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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/28816544/animal-inflammation-based-models-of-depression-and-their-application-to-drug-discovery
#1
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/28814986/2-deoxy-d-glucose-restore-glucocorticoid-sensitivity-in-acute-lymphoblastic-leukemia-via-modification-of-n-linked-glycosylation-in-an-oxygen-tension-independent-manner
#2
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/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
#3
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/28797006/amiloride-is-effective-in-the-management-of-abiraterone-induced-mineralocorticoid-excess-syndrome-without-interfering-with-its-antineoplastic-activity
#4
Francesca Bedussi, Diego Galli, Martina Fragni, Francesca Valcamonico, Elisa Rossini, Alberto Dalla Volta, Sara Vezzoli, Elisa Roca, Vittorio Ferrari, Barbara Lazzari, Maurizio Memo, Sandra Sigala, Alfredo Berruti
BACKGROUND: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). METHODS: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC)...
August 11, 2017: Pharmacology
https://www.readbyqxmd.com/read/28792718/mdr-1-and-cyp3a5-polymorphisms-in-pediatric-idiopathic-nephrotic-syndrome-impact-on-susceptibility-and-response-to-steroids-preliminary-results
#5
Amira Moussa, Sameh Mabrouk, Haithem Hamdouni, Maroua Ajmi, Miniar Tfifha, Asma Omezzine, Saoussen Abroug, Ali Bouslama
BACKGROUND: Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). However, resistance to this treatment has been observed in some patients. Here, we investigated the association of two steroid metabolism-related genes with susceptibility to childhood NS and the steroid response. METHODS: We genotyped the single nucleotide polymorphisms (SNP) of MDR-1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and the CYP3A5 gene (A6986G) in 63 NS patients and 110 age and gender matched controls by PCR-RFLP...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28782595/dhea-supplementation-to-dexamethasone-treated-rabbits-alleviates-oxidative-stress-in-kidney-cortex-and-attenuates-albuminuria
#6
Anna Kiersztan, Nina Trojan, Aleksandra Tempes, Paweł Nalepa, Joanna Sitek, Katarzyna Winiarska, Michał Usarek
Our recent study has shown that dehydroepiandrosterone (DHEA) administered to rabbits partially ameliorated several dexamethasone (dexP) effects on hepatic and renal gluconeogenesis, insulin resistance and plasma lipid disorders. In the current investigation, we present the data on DHEA protective action against dexP-induced oxidative stress and albuminuria in rabbits. Four groups of adult male rabbits were used in the in vivo experiment: (1) control, (2) dexP-treated, (3) DHEA-treated and (4) both dexP- and DHEA-treated...
August 4, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28781259/-the-influence-of-methylprednisolone-on-the-ability-of-cd4-sup-sup-cd95-sup-sup-hla-dr-sup-sup-t-cells-to-produce-proinflammatory-medators-in-cultures-of-tcr-activated-cd3-sup-sup-cd45ro-sup-sup-t-lymphocytes-from-patients-with-rheumatoid-arthritis
#7
N M Todosenko, O G Khaziakhmatova, K A Yurova, I P Malinina, L S Litvinova
The effect of different concentrations of the glucocorticoid (GC) methylprednisolone (MP) on CD4+CD95+HLA-DR+ T-cells and their ability to produce proinflammatory mediators in cultures of TCR-stimulated CD3+CD45RO+ T-lymphocytes in the in vitro system was investigated. T cells were obtained from healthy donors and patients with rheumatoid arthritis (RA).Under conditions of TCR-activation, MP increased the number of CD4+HLA-DR+CD95+ cells in CD3+CD45RO+ cultures obtained from RA patients and did not change their content in the control group...
May 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28780627/primary-pediatric-hypertension-current-understanding-and-emerging-concepts
#8
REVIEW
Andrew C Tiu, Michael D Bishop, Laureano D Asico, Pedro A Jose, Van Anthony M Villar
The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms...
