Papers by Gabriella Fábián
Current Pharmaceutical Design, Jan 31, 2014
ABSTRACT Here we have studied regulatory changes of μ-opioid receptors accompanying in vivo 14-me... more ABSTRACT Here we have studied regulatory changes of μ-opioid receptors accompanying in vivo 14-methoxymetopon treatments of rats. Previously, this ligand has been shown to be an extremely potent, centrally acting μ-opioid specific analgesic with low physical dependence, tolerance, respiratory depression, constipation and other side effects. Our work shows that it is a highly potent full agonist of μ-opioid receptor coupled G-protein signaling in vitro, alike the well-known opioid agonist, etorphine. However, unlike etorphine, which desensitized and down-regulated the endogenous μ-opioid receptors, 14-methoxymetopon, given to rats intraperitoneally (i.p.) either acutely or chronically, did not change the binding or G-protein signaling of μ-opioid receptors in rat brain subcellular membranes. Thereby, these data provide further evidence that there is no direct relationship between the efficacy of the ligand in signaling and its ability to internalize or desensitize the receptor. Viewed collectively with published work, it is discussed that μ-opioid receptors display functional selectivity, also called 'biased agonism'. This concept implies that each ligand may induce unique, ligand-specific receptor conformation that can result in distinct agonist-directed trafficking and/or signal transduction pathways associated with the receptor. Ligand-specific signaling may open up new directions for designing potent analgesics that do not interact with unwanted signaling pathways, which mediate undesired side-effects, such as tolerance and dependence.
Wiener klinische Wochenschrift
Summary Purpose To establish a transborder virtual tumor board (VTB) fostering state-of-the-art m... more Summary Purpose To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE). Methods We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment. Results A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time ...
Frontiers in Pharmacology, 2014
Lipids in Health and Disease, 2013
In vivo (Athens, Greece)
Radiation-induced heart disease (RIHD) is a concern during radiotherapy. For its comprehensive st... more Radiation-induced heart disease (RIHD) is a concern during radiotherapy. For its comprehensive study, an in vivo selective heart irradiation model was developed. Sprague-Dawley rats were irradiated with 50 Gy and functional imaging, biochemical (circulating growth differentiation factor-15 (GDF-15), transforming growth factor-beta (TGF-beta) and morphological (picrosirius red staining of the heart) objectives were tested. Signs and symptoms of RIHD occurred >12 weeks after irradiation with tachypnea, systolic and diastolic dysfunction, cardiac hypertrophy and body development retardation. Plasma GDF-15 was increased 3, 12 and 26, while plasma TGF-beta was increased 12 weeks after irradiation. At autopsy, extensive pleural fluid was found in the irradiated animals. Interstitial fibrosis could be reliably detected and quantified in irradiated hearts after a follow-up time of 19 weeks. The studied parameters could be used in future experiments for testing protective agents for preve...
Pharmacological Research, 2016
Pathology & Oncology Research, 2016
Current pharmaceutical design
Current pharmaceutical design, 2013
Here we have studied regulatory changes of µ-opioid receptors accompanying in vivo 14-methoxymeto... more Here we have studied regulatory changes of µ-opioid receptors accompanying in vivo 14-methoxymetopon treatments of rats. Previously, this ligand has been shown to be an extremely potent, centrally acting µ-opioid specific analgesic with low physical dependence, tolerance, respiratory depression, constipation and other side effects. Our work shows that it is a highly potent full agonist of µ-opioid receptor coupled G-protein signaling in vitro, alike the well-known opioid agonist, etorphine. However, unlike etorphine, which desensitized and down-regulated the endogenous µ-opioid receptors, 14-methoxymetopon, given to rats intraperitoneally (i.p.) either acutely or chronically, did not change the binding or G-protein signaling of µ-opioid receptors in rat brain subcellular membranes. Thereby, these data provide further evidence that there is no direct relationship between the efficacy of the ligand in signaling and its ability to internalize or desensitize the receptor. Viewed collect...
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Papers by Gabriella Fábián