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Dexamethasone suppression

M V Barbado, M Medrano, T Caballero-Velázquez, I Álvarez-Laderas, L I Sánchez-Abarca, E García-Guerrero, J Martín-Sánchez, I V Rosado, J I Piruat, P Gonzalez-Naranjo, N E Campillo, J A Páez, J A Pérez-Simón
Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined. Here we have investigated their anti-tumor effect in multiple myeloma (MM). We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells. This effect was mediated by caspase activation, mainly caspase-2, and was partially prevented by a pan-caspase inhibitor...
October 25, 2016: International Journal of Cancer. Journal International du Cancer
Ranjit Singh, Ranju Bansal
Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1β) might contribute neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models...
October 24, 2016: ACS Chemical Neuroscience
Kuo Zhang, Jingyu Yang, Fang Wang, Xing Pan, Jian Liu, Lijuan Wang, Guanyue Su, Jie Ma, Yinxu Dong, Zhili Xiong, Chufu Wu
ETHNOPHARMACOLOGICAL RELEVANCE: Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is often observed in the pathophysiology of depression. Antidepressant therapy can restore hippocampal neurogenesis to rescue the HPA axis regulation defects. Xiaochaihutang (XCHT), a famous Chinese herbal formula, has been used clinically in depressive disorders in China. Our previous studies have demonstrated XCHT improved depressive-like behaviors in chronic unpredictable mild stress rat, but the underlying mechanisms of XCHT on hippocampal neurogenesis and the HPA axis were still unclear...
October 13, 2016: Journal of Ethnopharmacology
Nuzzi Raffaele, Alessandro Marchese, Dario Ghigo
PURPOSE: The aim of this study is to determine if dexamethasone, prednisolone and triamcinolone acetonide (TA), three anti-inflammatory drugs commonly used for ocular treatments, could affect the oxidative status of cultured human cells of the retinal pigment epithelium (RPE) and protect them against oxidative injury. METHODS: ARPE-19 cells were used as an in vitro model of RPE. Glutathione (GSH) levels were assessed to evaluate the effects of dexamethasone, prednisolone and triamcinolone on cellular antioxidant status...
October 14, 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
Konrad Pazdrak, Christof Straub, Rosario Maroto, Susan Stafford, Wendy I White, William J Calhoun, Alexander Kurosky
The mechanisms contributing to persistent eosinophil activation and poor eosinopenic response to glucocorticoids in severe asthma are poorly defined. We examined the effect of cytokines typically overexpressed in the asthmatic airways on glucocorticoid signaling in in vitro activated eosinophils. An annexin V assay used to measure eosinophil apoptosis showed that cytokine combinations of IL-2 plus IL-4 as well as TNF-α plus IFN-γ, or IL-3, GM-CSF, and IL-5 alone significantly diminished the proapoptotic response to dexamethasone...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Nese Direk, Marieke J H J Dekker, Annemarie I Luik, Clemens Kirschbaum, Yolanda B de Rijke, Albert Hofman, Witte J G Hoogendijk, Henning Tiemeier
Determinants of the hypothalamic-pituitary-adrenal (HPA) axis functioning are increasingly explored in population-based studies. However, functional tests measuring the negative feedback of the HPA axis cannot easily be implemented into large observational studies. Furthermore, high doses of dexamethasone often completely suppress the HPA axis in healthy persons. This study aimed to detect the effects of the health, lifestyle and sociodemographic factors, psychiatric problems and cognitive functions on the negative feedback of the HPA axis using a very low-dose (0...
2016: PloS One
L Mascarell, S Airouche, N Berjont, C Gary, C Gueguen, G Fourcade, B Bellier, D Togbe, B Ryffel, D Klatzmann, V Baron-Bodo, P Moingeon
The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4(+) T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs...
