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A Balasubramanian, S W Wade, R A Adler, K Saag, N Pannacciulli, J R Curtis
PURPOSE: We evaluated systemic glucocorticoid exposure and fracture among patients with newly-diagnosed inflammatory and immune-modulated conditions. METHODS: Using administrative data, inception cohorts of RA, asthma/COPD, IBD, MS, lupus, and sarcoidosis patients age 18-64 years with benefits coverage ≥12 months before diagnosis (1/1/2005-12/31/2012) were followed to clinical fracture, cancer diagnosis, or 12/31/2012. Glucocorticoid users were new to therapy...
June 20, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Zhaoli Gao, Xianhua Li, Tao Peng, Zhao Hu, Jie Liu, Junhui Zhen, Yanxia Gao
INTRODUCTION: We report a case of systemic lupus erythematosus (SLE) with Guillian-Barre syndrome (GBS) as the first symptom. CASE PRESENTATION: A 30-year-old Chinese female with numbness and inductance of lower extremities 2 months previously. The electromyographic and cerebrospinal fluid findings supported inflammatory demyelinating disease, and the renal biopsy findings and rheumatoid-related results considered systemic lupus erythematosus. The patient received treatment with glucocorticoids and cyclophosphamide...
June 2018: Medicine (Baltimore)
Zhengru Liu, Ke Zhou, Shan Tian, Weiguo Dong
RATIONALE: Ulcerative colitis is a chronic and recurrent inflammatory disease involving the intestine. It is reported that about 40% of patients with ulcerative colitis have extraintestinal manifestations, where as the literature on neurological involvement as extraintestinal manifestation is rather limited. Guillain-Barré syndrome is an abnormal immune-mediated and acute-acquired demyelinating disease that mainly affects the peripheral nervous system and often has a phenomenon of protein-cell separation of cerebrospinal fluid...
June 2018: Medicine (Baltimore)
Philip Brandish, Anthony Palmieri, Svetlana Antonenko, Maribel Beaumont, Lia Benso, Mark Cancilla, Mangeng Cheng, Laurence Fayadat-Dilman, Guo Feng, Isabel Figueroa, Juhi Firdos, Robert M Garbaccio, Laura Garvin-Queen, Dennis Gately, Prasanthi Geda, Christopher Haines, SuChun Hseih, Douglas Hodges, Jeffrey C Kern, Nick Knudsen, Kristen Kwasnjuk, Linda Liang, Huiping Ma, Anthony Manibusan, Paul Miller, Lily Moy, Yujie Qu, Sanjiv Shah, John Shin, Peter Stivers, Ying Sun, Daniela Tomazela, Hyun Chong Woo, Dennis Zaller, Shuli Zhang, Yiwei Zhang, Mark Zielstorff
Glucocorticoids (GCs) are excellent anti-inflammatories but are dose-limited by on-target toxicity. We sought to solve this 13 problem by delivering GCs to immune cells with antibody drug conjugates (ADCs) using antibodies containing site-specific 14 incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel 15 glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone to human antigen-presenting immune cells to 16 afford GR activation that was dependent on the targeted antigen...
June 20, 2018: Bioconjugate Chemistry
Anisha Daxini, Keri Cronin, Antoine G Sreih
Recent experimental and genetic studies have implicated the role of programmed cell death protein 1 (PD-1), programmed cell death protein-ligand 1 (PDL-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in the pathogenesis of medium and large vessel vasculitis. This study sought to evaluate the occurrence and nature of vasculitis associated with cancer treatment using immune checkpoint inhibition (anti-PD-1, anti-PDL-1, and anti-CTLA4). A systematic review of the medical literature was conducted by searching all available clinical data up to February 2018 in several databases and search engines including Cochrane Library, Embase, Google Scholar, Medline, Scopus, Web of Science, and Clinicaltrials...
June 19, 2018: Clinical Rheumatology
Anastasia Tchoukaev, Jessica Taytard, Nathalie Rousselet, Carine Rebeyrol, Dominique Debray, Sabine Blouquit-Laye, Marie-Pierre Moisan, Aline Foury, Loic Guillot, Harriet Corvol, Olivier Tabary, Philippe Le Rouzic
Cystic fibrosis (CF) is characterized by a chronic pulmonary inflammation. In CF, glucocorticoids (GC) are widely used, but their efficacy and benefit/risk ratio are still debated. In plasma, corticosteroid-binding globulin (CBG) binds 90% of GC and delivers them to the inflammatory site. The main goal of this work was to study CBG expression in CF patients in order to determine whether CBG could be used to optimize GC treatment. The expression of CBG was measured in liver samples from CF cirrhotic and non-CF cirrhotic patients by qPCR and Western blot and in lung samples from non-CF and CF patients by qPCR...
