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Glucocorticoids

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https://www.readbyqxmd.com/read/28938470/genetic-disruption-of-21-hydroxylase-in-zebrafish-causes-interrenal-hyperplasia
#1
Helen Eachus, Andreas Zaucker, James A Oakes, Aliesha Griffin, Meltem Weger, Tülay Güran, Angela Taylor, Abigail Harris, Andy Greenfield, Jonathan L Quanson, Karl-Heinz Storbeck, Vincent T Cunliffe, Ferenc Müller, Nils Krone
Congenital adrenal hyperplasia is a group of common inherited disorders leading to glucocorticoid deficiency. Most cases are caused by 21-hydroxylase deficiency (21OHD). The systemic consequences of imbalanced steroid hormone biosynthesis due to severe 21OHD remains poorly understood. Therefore, we have developed a zebrafish model for 21OHD, which focuses on the impairment of glucocorticoid biosynthesis. A single 21-hydroxylase gene (cyp21a2) is annotated in the zebrafish genome based on sequence homology. Our in silico analysis of the Cyp21a2 protein sequence suggests a sufficient degree of similarity for the usage of zebrafish cyp21a2 to model aspects of human 21OHD in vivo...
September 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938459/selective-glucocorticoid-receptor-antagonist-cort125281-activates-brown-adipose-tissue-and-alters-lipid-distribution-in-male-mice
#2
Jan Kroon, Lisa L Koorneef, Jose K van den Heuvel, Cristy R C Verzijl, Nienke M van de Velde, Isabel M Mol, Hetty C M Sips, Hazel Hunt, Patrick C N Rensen, Onno C Meijer
Glucocorticoids influence a wide range of metabolic processes in the human body and excessive glucocorticoid exposure is known to contribute to the development of metabolic disease. We evaluated the utility of the novel glucocorticoid receptor (GR) antagonist CORT125281 for its potential to overcome adiposity, glucose intolerance and dyslipidaemia, and compared this head-to-head with classic GR antagonist RU486 (mifepristone). We show that, while RU486 displays cross-reactivity to the progesterone and androgen receptor, CORT125281 selectively inhibits GR transcriptional activity...
September 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938450/sex-specific-modulation-of-fetal-adipogenesis-by-gestational-bisphenol-a-and-bisphenol-s-exposure
#3
Yong Pu, Jeremy Gingrich, Juan P Steibel, Almudena Veiga-Lopez
The endocrine disrupting chemical bisphenol A (BPA) increases adipose tissue mass in vivo and promotes adipogenesis in vitro. However, mechanisms explaining BPA's obesogenic effect remain unknown. We investigated the effects of gestational BPA and its analogue, bisphenol S (BPS), exposure on the adipogenic differentiation ability of fetal preadipocytes and the role of endoplasmic reticulum stress in regulating this process. Pregnant sheep (n=7-8/group) mated to the same male were exposed to BPA or BPS from days 30 to 100 of gestation, and pregnancies terminated 20 days later...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938408/pioneer-factors-foxa1-and-foxa2-assist-selective-glucocorticoid-receptor-signaling-in-human-endometrial-cells
#4
Shannon Whirledge, Edwina P Kisanga, Robert N Taylor, John A Cidlowski
Successful pregnancy relies on dynamic control of cell signaling in order to achieve uterine receptivity and the necessary biological changes required for endometrial decidualization, embryo implantation, and fetal development. Glucocorticoids are master regulators of intracellular signaling and can directly regulate embryo implantation and endometrial remodeling during murine pregnancy. In immortalized human uterine cells, we have shown that glucocorticoids and estradiol co-regulate thousands of genes. Recently, glucocorticoids and estradiol were shown to co-regulate the expression of Left-right determination factor 1 (LEFTY1), previously implicated in the regulation of decidualization...