October 12, 2016: Mucosal Immunology
Gordon Parker, Stacey McCraw
BACKGROUND: The CORE measure was designed to assess a central feature of melancholia - signs of psychomotor disturbance (PMD) - and so provide an alternate non-symptom based measure of melancholia or of its probability. This review evaluates development and application studies undertaken over the last 25 years to consider how well it has met its original objectives. METHODS: All studies published using the CORE measure as either the only or an adjunctive measure of melancholia were obtained and are considered in this review...
September 25, 2016: Journal of Affective Disorders
Hwan-Hee Jang, Su-Yeon Cho, Mi-Ju Kim, Jung-Bong Kim, Sung-Hyen Lee, Mee-Young Lee, Young-Min Lee
BACKGROUND: Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. Here, the effects of 80 % ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory response were investigated. RESULTS: Salvia plebeia R. Br. inhibited production of pro-inflammatory cytokines, such as TNF-α and IL-6, as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine production was suppressed more effectively by SE of the aerial parts (SE-A) than of the roots (SE-R) of S...
October 5, 2016: Biological Research
Merel M Schreuder, Christiaan H Vinkers, Esther Mesman, Stephan Claes, Willem A Nolen, Manon H J Hillegers
Children of a parent with bipolar disorder (bipolar offspring) have an increased risk for mood disorders. While genetic factors play a significant role in this population, susceptibility to environmental stress may also significantly contribute to this vulnerability for mood disorders. Childhood trauma has consistently been found to increase the risk for mood disorders, with persisting consequences for hypothalamic-pituitary-adrenal (HPA) axis functionality. However, it is currently unknown whether childhood trauma specifically affects HPA axis activity in individuals with a familial risk for bipolar disorder...
September 24, 2016: Psychoneuroendocrinology
Tomohiro Mori, Nozomu Abe, Kazutomo Saito, Hiroaki Toyama, Yasuhiro Endo, Yutaka Ejima, Masanori Yamauchi, Mariko Goto, Hajime Mushiake, Itsuro Kazama
BACKGROUND: Besides their anti-inflammatory properties, corticosteroid drugs exert anti-allergic effects. Exocytosis of mast cells is electrophysiologically detected as the increase in the whole-cell membrane capacitance (Cm). Therefore, the lack of such increase after exposure to the drugs suggests their mast cell-stabilizing effects. METHODS: We examined the effects of 1, 10, 100 and 200μM hydrocortisone or dexamethasone on the degranulation from rat peritoneal mast cells...
September 5, 2016: Pharmacological Reports: PR
Yoichi Imai, Eri Ohta, Shu Takeda, Satoko Sunamura, Mariko Ishibashi, Hideto Tamura, Yan-Hua Wang, Atsuko Deguchi, Junji Tanaka, Yoshiro Maru, Toshiko Motoji
Multiple myeloma (MM) is a relapsed and refractory disease, one that highlights the need for developing new molecular therapies for overcoming of drug resistance. Addition of panobinostat, a histone deacetylase (HDAC) inhibitor, to bortezomib and dexamethasone improved progression-free survival (PFS) in relapsed and refractory MM patients. Here, we demonstrate how calcineurin, when inhibited by immunosuppressive drugs like FK506, is involved in myeloma cell growth and targeted by panobinostat. mRNA expression of PPP3CA, a catalytic subunit of calcineurin, was high in advanced patients...
April 21, 2016: JCI Insight
Jaxaira Maggi, Katina Schinnerling, Bárbara Pesce, Catharien M Hilkens, Diego Catalán, Juan C Aguillón
Tolerogenic dendritic cells (DCs) are a promising tool to control T cell-mediated autoimmunity. Here, we evaluate the ability of dexamethasone-modulated and monophosphoryl lipid A (MPLA)-activated DCs [MPLA-tolerogenic DCs (tDCs)] to exert immunomodulatory effects on naive and memory CD4(+) T cells in an antigen-specific manner. For this purpose, MPLA-tDCs were loaded with purified protein derivative (PPD) as antigen and co-cultured with autologous naive or memory CD4(+) T cells. Lymphocytes were re-challenged with autologous PPD-pulsed mature DCs (mDCs), evaluating proliferation and cytokine production by flow cytometry...
