Discovery of novel ketoxime ether derivatives with potent FXR agonistic activity, oral effectiveness and high liver/blood ratio

2021 ◽  
pp. 116280
Author(s):  
Xuehang Tang ◽  
Mengmeng Ning ◽  
Yangliang Ye ◽  
Yipei Gu ◽  
Hongyi Yan ◽  
...  
Keyword(s):  
Agonistic Activity ◽  
High Liver

Hepatobiliary Kinetics of 113mIn-Phenolphthalexon

1981 ◽  
Vol 20 (02) ◽  
pp. 90-93
Author(s):  
P.B. Parab ◽  
U.R. Raikar ◽  
R.D. Ganatra ◽  
M. C. Patel
Keyword(s):  
Biliary Excretion ◽  
Iminodiacetic Acid ◽  
Organ Distribution ◽  
Liver Uptake ◽  
On Line ◽  
Rapid Clearance ◽  
Chemical Purity ◽  
Kinetics Of ◽  
High Liver

Phenolphthalexon, a compound with iminodiacetic acid as a functional group, has been labelled with 113mIn to high chemical purity and its usefulness in studies of biliary excretion patency has been studied. Organ distribution of 113mIn-phenolphthalexon in mice was characterized by high liver uptake (50.8% of the administered dose after 5 min) and rapid clearance through the gall bladder. An animal model for studying obstruction of biliary excretion has been developed. Data on the kinetics of the radiopharmaceutical were obtained by collecting in-vivo data through an on-line computer.

scholarly journals The Threat of Multiple Liver Carcinogens in the Population of Laos: A Review

Livers ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 49-59
Author(s):  
Philavanh Sitbounlang ◽  
Agnès Marchio ◽  
Eric Deharo ◽  
Phimpha Paboriboune ◽  
Pascal Pineau
Keyword(s):  
Liver Cancer ◽  
Cancer Incidence ◽  
Primary Liver Cancer ◽  
Alcoholic Beverages ◽  
Fermented Fish ◽  
Dna Mutations ◽  
Liver Health ◽  
Cell Genome ◽  
Infectious Burden ◽  
High Liver

Laos is a landlocked country in South East Asia, ranking fifth for primary liver cancer incidence worldwide. Risk factors that might explain this worrying situation are poorly known. We conducted a review of the literature concerning the etiologies of terminal liver diseases in Laos. A double infectious burden with hepatitis B and C viruses and the liver fluke Opisthorchis viverrini seems to be the main cause of the high liver cancer incidence. Moreover, it was also suggested that mutagenic substances frequently found in tobacco, alcoholic beverages, fermented fish, and mold-contaminated cereals or nuts, which are all substances heavily consumed by Lao people, lead to the accumulation of DNA mutations in the liver cell genome causing tumor processes. However, the respective proportions of liver cancer cases attributable to each category of infections and substances consumed, as well as the histological nature of the neoplasia are still not precisely documented in Laos. The international medical and scientific communities as well as public health stakeholders should urgently consider the alarming situation of liver health in Laos to stimulate both research and subsequent implementation of prevention policies.

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

Development of a genetically modified hepatoma cell line with heat-inducible high liver function

2021 ◽  
Author(s):  
Hiroyuki Kitano ◽  
Yuki Nagae ◽  
Yoshinori Kawabe ◽  
Akira Ito ◽  
Masamichi Kamihira
Keyword(s):  
Liver Function ◽  
Cell Line ◽  
Genetically Modified ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
High Liver

scholarly journals Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

2020 ◽  
Vol 16 ◽  
pp. 297-304 ◽  
Author(s):  
Amit Raj Sharma ◽  
Enjuro Harunari ◽  
Naoya Oku ◽  
Nobuyasu Matsuura ◽  
Agus Trianto ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Spectroscopic Analysis ◽  
Culture Broth ◽  
Peroxisome Proliferator ◽  
Simulation Studies ◽  
Fish Pathogen ◽  
Chemical Structures ◽  
Agonistic Activity ◽  
Isoform Specificity ◽  
Peroxisome Proliferator Activated Receptors

