toxicology
Hajime Yamazaki, Tsukasa Kamitani, Takeshi Matsui, Yosuke Yamamoto, Shunichi Fukuhara
BACKGROUND & AIM: Alanine aminotransferase (ALT) is an important enzyme for amino acid metabolism and gluconeogenesis, and low ALT is an indicator of vitamin B6 deficiency. However, it is unknown whether individuals with low ALT are likely to develop loss of independence (LOI) or death. We investigated the association of low ALT with LOI or death in the elderly. METHODS: Between 2008 and 2010, 2484 elderly individuals (≥65-years old) without functional dependency from the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS) were enrolled...
February 13, 2019: Journal of Gastroenterology and Hepatology
Feifan Xie, An Vermeulen, Pieter Colin, Zeneng Cheng
AIMS: Agomelatine is an antidepressant for major depressive disorders. It undergoes extensive first-pass hepatic metabolism, and displays irregular absorption profiles and large interindividual variability (IIV) and interoccasion variability (IOV) of pharmacokinetics. The objective of this study was to characterize the complex pharmacokinetics of agomelatine and its metabolites in healthy subjects. METHODS: Plasma concentration-time data of agomelatine and its metabolites were collected from a four period, cross-over bioequivalence study, in which 44 healthy subjects received 25 mg agomelatine tablets orally...
February 14, 2019: British Journal of Clinical Pharmacology
Arie Regev, Melissa Palmer, Mark I Avigan, Lara Dimick-Santos, William R Treem, John F Marcinak, Daniel Seekins, Gopal Krishna, Frank A Anania, James W Freston, James H Lewis, Arun J Sanyal, Naga Chalasani
BACKGROUND: The last decade has seen a rapid growth in the number of clinical trials enrolling patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). Due to the underlying chronic liver disease, patients with NASH often require different approaches to the assessment and management of suspected drug-induced liver injury (DILI) compared to patients with healthy livers. However, currently no regulatory guidelines or position papers systematically address best practices pertaining to DILI in NASH clinical trials...
February 13, 2019: Alimentary Pharmacology & Therapeutics
Albert J Czaja
BACKGROUND: Disturbances in iron regulation have been described in diverse chronic liver diseases other than hereditary haemochromatosis, and iron toxicity may worsen liver injury and outcome. AIMS: To describe manifestations and consequences of iron dysregulation in chronic liver diseases apart from hereditary haemochromatosis and to encourage investigations that clarify pathogenic mechanisms, define risk thresholds for iron toxicity, and direct management METHODS: English abstracts were identified in PubMed by multiple search terms...
February 13, 2019: Alimentary Pharmacology & Therapeutics
Helal F Hetta, Asmaa M Zahran, Shima G Mansor, Mohamed O Abdel-Malek, Mohamed A Mekky, Wael A Abbas
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play a pivotal role in tumor immunity and induction of immune tolerance to a variety of antitumor effectors, including T-lymphocytes. Herein, we tried to evaluate the frequency and clinical significance of MDSCs and different lymphocyte subsets in HCV- related hepatocellular carcinoma (HCC). METHODS: Four groups were enrolled; chronic HCV (CHC, n=40), HCV related liver cirrhosis (HCV-LC, n= 40), HCV related HCC (HCV-HCC, n=75) and healthy control group (n=20)...
February 13, 2019: Journal of Medical Virology
Hannes Hagström, Tomas Hemmingsson, Andrea Discacciati, Anna Andreasson
BACKGROUND: Excess consumption of alcohol can lead to cirrhosis, but it is unclear whether the type of alcohol and pattern of consumption affects this risk. AIMS: We aimed to investigate whether type and pattern of alcohol consumption early in life could predict development of severe liver disease. METHODS: We examined 43,242 adolescent men conscribed to military service in Sweden in 1970. Self-reported data on total amount and type of alcohol (wine, beer, and spirits) and risk behaviors associated with heavy drinking were registered...
February 14, 2019: Digestive Diseases and Sciences
Wataru Miura, Nobuhiko Nagano, Ryota Kato, Aya Okahashi, Kayo Yoshikawa, Kensuke Ohashi, Tsugumichi Koshinaga, Ichiro Morioka
Intestinal failure-associated liver disease (IFALD) is a fatal complication of short bowel syndrome managed with parenteral nutrition. A clinical cohort study reported the usefulness of parenteral administration of fish-derived omega-3 fatty acids in improving IFALD; however, no biomarker has been developed as yet. The authors report the case of a preterm infant with IFALD complicated by extensive short bowel syndrome. Intravenous administration of omega-3 fatty acids were introduced using Omegaven®at the age of 4 mo for IFALD...
February 13, 2019: Indian Journal of Pediatrics
Lianne de Haan, Sarah J van der Lely, Anne-Loes K Warps, Quincy Hofsink, Pim B Olthof, Mark J de Keijzer, Daniël A Lionarons, Lionel Mendes-Dias, Bote G Bruinsma, Korkut Uygun, Hartmut Jaeschke, Geoffrey C Farrell, Narci Teoh, Rowan F van Golen, Tiangang Li, Michal Heger
Background: Liver regeneration following partial hepatectomy (PHx) is a complicated process involving multiple organs and several types of signaling networks. The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story. PHx is characterized by rapid but transient bile acid overload in the liver, which constitutes the first wave of proliferative signaling in the remnant hepatocytes. Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors...
May 28, 2018: Journal of Clinical and Translational Research
Monika Wetscher, Klaus Hackländer, Viktoria Faber, Ninon Taylor, Herbert Auer, Georg G Duscher
The Austrian province of Tyrol belongs to the areas where the alveolar echinococcosis (AE) caused by the fox tapeworm Echinococcus multilocularis ( E. multilocularis ) is highly endemic. In Central Europe and since 2011 in Austria, a growing incidence of human cases of AE has been observed, presumably linked with increasing fox populations infected by the fox tapeworm E. multilocularis . Hunting and the related activities put hunters in a high-risk group, and they are considered particularly vulnerable for the contraction of an AE...
2019: Frontiers in Public Health
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