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https://www.readbyqxmd.com/read/28817493/dna-methylation-of-the-glucocorticoid-receptor-gene-promoter-in-the-placenta-is-associated-with-blood-pressure-regulation-in-human-pregnancy
#1
Sulistyo E Dwi Putra, Christoph Reichetzeder, Martin Meixner, Karsten Liere, Torsten Slowinski, Berthold Hocher
BACKGROUND: Blood pressure (BP) regulation during pregnancy is influenced by hormones of placental origin. It was shown that the glucocorticoid system is altered in hypertensive pregnancy disorders such as preeclampsia. Epigenetic mechanism might influence the activity of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy. METHOD: In the current study, we analyzed the association of 5'-C-phosphate-G-3' (CpG) site methylation of different glucocorticoid receptor gene (NR3C1) promoter regions with BP during pregnancy...
August 16, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28817464/biologics-for-idiopathic-inflammatory-myopathies
#2
Siamak Moghadam-Kia, Rohit Aggarwal, Chester V Oddis
PURPOSE OF REVIEW: As treatment of refractory cases of idiopathic inflammatory myopathies (IIMs) has been challenging, there is growing interest in assessing novel biologics that target various pathways implicated in the pathogenesis of IIM. RECENT FINDINGS: In the largest clinical trial in adult and juvenile IIM assessing the effectiveness of rituximab, the primary outcome was not met but 83% of this refractory group of IIM patients met a predefined definition of improvement and rituximab demonstrated a significant glucocorticoid-sparing effect...
August 16, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28816544/animal-inflammation-based-models-of-depression-and-their-application-to-drug-discovery
#3
Li Ma, Konstantin A Demin, Tatyana O Kolesnikova, Sergey L Kharsko, Xiaokang Zhu, Xiaodong Yuan, Cai Song, Darya A Meshalkina, Brian E Leonard, Li Tian, Allan V Kalueff
Depression, anxiety and other affective disorders are globally widespread and severely debilitating human brain diseases. Despite their high prevalence and mental health impact, affective pathogenesis is poorly understood, and often remains recurrent and resistant to treatment. The lack of efficient antidepressants and presently limited conceptual innovation necessitate novel approaches and new drug targets in the field of antidepressant therapy. Areas covered: Herein, the authors discuss the emerging role of neuro-immune interactions in affective pathogenesis, which can become useful targets for CNS drug discovery, including modulating neuroinflammatory pathways to alleviate affective pathogenesis...
August 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28815318/-adrenal-crisis
#4
REVIEW
S Burger-Stritt, S Hahner
Patients with chronic adrenal insufficiency suffer from reduced quality of life and increased mortality. An association between mortality and adrenal crisis is assumed. The frequency of adrenal crisis is about 8/100 patient years. The main causes are infectious disease. Pathophysiology is poorly understood to date. An association with an exaggerated inflammatory response due to a lack of glucocorticoid modulation as well as mineralocorticoid deficiency and diminished adrenomedullary function are discussed. The therapy of adrenal crisis includes prompt parenteral administration of hydrocortisone combined with isotonic saline...
