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Edit Kun, Lóránt Dienes, Gábor Simonyi, Ervin Finta
The control and planning of the treatment of hypertensive patients need specific attention. As regards concomitant diseases and treatments, glaucoma and the use of eye drops should be taken into consideration. The ingredients of the administered eye drops get through the nasolacrimal canal and can be absorbed by the nasal mucosa. Because of the lack of enterohepatic 'first pass' effect, they can act systemically - like after intravenous administration. This way they can cause systemic side effects. The authors present a case of a patient, too, who was examined and medically checked regularly for years with negative results because of repeated syncope...
February 2019: Orvosi Hetilap
Qixiao Zhai, Yang Liu, Chen Wang, Dingwu Qu, Jianxin Zhao, Hao Zhang, Fengwei Tian, Wei Chen
The management of lead (Pb) exposure and toxicity remains a major public health priority worldwide. In our previous study, the probiotic strain Lactobacillus plantarum CCFM8661 prevented Pb absorption in mice via intestinal sequestration. This follow-up study aimed to evaluate the additional protective mechanism of L. plantarum CCFM8661 with a focus on its regulation of enterohepatic circulation. We first confirmed the relationship between the enterohepatic circulations of Pb and bile acid (BA) by administering a BA sequestrant, cholestyramine, to mice with a high Pb burden...
February 15, 2019: Food & Function
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
Suyuan Ji, Qingxu Liu, Shihao Zhang, Qinghua Chen, Cong Wang, Weiji Zhang, Chen Xiao, Yuxi Li, Cheng Nian, Jiaxin Li, Junhong Li, Jing Geng, Lixin Hong, Changchuan Xie, Ying He, Xing Chen, Xun Li, Zhen-Yu Yin, Han You, Kwang-Huei Lin, Qiao Wu, Chundong Yu, Randy L Johnson, Li Wang, Lanfen Chen, Fen Wang, Dawang Zhou
The external factors that modulate Hippo signaling remain elusive. Here, we report that FGF15 activates Hippo signaling to suppress bile acid metabolism, liver overgrowth, and tumorigenesis. FGF15 is induced by FXR in ileal enterocytes in response to increased amounts of intestinal bile. We found that circulating enterohepatic FGF15 stimulates hepatic receptor FGFR4 to recruit and phosphorylate NF2, which relieves the inhibitory effect of Raf on the Hippo kinases Mst1/2, thereby switching FGFR4's role from pro-oncogenic to anti-tumor signaling...
February 4, 2019: Developmental Cell
Pooja Acharya, Ramaprasad R Talahalli
In this study, the effect of n-3 fatty acids (FA) [α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] on the intestinal bile acid (BA) uptake, hepatic BA synthesis, and enterohepatic bile acid transporters (BAT) was assessed in young and aged dyslipidemic rats. Dyslipidemia was induced in young and aged rats by feeding a high-fat (HF) diet. Experimental groups received diets containing canola oil (HF + CNO) and fish oil (HF + FO) as a source of ALA and EPA + DHA, respectively...
February 10, 2019: Lipids
Ahter Tanay Tayyar, Ahmet Tayyar, Sukran Kozali, Resul Karakus, Nadiye Koroglu, Ilkbal Temel Yuksel, Gonca Yetkin Yildirim, Ismail Dag, Mustafa Eroglu
Introduction: Fibroblast growth factor-19 (FGF-19) and its co-receptor, beta-klotho, regulate bile acid synthesis in the liver as an enterohepatic feedback mechanism. In this study, our aim was to investigate the circulating FGF-19 and β-klotho levels in intrahepatic cholestasis of pregnancy (ICP) cases. Material and methods: A cross-sectional study including 40 women whose pregnancies were complicated with ICP were recruited for the study group. Forty randomly selected healthy pregnant women comprised the control group...
January 2019: Archives of Medical Science: AMS
Israel Rubinstein, Richard van Breemen, Daniel G Nosal, Guy Weinberg, Ronald C Hershow, Douglas L Feinstein
A recent multi-state outbreak of life-threatening bleeding following inhalation of synthetic cannabinoids has been attributed to contamination with the long-acting anticoagulant rodenticide (LAAR) brodifacoum, a second-generation, highly potent, long-acting derivative of the commonly used blood thinner warfarin. While long-term treatment with high-dose vitamin K1 restores coagulation, it does not affect brodifacoum metabolism or clearance, and, consequently, brodifacoum remains in the human body for several months, thereby predisposing to risk of bleeding recurrence and development of coagulation-independent injury in extrahepatic tissues and fetuses...