2018: Frontiers in Pharmacology
Isabelle Laverdière, Meaghan Boileau, Andrea L Neumann, Héloïse Frison, Amanda Mitchell, Stanley W K Ng, Jean C Y Wang, Mark D Minden, Kolja Eppert
Therapy for acute myeloid leukemia (AML) involves intense cytotoxic treatment and yet approximately 70% of AML are refractory to initial therapy or eventually relapse. This is at least partially driven by the chemo-resistant nature of the leukemic stem cells (LSCs) that sustain the disease, and therefore novel anti-LSC therapies could decrease relapses and improve survival. We performed in silico analysis of highly prognostic human AML LSC gene expression signatures using existing datasets of drug-gene interactions to identify compounds predicted to target LSC gene programs...
June 6, 2018: Blood Cancer Journal
Paschalis Efstathopoulos, Filip Andersson, Philippe A Melas, Liu L Yang, J Carlos Villaescusa, Joëlle Rȕegg, Tomas J Ekström, Yvonne Forsell, Maria Rosaria Galanti, Catharina Lavebratt
The disruption of key epigenetic processes during critical periods of brain development can increase an individual's vulnerability to psychopathology later in life. For instance, DNA methylation in the glucocorticoid receptor gene (NR3C1) in adulthood is known to be associated with early-life adversities and has been suggested to mediate the development of stress-related disorders. However, the association between NR3C1 methylation and the emergence of internalizing symptoms in childhood and adolescence has not been studied extensively...
June 19, 2018: Translational Psychiatry
Stefan Fischli
CME: Adrenal Insufficiency Abstract. Patients suffering from adrenal insufficiency (AI) often present with unspecific symptoms. Therefore, the diagnosis of AI, a potential life-threatening condition, can be missed. Lab tests, especially the ACTH-stimulation test, play a crucial role in the diagnosis of AI. According to the different etiologies, AI can be grouped into a primary (adrenal) or central (hypothalamic or pituitary, respectively) form. However, the most common cause is the treatment with glucocorticoids, which can lead to central AI...
June 2018: Praxis
Angus Erland McMillan, Alan Steven, Ian W Ashworth, Alexander K Mullen, Lai Chun Chan, Maria Rita Galan Espinosa, Michael John Pilling, Steven Anthony Raw, Martin F Jones
A selective aziridinium ring-opening was used to etherify an α-aryl-β-amino-alcohol with stereochemical retention. This transformation was achieved in a biphasic system to address phenoxide solubility and the formation of a sulfonate ester im-purity. The protecting group strategy was directed by a stability study of the activated α-aryl-β-amino-alcohol in this system. Process analytical techniques were used to establish reaction understanding and mixing on large scale was modelled in silico. The process provided a selective and efficient method of preparing the non-steroidal, inhaled selective glucocorticoid receptor modulator, AZD7594...
June 19, 2018: Journal of Organic Chemistry
Mathias Vétillard, Géraldine Schlecht-Louf
Dendritic cells (DCs) are key antigen-presenting cells that control the induction of both tolerance and immunity. Understanding the molecular mechanisms regulating DCs commitment toward a regulatory- or effector-inducing profile is critical for better designing prophylactic and therapeutic approaches. Initially identified in dexamethasone-treated thymocytes, the glucocorticoid-induced leucine zipper (GILZ) protein has emerged as a critical factor mediating most, but not all, glucocorticoids effects in both non-immune and immune cells...
2018: Frontiers in Immunology
Mattia Barbot, Filippo Ceccato, Carla Scaroni
Associated with important comorbidities that significantly reduce patients' overall wellbeing and life expectancy, Cushing's disease (CD) is the most common cause of endogenous hypercortisolism. Glucocorticoid excess can lead to diabetes, and although its prevalence is probably underestimated, up to 50% of patients with CD have varying degrees of altered glucose metabolism. Fasting glycemia may nevertheless be normal in some patients in whom glucocorticoid excess leads primarily to higher postprandial glucose levels...
2018: Frontiers in Endocrinology
Yoshiaki Tsukizawa, Keisuke Kondo, Toshihisa Ichiba, Hiroshi Naito, Kazuhito Mizuki, Ken Masuda
Nivolumab, a new immune checkpoint inhibitor that has been found to improve outcomes for patients with some advanced cancers, is being increasingly used. Immune checkpoint inhibitors can cause immune-related adverse events, including dermatitis, enterocolitis, hepatitis and hypophysitis, but adrenal insufficiency rarely occurs. We present a case of Nivolumab-induced adrenal insufficiency in a man who complained of refractory hypotension. A 52-year-old man with non-small cell lung cancer visited our emergency department complaining of fatigue and diarrhea...
