Lu YC, Evans CH, Grodzinsky AJ. Effects of short-term glucocorticoid treatment on changes in cartilage matrix degradation and chondrocyte gene expression induced by mechanical injury and inflammatory cytokines. Arthritis Res Ther. 2011; 13(5):R142 ...
Glucocorticoids are commonly used in treatment of paediatric diseases, but evidence of associated adverse cerebral effects is accumulating. The various pharmacokinetic profiles of the exogenous glucocorticoids and the changes in pharmacodynamics during childhood, result in different exposure of nervous tissue to exogenous glucocorticoids. Glucocorticoids activate two types of intracellular receptors, the mineralocorticoid receptor and the glucocorticoid receptor. The two receptors differ in cerebral distribution, affinity and effects. Exogenous glucocorticoids favor activation of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral ...
There is convincing evidence for the known and unambiguously accepted beneficial effects of glucocorticoids at low dosages. However, the implementation of existing recommendations and guidelines on the management of glucocorticoid therapy in rheumatic diseases is lagging behind. As a first step to improve implementation, we aimed at defining conditions under which long-term glucocorticoid therapy may have an acceptably low level of harm. A multidisciplinary European League Against Rheumatism task force group of experts including patients with rheumatic diseases was assembled. After a systematic literature search, breakout groups critically reviewed the evidence on the four most worrisome adverse effects of glucocorticoid therapy (osteoporosis, hyperglycaemia/diabetes mellitus, cardiovascular diseases and infections) and presented their results to the other group members following a structured questionnaire for final discussion and consensus finding. Robust evidence on the risk of harm of long-term
Side effects for SGC_Cases and non-cases_Treatment_Demographics is a random sample of 3000 dogs under primary veterinary care that had systemic glucocorticoid treatment in 2013, taken from the VetCompass dataset. The data provide the demographic characteristics, active substance and route of administration for these dogs.. ...
TY - JOUR. T1 - An evaluation of managing and educating patients on the risk of glucocorticoid-induced osteoporosis. AU - McDonough, Randy P.. AU - Doucette, William R.. AU - Kumbera, Patty. AU - Klepser, Donald G.. N1 - Funding Information: Source of financial support: This study was supported by an unrestricted educational grant from Merck and Co., Inc. and by the Center for Improving Medication Use in the Community at the University of Iowa.. PY - 2005. Y1 - 2005. N2 - Objective: To assess the impact of risk management activities on patient risk of glucocorticoid-induced osteoporosis. Methods: Ninety-six adult patients taking chronic glucocorticoid therapy in 15 community pharmacies. Patients in the control group received usual and customary care. Patients in the treatment pharmacies received education and an educational pamphlet about the risks of glucocorticoid-induced osteoporosis. In addition, the treatment group pharmacists monitored the patients drug therapy, to identify and address ...
TY - JOUR. T1 - Effects of glucocorticoid treatment on bone strength. AU - Manolides, Andrew S.. AU - Cullen, Diane M.. AU - Akhter, Mohammed P.. PY - 2010/9/1. Y1 - 2010/9/1. N2 - Glucocorticoids (GCs) are prescribed for the treatment of several diseases, but their long-term use causes osteoporosis. Current research suggests that GCs suppress the canonical Wnt/β pathway, resulting in decreased expression of critical bone proteins. This study examined how bone structure and strength of high bone mass (HBM) mice and low density lipoprotein receptor-related protein 5 (LRP5) knockout (KO+/-) mice are affected by GC treatment in comparison to wild-type (WT) mice, and if changes were specific to either trabecular or cortical bone. Mice were treated with either prednisone or placebo. The femurs and L4 vertebral bodies were analyzed by micro-CT for structure and mechanically tested to determine strength and apparent material strength properties. Differences in all measured variables corresponding to ...
BACKGROUND: Treatment with glucocorticoids is the leading cause of drug-induced osteoporosis. Currently available guidelines indicate that patients receiving long-term glucocorticoid therapy should receive measures to prevent osteoporosis. OBJECTIVES: To examine whether patients receiving long-term glucocorticoid therapy in a managed care setting received preventive therapy or prescribed medications for osteoporosis and to identify patient and provider characteristics associated with treatment. SUBJECTS AND METHODS: A cohort of 224 health plan enrollees 20 years and older who were dispensed at least 1 oral glucocorticoid prescription per quarter during the period October 1997 through September 1998 was identified from administrative data. Medical charts and administrative data were reviewed to determine use of preventive therapy and prescribed medications for osteoporosis. RESULTS: Of the 224 patients, 62% had at least 1 documented intervention aimed at osteoporosis prevention (counseling about calcium
We examined the direct effects of glucocorticoid treatment on neutrophil survival and function in vitro. Four different glucocorticoids caused a dose-dependent inhibition of apoptosis leading to increased survival of neutrophils. Maximal effects were found with dexamethasone at 10(-6) M, 16.6 +/- 6.2 vs 54.6 +/- 6.9, at 24 h (p , 0.05). Nonglucocorticoid steroids did not modulate apoptosis in neutrophils. Furthermore, the effect was inhibited in a dose-dependent manner by the glucocorticoid antagonist RU 486. Glucocorticoid-treated neutrophils produced significantly more superoxide in response to FMLP than untreated controls (p , 0.05). However, both basal and stimulated superoxide production were less than that found with freshly isolated cells. Such lack of priming or activation by glucocorticoids is in contrast to previous experience when increased survival was accompanied by cell activation. When compared with other stimuli, the effect of glucocorticoids at 24 h was similar to that of LPS ...
We have investigated the effect of long-term glucocorticoid (GC) administration on bone turnover in two frequently used mouse strains; C57BL/6J and CD1, in order to assess the influence of their genetic background on GC-induced osteoporosis (GIO). GIO was induced in 12 weeks old female C57BL/6J and CD1 mice by subcutaneous insertion of long-term release prednisolone or placebo pellets. Biomechanical properties as assessed by three point bent testing revealed that femoral elasticity and strength significantly decreased in CD1 mice receiving GC, whereas C57BL/6J mice showed no differences between placebo and prednisolone treatment. Bone turnover assessed by microcomputer tomography revealed that contrary to C57BL/6J mice, prednisolone treated CD1 mice developed osteoporosis. In vitro experiments have underlined that, at a cellular level, C57BL/6J mice osteoclasts and osteoblasts were less responsive to GC treatment and tolerated higher doses than CD1 cells. Whilst administration of long-term release
TY - JOUR. T1 - Hydrogen peroxide signaling is required for glucocorticoid-induced apoptosis in lymphoma cells. AU - Tome, Margaret E.. AU - Jaramillo, Melba C.. AU - Briehl, Margaret M.. PY - 2011/12/1. Y1 - 2011/12/1. N2 - Glucocorticoid-induced apoptosis is exploited clinically for the treatment of hematologic malignancies. Determining the required molecular events for glucocorticoid-induced apoptosis will identify resistance mechanisms and suggest strategies for overcoming resistance. In this study, we found that glucocorticoid treatment of WEHI7.2 murine thymic lymphoma cells increased the steady-state [H 2O 2] and oxidized the intracellular redox environment before cytochrome c release. Removal of glucocorticoids after the H 2O 2 increase resulted in a 30% clonogenicity; treatment with PEG-CAT increased clonogenicity to 65%. Human leukemia cell lines also showed increased H 2O 2 in response to glucocorticoids and attenuated apoptosis after PEG-CAT treatment. WEHI7.2 cells that overexpress ...