August 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938402/the-pathophysiological-sequence-of-glucocorticoid-induced-osteonecrosis-of-the-femoral-head-in-male-mice
#5
Robert S Weinstein, Erin A Hogan, Michael J Borrelli, Serguei Liachenko, Charles A O'Brien, Stavros C Manolagas
In search of the sequence of pathogenic events leading to glucocorticoid-induced osteonecrosis, we determined the molecular, biomechanical, cellular, and vascular changes in the femur of C57BL/6 mice receiving prednisolone for 14, 28 or 42 days. The femoral head, but not the distal femur, of mice treated for 14 days showed a decrease in the expression of the hypoxia-inducible factor (Hif-1α) and vascular endothelial growth factor (VEGF), the number of osteoblasts, bone formation rate and strength and an increase in osteoclasts...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938251/critical-illness-related-corticosteroid-insufficiency-circi-a-narrative-review-from-a-multispecialty-task-force-of-the-society-of-critical-care-medicine-sccm-and-the-european-society-of-intensive-care-medicine-esicm
#6
Djillali Annane, Stephen M Pastores, Wiebke Arlt, Robert A Balk, Albertus Beishuizen, Josef Briegel, Joseph Carcillo, Mirjam Christ-Crain, Mark S Cooper, Paul E Marik, Gianfranco Umberto Meduri, Keith M Olsen, Bram Rochwerg, Sophia C Rodgers, James A Russell, Greet Van den Berghe
OBJECTIVE: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). PARTICIPANTS: A multi-specialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews...
September 21, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28937774/selective-non-steroidal-glucocorticoid-receptor-modulators-for-the-inhaled-treatment-of-pulmonary-diseases
#7
Martin Hemmerling, Stinabritt Nilsson, Karl Edman, Stefan Eirefelt, Wayne Russell, Ramon Hendrickx, Eskil Johnsson, Carina Kärrman-Mårdh, Markus Berger, Hartmut Rehwinkel, Anna Abrahamsson, Jan Dahm Eacute N, Anders R Eriksson, Balint Gabos, Krister Henriksson, Nafizal Hossain, Svetlana Ivanova, Anne-Helene Jansson, Tina J Jensen, Anders Jerre, Henrik Johansson, Tomas Klingstedt, Matti Lepistö, Martin Lindsjö, Irene Mile, Grigorios Nikitidis, John Steele, Ulrika Tehler, Lisa Wissler, Thomas Hansson
A class of potent, non-steroidal, selective indazole ether based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment of respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft drug strategy was implemented to ensure rapid elimination of drug candidates and minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution...
September 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28937502/type-iii-interferons-in-systemic-lupus-erythematosus-association-between-interferon-%C3%AE-3-disease-activity-and-anti-ro-ssa-antibodies
#8
Luis M Amezcua-Guerra, Ricardo Márquez-Velasco, Adriana K Chávez-Rueda, Diana Castillo-Martínez, Felipe Massó, Araceli Páez, Juan Colín-Fuentes, Rafael Bojalil
OBJECTIVE: The aim of this study was to assess associations between serum type III (λ) interferons (IFN-λ) and disease activity in systemic lupus erythematosus (SLE). METHODS: Serum levels of IFN-λ1, IFN-λ2, and IFN-λ3 were measured in 93 SLE patients and 67 healthy individuals. The associations with overall disease activity, organ-specific damage, and SLE-related antibodies were assessed. RESULTS: Median IFN-λ1 levels were 0 pg/mL (range, 0-510 pg/mL) and 0 pg/mL (0-171 pg/mL; P = 0...
September 21, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28937472/type-iii-interferons-in-systemic-lupus-erythematosus-association-between-interferon-%C3%AE-3-disease-activity-and-anti-ro-ssa-antibodies
#9
Luis M Amezcua-Guerra, Ricardo Márquez-Velasco, Adriana K Chávez-Rueda, Diana Castillo-Martínez, Felipe Massó, Araceli Páez, Juan Colín-Fuentes, Rafael Bojalil
OBJECTIVE: The aim of this study was to assess associations between serum type III (λ) interferons (IFN-λ) and disease activity in systemic lupus erythematosus (SLE). METHODS: Serum levels of IFN-λ1, IFN-λ2, and IFN-λ3 were measured in 93 SLE patients and 67 healthy individuals. The associations with overall disease activity, organ-specific damage, and SLE-related antibodies were assessed. RESULTS: Median IFN-λ1 levels were 0 pg/mL (range, 0-510 pg/mL) and 0 pg/mL (0-171 pg/mL; P = 0...
