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Glucocorticoid resistance

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https://www.readbyqxmd.com/read/28928407/correlation-between-polymorphisms-of-the-nr3c1-gene-and-glucocorticoid-effectiveness-in-patients-with-pemphigus-vulgaris
#1
Si-Yue Fang, Chun-Lei Li, Xiao-Song Liu, Feng Chen, Hong Hua
Glucocorticoid (GC) resistance is the major obscule in the treatment of pemphigus vulgaris (PV) for both patients and clinicans with unclear mechanism. A hypotheis for this resistance is the mutations or polymorphisms present in the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene that encodes receptors for steroid hormones. This study aimed to investigate the association between NR3C1 gene polymorphisms and GC effectiveness in PV patients. 94 PV patients (64 GC-sensitive and 30 GC-resistant) and 100 healthy volunteers were enrolled in this case-control study...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923179/drugs-and-hyperglycemia-a-practical-guide
#2
REVIEW
Vandana Jain, Ronak Kumar Patel, Zaureen Kapadia, Sneha Galiveeti, Maryann Banerji, Lisel Hope
Drug-induced diabetes is one of the factors contributing to the increasing incidence of diabetes worldwide. This review considers the frequency, pathogenesis and treatment of drug-induced diabetes. Drugs that induce diabetes include hormonal therapy, especially glucocorticoids and androgen blockers, cardiovascular drugs, especially statins, beta-blockers and diuretics, antipsychotics, especially clozapine, olanzapine and quetiapine, antiretrovirals (protease inhibitors and non-reverse transcriptase inhibitors - NRTIs) and other drugs (mechanistic target of rapamycin inhibitors -mTORs, post organ transplantation drugs, tyrosine kinase inhibitors and interferon-alpha)...
October 2017: Maturitas
https://www.readbyqxmd.com/read/28918421/macrophage-activation-syndrome-at-the-onset-of-glucocorticoid-resistant-systemic-lupus-erythematosus-a-case-report
#3
Delia Tulbă, Marius Balea, Cristian Băicuș
INTRODUCTION: Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory state mediated by uncontrolled cytokine storm and haemophagocytosis. Although rarely reported, MAS might occur in systemic lupus erythematosus (SLE), notably as an inaugural manifestation. Glucocorticoids (GCs) are the cornerstone of SLE therapy. However, in some cases high doses of GCs are required to achieve remission (i.e. glucocorticoid-resistance), leading to significant side effects. CASE REPORT: A 28-year-old Romani male was admitted to our hospital for polyarthralgia, polyserositis and fatigability...
September 16, 2017: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/28903579/loneliness-social-isolation-and-cardiovascular-health
#4
Ning Xia, Huige Li
SIGNIFICANCE: Social and demographic changes have led to an increased prevalence of loneliness and social isolation in modern society. Recent Advances: Population-based studies have demonstrated that both objective social isolation and perceived social isolation (loneliness) are associated with increased mortality and that both are clearly risk factors for cardiovascular disease. Lonely individuals have increased peripheral vascular resistance and elevated blood pressure. Socially isolated animals develop more atherosclerosis than those housed in groups...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28892924/comparison-of-pioglitazone-and-metformin-efficacy-against-glucocorticoid-induced-atherosclerosis-and-hepatic-steatosis-in-insulin-resistant-rats
#5
I M Nagendra Nayak, Koyagura Narendar, Patil Ashok M, M G Jamadar, V Hemanth Kumar
INTRODUCTION: Insulin Resistance is a major cause of Atherosclerosis (AS) and Non Alcoholic Fatty Liver Disease (NAFLD). These lipid alterations in blood vessels and liver may progress to cardiovascular abnormalities and cirrhosis respectively. Drugs like pioglitazone (PIO) and metformin (MET) are effective insulin sensitizers used in T2DM. But their efficacy and tolerability needs to be compared in IR associated abnormalities. AIM: To compare the efficacy of PIO and MET in glucocorticoid induced AS, Hepatic Steatosis (HS) and IR in albino rats...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891793/regulation-of-the-glucocorticoid-receptor-via-a-bet-dependent-enhancer-drives-antiandrogen-resistance-in-prostate-cancer
#6
Neel Shah, Ping Wang, John Wongvipat, Wouter R Karthaus, Wassim Abida, Joshua Armenia, Shira Rockowitz, Yotam Drier, Bradley E Bernstein, Henry W Long, Matthew L Freedman, Vivek K Arora, Deyou Zheng, Charles L Sawyers
In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals...
September 11, 2017: ELife
https://www.readbyqxmd.com/read/28885689/systematic-analysis-of-mrna-expression-profiles-in-skeletal-muscle-of-patients-with-type-ii-diabetes-the-glucocorticoid-was-central-in-pathogenesis
#7
Kan Shao, Li-Sha Shen, Hui-Hua Li, Shan Huang, Yong Zhang
Since the past thirty years, the prevalence of diabetes has more than doubled, making it an urgent challenge globally. We carried out systematic analysis with the public data of mRNA expression profiles in skeletal muscle to study the pathogenesis, since insulin resistance in the skeletal muscle is an early feature. We utilized three GEO datasets, containing total 60 cases and 63 normal samples. After the background removal, R package QC was utilized to finish the preprocessing of datasets. We obtained a dataset containing 2481 genes and 123 samples after the pre-processing...