Glucocorticoids are frequently used as anti-inflammatory and immunosuppressive agents. However, high doses and/or prolonged use induce undesired secondary effects such as muscular atrophy. Recently, de novo expression of connexin43 and connexin45 hemichannels (Cx43 HCs and Cx45 HCs, respectively) has been proposed to play a critical role in the mechanism underlying myofiber atrophy induced by dexamethasone (Dex: a synthetic glucocorticoid), but their involvement in specific muscle changes promoted by Dex remains poorly understood. Moreover, treatments that could prevent the undesired effects of glucocorticoids on skeletal muscles remain unknown. In the present work, a 7-day Dex treatment in adult mice was found to induce weight loss and skeletal muscle changes including expression of functional Cx43/Cx45 HCs, elevated atrogin immunoreactivity, atrophy, oxidative stress and mitochondrial dysfunction. All these undesired effects were absent in muscles of mice simultaneously treated with Dex and ...
First described for their metabolic and immunosuppressive effects, glucocorticoids are widely prescribed in clinical settings of inflammation. However, glucocorticoids are also potent inducers of apoptosis in many cell types and tissues. This review will focus on the established mechanisms of glucocorticoid-induced apoptosis and outline what is known about the apoptotic response in cells and tissues of the body after exposure to glucocorticoids. Glucocorticoid-induced apoptosis affects the skeletal system, muscular system, circulatory system, nervous system, endocrine system, reproductive system, and the immune system. Interestingly, several cell types have an anti-apoptotic response to glucocorticoids that is cytoprotective. Lastly, we will discuss the pro- and anti-apoptotic effects of glucocorticoids in cancers and their clinical implications.
The soon-to-be-delivered fetus and preterm infant have been treated with glucocorticoids to prepare for postnatal life, historically for more than 40 years. The use of glucocorticoids is as much for replacement of cortisol in the setting of a poorly functioning hypothalamic-pituitary-adrenal axis in the preterm infant, as it is for prevention of long-term lung dysfunction. Potential negative effects of glucocorticoid treatment on brain development and function have been observed more often with dexamethasone therapy than with use of other glucocorticoids. Overall, glucocorticoid treatment has improved the outcome of the preterm infant.
in Arthritis Research & Therapy (2016), 18(1), 219. BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of ... [more ▼]. BACKGROUND: Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts. The purpose of this study was to position GILZ in OA through its involvement in the anti-inflammatory activities of glucocorticoids and/or in the metabolic pathway of leptin induction. The influences of ...
1. Glucocorticoids are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, rheumatoid arthritis, inflammatory bowel disease and autoimmune diseases, all of which are associated with increased expression of inflammatory genes. The molecular mechanisms involved in this antiinflammatory action of glucocorticoids is discussed, particularly in asthma, which accounts for the highest clinical use of these agents.. 2. Glucocorticoids bind to glucocorticoid receptors in the cytoplasm which then dimerize and translocate to the nucleus, where they bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, resulting in increased transcription. Glucocorticoids may increase the transcription of genes coding for antiinflammatory proteins, including lipocortin-1, interleukin-10, interleukin-1 receptor antagonist and neutral endopeptidase, but this is unlikely to account for all of the widespread anti-inflammatory actions of ...
To evaluate the risk of fracture in patients receiving intermittent therapy with high-dose oral glucocorticoids (GCs).The study group comprised 191,752 patients from the UK General Practice Database who were 40 years of age and older and received therapy with GCs. The followup time period was divided into the categories of current and no exposure. The daily dose and cumulative dose for each time period were determined. Relative risks were estimated using Cox proportional hazards models, adjusted for age, sex, body mass index, smoking, disease history, and drug history. Fractures of the radius/ulna, humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation.Patients who intermittently received high-dose GCs (daily dose | or =15 mg) and had no or little previous exposure to GCs (cumulative exposure | or =1 gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this risk increased substantially with increasing cumulative exposure. Among patients who received a
Therapy with antihistamines and oral glucocorticoids should probably continue at home for another 2-3 days to prevent recurrence.
OBJECTIVE: The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. METHODS: Using linked administrative and pharmacy claims, adults receiving |or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. RESULTS: Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE
Glucocorticoids are frequently used in the treatment of chronic obstructive pulmonary disease (COPD). Patients may take inhaled corticosteroids on a regular basis. In addition, systemic glucocorticoids may be used to treat acute exacerbations. One of the serious side effects of glucocorticoid therapy is osteoporosis. The loss of bone mass and increased fracture risk are related to the cumulative amount of glucocorticoids used. Numerous studies have shown that the use of glucocorticoids in male patients increases their risk for fractures, but few studies have looked at the impact of various treatment regimens on bone mass in this group. Dubois and associates studied the impact of different glucocorticoid treatment regimens on bone density measurements in adult men with COPD.. Male patients with the diagnosis of COPD who were cared for in a pulmonary clinic over a one-year period were evaluated for the study. To be included in the study, patients had to have a diagnosis of COPD that had been ...
Glucocorticoids are prescribed for their immunosuppressive, antiproliferative, anti-inflammatory, and antiallergenic effects and are integral to the management of numerous conditions, including malignancies, transplantation, autoimmune and allergic d
Glucocorticoids and NSAIDs inhibit prostaglandin biosynthesis through different mechanisms. NSAIDs inhibit prostaglandin biosynthesis by noncompetitive inhibition of both COX-1 and COX-2 enzymatic activity. Glucocorticoids are the most potent, endogenous, and specific COX-2 inhibitors. Glucocorticoids suppress prostaglandin production through inhibiting cytosolic phospholipase A2 activity and suppressing COX-2 and mPGES-1 expression. The actions of glucocorticoids are regulated systemically and locally (7). Circulating glucocorticoid levels are regulated by the hypothalamic-pituitary-adrenal axis. Within target tissues, the actions of glucocorticoids are downregulated by 11ßHSD2-mediated metabolism. 11ßHSD2 is expressed predominantly in mineralocorticoid responsive tissues such as the kidney and colon to convert glucocorticoids to their inactive keto-forms, thus providing mineralocorticoid receptor selectivity to aldosterone.. Glucocorticoids are known to inhibit cell proliferation and induce ...
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by ...
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by ...
In the UK, over 250 000 patients take continuous oral glucocorticoids (GCs), yet no more than 14% receive any therapy to prevent bone loss, a major complication of GC treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. This review, based wherever possible on …
The initial search produced 217 citations, and 15 were added from experts, abstracts and review of reference lists. Authors of 4 trials being prepared for publication (and subsequently published) kindly shared their data. After application of eligibility criteria 15 studies and 1,414 patients were included. The majority of trials studied early RA (disease duration up to 2 years), and the mean cumulative dose of glucocorticoid was 2,300 mg prednisone equivalent (range 270 mg - 5,800 mg) over the first year. Glucocorticoids were mostly added to other disease modifying anti-rheumatoid drug (DMARD) treatment. The standardised mean difference in progression was 0.40 in favour of glucocorticoids (95% CI 0.27, 0.54). In studies lasting 2 years (806 patients included), the standardised mean difference in progression in favour of glucocorticoids at 1 year was 0.45 (0.24, 0.66) and at 2 years was 0.42 (0.30, 0.55). All studies except one showed a numerical treatment effect in favour of glucocorticoids. ...