August 16, 2017: Der Internist
https://www.readbyqxmd.com/read/28815044/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#5
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28814986/2-deoxy-d-glucose-restore-glucocorticoid-sensitivity-in-acute-lymphoblastic-leukemia-via-modification-of-n-linked-glycosylation-in-an-oxygen-tension-independent-manner
#6
Zaira Leni, Paulina Ćwiek, Valeriya Dimitrova, Andrea S Dulcey, Nicola Zamboni, Cedric Simillion, Geetha Rossi, Kurt Leibundgut, Alexandre Arcaro
In childhood acute lymphoblastic leukemia, treatment failure is associated with resistance to glucocorticoid agents. Resistance to this class of drugs represents one of the strongest indicators of poor clinical outcome. We show that leukemic cells, which are resistant to the glucocorticoid drug methylprednisolone, display a higher demand of glucose associated with a deregulation of metabolic pathways, in comparison to sensitive cells. Interestingly, a combinatorial treatment of glucocorticoid and the glucose analog 2-deoxy-D-glucose displayed a synergistic effect in methylprednisolone-resistant cells, in an oxygen tension-independent manner...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28814383/high-resolution-accurate-mass-hram-mass-spectrometry-urine-steroid-profiling-in-the-diagnosis-of-adrenal-disorders
#7
Jolaine M Hines, Irina Bancos, Cristian Bancos, Raman D Singh, Aditya V Avula, William F Young, Stefan K Grebe, Ravinder J Singh
BACKGROUND: Steroid profiling is a promising diagnostic tool for those with adrenal tumors, Cushing syndrome (CS), and disorders of steroidogenesis. Our objective was to develop a multiple-steroid assay using liquid-chromatography, high-resolution, accurate-mass mass spectrometry (HRAM LC-MS) and to validate the assay in patients with various adrenal disorders. METHODS: We collected 24-h urine samples from 114 controls and 71 patients with adrenal diseases. An HRAM LC-MS method was validated for quantitative analysis of 26 steroid metabolites in hydrolyzed urine samples...
August 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28813704/p38-kinase-sgk1-and-nf-%C3%AE%C2%BAb-dependent-up-regulation-of-na-ca2-exchanger-expression-and-activity-following-tgf%C3%A3-1-treatment-of-megakaryocytes
#8
Tamer Al-Maghout, Lisann Pelzl, Itishri Sahu, Basma Sukkar, Zohreh Hosseinzadeh, Ravi Gutti, Stefan Laufer, Jakob Voelkl, Burkert Pieske, Meinrad Gawaz, Florian Lang
BACKGROUND: TGFβ1, a decisive regulator of megakaryocyte maturation and platelet formation, has previously been shown to up-regulate both, store operated Ca2+ entry (SOCE) and Ca2+ extrusion by Na+/Ca2+ exchange. The growth factor thus augments the increase of cytosolic Ca2+ activity ([Ca2+]i) following release of Ca2+ from intracellular stores and accelerates the subsequent decline of [Ca2+]i. The effect on SOCE is dependent on a signaling cascade including p38 kinase, serum & glucocorticoid inducible kinase SGK1, and nuclear factor NFκB...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28813652/gr-extinguishes-inflamed-chromatin-and-nf-%C3%AE%C2%BAb-evacuates
#9
Maria Fasolino, Golnaz Vahedi
In this issue of Immunity,Oh et al. (2017) provide insight into the molecular effects of glucocorticoid receptor (GR) activation at a clinically relevant time point, after an inflammatory stimulus. They report that GR activation causes a global reduction in NF-κB binding, as well as time-dependent transcriptional effects.
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813312/neuroendocrine-and-neuroimmune-markers-in-ptsd-pre-peri-and-post-trauma-glucocorticoid-and-inflammatory-dysregulation
#10
REVIEW
Miranda Olff, Mirjam van Zuiden
We review current knowledge on how posttraumatic stress disorder (PTSD) is associated with dysregulation of the most commonly studied markers of the endocrine and immune systems pre-, peri- and post-trauma. Lower basal cortisol output, enhanced glucocorticoid receptor function, and a proinflammatory state have been most consistently found in PTSD, with considerable variability among studies and participants. Longitudinal research is scarce, but there is converging evidence that biological dysregulation is present before PTSD onset...