September 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28882485/zinc-chloride-rapidly-stimulates-efflux-transporters-in-renal-proximal-tubules-of-killifish-fundulus-heteroclitus
#8
Alexander Zaremba, David S Miller, Gert Fricker
Multidrug resistance-related protein 2 (Mrp2) is an ATP-driven efflux pump at the luminal membrane in renal proximal tubules. It acts as detoxification mechanism by transporting xenobiotics and metabolic products into urine. The trace element zinc is essential for cellular growth, differentiation and survival. It modulates immune response and is used as dietary supplement. Here, we found that 0.1-10μM ZnCl2 rapidly stimulated transport of the Mrp2 probe substrate Texas Red (TR) in isolated killifish renal proximal tubules, which provide an established model system to measure efflux transporter activity by using fluorescent probe substrates, confocal microscopy and image analysis...
September 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28879047/treatment-of-polyarteritis-nodosa-with-tocilizumab-a-new-therapeutic-approach
#9
Aurélie Saunier, Nahéma Issa, Marie-Anne Vandenhende, Philippe Morlat, Marie-Sylvie Doutre, Fabrice Bonnet
We describe the effect of interleukin 6 (IL-6) blockade using tocilizumab (TCZ) for inducing and maintaining remission of refractory polyarteritis nodosa (PAN). Three patients with refractory PAN defined according to the American College of Rheumatology criteria were treated with TCZ infusions (8 mg/kg) on a monthly basis. All of them had severe cutaneous and articular involvement with elevated biological inflammatory markers. One suffered from a neuritis multiplex and one from renal and digestive damage...
2017: RMD Open
https://www.readbyqxmd.com/read/28851976/linoleic-acid-metabolite-leads-to-steroid-resistant-asthma-features-partially-through-nf-%C3%AE%C2%BAb
#10
Lipsa Panda, Atish Gheware, Rakhshinda Rehman, Manish K Yadav, B S Jayaraj, SubbaRao V Madhunapantula, Padukudru Anand Mahesh, Balaram Ghosh, Anurag Agrawal, Ulaganathan Mabalirajan
Studies have highlighted the role of nutritional and metabolic modulators in asthma pathobiology. Steroid resistance is an important clinical problem in asthma but lacks good experimental models. Linoleic acid, a polyunsaturated fatty acid, has been linked to asthma and glucocorticoid sensitivity. Its 12/15-lipoxygenase metabolite, 13-S-hydroxyoctadecadienoic acid (HODE) induces mitochondrial dysfunction, with severe airway obstruction and neutrophilic airway inflammation. Here we show that HODE administration leads to steroid unresponsiveness in an otherwise steroid responsive model of allergic airway inflammation (AAI)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28839007/curcumin-limits-weight-gain-adipose-tissue-growth-and-glucose-intolerance-following-the-cessation-of-exercise-and-caloric-restriction-in-rats
#11
Trevor Teich, Jacklyn A Pivovarov, Deanna P Porras, Emily C Dunford, Michael C Riddell
Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. We investigated the effect of curcumin on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wks old) underwent a 'training' protocol of 24 hr voluntary running wheel access and CR (15-20 g/day) for 3 wks ('All Trained') or were sedentary and fed ad libitum ('Sed'). After 3 wks, 'All Trained' were randomly divided into one group which was terminated immediately ('Trained'), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk...
August 24, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28837059/novel-drug-delivery-systems-tailored-for-improved-administration-of-glucocorticoids
#12
REVIEW
Fred Lühder, Holger M Reichardt
Glucocorticoids (GC) are one of the most popular and versatile classes of drugs available to treat chronic inflammation and cancer, but side effects and resistance constrain their use. To overcome these hurdles, which are often related to the uniform tissue distribution of free GC and their short half-life in biological fluids, new delivery vehicles have been developed including PEGylated liposomes, polymeric micelles, polymer-drug conjugates, inorganic scaffolds, and hybrid nanoparticles. While each of these nanoformulations has individual drawbacks, they are often superior to free GC in many aspects including therapeutic efficacy when tested in cell culture or animal models...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28816544/animal-inflammation-based-models-of-depression-and-their-application-to-drug-discovery
#13
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
#14
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-graft-versus-host-disease-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 1 of the major complications after allogeneic hematopoietic stem cell transplantation that is mainly treated with glucocorticoids such as prednisolone. In this study the influence of monocyte subpopulations, prednisolone, and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on the induction of a proinflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multidrug resistance protein type 1 (MDR1) was investigated...
August 12, 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
#16
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
#17
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
#18
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
#19
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
#20
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
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