PURPOSE: To analyze the incidence of adrenal suppression and the glucocorticoid (GC) dose per kilogram body weight given in infants treated with standard protocol for topical ophthalmic GCs after congenital cataract surgery.. DESIGN: Retrospective, consecutive case series.. PARTICIPANTS: All children younger than 2 years of age who underwent operation for congenital cataract between January 2011 and May 2015 in 1 center.. METHODS: Patient charts were reviewed to collect data on results and timing of a standard corticotropin (adrenocorticotropic hormone [ACTH]) stimulation test and GC dose per kilogram body weight.. MAIN OUTCOME MEASURES: Incidence of adrenal suppression in children tested on GC treatment. Glucocorticoid dose per kilogram body weight.. RESULTS: Among 26 consecutive infants, 15 (58%) were tested while they were still on GC treatment. Ten of these 15 infants (67%) had adrenal suppression, 2 of whom had obvious clinical signs of Cushings syndrome and 1 of whom had signs of ...
Pharmacology - Glucocorticoids have effects on virtually every cell type and system in mammals. An overview of the effects of these agents follows:. Cardiovascular System: Glucocorticoids can reduce capillary permeability and enhance vasoconstriction. A relatively clinically insignificant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the drugs vasoconstrictive properties and increased blood volume that may be produced.. Cells: Glucocorticoids inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lymphocytes and the cellular response to mediators of inflammation. Glucocorticoids stabilize lysosomal membranes.. CNS/Autonomic Nervous System: Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyrogens, stimulate appetite and maintain alpha rhythm. Glucocorticoids are necessary for normal adrenergic receptor sensitivity.. Endocrine ...
Glucocorticoids Definition Glucocorticoids are naturally-produced steroid hormones, or synthetic compounds, that inhibit the process of inflammation. Purpose The target of glucocorticoids: inflammation Glucocorticoids are used to stop the inflammation process.
臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。. To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of NTU Repository with Academic Hub to form NTU Scholars.. ...
Glucocorticoid administration is frequently used to suppress inflammation and treat a variety of conditions in the VA patient population. One of the most signif...
Activation of the hypothalamic-pituitary-adrenal (HPA) axis stimulates the synthesis and release of glucocorticoids, such as cortisol, from the adrenal cortex into the blood. These factors then activate cytosolic receptors in target cells to induce target gene expression. The HPA axis is activated in response to systemic inflammation and during viral infection and is required to resolve inflammation and restore homeostasis. To better define the mechanisms by which glucocorticoids modulate immune responses, Quatrini et al. knocked out the glucocorticoid receptor (GR) mostly in natural killer (NK) cells in mice and examined the effects on infection by the virus MCMV. After MCMV infection, endogenous glucocorticoids increased the cell surface abundance of the checkpoint inhibitor programmed cell death 1 (PD-1) on wild-type, but not GR-deficient, NK cells in the spleen, but not the liver. In vitro studies showed that the cytokine interleukin-15 (IL-15), which was abundant in the spleen, acted with ...
Antenatal glucocorticoid therapy reduces mortality in the preterm infant, but evidence suggests off-target adverse effects on the developing cardiovascular system. Whether deleterious effects are direct on the offspring or secondary to alterations in uteroplacental physiology is unclear. Here, we isolated direct effects of glucocorticoids using the chicken embryo, a model system in which the effects on the developing heart and circulation of therapy can be investigated, independent of effects on the mother and/or the placenta. Fertilized chicken eggs were incubated and divided randomly into control (C) or dexamethasone (Dex) treatment at day 14 out of the 21-day incubation period. Combining functional experiments at the isolated organ, cellular and molecular levels, embryos were then studied close to term. Chicken embryos exposed to dexamethasone were growth restricted and showed systolic and diastolic dysfunction, with an increase in cardiomyocyte volume but decreased cardiomyocyte nuclear ...
Fos expression is selectively and differentially regulated by endogenous glucocorticoids in the paraventricular nucleus of the hypothalamus and the dentate gyrus Journal Article ...
We investigated the expression differences of the TEL-AML1 fusion gene in a leukemia glucocorticoid (GC)-sensitive cell line (CEM) and a GC-resistant cell line (Jurkat). Changes in TEL-AML1 expression before and after GC exposure were analyzed. Expression of GC-sensitive and GC-resistant leukemia cells following initial diagnosis and during treatment was simulated. Leukemia cells were divided into a GC-unexposed or a GC-exposed group.
A number of childhood conditions that require chronic GC therapy may themselves predispose the child to abnormalities of growth and bone health. For instance, poor linear growth and osteoporosis may be presenting features in a child with inflammatory bowel disease. The interaction with other factors such as inflammatory cytokine production, diminished physical activity, alterations in nutritional status, and the use of other immunomodulatory agents that may also have bone adverse effects greatly increase the risks posed to the growth and bone health of the child on chronic GC therapy.. The clinical effects on bone health can be divided into those occurring in the short term (fractures and avascular necrosis) and those that may occur over the longer term-that is, increased predisposition for osteoporosis and skeletal deformity. Current studies and clinical observations suggest that children who require long term systemic GC therapy (for more than three months) have a higher incidence of fractures ...
In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was non-inferior to 14-day treatment with regard to re-exacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
In the present work, we have set up and propose a rational computational analysis framework, in order to aid the elucidation of the molecular mechanisms of glucocorticoid resistance and specifically whether these are to a larger extent inherent or acquired. To the best of our knowledge, there are no reports trying to analyze systematically the underlying, inherent or acquired molecular mechanisms of GC resistance. The issue whether leukemic cells possess the inherent genetically imprinted resistance mechanisms or it is rather a post effect of evolutionary adoption of originally sensitive cells upon GC treatment is still a controversial one, with potentially significant interest for design of novel therapeutic approaches in cancer treatment. A similar work [77] reported recently that in ex vivo samples, leukemic cells exhibit an at least in part, intrinsic mechanism of reaction. In another work [78], it has also been mentioned that glucocorticoids can induce intrinsic mechanisms of GC-resistance ...
The most important first step in the management of patients with suspected Cushings syndrome is to establish the correct diagnosis. Most mistakes in clinical management, leading to unnecessary imaging or surgery, are made because the diagnostic protocol is not followed (Fig. 342-9). This protocol requires establishing the diagnosis of Cushings beyond doubt prior to employing any tests used for the differential diagnosis of the condition. In principle, after excluding exogenous glucocorticoid use as the cause of clinical signs and symptoms, suspected cases should be tested if there are multiple and progressive features of Cushings, particularly features with a potentially higher discriminatory value. Exclusion of Cushings is also indicated in patients with incidentally discovered adrenal masses. ...
This project will study blood obtained from babies shortly after birth and in guinea pigs early in life to discover how genes throughout the genome respond to glucocorticoid treatment. This research has important implications for the fundamental understanding of biological responses to glucocorticoid treatment. The team anticipates that this study will ultimately inform clinical practice in Canada, where a majority of women at risk of preterm birth (more than 10% of all pregnancies) are treated with glucocorticoids in pregnancy.. ...
