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https://www.readbyqxmd.com/read/28819359/screening-for-cushing-syndrome-at-the-primary-care-level-what-every-general-practitioner-must-know
#1
REVIEW
Ernest Yorke, Yacoba Atiase, Josephine Akpalu, Osei Sarfo-Kantanka
Cushing's syndrome is a rare entity, and a high index of suspicion is needed for screening in a primary care setting. The clinical awareness of the primary care physician (PCP) to the highly indicative signs and symptoms such as facial plethora, proximal myopathy, reddish purple striae, and easy bruisability should alert him to look for biochemical evidence of Cushing's syndrome through any of the first-line screening tests, namely, 24-hour urinary free cortisol, overnight dexamethasone suppression test, or late-night salivary cortisol...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28811496/genome-wide-expression-differences-in-anti-vegf-and-dexamethasone-treatment-of-inflammatory-angiogenesis-in-the-rat-cornea
#2
Pierfrancesco Mirabelli, Anthony Mukwaya, Anton Lennikov, Maria Xeroudaki, Beatrice Peebo, Mira Schaupper, Neil Lagali
Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was investigated in a suture-induced corneal neovascularization model in rats, to investigate factors differentially targeted by dexamethasone and anti-Vegf. Topical treatment with either rat-specific anti-Vegf, dexamethasone, or normal goat IgG (sham) was given to sutured corneas for 48 hours, after which in vivo imaging, tissue processing for RNA microarray, and immunofluorescence were performed...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28809847/genome-wide-expression-datasets-of-anti-vegf-and-dexamethasone-treatment-of-angiogenesis-in-the-rat-cornea
#3
Anthony Mukwaya, Pierfrancesco Mirabelli, Anton Lennikov, Maria Xeroudaki, Mira Schaupper, Beatrice Peebo, Neil Lagali
Therapeutics against pathologic new blood vessel growth, particularly those targeting vascular endothelial growth factor (VEGF) are of enormous clinical interest. In the eye, where anti-VEGF agents are in widespread clinical use for treating retinal and corneal blindness, only partial or transient efficacy and resistance to anti-VEGF agents are among the major drawbacks. Conversely, corticosteroids have long been used in ophthalmology for their potency in suppressing inflammation and angiogenesis, but their broad biological activity can give rise to side effects such as glaucoma and cataract...
August 15, 2017: Scientific Data
https://www.readbyqxmd.com/read/28808239/compound-a-influences-gene-regulation-of-the-dexamethasone-activated-glucocorticoid-receptor-by-alternative-cofactor-recruitment
#4
S J Desmet, N Bougarne, L Van Moortel, L De Cauwer, J Thommis, M Vuylsteke, D Ratman, R Houtman, J Tavernier, K De Bosscher
The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28804590/feminizing-adrenocortical-carcinoma-without-gynecomastia
#5
Farida Chentli, Fadila Chabour, Djafer Bouchibane, Nouria Nouar
Malignant feminizing adrenocortical tumors are exceedingly rare. Their main presentation is gynecomastia. In these estrogen secreting tumors (with or without other adrenocortical hormones) lack of gynecomastia is exceptional as in our case. A 44-year-old man presented with abdominal pain. Radiological assessment revealed a tumor measuring 120 × 95 mm in the retroperitoneal area with numerous metastases. Pathological examination pleaded for an adrenal origin with a Weiss's score of 5. Six months later, the tumor relapsed, and he had a second surgery and was sent for hormone assessment...
July 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28801263/glucocorticoids-regulate-mir-29c-levels-in-vascular-smooth-muscle-cells-through-transcriptional-and-epigenetic-mechanisms
#6
Tsai-Der Chuang, Omid Khorram
AIMS: The objective of this study was to determine the underlying mechanism by which glucocorticoids (GCs) induce of miR-29c expression in vascular smooth muscle cells. MAIN METHODS: QRT-PCR was used for miR-29c detection. Protein levels were determined by western blotting. Knockdown of SP1, DNMT1 and DNMT3A was achieved through transfection with their specific respective siRNAs. The effect of GCs on SP1 activity was determined by luciferase reporter assay and the methylation status in miR-29c promoter was detected by methylation specific PCR...