2016: Frontiers in Immunology
Todd D Nebesio, Jamie L Renbarger, Zeina M Nabhan, Sydney E Ross, James E Slaven, Lang Li, Emily C Walvoord, Erica A Eugster
BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI)...
2016: International Journal of Pediatric Endocrinology
G B Cansu, R Sarı, N Yılmaz, S Özdem, M Çubuk
Introduction: Data regarding cardiovascular risk in patients with non-functional adrenal incidentaloma (NFAI) are limited. The objectives of this study are to investigate markers of subclinical cardiovascular disease like carotid intima media thickness (CIMT), pulse wave velocity (PWV), augmentation index (AIx), soluble CD40 ligand (sCD40L) and leptin levels in NFAI patients without traditional cardiovascular risk factors and healthy control group. Methods: This study involved 35 patients with NFAI (11 males, 24 females; mean age, 52...
September 29, 2016: Experimental and Clinical Endocrinology & Diabetes
Michael Deuschle, Ulrike Gotthardt, Ulrich Schweiger, Michael Dettling, Florian Holsboer, Isabella Heuser
Animal studies suggest that repeated episodes of elevated glucocorticoids lead to a dysregulation of the hypothalamus-pituitary-adrenal (HPA) system at a supra-pituitary level, and to impaired mnemonic function. We compared cognitive tests and both, feedback integrity and stress responsivity of the HPA system, between 11 elderly, male marathon runners - a model of repeated HPA system activation - and 10 sedentary controls. Marathon runners had significantly increased baseline, stress and post-stress ACTH, but not cortisol concentrations...
September 28, 2016: Neuroendocrinology
Ken-Ichiro Tanaka, Fumiya Tamura, Toshifumi Sugizaki, Masahiro Kawahara, Keiji Kuba, Yumiko Imai, Tohru Mizushima
RATIONALE: For acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is a life-saving intervention without alternative, however, MV can cause ventilator-induced lung injury (VILI). Reactive oxygen species (ROS) play important roles in the pathogenesis of both ARDS and VILI. Lecithinized superoxide dismutase (PC-SOD) has overcome limitations of SOD such as low tissue affinity and low stability in plasma. OBJECTIVES: In this study, we have examined the effect of PC-SOD on tissue injury, edema and inflammation in the lung and other organs of mice subjected to cecal ligation and puncture (CLP), lipopolysaccharide (LPS) administration or MV...
September 26, 2016: American Journal of Respiratory Cell and Molecular Biology
Amy E Anderson, David J Swan, Oi Yean Wong, Matthew Buck, Oliver Eltherington, Rachel A Harry, Angela M Patterson, Arthur G Pratt, Gary Reynolds, John-Paul Doran, John A Kirby, John D Isaacs, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4(+) T-cells. Lack of IL-12p70 production is a key immunoregulatory attribute of tolDC but does not fully explain their action. Here we show that tolDC express TGF-β1 at both mRNA and protein level, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC...
September 26, 2016: Clinical and Experimental Immunology
Masahide Matsuda, Tetsuya Yamamoto, Eiichi Ishikawa, Hiroyoshi Akutsu, Shingo Takano, Akira Matsumura
Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy...
September 23, 2016: Neurologia Medico-chirurgica
Syh-Jae Lin, Ming-Ling Kuo, Hsiu-Shan Hsiao, Pei-Tzu Lee
Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory activity aside from its antimicrobial effect, a feature that may ameliorate certain inflammatory disorders and prevent graft-versus-host disease in patients receiving stem cell transplantation. In the present study, we investigated the ability of AZM to influence the function of human monocyte-derived dendritic cells (DCs) and CD4(+) T cells. We found that AZM down-regulated CD80, CD86, and HLA-DR expression in lipopolysaccharide (LPS)-stimulated DCs and suppressed interleukin (IL)-6, IL-10, IL-12, and tumor necrosis factor-alpha production in these cells...
September 21, 2016: International Immunopharmacology
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