A new study reveals that steroid injections used to prevent premature birth might increase future risks of behavioral and emotional problems in the developing children.. Expectant mothers who might give birth prematurely are often treated with an infusion of glucocorticoids. These drugs, wrote Psych Central, are cortisol mimickers; cortisol is a natural hormone. The treatment is meant to assist in the developing babys lung development; however new concerns have arisen that high glucocorticoids exposure in the womb might lead to dangerous, long-term effects on brain development.. Cortisol is naturally produced in the fetus during later pregnancy stages and works to help the lungs develop appropriately, according to Medical Daily. Premature babies often miss this important development stage, which leads to lung problems and life-threatening breathing issues.. Synthetic glucocorticoids are known to copy the effect of natural cortisol and, when given prior to birth, the glucocorticoid, ...
Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant ...
Glucocorticoid therapy is associated with an appreciable risk of bone loss, which is most pronounced in the first few months of use. In addition, glucocorticoids increase fracture risk, and fractures occur at higher bone mineral density (BMD) values
Objectives To study tendencies used of dental glucocorticoids (GCs) among adults, features of dental GC initiators and prescriptions for preventing potential undesireable effects connected with GC therapy. exclusive reimbursement) and over fifty percent of short-term users had taken concurrent antibiotics or respiratory/otological medications. Chronic users (6?reimbursements/calendar year) represented 1.8% (n=3789) from the cohort. The percentage of persistent users with comorbidities apt to be worsened by GC make use of (diabetes, psychotic disorders, osteoporosis) was 25%. Among sufferers at increased threat of osteoporosis, 62% received particular prevention/monitoring measures in support of 27% acquired a bisphosphonate. Half of persistent dental GC users acquired a concurrent reimbursement of the proton pump inhibitor in the lack of nonsteroidal anti-inflammatory medication make use of. Conclusions Mouth GC make use of was highly popular and elevated among adults from 2007 to 2014. The ...
Dexamethasone (Dex) pretreatment significantly increased cardiac contractile force ex vivo in Langendorff-perfused Sprague-Dawley rat hearts (2 mg/kg BW i.p. Dex 24 h prior to experiment). Moreover, Ca transient amplitude as well as fractional shortening were significantly enhanced in Fura-2-loaded isolated rat ventricular myocytes exposed to Dex (1 mg/mL Dex, 24 h). Interestingly, these Dex-dependent effects could be abolished in the presence of SOCE-inhibitors SKF-96356 (SKF, 2 μM) and BTP2 (5 μM). Ca transient kinetics (time to peak, decay time) were not affected by SOCE stimulation. Direct SOCE measurements revealed a negligible magnitude in untreated myocytes but a dramatic increase in SOCE upon Dex-pretreatment. Importantly, the Dex-dependent stimulation of SOCE could be blocked by inhibition of serum and glucocorticoid-regulated kinase 1 (SGK1) using EMD638683 (EMD, 50 μM). Dex preincubation also resulted in increased mRNA expression of proteins involved in SOCE (stromal interaction ...
Even though many in the ALS money making industry maintain otherwise, there is no question that ALS is an autoimmune disease. This is why my wife and other ALS sufferers have experienced strong improvements after injection with anti-inflammatory drugs. This is not the first time that glucocorticoid drugs have been implicated in spectacular ALS remissions. In 2011, famous ALS patient Ted Harada experienced an amazing recovery after being anesthetized for up to five hours during stem cell treatment and given several anti-inflammatory glucocorticoids to prevent rejection. In June 2013, Ernie Schmid published an ALS remission story in which he explained how he kept his ALS under control with powerful glucocorticoids. There is also the story of US Authors Guilds director Paul Aiken whose ALS went into remission after injections with the glucocorticoid drug Kenalog. Other ALS sufferers have reported strong improvements in their speech and ability to swallow after a visit to the dentist. It turns out ...
Taves, Matthew Donald et al Paracrine rather than systemic glucocorticoids are biologically active in the thymus. The Journal of Immunology 198.1 Supplement (2017): 202.1. Web. 16 Dec. 2017. ...
TY - JOUR. T1 - Adrenal gland hypofunction in active polymyalgia rheumatica. Effect of glucocorticoid treatment on adrenal hormones and interleukin 6. AU - Cutolo, Maurizio. AU - Straub, Rainer H.. AU - Foppiani, Luca. AU - Prete, Camilla. AU - Pulsatelli, Lia. AU - Sulli, Alberto. AU - Boiardi, Luigi. AU - Macchioni, Pierluigi. AU - Giusti, Massimo. AU - Pizzorni, Carmen. AU - Seriolo, Bruno. AU - Salvarani, Carlo. PY - 2002. Y1 - 2002. N2 - Objective. To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Methods. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, ...
Risk Associated with Cumulative Oral Glucocorticoid Use in Patients with Giant Cell Arteritis in Real-World Databases from the USA and ...
Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts. The purpose of this study was to position GILZ in OA through its involvement in the anti-inflammatory activities of glucocorticoids and/or in the metabolic pathway of leptin induction. The influences of mineralocorticoids on GILZ and leptin expression were also investigated. Human synovial fibroblasts were isolated from OA patients during knee replacement surgery. Then, the cells were treated with a glucocorticoid (prednisolone), a mineralocorticoid (aldosterone), a glucocorticoid receptor (GR)
Glucocorticoid-induced leucine zipper (GILZ) is a mediator of the anti-inflammatory activities of glucocorticoids. However, GILZ deletion does not impair the anti-inflammatory activities of exogenous glucocorticoids in mice arthritis models and GILZ could also mediate some glucocorticoid-related adverse events. Osteoarthritis (OA) is a metabolic disorder that is partly attributed to adipokines such as leptin, and we previously observed that glucocorticoids induced leptin secretion in OA synovial fibroblasts. The purpose of this study was to position GILZ in OA through its involvement in the anti-inflammatory activities of glucocorticoids and/or in the metabolic pathway of leptin induction. The influences of mineralocorticoids on GILZ and leptin expression were also investigated. Human synovial fibroblasts were isolated from OA patients during knee replacement surgery. Then, the cells were treated with a glucocorticoid (prednisolone), a mineralocorticoid (aldosterone), a glucocorticoid receptor (GR)
Management of glucocorticoid-induced osteoporosis: prevalence, and emerging treatment options Juraj Payer, Kristina Brazdilova, Peter Jackuliak5th Department of Internal Medicine, Medical Faculty of Comenius University and Faculty Hospital Bratislava, Bratislava, SlovakiaAbstract: An excess amount of glucocorticoids represents the primary and most frequent etiological factor influencing secondary osteoporosis. Patients receiving glucocorticoids, but also those with the endogenous form of hypercorticism, are at high risk for the loss of bone density, with the subsequent occurrence of pathological fractures. In this review, we summarize the currently available methods of prevention and the treatment of glucocorticoid-induced osteoporosis. We also include a proposal for both a prophylactic and therapeutic approach that takes into account the risk factors typical for long-term users of glucocorticoids.Keywords: glucocorticoid-induced osteoporosis, bone mineral density, osteoporotic fractures, calcium and
Glucocorticoids, Steroids (Prednisone) Warnings for (such as prednisone) gamut of adverse effects generally linked with use of glucocorticosteroids. Prednisone or prednisolone) do not have significant mineralocorticoid,. Generic. Low Prices, 24/7 online support, available with glucocorticosteroids prednisone World Wide Delivery. 10% OFF Your Next Order. No. Glucocorticosteroids Prednisone. Discreet Packaging. Save on prescription drugs online or by mail order Major side effects of systemic glucocorticoids. Generic Viagra. Free shipping, quality, privacy, secure. Prednisone Rating. Free Bonus Pills with Every Order. Niall Filipos hove their etherifies and avers lot! 1. glucocorticosteroids prednisone Glucocorticosteroids Prednisone! Where to buy generic drugs online? Prednisone -induced leukocytosis Prednisone 20 Mg Medication - best choice! Fuddle right of Bryant, his barrack untune supplements intelligently. Glucocorticoids are also known as glucocorticosteroids, dose of glucocorticoid was ...