September 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28777460/phosphatidylinositol-3-kinase-inhibition-potentiates-glucocorticoid-response-in-b-cell-acute-lymphoblastic-leukemia
#9
Cecilia Evangelisti, Alessandra Cappellini, Mariana Oliveira, Rita Fragoso, João T Barata, Alice Bertaina, Franco Locatelli, Carolina Simioni, Luca M Neri, Francesca Chiarini, Annalisa Lonetti, Francesca Buontempo, Ester Orsini, Andrea Pession, Lucia Manzoli, Alberto Maria Martelli, Camilla Evangelisti
Despite remarkable progress in polychemotherapy protocols, pediatric B-cell acute lymphoblastic leukemia (B-ALL) remains fatal in around 20% of cases. Hence, novel targeted therapies are needed for patients with poor prognosis. Glucocorticoids (GCs) are drugs commonly administrated for B-ALL treatment. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway is frequently observed in B-ALL and contributes to GC-resistance. Here, we analyzed for the first time to our knowledge, the therapeutic potential of pan and isoform-selective PI3K p110 inhibitors, alone or combined with dexamethasone (DEX), in B-ALL leukemia cell lines and patient samples...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28774373/-association-between-bim-gene-and-glucocorticoid-resistance-in-children-with-acute-lymphoblastic-leukemia
#10
Jin-Yun Xu, Jian-Ming Luo
Acute lymphoblastic leukemia (ALL) is the most common malignant hematological disease in childhood. Glucocorticoids are frequently used in the chemoradiotherapy regimen for ALL and can induce the apoptosis of ALL cells through several signaling pathways, but about 10% of ALL children have poor response to glucocorticoids. Studies have revealed that glucocorticoids induce the apoptosis of ALL cells by upregulating the expression of BIM gene, and BIM gene is associated with glucocorticoid resistance in childhood ALL...
August 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28768176/a-hypothalamic-phosphatase-switch-coordinates-energy-expenditure-with-feeding
#11
Garron T Dodd, Zane B Andrews, Stephanie E Simonds, Natalie J Michael, Michael DeVeer, Jens C Brüning, David Spanswick, Michael A Cowley, Tony Tiganis
Beige adipocytes can interconvert between white and brown-like states and switch between energy storage versus expenditure. Here we report that beige adipocyte plasticity is important for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons, repressed the browning of white fat and decreased energy expenditure. Conversely feeding reduced hypothalamic TCPTP, to increase AgRP/NPY neuronal insulin signaling, white adipose tissue browning and energy expenditure...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28768158/differential-effects-of-stress-on-fear-learning-and-activation-of-the-amygdala-in-pre-adolescent-and-adult-male-rats
#12
Georgia Barbayannis, Daly Franco, Solange Wong, Josselyn Galdamez, Russell D Romeo, Elizabeth P Bauer
Adolescence is accompanied by the maturation of several stress-responsive areas of the brain including the amygdala, a key region for the acquisition and expression of conditioned fear. These changes may contribute to the development of stress-related disorders in adolescence, such as anxiety and depression, and increase the susceptibility to these psychopathologies later in life. Here, we assessed the effects of acute restraint stress on fear learning and amygdala activation in pre-adolescent and adult male rats...
July 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28765040/the-cortisol-activating-enzyme-11%C3%AE-hydroxysteroid-dehydrogenase-type-1-in-skeletal-muscle-in-the-pathogenesis-of-the-metabolic-syndrome
#13
REVIEW
Christine Loerz, Edmund Maser
The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) contributes to intracellular glucocorticoid action by converting inactive cortisone to its receptor-active form cortisol (11-dehydrocorticosterone and corticosterone in mice and rats). The potential role of 11β-HSD1 in the pathogenesis of the metabolic syndrome has emerged over the past three decades. However, the precise impact of 11β-HSD1 in obesity-related diseases remains uncertain. Many studies from animal experiments to clinical studies have investigated liver and adipose tissue 11β-HSD1 in relation to obesity and its metabolic disorders including insulin resistance...
July 29, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28763903/-role-of-roxithromycin-on-glucocorticoid-resistance-of-human-bronchial-epithelial-cells-and-its-mechanism
#14
D D Sun, T T Xu, W F Zhou, Y R Dai
Objective: To explore the effects of roxithromycin (RXM) on glucocorticoid resistance of human bronchial epithelial cells exposed to smoke and its mechanism. Methods: Beas-2B cells as the research object were grouped into: control group, 10%cigarette smoke extract (CSE) group, roxithromycin (RXM)+ 10%CSE group. With 10%CSE intervention in the 10%CSE group, 10%CSE and RXM intervention in the RXM+ 10%CSE group, complete culture solution intervention in the control group. Interleukin-8 (IL-8) levels were measured by enzyme linked immunosorbent assay (ELISA) and IL-8 inhibition rate and dexamethasone half inhibitory concentration (IC50-Dex) were calculated; the expression of histone deacetylase 2 (HDAC2) protein was detected by immunofluorescence (IF) and Western blotting (WB)...
