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https://www.readbyqxmd.com/read/27933748/exploring-glucocorticoid-receptor-agonists-mechanism-of-action-through-mass-cytometry-and-radial-visualizations
#1
Yann Abraham, Bertran Gerrits, Marie-Gabrielle Ludwig, Michael Rebhan, Caroline Gubser Keller
Recent advances in combining flow cytometry and mass spectrometry have led to the development of mass cytometry, allowing for the interrogation of complex cell populations on an unprecedented scale. The volumes and high dimensionality of mass cytometry data pose significant challenges in terms of analysis and visualization. We implement a method called Radviz (1-3), where multidimensional single cell data can be visualized as a projection that maintains the original dimensions and data complexity whilst facilitating analysis and visualization...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933465/nano-mechanical-characterization-of-ataxia-telangiectasia-cells-treated-with-dexamethasone
#2
Michele Menotta, Sara Biagiotti, Giulia Bartolini, Bianchi Marzia, Sara Orazi, Aldo Germani, Luciana Chessa, Mauro Magnani
Ataxia telangiectasia is a rare genetic disease and no therapy is currently available. Glucocorticoid analogues have been shown to improve the neurological symptoms of treated patients. In the present study ataxia telangiectasia and wild type cells were used as a cellular model and treated with dexamethasone. The cells were subsequently investigated for membrane and whole cell mechanical properties by atomic force microscopy. In addition, cytoskeleton protein dynamics and nuclear shapes were assayed by fluorescence microscopy, while western blots were used to assess actin and tubulin content...
December 8, 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27933390/-de-escalation-of-therapy-in-anca-associated-vasculitides
#3
REVIEW
S Schinke, G Riemekasten, P Lamprecht
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) require a differentiated therapeutic approach depending on the degree of organ dysfunction and disease activity. In organ dysfunction and life-threatening AAV cyclophosphamide and rituximab are recommended for the induction of remission. For remission induction with a lack of organ dysfunction and non-life-threatening AAV, methotrexate or mycophenolate mofetil are recommended. For remission maintenance therapy azathioprine or methotrexate are used...
December 8, 2016: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/27933196/independent-association-of-glucocorticoids-with-damage-accrual-in-sle
#4
Diane Apostolopoulos, Rangi Kandane-Rathnayake, Sudha Raghunath, Alberta Hoi, Mandana Nikpour, Eric F Morand
OBJECTIVES: To determine factors associated with damage accrual in a prospective cohort of patients with SLE. METHODS: Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI))...
2016: Lupus Science & Medicine
https://www.readbyqxmd.com/read/27933170/growth-of-a-progesterone-receptor-positive-meningioma-in-a-female-patient-with-congenital-adrenal-hyperplasia
#5
T O'Shea, R K Crowley, M Farrell, S MacNally, P Govender, J Feeney, J Gibney, M Sherlock
: Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27932681/acute-intermittent-hypoxia-in-rats-activates-muscle-proteolytic-pathways-through-a-glucocorticoid-dependent-mechanism
#6
Franciele Przygodda, Leandro Henrique Manfredi, Juliano Machado, Dawit A P Gonçalves, Neusa Maria Zanon, Leni G H Bonagamba, Benedito H Machado, Isis do Carmo Kettelhut, Luiz C C Navegantes
Although it is well known that chronic hypoxia induces muscle wasting, the effects of intermit-tent hypoxia on skeletal muscle protein metabolism remains unclear. We hypothesized that acute intermittent hypoxia (AIH), a challenge that activates the hypothalamic-pituitary-adrenal axis, would alter muscle protein homeostasis through a glucocorticoid-dependent mechanism. Three-week-old rats were submitted to adrenalectomy (ADX) and exposed to 8 h of AIH (6% O2 for 40s at 9 min intervals). Animals were sacrificed and the soleus and extensor digitorum longus (EDL) muscles were harvested and incubated in vitro for measurements of protein turn-over...
December 8, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27932421/myb89-transcription-factor-represses-seed-oil-accumulation
#7
Dong Li, Changyu Jin, Shaowei Duan, Yana Zhu, Shuanghui Qi, Kaige Liu, Chenhao Gao, Haoli Ma, Meng Zhang, Yuncheng Liao, Mingxun Chen
In many higher plants, seed oil accumulation is precisely controlled by intricate multi-level regulatory networks, among which transcriptional regulation mainly influences oil biosynthesis. In Arabidopsis, the master positive transcription factors, WRINKLED1 (WRI1) and LEAFY COTYLEDON1-LIKE (L1L), are important for seed oil accumulation. We found that an R2R3-MYB transcription factor, MYB89, was predominantly expressed in developing seeds during maturation. Oil and major fatty acid biosynthesis in seeds was significantly promoted by myb89-1 mutation and MYB89 knockdown; MYB89 was thus an important repressor during seed oil accumulation...