It is generally accepted that bone formation is depressed during corticosteroid treatment, but the effects of glucocorticoids on bone resorption are less well characterized. We have investigated the effects of short-term treatment with high-dose oral glucocorticoids on biochemical markers of bone turnover in 20 consecutive patients with asthma who sought help for acute respiratory obstruction in our emergency department. Serum concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen (1CTP), reflecting bone resorption, and the carboxy-terminal propeptide of type 1 procollagen (P1CP), reflecting bone formation, were measured by radioimmunoassay. Changes of the circulating levels of the bone resorption marker 1CTP after treatment were age dependent with a significant negative correlation (r = -0.54, P = 0.01). The dependency on age remained when correcting, in a multiple linear regression analysis, for 1CTP levels at admission, weight, sex, and daily maintenance dose of ...
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Centers RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.. ...
Induction of the glucocorticoid-induced leucine zipper (GILZ) by glucocorticoids plays a role in their antiinflammatory action, whereas GILZ expression is reduced under inflammatory conditions. The mechanisms regulating GILZ expression during inflammation, however, have not yet been characterized. H …
OBJECTIVE: The metabolic effects of low-dose prednisolone and optimal management of glucocorticoid-induced diabetes are poorly characterized. The aims were to investigate the acute effects of low-dose prednisolone on carbohydrate metabolism and whether long-term low-dose prednisolone administration increases visceral adiposity, amplifying metabolic perturbations. RESEARCH DESIGN AND METHODS: Subjects with inflammatory rheumatologic disease without diabetes mellitus were recruited. Nine subjects (age, 59 +/- 11 years) not using oral glucocorticoids were studied before and after a 7- to 10-day course of oral prednisolone 6 mg daily. Baseline data were compared with 12 subjects (age, 61 +/- 8 years) using continuous long-term prednisolone (6.3 +/- 2.2 mg/day). Basal endogenous glucose production (EGP) was estimated by 6,6-(2)H2 glucose infusion, insulin sensitivity was estimated by two-step hyperinsulinemic-euglycemic clamp, insulin secretion was estimated by intravenous glucose tolerance test, and adipose
To determine if a patient has glucocorticoid-induced osteoporosis, you can measure the bone mineral density (BMD) at different parts of the patients body, such as the spine and hip. Dual energy X-ray absorptiometry (DXA) is currently the best test to measure BMD. The test is quick and painless; it is similar to having an X-ray taken, but uses much less radiation. DXA results are scored in comparison to the BMD of young, healthy individuals, resulting in a measurement called a T-score. Patients with T-scores of -2.5 or lower are considered to have osteoporosis and are at a higher risk for a fracture.. According to patient fact-sheet writer Shreyasee Amin, MD, the major goal in the management of glucocorticoid-induced osteoporosis is the prevention of fractures and to help decrease bone loss. At a minimum, she suggests that patients should take 1,000 to 1,500 milligrams of calcium and 400 to 800 IU of vitamin D supplements on a daily basis.. ...
Aims: The use of antenatal glucocorticoids in women with preterm labor has dramatically improved outcomes for premature infants. The most commonly used antenatal glucocorticoids are betamethasone and dexamethasone. Glucocorticoids accelerate fetal lung growth by several mechanisms, including the maturation of type II pneumocytes enabling surfactant production. Furthermore, the lipids in the lung share similarity with those in the skin. Therefore, antenatal administration of glucocorticoids may have effects on the structure and function of the developing epidermal barrier in fetuses and neonates.. Methods: We performed a systematic review to characterize these effects, identifying 11 studies (six animal and five human studies).. Results: Five out of the six animal studies used a rodent model for investigating the effects of antenatally administered glucocorticoids, while the other used an ovine model. Antenatally administered glucocorticoids accelerated skin maturation in animal studies, but ...
Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p,0.05) and the trabecular bone density (p,0.01). Among patients , or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p,0.05), total bone mineral density (p,0.01) and cortical bone mineral density (p,0.01). Bone mineral density in the distal radius ...
TY - JOUR. T1 - Direct Reversal of Glucocorticoid Resistance by AKT Inhibition in Acute Lymphoblastic Leukemia. AU - Piovan, Erich. AU - Yu, Jiyang. AU - Tosello, Valeria. AU - Herranz, Daniel. AU - Ambesi-Impiombato, Alberto. AU - DaSilva, Ana Carolina. AU - Sanchez-Martin, Marta. AU - Perez-Garcia, Arianne. AU - Rigo, Isaura. AU - Castillo, Mireia. AU - Indraccolo, Stefano. AU - Cross, Justin R.. AU - deStanchina, Elisa. AU - Paietta, Elisabeth. AU - Racevskis, Janis. AU - Rowe, Jacob M.. AU - Tallman, Martin S.. AU - Basso, Giuseppe. AU - Meijerink, Jules P.. AU - Cordon-Cardo, Carlos. AU - Califano, Andrea. AU - Ferrando, Adolfo A.. PY - 2013/12/9. Y1 - 2013/12/9. N2 - Glucocorticoid resistance is a major driver of therapeutic failure in Tcell acute lymphoblastic leukemia (T-ALL). Here, we identify the AKT1 kinase as a major negative regulator of the NR3C1 glucocorticoid receptor protein activity driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 impairs glucocorticoid-induced ...
Results Both groups of patients were matched in gender, disease type and cumulative glucocorticoid dose (p,0.1). Patients in the fracture group were older (63±14 vs 59±12 years, p,0.01), of lower body mass index [22.7±3.5vs 24±3.7kg/m2, p,0.05], with a higher prevalence of previous fracture [38 (34.5%) vs 5 (4.5%), p,0.01], use of vitamin D [77 (70%)vs 54 (49.1%), p,0.01] and bisphosphonates [23 (20.9%) vs 7 (6.4%), p,0.01]. A receiver operating characteristic (ROC) curve analysis was performed to determine the ability of FRAX score with or without BMD and BMD alone to discriminate fracture status (Table 1). BMD at the femoral neck and FRAX score with BMD were able to provide adequate discrimination with their area under curve (AUC) ,0.70. With regards to treatment indication, only 53/110 (48.2%) of the patients with vertebral fracture were identified as having osteoporosis (T-score ≤ -2.5 at hip/spine) by DXA. In contrast, FRAX with BMD were able to identify 71/110 (64.5%) of the fracture ...