August 8, 2017: Life Sciences
https://www.readbyqxmd.com/read/28800463/combination-of-dexamethasone-and-avastin-%C3%A2-by-supramolecular-hydrogel-attenuates-the-inflammatory-corneal-neovascularization-in-rat-alkali-burn-model
#7
Jinhai Huang, Wenwen Wang, Jing Yu, Xinxin Yu, Qianqian Zheng, Fangli Peng, Zhifen He, Wenguang Zhao, Zhaoliang Zhang, Xingyi Li, Qinmei Wang
Corneal neovascularization (CNV) is one of the leading causes of vision loss and a high-risk factor for transplant rejection. The present study proposed a supramolecular hydrogel comprised of MPEG-PCL micelles and α-cyclodextrin (α-CD) for co-delivery of dexamethasone sodium phosphate (Dexp) and Avastin(®) (Ava), and further evaluated its therapeutic efficacy in rat alkali burn model. A physical mixing of Dexp/Ava, MPEG-PCL micelles, and α-CD aqueous solution leads to a spontaneous formation of the supramolecular hydrogel via a "host-guest" recognition between MPEG and α-CD...
July 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28794031/combinatorial-effects-of-the-glucocorticoid-receptor-and-kr%C3%A3-ppel-like-transcription-factor-15-on-bovine-herpesvirus-1-transcription-and-productive-infection
#8
Fouad S El-Mayet, Laximan Sawant, Prasanth Thunuguntla, Clinton Jones
Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes life-long latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bICP0 and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs). Several Krüppel-like transcription factors (KLF), including KLF15, are induced during reactivation from latency and they stimulate certain viral promoters and productive infection...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790339/preventing-inflammation-inhibits-biopsy-mediated-changes-in-tumor-cell-behavior
#9
Maria Alieva, Andreia S Margarido, Tamara Wieles, Erik R Abels, Burcin Colak, Carla Boquetale, Herke Jan Noordmans, Tom J Snijders, Marike L Broekman, Jacco van Rheenen
Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782485/a-low-concentration-of-tacrolimus-semifluorinated-alkane-sfa-eyedrop-suppresses-intraocular-inflammation-in-experimental-models-of-uveitis
#10
S De Majumdar, M Subinya, J Korward, A Pettigrew, D Scherer, H Xu
PURPOSE: Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration. The aim of this study was to evaluate the therapeutic potential of 0.03% tacrolimus eyedrop in mouse models of uveitis. METHODS: 0.03% tacrolimus in perfluorobutylpentane (F4H5) (0...
August 7, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28764237/local-injection-of-triamcinolone-acetonide-a-forgotten-aetiology-of-cushing-s-syndrome
#11
Weera Sukhumthammarat, Prapaipan Putthapiban, Chutintorn Sriphrapradang
Many different non systemic corticosteroid administrations can cause iatrogenic Cushing's Syndrome (CS). We herein report a case series of iatrogenic CS from keloid scars treatment and aesthetic regimen called mesotherapy. Our first patient developed CS after having exceeded recommended dose of intralesional injection of Triamcinolone Acetonide (TAC). Second case presented with CS followed by unidentified mesotherapy treatment for local fat reduction. Subcutaneous injections of dexamethasone were found to be the part of mesotherapy regimen in one case...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28762136/predicting-cortisol-exposure-from-paediatric-hydrocortisone-formulation-using-a-semi-mechanistic-pharmacokinetic-model-established-in-healthy-adults
#12
Johanna Melin, Zinnia P Parra-Guillen, Niklas Hartung, Wilhelm Huisinga, Richard J Ross, Martin J Whitaker, Charlotte Kloft
BACKGROUND AND OBJECTIVE: Optimisation of hydrocortisone replacement therapy in children is challenging as there is currently no licensed formulation and dose in Europe for children under 6 years of age. In addition, hydrocortisone has non-linear pharmacokinetics caused by saturable plasma protein binding. A paediatric hydrocortisone formulation, Infacort(®) oral hydrocortisone granules with taste masking, has therefore been developed. The objective of this study was to establish a population pharmacokinetic model based on studies in healthy adult volunteers to predict hydrocortisone exposure in paediatric patients with adrenal insufficiency...
July 31, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28759007/generating-diversity-in-human-glucocorticoid-signaling-through-a-racially-diverse-polymorphism-in-the-beta-isoform-of-the-glucocorticoid-receptor
#13
Shannon D Whirledge, Christine M Jewell, Lisa M Barber, Xiaojiang Xu, Kevin S Katen, Stavros Garantziotis, John A Cidlowski
Alternative splicing of the human glucocorticoid receptor gene generates two isoforms, hGRα and hGRβ. hGRβ functions as a dominant-negative regulator of hGRα activity and but also has inherent transcriptional activity, collectively altering glucocorticoid sensitivity. Single-nucleotide polymorphisms in the 3' UTR of hGRβ have been associated with altered receptor protein expression, glucocorticoid sensitivity, and disease risk. Characterization of the hGRβ G3134T polymorphism has been limited to a relatively small, homogenous population...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28755856/th9-cells-induce-steroid-resistant-bronchial-hyperresponsiveness-in-mice
#14
Mayumi Saeki, Osamu Kaminuma, Tomoe Nishimura, Noriko Kitamura, Akio Mori, Takachika Hiroi
BACKGROUND: Reduced responsiveness to corticosteroid therapy is a major problem for patients with severe asthma. Although Th9 cells, along with Th2 cells, facilitate antigen-induced airway eosinophilia and bronchial hyperresponsiveness (BHR), the sensitivity of Th9 cell-mediated responses to steroid therapy remains unknown. In this study, we investigated the effect of dexamethasone (Dex) on antigen-induced airway inflammation in Th9 cell-transferred mice. METHODS: Ovalbumin (OVA)-specific Th2 and Th9 cells were polarized from the CD4(+) T cells of DO11...