October 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28937237/selective-inhibition-of-nf-kappab-and-surfactant-therapy-in-experimental-meconium-induced-lung-injury
#10
J Kopincova, P Mikolka, M Kolomaznik, P Kosutova, A Calkovska, D Mokra
Meconium aspiration syndrome (MAS) in newborns is characterized mainly by respiratory failure due to surfactant dysfunction and inflammation. Previous meta-analyses did not prove any effect of exogenous surfactant treatment nor glucocorticoid administration on final outcome of children with MAS despite oxygenation improvement. As we supposed there is the need to intervene in both these fields simultaneously, we evaluated therapeutic effect of combination of exogenous surfactant and selective inhibitor of NF-kappaB (IKK-NBD peptide)...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28936179/seasonal-variations-in-heart-rate-variability-as-an-indicator-of-stress-in-free-ranging-pregnant-przewalski-s-horses-e-ferus-przewalskii-within-the-hortob%C3%A3-gy-national-park-in-hungary
#11
Friederike Pohlin, Kristin Brabender, Gerhard Fluch, Gabrielle Stalder, Thierry Petit, Chris Walzer
Background: Ecosystems with seasonal fluctuations in climate and food availability present physiological challenges to resident mammals and may cause "stress." The two predominant physiological responses to stressors are (1) the activation of the hypothalamic-pituitary-adrenal axis and (2) the modulation of the autonomic nervous system. To date, the primary indicator for "stress" in wildlife- and zoo animal research are glucocorticoid levels. By measuring the autonomic regulation of cardiac activity, particularly the vagal tone, heart rate variability (HRV) is presently emerging as a suitable indicator of "stress" in farm- and domestic animal research...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28935925/interference-of-stress-with-the-somatotropic-axis-in-pigs-lights-on-new-biomarkers
#12
Elisa Wirthgen, Martin Kunze, Sébastien Goumon, Christina Walz, Christine Höflich, Marion Spitschak, Julia Brenmoehl, Ellen Kanitz, Margret Tuchscherer, Winfried Otten, Ulrike Gimsa, Peter Schön, Christian Manteuffel, Armin Tuchscherer, Ralf Pfuhl, Cornelia C Metges, Bernd Stabenow, Sandra Erdmann, Kathleen Schluricke, Luigi Faucitano, Andreas Hoeflich
The acceptance of animal products is increasingly associated with standardized animal welfare, which relates to appropriate animal husbandry from birth to slaughter. In particular, shipment to the slaughterhouse is considered as a critical process exposing the animals to a number of, in part severe, stressors. New biomarkers may be useful for the assessment of animal welfare. The IGF-system has been assessed in a commercial pig transport in conjunction with established markers of stress response. Furthermore, the effect of repeated restraint as an experimental model for repeated acute stress was investigated...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935859/a-non-transcriptional-role-for-the-glucocorticoid-receptor-in-mediating-the-cell-stress-response
#13
Marina Ptushkina, Toryn Poolman, Mudassar Iqbal, Mark Ashe, Janni Petersen, Joanna Woodburn, Magnus Rattray, Anthony Whetton, David Ray
The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal transactivation domain, and the C-terminal ligand binding domain, but not the DNA-binding domain of the GR. This effect was not affected by GR ligand exposure, and occurred without significant GR nuclear accumulation...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935820/lack-of-serum-and-glucocorticoid-inducible-kinase-3-leads-to-podocyte-dysfunction
#14
Li-Qin Peng, Hong Zhao, Song Liu, Ya-Pei Yuan, Cheng-Yan Yuan, Mercy-Julian Mwamunyi, David Pearce, Li-Jun Yao
Serum- and glucocorticoid-inducible kinase 3 (SGK3) is a downstream mediator of PI3K, which is essential for maintaining the functional integrity of podocytes. However, little is known about the role of SGK3 in podocyte function. Herein, we demonstrated that SGK3 contributes to the maintenance of podocyte integrity. Conditionally immortalized mouse podocyte cells (MPCs) were treated with puromycin aminonucleoside (PAN). PAN treatment inhibited the activity of SGK3 and the expression of podocin. Short hairpin RNA (shRNA)-mediated knockdown of SGK3 also reduced podocin expression in the absence of PAN...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28935580/higher-growth-rate-and-gene-expression-in-male-zebra-finch-embryos-are-independent-of-manipulation-of-maternal-steroids-in-the-eggs
#15
Dorota Lutyk, Makhsud Tagirov, Szymon Drobniak, Joanna Rutkowska
Sexual dimorphism in prenatal development is widespread among vertebrates, including birds. Its mechanism remains unclear, although it has been attributed to the effect of maternal steroid hormones. The aim of this study was to investigate how increased levels of steroid hormones in the eggs influence early embryonic development of male and female offspring. We also asked whether maternal hormones take part in the control of sex-specific expression of the genes involved in prenatal development. We experimentally manipulated hormones' concentrations in the egg yolk by injecting zebra finch females prior to ovulation with testosterone or corticosterone...