Tenascin, a predominantly mesenchymal extracellular matrix (ECM) glycoprotein has a rather restricted tissue distribution, but until now factors that inhibit its expression have not been identified. Glucocorticoids are known to be beneficial for establishment of myelopoiesis in long-term bone marrow cultures. Tenascin was found to be expressed in the bone marrow, and glucocorticoids were found to affect bone marrow tenascin expression. Both tenascin mRNAs and the mRNA of another ECM protein, laminin B1 chain, were drastically downregulated by glucocorticoids during initiation of bone marrow cultures. However, in already established long-term cultures glucocorticoids did not affect laminin B1 chain mRNA levels although tenascin mRNAs continued to be downregulated. Studies with a stromal cell line (MC3T3-G2/PA6) and fibroblasts (3T3) suggested that glucocorticoids act directly on the stromal cells that produce tenascin. In 3T3 cells this downregulation occurred within 12 h of ...
TY - JOUR. T1 - Tissue- and context-dependent modulation of hormonal sensitivity of glucocorticoid-responsive genes by hexamethylene bisacetamide-inducible protein 1. AU - Shimizu, Noriaki. AU - Yoshikawa, Noritada. AU - Wada, Tadashi. AU - Handa, Hiroshi. AU - Sano, Motoaki. AU - Fukuda, Keiichi. AU - Suematsu, Makoto. AU - Sawai, Takashi. AU - Morimoto, Chikao. AU - Tanaka, Hirotoshi. PY - 2008/12/1. Y1 - 2008/12/1. N2 - Physiological and pharmacological processes mediated by glucocorticoids involve tissue- and context-specific regulation of glucocorticoid-responsive gene expression via glucocorticoid receptor (GR). However, the molecular mechanisms underlying such highly coordinated regulation of glucocorticoid actions remain to be studied. We here addressed this issue using atp1a1 and scnn1a, both of which are up-regulated in response to corticosteroids in human embryonic kidney-derived 293 cells, but resistant in liver-derived HepG2 cells. Hexamethylene bisacetamide-inducible protein 1 ...
387431079 - EP 0809500 A4 20000105 - NOVEL GLUCOCORTICOID RESPONSE ELEMENTS - [origin: WO9624357A1] The invention features an isolated herpersvirus glucocorticoid response element comprising a DNA sequence comprising two consensus hexanucleotide glucocorticoid receptor binding sequences having at least five nucleotides positioned therebetween. The invention further features compositions and methods for preventing herpesvirus replication and reactivation.[origin: WO9624357A1] The invention features an isolated herpersvirus glucocorticoid response element comprising a DNA sequence comprising two consensus hexanucleotide glucocorticoid receptor binding sequences having at least five nucleotides positioned therebetween. The invention further features compositions and methods for preventing herpesvirus replication and reactivation.
Developmentally, the pancreas and liver are closely related and pathological conditions − including elevated glucocorticoid levels − result in the appearance of hepatocytes in the pancreas. The role of the WNT signalling pathway in this process has been examined in the model transdifferentiating pancreatic acinar AR42J-B-13 (B-13) cell. Glucocorticoid treatment resulted in a transient loss of constitutive WNT3a expression, phosphorylation and depletion of β-catenin, loss of β-catenin nuclear localisation, and significant reductions in T-cell factor/lymphoid enhancer factor (Tcf/Lef) transcriptional activity before overt changes in phenotype into hepatocyte-like (B-13/H) cells. A return to higher Tcf/Lef transcriptional activity correlated with the re-expression of WNT3a in B-13/H cells. β-catenin knock down alone substituted for and enhanced glucocorticoid-dependent transdifferentiation. Overexpression of a mutant β-catenin (pt-Xβ-cat) protein that blocked glucocorticoid-dependent ...
In this study, we compared the monocyte glucocorticoid sensitivity between middle aged men and women while controlling for known risk factors for cardiovascular disease. We used an in vitro assay to measure monocyte cytokine release in response to a standardised dose of lipopolysaccharide and to assess the extent to which this cytokine release was inhibited by increasing concentrations of two glucocorticoids.. The main finding of our study is that, even when controlling for well known cardiovascular risk factors, blood samples from men required larger quantities of either dexamethasone or hydrocortisone to inhibit lipopolysaccharide stimulated release of IL-6 and TNFα than did samples from women, while the cytokine release without glucocorticoid co-incubation was higher in samples from men than in those from women. The findings suggest higher proinflammatory activity in blood monocytes of men than in monocytes harvested from women. This notion becomes even stronger given that we controlled for ...
TY - JOUR. T1 - L-Carnitine is a modulator of the glucocorticoid receptor alpha. AU - Alesci, Salvatore. AU - De Martino, Massimo U.. AU - Kino, Tomoshige. AU - Ilias, Ioannis. PY - 2004/1/1. Y1 - 2004/1/1. N2 - L-Carnitine (LC) is a nutrient with an essential role in cellular energy production. At high doses, LC can mimic some of the biological activities of glucocorticoids, particularly immunomodulation. To explore the molecular bases of this property, we tested the influence of LC on glucocorticoid receptor-α (GRα) functions. LC reduced the binding capacity of GRα, induced its nuclear translocation, and stimulated its transcriptional activity. Moreover, LC suppressed TNFα and IL-12 release from human monocytes in glucocorticoid-like fashion. We conclude that pharmacologic doses of LC can activate GRα and, via this mechanism, regulate glucocorticoid-responsive genes, potentially sharing some of the biological and therapeutic properties of glucocorticoids.. AB - L-Carnitine (LC) is a ...
We studied 534 neonatal survivors at 30 years of age from the first and largest randomised controlled trial of antenatal betamethasone for the prevention of neonatal RDS. We found that antenatal exposure to betamethasone in the doses used in this study did not alter lung function or prevalence of wheeze and asthma at 30 years of age.. Our study is the first to report long term lung function in adulthood following exposure to antenatal betamethasone. The data are consistent with three smaller studies conducted in childhood and early adolescence that also found no difference between betamethasone and placebo exposed groups,6,7,14 and also with follow up of children exposed to postnatal glucocorticoids.15 The only other report of outcome in adulthood following exposure to antenatal glucocorticoids was from a study of 81 participants at a mean age of 20.5 That study found greater medication use in the glucocorticoid exposed group, with the majority of participants taking medication for allergies or ...
For the first time in seven years, the ACR has new treatment recommendations for glucocorticoid-induced osteoporosis. In this slideshow, we highlight the new guidelines.
See American College of Rheumatology (ACR) Recommendations for the Prevention and Treatment of Glucocorticoid-induced Osteoporosis.