April 2017: Current Opinion in Psychology
https://www.readbyqxmd.com/read/28811198/house-sparrows-mitigate-growth-effects-of-post-natal-glucocorticoid-exposure-at-the-expense-of-longevity
#11
Jacquelyn K Grace, Louise Froud, Alizée Meillère, Frédéric Angelier
Acute, short-term effects of early-life stress and associated glucocorticoid upregulation on physiology and survival are widely documented across vertebrates. However, the persistence and severity of these effects are largely unknown, especially through the adult stage and for natural systems. Here, we investigate physiological, morphological, and survival effects of post-natal glucocorticoid upregulation across the nestling, juvenile, and adult life stages in house sparrows (Passer domesticus). We manipulate circulating corticosterone concentration in wild, free-living house sparrow nestlings and monitor body size, size-corrected mass, two measures of health (hematocrit and phytohemagglutinin-induced skin swelling), and survival in a captive environment until adulthood...
August 12, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28808564/effects-of-parasitic-infection-and-reproduction-on-corticosterone-plasma-levels-in-gal%C3%A3-pagos-land-iguanas-conolophus-marthae-and-c-subcristatus
#12
Michela Onorati, Giulia Sancesario, Donatella Pastore, Sergio Bernardini, Marilyn Cruz, Jorge E Carrión, Monica Carosi, Leonardo Vignoli, Davide Lauro, Gabriele Gentile
In vertebrates, one main feature of stress response is the release of glucocorticoids (corticosterone in reptiles), steroid hormones whose synthesis is regulated by the hypothalamic-pituitary-adrenal axis (HPA). In the Galápagos Islands, populations of land iguanas are differentially impacted by a tick-transmitted apicomplexan hemoparasite of genus Hepatozoon, which could cause diseases and ultimately reduce fitness. Using competitive enzyme-linked immunosorbent assays (ELISA), we examined baseline plasma corticosterone levels of two syntopic and highly parasitized populations of the land iguana species Conolophus marthae and C...
August 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28808483/therapeutic-immune-monitoring-of-cd4-cd25-t-cells-in-chronic-myeloid-leukemia-patients-treated-with-tyrosine-kinase-inhibitors
#13
Ziyuan Lu, Na Xu, Xuan Zhou, Guanlun Gao, Lin Li, Jixian Huang, Yuling Li, Qisi Lu, Bolin He, Chengyun Pan, Xiaoli Liu
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib, are effective forms of therapy for various types of solid cancers and Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia. A number of TKIs have been known to have strong effects on T cells, particularly cluster of differentiation (CD) 4(+)CD25(+) T cells, also known as regulatory T cells (Tregs). There is currently a deficit in the available clinical data regarding this area of study. In the present study, a total of 108 peripheral blood samples were collected from patients with chronic myeloid leukemia (CML) at diagnosis (n=31), and at 3 and 6 months following treatment with TKI [imatinib (n=12), dasatinib (n=11) and nilotinib groups (n=8)] and healthy controls (n=15)...
August 2017: Oncology Letters
https://www.readbyqxmd.com/read/28808239/compound-a-influences-gene-regulation-of-the-dexamethasone-activated-glucocorticoid-receptor-by-alternative-cofactor-recruitment
#14
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/28807771/increase-of-intermediate-monocytes-in-gvhd-correlation-with-mdr1-th17-1-levels-and-the-effect-of-prednisolone-and-1%C3%AE-25-dihydroxyvitamin-d3
#15
Katharina Reinhardt-Heller, Insa Hirschberg, Peter Lang, Thomas Vogl, Rupert Handgretinger, Wolfgang A Bethge, Ursula Holzer
Graft-versus-host disease (GvHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation which is mainly treated with glucocorticoids such as prednisolone. In this study, the influence of monocyte subpopulations, prednisolone and 1α,25-Dihydroxyvitamin D3 on the induction of a pro-inflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multi-drug resistance protein type 1 (MDR1) was investigated...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28807145/a-benzothiadiazine-derivative-and-methylprednisolone-are-novel-and-selective-activators-of-transient-receptor-potential-canonical-5-trpc5-channels