May 2018: Nagoya Journal of Medical Science
Magda F Serra, Amanda C Cotias, Camila R R Pão, Julio B Daleprane, Patricia B Jurgilas, Gina C Couto, Edna A Anjos-Valotta, Renato S B Cordeiro, Vinicius F Carvalho, Patricia M R Silva, Marco A Martins
The importance of developing new animal models to assess the pathogenesis of glucocorticoid (GC)-insensitive asthma has been stressed. Because of the asthma-prone background of A/J mice, we hypothesized that asthma changes in these animals would be or become resistant to GCs under repeated exposures to an allergen. A/J mice were challenged with OVA for 2 or 4 consecutive d, starting on day 19 postsensitization. Oral dexamethasone or inhaled budesonide were given 1 h before challenge, and analyses were done 24 h after the last challenge...
June 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Roxane Boivin, Amandine Vargas, Patricia Cano, Jean-Pierre Lavoie
Recurrent inflammation in severe equine asthma causes a remodeling of the airways leading to incompletely reversible airway obstruction. Despite the improvement of clinical signs and lung function with glucocorticoids (GC), inflammation, translated by an increased percentage of neutrophils, persists in the airways. Regulatory T cells (Treg) have been shown to have anti-inflammatory properties and play an important role in balancing the immune response by suppressing effector lymphocyte activity. However, interactions between Treg, neutrophils and glucocorticosteroids in vivo are unclear, particularly in asthma...
July 2018: Veterinary Immunology and Immunopathology
Yuzaburo Inoue, Kanako Mitsunaga, Takeshi Yamamoto, Koki Chiba, Fumiya Yamaide, Taiji Nakano, Yoshinori Morita, Akiko Yamaide, Shuichi Suzuki, Takayasu Arima, Ken-Ichi Yamaguchi, Minako Tomiita, Naoki Shimojo, Yoichi Kohno
BACKGROUND: Bisphosphonates are recommended for use as first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis in adults. However, the appropriate usage of bisphosphonates for the prevention or treatment of glucocorticoid-induced osteoporosis in children remains unclear. METHODS: We performed a cross-sectional study to clarify the factors associated with the development of glucocorticoid-induced bone loss and osteoporosis in patients with childhood-onset rheumatic disease and to investigate the impact of the early use of alendronate...
June 18, 2018: Pediatric Rheumatology Online Journal
Heli Järvinen, Heidi Taipale, Marjaana Koponen, Antti Tanskanen, Jari Tiihonen, Anna-Maija Tolppanen, Sirpa Hartikainen
BACKGROUND: Persons with Alzheimer's disease (AD) are frequently hospitalized from infection-related causes. There are no previous studies investigating hospitalization associated with antibiotic initiation in persons with AD. OBJECTIVE: To investigate the frequency and risk of hospitalization associated with oral antibiotic initiation among community dwellers with and without AD. METHODS: We performed a retrospective register-based study utilizing register-based Medication Use and Alzheimer's disease (MEDALZ) cohort...
June 8, 2018: Journal of Alzheimer's Disease: JAD
Diego J Maselli, Jay I Peters
No abstract text is available yet for this article.
June 19, 2018: Annals of Internal Medicine
Anne-Birgitte Blavnsfeldt, Annette de Thurah, Malissa Dawn Thomsen, Simon Tarp, Bente Langdahl, Ellen-Margrethe Hauge
PURPOSE: The role of glucocorticoids in the treatment of rheumatoid arthritis (RA) is widely debated. Impairment of bone formation may be counter-balanced by reduced systemic inflammation. This review aims to assess the effect of prednisolone/prednisone on bone mineral density (BMD) in patients with RA analyzed in randomized, controlled trials. METHODS: We performed a systematic literature search and identified randomized, double-blinded placebo-controlled studies including patients with RA and using prednisolone or prednisone as the intervention...
June 15, 2018: Bone
Lucas A Zena, Danielle Dillon, Kathleen E Hunt, Carlos A Navas, Kênia C Bícego, C Loren Buck
The tegu lizard Salvator merianae is a large, widely distributed teiid lizard endemic to South America that exhibits annual cycles of high activity during the spring and summer, and hibernation during winter. This pattern of activity and hibernation is accompanied by profound seasonal changes in physiology and behavior, including endothermy during the austral spring. The unusual combination of seasonal endothermy, hibernation and oviparity, in a non-avian, non-mammalian species, makes S. merianae an interesting subject for study of comparative aspects of endocrine regulation of seasonal changes in physiology...
June 15, 2018: General and Comparative Endocrinology
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