TY - JOUR. T1 - Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGRαR477H and hGRαG679S associated with generalized glucocorticoid resistance. AU - Charmandari, Evangelia. AU - Kino, Tomoshige. AU - Ichijo, Takamasa. AU - Zachman, Keith. AU - Alatsatianos, Anton. AU - Chrousos, George P.. PY - 2006/4. Y1 - 2006/4. N2 - Background: Glucocorticoid resistance is often a result of mutations in the human glucocorticoid receptor α (hGRα) gene, which impair one or more of hGRαs functions. We investigated the molecular mechanisms through which two previously described mutant receptors, hGRαR477H and hGRαG679S, with amino acid substitutions in the DNA- and ligand-binding domains, respectively, affect glucocorticoid signal transduction. Methods and Results: In transient transfection assays, hGRαR477H displayed no transcriptional activity, whereas hGRαG679S showed a 55% reduction in its ability to stimulate the transcription of the glucocorticoid-responsive ...
the anterior pituitary gland, the adrenal cortex produces In attempting to assess animal well-being, a number of glucocorticoids, the most important being cortisol and cor- precautionary factors must be considered. Principal con- ticosterone. Glucocorticoids are central to many of the siderations in any assessment of well-being are recogni- physiologic responses to aversive situations. Although an tion and control of independent variables and interaction increase in glucocorticoid concentrations in response to of physical and psychological states (38). The multitude of aversive stimuli can represent a sensitive index of the in- responses to aversive situations complicates the assessment tensity of discomfort or distress experienced by animals, of well-being and limits the significance of any single mea- the adrenal cortex does not respond to all aversive stimuli sure. Thorough evaluation of well-being requires consider- (21). Thus, a simple determination of the plasma concen- ation of multiple ...
Glucocorticoids (GCs) are often prescribed for the treatment of inflammatory diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and psoriasis[1-3]. Despite their excellent efficacy, usage is limited because of side-effects such as insulin resistance, glucose intolerance, diabetes, central adiposity, dyslipidemia, skeletal muscle wasting and osteoporosis[4-8].. GCs bind to the glucocorticoid receptor (GR), which then dimerizes and translocates to the nucleus where it influences gene transcription. Positive regulation of genes (transactivation) is mainly mediated by direct binding of the GR-GC complex to glucocorticoid response elements located in the regulatory region of a target gene. The GR-GC complex may also bind to negative glucocorticoid response elements, which leads to a negative regulation of genes (transrepression). It is believed that transrepression, in which proinflammatory genes are downregulated, is mainly responsible for the efficacy of GCs as ...
TY - JOUR. T1 - Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts. T2 - Novel mechanism of glucocorticoid-induced osteoporosis. AU - Ohnaka, Keizo. AU - Taniguchi, Hiroshi. AU - Kawate, Hisaya. AU - Nawata, Hajime. AU - Takayanagi, Ryoichi. PY - 2004/5/21. Y1 - 2004/5/21. N2 - To clarify the underlying mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on the expression of dickkopf-1 (Dkk-1), an antagonist of Wnt signaling, in primary cultured human osteoblasts. Dexamethasone markedly induced the expression of mRNA for Dkk-1 in a dose- and time-dependent manner. The expression of Kremen1, a receptor for Dkk, did not change by the treatment with dexamethasone, while that of low-density lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor, slightly decreased by the treatment with dexamethasone. Dexamethasone increased the transcriptional activity of the Dkk-1 gene promoter in human osteoblasts. Serial deletion and ...
Glucocorticoids, secreted by the adrenals in response to stress, profoundly affect structure and plasticity of neurons. Glucocorticoid action in neurons is mediated by glucocorticoid receptors (GR) that operate as transcription factors in the regulation of gene expression and either bind directly to genomic glucocorticoid response elements (GREs) or indirectly to the genome via interactions with bound transcription factors. These two modes of action, respectively called transactivation and transrepression, result in the regulation of a wide variety of genes important for neuronal function. The objective of the present study was to identify genome-wide glucocorticoid receptor binding sites in neuronal PC12 cells using Chromatin ImmunoPrecipitation combined with next generation sequencing (ChIP-Seq). In total we identified 1183 genomic binding sites of GR, the majority of which were novel and not identified in other ChIP-Seq studies on GR binding. More than half (58%) of the binding sites contained a GRE.
rdf:RDF xmlns:dcterms=http://purl.org/dc/terms/ xmlns:dc=http://purl.org/dc/elements/1.1/ xmlns:rdf=http://www.w3.org/1999/02/22-rdf-syntax-ns# xmlns:bibo=http://purl.org/ontology/bibo/ xmlns:dspace=http://digital-repositories.org/ontologies/dspace/0.1.0# xmlns:foaf=http://xmlns.com/foaf/0.1/ xmlns:void=http://rdfs.org/ns/void# xmlns:xsd=http://www.w3.org/2001/XMLSchema# , ,rdf:Description rdf:about=https://kops.uni-konstanz.de/rdf/resource/123456789/30976, ,dspace:hasBitstream rdf:resource=https://kops.uni-konstanz.de/bitstream/123456789/30976/1/Wirtz_0-277012.pdf/, ,dc:creator,Frey, Karl,/dc:creator, ,dcterms:rights rdf:resource=http://nbn-resolving.de/urn:nbn:de:bsz:352-20150305140228786-3747162-5/, ,dc:contributor,Frey, Karl,/dc:contributor, ,dc:creator,Fischer, Joachim E.,/dc:creator, ,dc:creator,Ehlert, Ulrike,/dc:creator, ,dcterms:issued,2004,/dcterms:issued, ,dcterms:title,Glucocorticoid sensitivity of circulating monocytes in essential hypertension,/dcterms:title, ...
China Betamethasone Is a Potent Glucocorticoid Steroid with Anti-Inflammatory and Immunosuppressive Properties, Find details about China Durabolin, Decanoate from Betamethasone Is a Potent Glucocorticoid Steroid with Anti-Inflammatory and Immunosuppressive Properties - Wuhan Lianshangwang Technology Co., Ltd.
11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the conversion of the glucocorticoid corticosterone (cortisol in humans) to inert 11-dehydrocorticosterone (cortisone). 11 beta-HSD activity is present in the hippocampus, where it is induced by glucocorticoids and stress in vivo, prompting suggestions that the enzyme may attenuate the deleterious effects of chronic glucocorticoid excess on neuronal function and survival. Two isoforms exist: 11 beta-HSD1, a bidirectional NADPH-dependent enzyme, and 11 beta-HSD2, an NAD(+)- dependent exclusive 11 beta-dehydrogenase (corticosterone-inactivating enzyme). In this study, 11 beta-HSD1 activity and mRNA synthesis were demonstrated in primary fetal hippocampal cell cultures. Unexpectedly, the reaction direction in intact hippocampal cells was 11 beta- reduction (reactivation of inert 11-dehydrocorticosterone), although homogenization revealed that the enzyme was capable of 11 beta- dehydrogenation when removed from its normal cellular context. ...
In an unbiased gene expression and chemical genomics screen, PDE4B was found as one of the highest expressed genes in glucocorticoid-resistant acute lymphoid leukemia (ALL).37 Furthermore, PDE4B variants were associated with a higher rate of relapse in childhood ALL.38 Corroborating these observations, genes associated with glucocorticoid resistance in ALL were enriched in DLBCLs that express high levels of PDE4B,8 whereas PDE4 inhibitors restored glucocorticoid sensitivity and reduced tumor burden in in vivo preclinical models of human lymphoma.8 In these studies, the effects of PDE4 on glucocorticoid sensitivity were associated with modulation of PI3K/AKT signals.8 These data informed the design of a first-in-cancer clinical trial of the PDE4 inhibitor roflumilast (FDA-approved for severe chronic obstructive pulmonary disease). In this single-arm, pharmacokinetics and pharmacodynamics phase Ib study (clinicaltrials.gov identifier NCT01888952), the combination of roflumilast with prednisone was ...