July 26, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28754594/microrna-125b-5p-modulates-the-inflammatory-state-of-macrophages-via-targeting-b7-h4
#15
Wenli Diao, Lin Lu, Shan Li, Jiangning Chen, Ke Zen, Limin Li
As a newly identified negative costimulatory molecule of B7 family, B7-H4 suppresses T cell function via inhibiting cell proliferation and cytokine secretion. Although B7-H4 mRNA is widely distributed in various tissues, its protein expression is strongly limited, suggesting B7-H4 may be regulated post-transcriptionally. However, the mechanism underlying the inducement of B7-H4 expression remains unclear. In the present study, we identified specific targeting sites for miR-125b-5p in the 3'-UTR of B7-H4 gene, and showed that overexpression of miR-125b-5p downregulated B7-H4 expression in macrophages...
July 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28744067/helminth-products-potently-modulate-experimental-autoimmune-encephalomyelitis-by-downregulating-neuroinflammation-and-promoting-a-suppressive-microenvironment
#16
Alberto N Peón, Yadira Ledesma-Soto, Jonadab E Olguín, Marcel Bautista-Donis, Edda Sciutto, Luis I Terrazas
A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES) that may suppress EAE development were sought for...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28740545/e-selectin-targeted-sialic-acid-peg-dexamethasone-micelles-for-enhanced-anti-inflammatory-efficacy-for-acute-kidney-injury
#17
Jing-Bo Hu, Xu-Qi Kang, Jing Liang, Xiao-Juan Wang, Xiao-Ling Xu, Ping Yang, Xiao-Ying Ying, Sai-Ping Jiang, Yong-Zhong Du
The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis(x) antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65...
2017: Theranostics
https://www.readbyqxmd.com/read/28735378/a-phase-i-ii-trial-and-pharmacokinetic-study-of-mithramycin-in-children-and-adults-with-refractory-ewing-sarcoma-and-ews-fli1-fusion-transcript
#18
Patrick J Grohar, John Glod, Cody J Peer, Tristan M Sissung, Fernanda I Arnaldez, Lauren Long, William D Figg, Patricia Whitcomb, Lee J Helman, Brigitte C Widemann
PURPOSE: In a preclinical drug screen, mithramycin was identified as a potent inhibitor of the Ewing sarcoma EWS-FLI1 transcription factor. We conducted a phase I/II trial to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of mithramycin in children with refractory solid tumors, and the activity in children and adults with refractory Ewing sarcoma. PATIENTS AND METHODS: Mithramycin was administered intravenously over 6 h once daily for 7 days for 28 day cycles...
July 22, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28732066/inhibition-of-pulmonary-%C3%AE-carotene-15-15-oxygenase-expression-by-glucocorticoid-involves-ppar%C3%AE
#19
Xiaoming Gong, Raju Marisiddaiah, Lewis P Rubin
β-carotene 15,15'-oxygenase (BCO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. This enzyme is expressed in a variety of developing and adult tissues, suggesting that its activity may regulate local retinoid synthesis. Vitamin A and related compounds (retinoids) are critical regulators of lung epithelial development, integrity, and injury repair. A balance between the actions of retinoids and glucocorticoids (GCs) promotes normal lung development and, in particular, alveolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28726485/annals-express-20%C3%AE-and-20%C3%AE-dihydrocortisone-may-interfere-in-lc-ms-ms-determination-of-cortisol-in-saliva-and-urine
#20
Marlen Israelsson, Ralph Brattsand, Goran Brattsand
BACKGROUND: LC-MS/MS methods offer high selectivity in cortisol determinations. However, endogenous steroid metabolites may still interfere and compromise the results, for example in the diagnosis of Cushing´s syndrome. Erroneously elevated cortisol may, in particular, be misleading at the low concentrations found in salivary samples obtained at late night and after dexamethasone suppression. METHODS: Interferences in our LC-MS/MS method used for determination of cortisol in saliva and urine were identified by comparing their retention times and mass spectra with those of pure candidate substances...
January 1, 2017: Annals of Clinical Biochemistry
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