September 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28935268/repeated-cortisol-administration-does-not-reduce-intrusive-memories-a-double-blind-placebo-controlled-experimental-study
#16
Alexandra Heike Graebener, Tanja Michael, Elena Holz, Johanna Lass-Hennemann
PTSD is a severe mental disorder, which may develop after exposure to traumatic events and is characterized by intrusive memories. Intrusions are sudden brief sensory memories of the traumatic event, that cause immense distress and impairment in every day functioning. Thus, the reduction of intrusive memories is one of the main aims of PTSD therapy. Recently, the glucocorticoid cortisol has been proposed as a pharmacological option to reduce intrusive memories, because cortisol is known to have memory retrieval inhibiting effects...
September 18, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28933291/pharmacotranscriptomic-biomarkers-in-glucocorticoid-treatment-of-pediatric-inflammatory-bowel-disease
#17
Marianna Lucafò, Biljana Stankovic, Nikola Kotur, Alessia Di Silvestre, Stefano Martelossi, Alessandro Ventura, Branka Zukic, Sonya Pavlovic, Giuliana Decorti
Pharmacotranscriptomics aims to reach more accurate drug dosing based on interindividual transcriptome variations. Here, we provide an overview of RNA biomarkers that could predict the response to glucocorticoids (GCs), considered the standard for treatment of inflammatory bowel diseases (IBD), both in adult and pediatric patients. Although new biological agents are very effective in the IBD treatment, GCs are still widely used for induction of remission in IBD patients with moderate to severe disease. It is important to identify patients that are poor responders to GCs therapy, because suboptimal response is frequent and associated with various side effects...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933275/a-case-of-inappropriate-self-medication-compounded-with-prescribing-vis-%C3%A3-vis-dispensing-errors-and-the-hazardous-consequence
#18
Sukalyan Saha Roy, Anupam Roy, Ranjita Santra Dhali, Chiranjib Bagchi, Gautam Banerjee, Santanu K Tripathi
INTRODUCTION Dispensing error, a type of medication error, is not infrequent but seldom reported. Self-medication behavior appears to be a commonplace. And when it is ignorant it may prove dangerous. We report here a case of acute vesico-bullous eruptions from methotrexate in a patient of psoriasis who indulged in self-medication and was wrongfully dispensed higher doses of methotrexate. CASE DESCRIPTION A 50-year-old gentleman presented to the dermatology OPD with erythematous, vesico-bullar lesions spread all over the body including both limbs and scalp, with oral mucosal involvement without any history of fever...
September 19, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28932959/the-role-and-regulation-of-the-11-beta-hydroxysteroid-dehydrogenase-enzyme-system-in-patients-with-inflammatory-bowel-disease
#19
M Hussey, G Holleran, S Smith, Mark Sherlock, D McNamara
INTRODUCTION: Glucocorticoids are known to modulate a number of immunological responses including counteracting inflammation. Within tissues expressing the glucocorticoid and mineralocorticoid receptors including the colon, glucocorticoid metabolism is regulated by the isoenzymes of 11ß-hydroxysteroid dehydrogenase (11β-HSD). 11β-HSD1 acts as an oxidoreductase converting inactive cortisone into active cortisol, while 11β-HSD2 acts as a dehydrogenase converting active cortisol to inactive cortisone...
September 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28932400/mediastinal-peripheral-t-cell-lymphoma-diagnosed-by-repeated-biopsies-after-an-initial-diagnosis-of-fibrosing-mediastinitis
#20
Naoko Kakuta, Mitsuhiro Sumitani, Arata Sugitani, Kenji Nakahama, Yuzo Miki, Seichi Syoji
We report a case of mediastinal peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) diagnosed by repeated biopsies. A 44-year-old man was admitted to our hospital with a 2-week history of facial swelling, neck distension, and dyspnoea on exertion. Computed tomography of the chest showed a mediastinal mass. Initial needle biopsy and video-assisted thoracoscopic biopsy revealed the pathological diagnosis of fibrosing mediastinitis (FM). Glucocorticoid therapy (prednisolone) was temporarily effective in reducing tumour size...
November 2017: Respirology Case Reports
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