December 8, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27930715/apparent-hypothalamic-pituitary-adrenal-axis-suppression-via-reduction-of-interleukin-6-by-glucocorticoid-therapy-in-systemic-autoimmune-diseases
#8
Natsuki Fujio, Shotaro Masuoka, Kotaro Shikano, Natsuko Kusunoki, Toshihiro Nanki, Shinichi Kawai
CONTEXT: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a serious complication of systemic glucocorticoid therapy. OBJECTIVE: To clarify the influence of proinflammatory cytokines on the HPA axis after onset of glucocorticoid therapy in patients with systemic autoimmune diseases. PATIENTS AND METHODS: Forty-eight glucocorticoid-naïve patients with systemic autoimmune diseases (28 women) who were starting prednisolone therapy according to our standard regimens were prospectively observed...
2016: PloS One
https://www.readbyqxmd.com/read/27929385/the-metabolic-implications-of-glucocorticoids-in-a-high-fat-diet-setting-and-the-counter-effects-of-exercise
#9
REVIEW
Emily C Dunford, Michael C Riddell
Glucocorticoids (GCs) are steroid hormones, naturally produced by activation of the hypothalamic-pituitary-adrenal (HPA) axis, that mediate the immune and metabolic systems. Synthetic GCs are used to treat a number of inflammatory conditions and diseases including lupus and rheumatoid arthritis. Generally, chronic or high dose GC administration is associated with side effects such as steroid-induced skeletal muscle loss, visceral adiposity, and diabetes development. Patients who are taking exogenous GCs could also be more susceptible to poor food choices, but the effect that increasing fat consumption in combination with elevated exogenous GCs has only recently been investigated...
December 5, 2016: Metabolites
https://www.readbyqxmd.com/read/27928728/clinical-perspectives-in-congenital-adrenal-hyperplasia-due-to-11%C3%AE-hydroxylase-deficiency
#10
REVIEW
Krupali Bulsari, Henrik Falhammar
Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is a rare autosomal recessive genetic disorder. It is caused by reduced or absent activity of 11β-hydroxylase (CYP11B1) enzyme and the resultant defects in adrenal steroidogenesis. The most common clinical features of 11 beta-hydroxylase deficiency are ambiguous genitalia, accelerated skeletal maturation and resultant short stature, peripheral precocious puberty and hyporeninemic hypokalemic hypertension. The biochemical diagnosis is based on raised serum 11-deoxycortisol and 11-deoxycorticosterone levels together with increased adrenal androgens...
December 7, 2016: Endocrine
https://www.readbyqxmd.com/read/27928506/get-the-most-out-of-blow-hormones-validation-of-sampling-materials-field-storage-and-extraction-techniques-for-whale-respiratory-vapour-samples
#11
Elizabeth A Burgess, Kathleen E Hunt, Scott D Kraus, Rosalind M Rolland
Studies are progressively showing that vital physiological data may be contained in the respiratory vapour (blow) of cetaceans. Nonetheless, fundamental methodological issues need to be addressed before hormone analysis of blow can become a reliable technique. In this study, we performed controlled experiments in a laboratory setting, using known doses of pure parent hormones, to validate several technical factors that may play a crucial role in hormone analyses. We evaluated the following factors: (i) practical field storage of samples on small boats during daylong trips; (ii) efficiency of hormone extraction methods; and (iii) assay interference of different sampler types (i...
2016: Conservation Physiology
https://www.readbyqxmd.com/read/27927697/absence-of-11-keto-reduction-of-cortisone-and-11-ketotestosterone-in-the-model-organism-zebrafish
#12
Maria Tsachaki, Arne Meyer, Benjamin Weger, Denise V Kratschmar, Janina Tokarz, Jerzy Adamski, Heinz-Georg Belting, Markus Affolter, Thomas Dickmeis, Alex Odermatt
Zebrafish are widely used as model organism. Their suitability for endocrine studies, drug screening and toxicity assessements depends on the extent of conservation of specific genes and biochemical pathways between zebrafish and human. Glucocorticoids consist of inactive 11-keto (cortisone, 11-dehydrocorticosterone) and active 11β-hydroxyl forms (cortisol, corticosterone). In mammals, two 11β-hydroxysteroid dehydrogenases (11β-HSD1, 11β-HSD2) interconvert active and inactive glucocorticoids, allowing tissue-specific regulation of glucocorticoid action...
December 7, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27926596/donor-genotype-and-intragraft-expression-of-cyp3a5-reflect-the-response-to-steroid-treatment-during-acute-renal-allograft-rejection
#13
N V Rekers, T M Flaig, M J K Mallat, M J Spruyt-Gerritse, M Zandbergen, J D H Anholts, I M Bajema, M C Clahsen-van Groningen, J Yang, J W de Fijter, F H J Claas, S Brakemeier, N Lachmann, R Kreutz, E de Heer, K Budde, J Bolbrinker, M Eikmans
BACKGROUND: Glucocorticoid-refractory acute rejection is a risk factor for inferior renal allograft outcome. We investigated genetic predisposition to the response to steroid treatment of acute allograft rejection. METHODS: Single nucleotide polymorphisms of genes involved in glucocorticoid signaling (GR, GLCCI1) and drug metabolism and transport (CYP3A5, ABCB1, and PXR) were analyzed in kidney transplant recipients (1995-2005, Leiden cohort, n=153) treated with methylprednisolone...