#16
Holger Beckmann, Julia Richter, Kerstin Hill, Nicole Urban, Horst Lemoine, Michael Schaefer
The transient receptor potential canonical channel 5 (TRPC5) is a Ca(2+)-permeable ion channel, which is predominantly expressed in the brain. TRPC5-deficient mice exhibit a reduced innate fear response and impaired motor control. In addition, outgrowth of hippocampal and cerebellar neurons is retarded by TRPC5. However, pharmacological evidence of TRPC5 function on cellular or organismic levels is sparse. Thus, there is still a need for identifying novel and efficient TRPC5 channel modulators. We, therefore, screened compound libraries and identified the glucocorticoid methylprednisolone and N-[3-(adamantan-2-yloxy)propyl]-3-(6-methyl-1,1-dioxo-2H-1λ(6),2,4-benzothiadiazin-3-yl)propanamide (BTD) as novel TRPC5 activators...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28807056/agonist-anti-gitr-antibody-significantly-enhances-the-therapeutic-efficacy-of-listeria-monocytogenes-based-immunotherapy
#17
Rajeev Shrimali, Shamim Ahmad, Zuzana Berrong, Grigori Okoev, Adelaida Matevosyan, Ghazaleh Shoja E Razavi, Robert Petit, Seema Gupta, Mikayel Mkrtichyan, Samir N Khleif
BACKGROUND: We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4(+) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806969/pharmacokinetic-and-urinary-profiling-reveals-the-prednisolone-cortisol-ratio-as-a-valid-biomarker-for-prednisolone-administration
#18
Lieven Van Meulebroek, Nathalie De Clercq, Julie Vanden Bussche, Mathias Devreese, Eric Fichant, Philippe Delahaut, Siska Croubels, Lynn Vanhaecke
BACKGROUND: In Europe, synthetic corticosteroids are not allowed in animal breeding for growth-promoting purposes. Nevertheless, a high prevalence of non-compliant urine samples was recently reported for prednisolone, however, without any indication of unauthorized use. Within this context, 20β-dihydroprednisolone and the prednisolone/cortisol ratio have been suggested as potential tools to discriminate between exogenous and endogenous urinary prednisolone. In this study, the validity of these strategies was verified by investigating the plasma pharmacokinetic and urinary excretion profiles of relevant glucocorticoids in bovines, subjected to exogenous prednisolone treatment or tetracosactide hexaacetate administration to induce endogenous prednisolone formation...
August 14, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28806788/chronic-unpredictable-stress-exacerbates-surgery-induced-sickness-behavior-and-neuroinflammatory-responses-via-glucocorticoids-secretion-in-adult-rats
#19
Na Wang, Hong Ma, Zhe Li, Yalei Gao, Xuezhao Cao, Yanhua Jiang, Yongjian Zhou, Sidan Liu
METHODS: Sprague-Dawley adult male rats (12-14 weeks old) were exposed to 14-day CUS and then subjected to partial hepatectomy 24 h after the last stress session. The rats were pretreated with an antagonist of the glucocorticoids (GCs) receptor RU486 (30 mg/kg, i.p.) 1 h prior to stress exposure. The behavioral changes were evaluated with open field test and elevated plus-maze test. The hippocampal cytokines interleukin (IL)-1β and IL-6 were measured on postoperative days 1, 3 and 7...
2017: PloS One
https://www.readbyqxmd.com/read/28806184/noninfectious-aortitis-what-the-cardiologist-needs-to-know
#20
Ingolf Töpel
PURPOSE OF REVIEW: To sum up a group of noninfectious inflammatory diseases of the aorta and its branches relevant to a cardiologist's daily routine. To describe pathogenetic and clinical advances as well as modern diagnostic tools. To overview most recent treatment options and patient-tailored therapies. To provide an insight in future directions of research. RECENT FINDINGS: Pathophysiology of large vessel vasculitides (LVV) are still poorly defined. At least a certain number of patients with idiopathic periaortitis seem to part of the group of IgG4-related diseases which has implications for therapy...
August 12, 2017: Current Opinion in Cardiology
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