A pair of geometrically isomeric unsaturated keto fatty acids, (6E,8Z)- and (6E,8E)-5-oxo-6,8-tetradecadienoic acids (1 and 2), were isolated from the culture broth of an actinomycete of the genus Micrococcus, which was associated with a stony coral, Catalaphyllia sp. Their chemical structures were elucidated by spectroscopic analysis including NMR and MS, with special assistance of spin system simulation studies for the assignment of an E geometry at C8 in 2. As metabolites of microbes, compounds 1 and 2 are unprecedented in terms of bearing a 2,4-dienone system. Both 1 and 2 showed antibacterial activity against the plant pathogen Rhizobium radiobacter and the fish pathogen Tenacibaculum maritimum, with a contrasting preference that 1 is more effective to the former strain while 2 is so to the latter. In addition, compounds 1 and 2 displayed agonistic activity against peroxisome proliferator-activated receptors (PPARs) with an isoform specificity towards PPARα and PPARγ.

scholarly journals High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers

Hepatology ◽  
2015 ◽  
Vol 61 (4) ◽  
pp. 1261-1268 ◽  
Author(s):  
Beomseok Suh ◽  
Sehhoon Park ◽  
Dong Wook Shin ◽  
Jae Moon Yun ◽  
Hyung-Kook Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Fibrosis Index ◽  
High Liver

Liver steatosis coexists with myocardial insulin resistance and coronary dysfunction in patients with type 2 diabetes

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Liver Steatosis ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Artery Disease ◽  
Myocardial Insulin Resistance ◽  
High Liver

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.

Clonidine — Recurrent Apnea following Overdose

1979 ◽  
Vol 13 (12) ◽  
pp. 778-780
Author(s):  
Brian Grabert ◽  
Christopher S. Conner ◽  
Barry H. Rumack ◽  
Robert G. Peterson
Keyword(s):  
Respiratory Depression ◽  
High Serum ◽  
Serum Concentrations ◽  
Mediated Effects ◽  
Agonistic Activity

Recurrent episodes of apnea are described in two children following overdosage of clonidine. Respiratory depression and apnea requiring intubation may not occur for up to 2½ hours following ingestion of clonidine. Hypotension was absent in one case, suggesting opposition to centrally mediated effects by peripheral alpha-agonistic activity in the presence of high serum concentrations of clonidine. General symptoms and treatment of clonidine overdosage are discussed.

scholarly journals Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor

2002 ◽  
pp. 789-799 ◽  
Author(s):  
M Quinkler ◽  
B Meyer ◽  
C Bumke-Vogt ◽  
C Grossmann ◽  
U Gruber ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Mineralocorticoid Receptor ◽  
Antagonistic Activity ◽  
Luciferase Reporter ◽  
Protective Mechanism ◽  
Luciferase Reporter Gene ◽  
Binding Characteristics ◽  
Rabbit Reticulocyte Lysate System ◽  
Progesterone Metabolites ◽  
Agonistic Activity

OBJECTIVE: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g. pregnancy. One mechanism could be conversion of progesterone to inactive compounds in hMR target tissues. DESIGN: We analyzed the agonist and antagonist activities of 16 progesterone metabolites by their binding characteristics for hMR as well as functional studies assessing transactivation. METHODS: We studied binding affinity using hMR expressed in a T7-coupled rabbit reticulocyte lysate system. We used co-transfection of an hMR expression vector together with a luciferase reporter gene in CV-1 cells to investigate agonistic and antagonistic properties. RESULTS: Progesterone and 11beta-OH-progesterone (11beta-OH-P) showed a slightly higher binding affinity than cortisol, deoxycorticosterone and aldosterone. 20alpha-dihydro(DH)-P, 5alpha-DH-P and 17alpha-OH-P had a 3- to 10-fold lower binding potency. All other progesterone metabolites showed a weak affinity for hMR. 20alpha-DH-P exhibited the strongest agonistic potency among the metabolites tested, reaching 11.5% of aldosterone transactivation. The agonistic activity of 11beta-OH-P, 11alpha-OH-P and 17alpha-OH-P was 9, 5.1 and 4.1% respectively. At a concentration of 100 nmol/l, progesterone, 17alpha-OH-P and 20alpha-DH-P inhibit nearly 75, 40 and 35% of the transactivation by aldosterone respectively. All other progesterone metabolites tested demonstrate weaker affinity, and agonistic and antagonistic potency. CONCLUSIONS: The binding affinity for hMR and the agonistic and antagonistic activity diminish with increasing reduction of the progesterone molecule at C20, C17 and at ring A. We assume that progesterone metabolism to these compounds is a possible protective mechanism for hMR. 17alpha-OH-P is a strong hMR antagonist and could exacerbate mineralocorticoid deficiency in patients with congenital adrenal hyperplasia.

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