December 6, 2016: Transplantation
https://www.readbyqxmd.com/read/27925610/ex-vivo-cutaneous-bioavailability-of-topical-mometasone-furoate-in-an-o-w-preparation
#14
Johannes Wohlrab, Reinhard H H Neubert, Elfi Sommer, Julia Michael
Mometasone furoate (MMF) is a modern glucocorticoid of the 4th generation, which has been proven not only for inhalation but also for cutaneous treatment. Due to its lipophilic character, it is mainly used in ointments and creams with an outer lipophilic phase (W/O type). However, this study investigated the cutaneous cytotoxicology of MMF and tried to characterize its pharmacokinetic effects on the skin using an O/W preparation. An HPLC method has been developed and validated for the detection of MMF in cutaneous tissue, and concentration-time curves of MMF were created after cutaneous application on unaffected as well as lesional skin...
December 8, 2016: Skin Pharmacology and Physiology
https://www.readbyqxmd.com/read/27924855/the-efficacy-of-mycophenolate-mofetil-for-the-treatment-of-chinese-takayasu-s-arteritis
#15
Jing Li, Yunjiao Yang, Jiuliang Zhao, Mengtao Li, Xinping Tian, Xiaofeng Zeng
To investigate the therapeutic effect of mycophenolate mofetil(MMF) on Chinese Takayasu's arteritis(TAK) patients. Thirty consecutive TAK outpatients were prospectively enrolled during 2013 to 2015. MMF combined with glucocorticoid was the primary treatment regimen. If clinical stable disease could not be reached, another traditional immunosuppressive agent could be added. All patients were evaluated and followed up every 3 months and vascular image studies by Doppler ultrasonography were repeated every 6 months...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924737/-the-intra-articular-glucocorticoid-injection-short-term-success-with-potential-side-effects
#16
S E W Geraets, T Gosens
- Intra-articular injections have been in use for over 60 years. However, there is increasing awareness of potential side effects associated with the intra- and peri-articular use of both glucocorticoids and topical analgesics.- In this review we will discuss the effects and side effects of intra-articular glucocorticoid injections in the context of non-rheumatic knee and shoulder conditions. Other commonly used indications for glucocorticoid use are also described.- For almost all indications, intra-articular glucocorticoid injections provide a small and short-term pain-suppressing effect...
2016: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/27923976/early-restriction-of-placental-growth-results-in-placental-structural-and-gene-expression-changes-in-late-gestation-independent-of-fetal-hypoxemia
#17
Song Zhang, Paige Barker, Kimberley J Botting, Claire T Roberts, Christine M McMillan, Isabella Caroline McMillen, Janna L Morrison
Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, and glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results in early restriction of placental growth and either the development of chronic fetal hypoxemia (PaO2≤17 mmHg) in late gestation or in compensatory placental growth and the maintenance of fetal normoxemia (PaO2>17 mmHg)...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/27923708/acth-modulation-on-corticosterone-melatonin-testosterone-and-innate-immune-response-in-the-tree-frog-hypsiboas-faber
#18
Adriana Maria Giorgi Barsotti, Vania Regina de Assis, Stefanny Christie Monteiro Titon, Braz Titon Junior, Zulma Felisbina da Silva Ferreira, Fernando Ribeiro Gomes
The modulation exerted by glucocorticoids in physiological responses to stressors is essential for maintaining short-term homeostasis. However, highly frequent and/or prolonged activation of the hypothalamic-pituitary-adrenal/interrenal axis may inhibit processes that are important to long-term fitness and health, including reproduction and immunocompetence. The present study evaluates the response to adrenocorticotropic hormone (ACTH) injection in the adult male tree frog, Hypsiboas faber, as indicated by levels of plasma corticosterone (CORT), plasma testosterone (T), ocular melatonin (MEL), hematocrit and immune functioning (total leukocyte count and bacterial killing ability against Escherichia coli)...
December 3, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27923376/immunomodulation-after-ischemic-stroke-potential-mechanisms-and-implications-for-therapy
#19
REVIEW
Cynthia Santos Samary, Paolo Pelosi, Pedro Leme Silva, Patricia Rieken Macedo Rocco
Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection...
December 7, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27923288/toll-like-receptor-4-protects-against-stress-induced-ulcers-via-regulation-of-glucocorticoid-production-in-mice
#20
Liang Wang, Pengfei Luo, Fang Zhang, Yuelu Zhang, Xingtong Wang, Fei Chang, Yuechan Zhang, Hongtai Tang, Zhaofan Xia
Stress-induced gastric ulcer is an important life-threatening condition, while the molecular basis of its development is incompletely understood. Toll-like receptor 4 (TLR4), an innate immune pattern recognition receptor, can induce pro-inflammatory transcription, aggravating a stress ulcer. The present study found that TLR4 played a protective role in a mouse model of water immersion (23 °C) restraint stress. Wild-type (WT) and TLR4(-/-) male mice were respectively divided into five groups (5 per group), and exposed to the stressor for 0, 0...
December 6, 2016: Stress: the International Journal on the Biology of Stress
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