January 28, 2019: Drugs in R&D
Lilian H J Richter, Jennifer Herrmann, Anastasia Andreas, Yu Mi Park, Lea Wagmann, Veit Flockerzi, Rolf Müller, Markus R Meyer
New psychoactive substances (NPS) are an emerging topic amongst abused compounds. New varieties appear constantly on the market, without any knowledge about their toxicodynamic and/or -kinetic properties and knowledge of their metabolism is crucial for the development of analytical methods employed for their detection. Controlled human studies would of course be best suited but due to ethical reasons and lack of preclinical safety data, they are usually not available. Often, in vitro models are used to evaluate similarities to human in vivo hepatic phase I and II metabolism and systems explored include primary human hepatocytes, pooled human S9 fraction, and HepaRG, a human hepatic cell line...
January 22, 2019: Toxicology Letters
Te-An Kung, Shu-Hui Lee, Wei-Hsien Wang
A precise and reliable analytical method to measure trace levels of sulfamonomethoxine (SMM) and N4 -acetyl metabolite in tilapia samples using liquid chromatography-tandem mass spectrometry was developed. Optimized chromatographic separation was performed on C18 reversed-phase columns using gradient elution with methanol and 5 mmol/L of an ammonium acetate aqueous solution (adjusted to pH 3.5 using formic acid). This study investigated the pharmacokinetic properties and tissue distribution of SMM and its major metabolite N4 -acetyl sulfamonomethoxine (AC-SMM) in tilapia after a single dose of 100 mg kg-1 body weight of orally administered SMM...
January 2019: Journal of Food and Drug Analysis
Won Jae Yoon, Han-Na Kim, Eunkyo Park, Seungho Ryu, Yoosoo Chang, Hocheol Shin, Hyung-Lae Kim, Sun Young Yi
Cholecystectomy alters the bile flow into the intestine and the enterohepatic circulation of the bile acids; this may affect the gut microbiota. We assessed the gut microbiota composition of patients who had undergone cholecystectomy and compared with those who had not. From a cohort of 1463 adult participants who underwent comprehensive health screening examinations, 27 subjects who had undergone cholecystectomy (cholecystectomy group) and 81 age- and sex-matched subjects who had not (control group) were selected...
January 11, 2019: Journal of Clinical Medicine
Shudong Yang, Haiying Bao, Hui Wang, Qingjie Li
Inonotus hispidus is an anti-tumour drug used in folk medicine. (4S,5S)-4-Hydroxy-3,5-dimethoxycyclohex-2-enone (HDE) is a compound isolated from Inonotus hispidus for the first time. However, the mechanisms underlying its therapeutic effects have not been elucidated. In this study, the in vitro screening, in vivo anti-tumour effects, mechanism of action, pharmacokinetics, and tissue distribution of HDE were investigated. HDE could inhibit the proliferation of HepG2 cells. Additionally, its half-maximal inhibitory concentration was 7...
2019: Biological & Pharmaceutical Bulletin
Huan-Xi Zhang, Chang-Cheng Sheng, Long-Shan Liu, Bi Luo, Qian Fu, Qun Zhao, Jun Li, Yan-Feng Liu, Rong-Hai Deng, Zheng Jiao, Chang-Xi Wang
AIMS: Various mycophenolate mofetil (MMF) population pharmacokinetic (popPK) models have been developed to describe its PK characteristics and facilitate its optimal dosing in adult kidney transplant recipients co-administered with tacrolimus. However, the external predictive performance has been unclear. Thus, this study aimed to comprehensively evaluate the external predictability of published MMF popPK models in such populations and investigate the potential influencing factors. METHODS: The external predictability of qualified popPK models was evaluated using an independent dataset...
December 29, 2018: British Journal of Clinical Pharmacology
Liping Wang, Rongjin Sun, Qisong Zhang, Qing Luo, Sijing Zeng, Xiaoyan Li, Xia Gong, Yuhuan Li, Linlin Lu, Ming Hu, Zhongqiu Liu
Polyphenols, which are widely distributed in plants and the human diets, are known to have numerous biological activities. However, the low bioavailability of polyphenols is mediated by coupled metabolic pathways. Areas covered: The key role of the interplay between drug metabolic enzymes (DMEs) and efflux transporters (ETs), nuclear receptors (NRs), and intestinal microflora in the disposition of polyphenols is summarized. Expert opinion: ETs are shown to act as a 'revolving door', facilitating and/or controlling cellular polyphenol glucuronide/sulfate excretion...
December 24, 2018: Expert Opinion on Drug Metabolism & Toxicology
Malika Lahiani-Skiba, Francois Hallouard, Frederic Bounoure, Nicolas Milon, Youness Karrout, Mohamed Skiba
Cyclosporine (CsA) has a selective property of suppressing various T-lymphocyte functions. This is of utmost importance in preventing allograft rejection by several organ transplantations, as well as in the treatment of systemic and local autoimmune disorders. However, the poor water solubility of CsA can be a major hurdle for its absorption into the blood stream, which leads to low bioavailability and thus less efficacy. The aim of this study was to prepare, characterize, and evaluate in vitro as well as in vivo, the potential of the innovative CsA drug delivery system...