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28761902/glucocorticoid-associated-blood-glucose-response-and-ms-relapse-recovery
#15
Myla D Goldman, Scott Koenig, Casey Engel, Christopher R McCartney, Min-Woong Sohn
OBJECTIVE: To determine the relationship between MS relapse recovery and blood glucose (BG) response to IV methylprednisolone (IVMP) treatment. METHODS: We retrospectively identified 36 patients with MS admitted for IVMP treatment of acute relapse who had adequate data to characterize BG response, relapse severity, and recovery. The relationship between glucocorticoid-associated nonfasting BG (NFBG) and relapse recovery was assessed. RESULTS: Highest recorded nonfasting BG (maximum NFBG [maxNFBG]) values were significantly higher in patients with MS without relapse recovery compared with those with recovery (271 ± 68 vs 209 ± 48 mg/dL, respectively; p = 0...
September 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28755856/th9-cells-induce-steroid-resistant-bronchial-hyperresponsiveness-in-mice
#16
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/28754022/unfolding-novel-mechanisms-of-polyphenol-flavonoids-for-better-glycaemic-control-targeting-pancreatic-islet-amyloid-polypeptide-iapp
#17
REVIEW
Ivana R Sequeira, Sally D Poppitt
Type 2 diabetes (T2D) is characterised by hyperglycaemia resulting from defective insulin secretion, insulin resistance, or both. The impact of over-nutrition and reduced physical activity, evidenced by the exponential rise in obesity and the prevalence of T2D, strongly supports the implementation of lifestyle modification programs. Accordingly, an increased consumption of fruits and plant-derived foods has been advocated, as their intake is inversely correlated with T2D prevalence; this has been attributed, in part, to their contained polyphenolic compounds...
July 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28750217/association-of-hsd11b1-gene-polymorphisms-with-type-2-diabetes-and-metabolic-syndrome-in-south-indian-population
#18
Nayana Devang, Kapaettu Satyamoorthy, Padmalatha S Rai, M Nandini, Satish Rao, Nagaraja M Phani, Prabha Adhikari
BACKGROUND: 11beta-hydroxysteroid dehydrogenase Type 1 (11β-HSD1) is an NADP or NADPH-dependent enzyme that generates cortisol from cortisone for a local glucocorticoid action. Functional polymorphisms within 11beta-hydroxysteroid dehydrogenase Type 1 (HSD11B1) gene have shown an association with various factors, including insulin resistance (IR) and hypertension. In our study, we have assessed the association of HSD11B1 (rs12086634 and rs846910) gene polymorphisms with type 2 diabetes (T2D) and metabolic syndrome (metS)...
July 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28747606/effective-therapy-with-infliximab-for-clinically-mild-encephalitis-encephalopathy-with-a-reversible-splenial-lesion-in-an-infant-with-kawasaki-disease
#19
Yoshie Kurokawa, Hiroshi Masuda, Tohru Kobayashi, Hiroshi Ono, Hitoshi Kato, Ken-Ichi Imadome, Jun Abe, Yuichi Abe, Shuichi Ito, Akira Ishiguro
  Kawasaki disease (KD) is a systemic vasculitis in infants. In KD, encephalopathy is rarely (0.1%) associated, however, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) has previously been reported in some pediatric patients. Here, we report on a 2-year-old girl who had KD complicated with MERS. The patient experienced generalized clonic convulsion and prolonged consciousness disturbance with fever for 2 days. Her head MRI showed a high signal intensity lesion in the splenium of the corpus callosum in diffusion-weighted images, and low apparent diffusion coefficient (ADC) values on day 3...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28743803/the-glucocorticoid-angptl4-ceramide-axis-induces-insulin-resistance-through-pp2a-and-pkc%C3%AE
#20
Tzu-Chieh Chen, Daniel I Benjamin, Taiyi Kuo, Rebecca A Lee, Mei-Lan Li, Darryl J Mar, Damian E Costello, Daniel K Nomura, Jen-Chywan Wang
Chronic glucocorticoid exposure is associated with the development of insulin resistance. We showed that glucocorticoid-induced insulin resistance was attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced lipolysis in white adipose tissue. Through metabolomic profiling, we revealed that glucocorticoid treatment increased hepatic ceramide concentrations by inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent manner...
July 25, 2017: Science Signaling
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