December 18, 2018: Pharmaceutics
Urs Duthaler, Claudia Suenderhauf, Mats O Karlsson, Janine Hussner, Henriette Meyer Zu Schwabedissen, Stephan Krähenbühl, Felix Hammann
AIMS: The anthelminthic ivermectin is receiving new attention as it is being repurposed for new indications such as mass drug administrations for the treatment of scabies or in malaria vector control. As its pharmacokinetics are still poorly understood, we aimed to characterize the population pharmacokinetics of ivermectin in plasma and dried blood spots (DBS), a sampling method better suited to field trials, with special focus on the influence of body composition and enterohepatic circulation...
December 19, 2018: British Journal of Clinical Pharmacology
Han Zheng, Yang You, Meiyun Hua, Pengfei Wu, Yu Liu, Zishuo Chen, Li Zhang, Haoche Wei, Yan Li, Mei Luo, Yilan Zeng, Yong Liu, Dong-Xia Luo, Jie Zhang, Min Feng, Richard Hu, Stephen J Pandol, Yuan-Ping Han
Liver fibrosis is an abnormal wound healing response and a common consequence of chronic liver diseases from infection or alcohol/xenobiotic exposure. At the cellular level, liver fibrosis is mediated by trans-differentiation of hepatic stellate cells (HSCs), which is driven by persistent hepatic and systemic inflammation. However, impaired enterohepatic circulation and gut dysbiosis may indirectly contribute to the liver fibrogenesis. The composition of the gut microbiota depends on diet composition and host factors...
2018: Frontiers in Physiology
Ida M Gether, Christina Nexøe-Larsen, David P Sonne, Pilip K Knop
As cases of gallbladder-related adverse events have been reported in patients treated with glucagon-like peptide (GLP)-1 receptor agonists and GLP-2 receptor agonists, studies have investigated the effects of these hormones on the enterohepatic circulation of bile acids and gallbladder motility. Results suggest, that bile acids and GLP-2 counteract postprandial cholecystokinin-mediated gallbladder contraction, while GLP-1 may delay gallbladder refilling. This provides important information on the effect and safety of drugs based on GLP-1 and GLP-2, respectively...
December 10, 2018: Ugeskrift for Laeger
Jing Wei, Jingrui Chen, Lingling Fu, Lifeng Han, Xiumei Gao, Michael Sarhene, Limin Hu, Youcai Zhang, Guanwei Fan
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb( Heshouwu, HSW) is commonly used in clinical medicine, while the hepatotoxicities of HSW are reported increasingly in recent years. Currently, researchers have demonstrated an essential role of Bile Acids (BAs) in liver diseases. The occurrence of hepatotoxicity cases linked to HSW are characterized by jaundice and cholestasis, suggesting an interaction that between BAs and HSW AIM OF THE STUDY: This study was designed to investigate the HSW-induced liver functional and histological changes in mice and the role of HSW on bile acid synthesis, metabolism, clearance and intestinal absorption...
December 6, 2018: Journal of Ethnopharmacology
Sonia L Ramírez-Garza, Emily P Laveriano-Santos, María Marhuenda-Muñoz, Carolina E Storniolo, Anna Tresserra-Rimbau, Anna Vallverdú-Queralt, Rosa M Lamuela-Raventós
The effect of resveratrol (RV) intake has been reviewed in several studies performed in humans with different health status. The purpose of this review is to summarize the results of clinical trials of the last decade, in which RV was determined in biological samples such as human plasma, urine, and feces. The topics covered include RV bioavailability, pharmacokinetics, effects on cardiovascular diseases, cognitive diseases, cancer, type 2 diabetes (T2D), oxidative stress, and inflammation states. The overview of the recent research reveals a clear tendency to identify RV in plasma, showing that its supplementation is safe...
December 3, 2018: Nutrients
Egil Ferkingstad, Asmundur Oddsson, Solveig Gretarsdottir, Stefania Benonisdottir, Gudmar Thorleifsson, Aimee M Deaton, Stefan Jonsson, Olafur A Stefansson, Gudmundur L Norddahl, Florian Zink, Gudny A Arnadottir, Bjarni Gunnarsson, Gisli H Halldorsson, Anna Helgadottir, Brynjar O Jensson, Ragnar P Kristjansson, Gardar Sveinbjornsson, David A Sverrisson, Gisli Masson, Isleifur Olafsson, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Hilma Holm, Ingileif Jonsdottir, Sigurdur Olafsson, Thora Steingrimsdottir, Thorunn Rafnar, Einar S Bjornsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Patrick Sulem, Kari Stefansson
Gallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1...
November 30, 2018: Nature Communications
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