Clinical similarities between Cushings syndrome and obesity/metabolic syndrome have led to speculation of a role for glucocorticoids (GCs) in the etiopathogenesis of obesity. People with idiopathic obesity have normal circulating cortisol concentrations. However, there may be considerable interindividual variation in GC sensitivity. The objective of this study was to determine whether enhanced GC sensitivity in the absence of GC excess was a characteristic of obese people with cushingoid features. We studied 12 obese subjects with cushingoid features in the absence of Cushings syndrome and six slim control participants. Data recorded included BMI, waist-to-hip ratio, blood pressure, glucose and insulin response to 75 g oral glucose challenge, and low-dose (0.25 mg) overnight dexamethasone (DEX) suppression test (ODST-0.25 mg). To study GC-sensitivity in vitro, we performed dose-response studies of DEX-induced suppression of interleukin-6 (IL-6) secretion in skin fibroblast cultures. Seven ...
Glucocorticoids such as dexamethasone are essential components of therapy for T-cell acute lymphoblastic leukemia (T-ALL) and other lymphoid malignancies. Primary glucocorticoid resistance, characterized by ineffective cytoreduction after 1 week of glucocorticoid therapy, occurs frequently in T-ALL and is associated with poor outcome. Glucocorticoids act by binding to nuclear receptor subfamily 3, group C, member 1 (NR3C1, otherwise known as the glucocorticoid receptor) in the cytoplasm, which then shuttles to the nucleus upon ligand binding to regulate glucocorticoid-dependent gene expression that induces apoptosis in T-ALL cells. Given that PI3K-AKT signaling promotes T-cell transformation and that increased AKT1 activity has been associated with glucocorticoid resistance in patients with ALL, Piovan and colleagues hypothesized that AKT1 might interfere with NR3C1 function. AKT1 bound NR3C1 in T-ALL lymphoblasts and phosphorylated NR3C1 on serine 134, suggesting that AKT1 might directly affect ...
Excess fragility of the microvasculature can lead to abnormal mucocutaneous bleeding. This is most commonly seen as a result of natural aging in the elderly but can also be seen as an aspect of Cushing Syndrome due to chronic glucocorticoid use as well as secondary to Vitamin C Deficiency and systemic amyloidosis. A discussion of these etiologies can be found on their respective pages but will not be considered further in this chapter ...
Background: Reducing postoperative complications remains a dominant challenge for all clinicians. By minimizing the incidence of adverse outcomes, health care costs and patient recovery can be improved. A number of studies have documented that fewer postoperative adverse events occur with the preoperative use of glucocorticoids (GC). Two small manuscripts support the use of GC with particular reference to liver resection.. Major hepatectomy can be associated with numerous adverse outcomes (hemorrhage, bile leak, liver failure, wound infection other infectious complications). This rate approaches 54% in some trials. Additionally, the liver is responsible for numerous metabolic functions and actively participates in the acute phase response via the generation of inflammatory mediators and cytokines. Glucocorticoids play an important role in suppressing the over-synthesis of pro-inflammatory cytokines and therefore may assist in reducing postoperative complications. These pro-inflammatory cytokines ...
Glucocorticoids are popular for altering bone tissue elevating and framework fracture risk. elevation. 1. History Besides their association with high-energy stress, almost all (51%) of latest pelvic band fractures are recorded in patients more than 65 years after small trauma, in feminine individuals [1C5] specifically. These fractures may occur with regards to an impaired bone tissue structure and share, for example, predicated on postmenopausal osteoporosis [5]. Additional pathological circumstances like arthritis rheumatoid with and without glucocorticoid (GC) therapy, malignancy, rays, chemotherapy, drugs such as for example bisphosphonates, metabolic CBLC bone tissue diseases, or pregnancy might donate to pelvic band fractures and a feasible lack of stability [6C12]. Furthermore, these fractures could be present without sufficient stress or atraumatically and so are frequently summarized as fragility fractures linked to an impaired bone tissue metabolism and structure [13]. Additionally, ...
TY - JOUR. T1 - Effects of representative glucocorticoids on TNFα- and CD40L-induced NF-κB activation in sensor cells. AU - Cechin, Sirlene R.. AU - Buchwald, Peter. N1 - Funding Information: Parts of this work were supported by grants from the National Institutes of Health National Institute of Allergy and Infectious Diseases ( 1R01AI101041-01 ; PI: P. Buchwald), the Juvenile Diabetes Research Foundation ( 17-2012-361 ), and the Diabetes Research Institute Foundation . PY - 2014/7. Y1 - 2014/7. N2 - Glucocorticoids are an important class of anti-inflammatory/ immunosuppressive drugs. A crucial part of their anti-inflammatory action results from their ability to repress proinflammatory transcription factors such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) upon binding to the glucocorticoid receptor (GR). Accordingly, sensor cells quantifying their effect on inflammatory signal-induced NF-κB activation can provide useful information regarding their potencies as well as their ...
Vertebrates release glucocorticoids during stressful events. If stress occurs during reproduction, the resulting offspring can show altered phenotypes that are thought to arise from increased exposure to maternal glucocorticoids. Developing offspring can metabolize maternal glucocorticoids, which can alter the pattern of exposure they encounter. For egg laying vertebrates, we are just beginning to understand how embryonic steroid metabolism impacts embryonic exposure to maternal glucocorticoids. Here we injected three doses of radioactive corticosterone into Japanese quail (Coturnix japonica) eggs to determine the degree of embryonic exposure at days six and nine of development. We found that increasing injection dose increased the amount of radioactivity found in the embryo at day six but by day nine the effect of injection dose disappeared as the amount of radioactivity within the embryo dropped to equivalent levels for all three doses. Interestingly, when examined as a percentage of initial dose,
We describe for the first time novel data relating to analyses of glucocorticoid hormone signaling in human skeletal myoblasts. Importantly, these results reveal key molecular mechanisms underlying recent suggestions that altered levels of glucocorticoid hormone action may play an important role in the etiology of the metabolic syndrome (12). Our analyses indicate important associations between in vivo features of the metabolic syndrome and levels of basal and glucocorticoid-dependent GRα expression and glucocorticoid-dependent 11β-HSD1 expression in skeletal myoblasts in vitro.. Studies investigating mechanisms underlying GR expression and GR downregulation by its ligand, cortisol, indicate that this occurs predominantly at the level of mRNA transcription and stability and, to a much lesser degree, through post-translational increases in GR turnover (23). Thus, most GR regulation studies have focused on analyses of GR mRNA expression (23,40). The close agreement between levels of GRα mRNA ...
Glucocorticoids or their metabolites can be measured in several body fluids or excreta, including plasma, saliva, urine and faeces. In recent years the measurement of glucocorticoid metabolites (GCMs) in faeces has gained increasing attention, because of its suitability for wild populations. In horses, however, the group-specific enzyme immunoassay described so far has a limited practicability due to its complex extraction procedure. Therefore, we tested the applicability of other enzyme immunoassays for glucocorticoid metabolites. The present study clearly proved that an enzyme immunoassay (EIA) for 11-oxoaetiocholanolone using 11-oxoaetiocholanolone-17-CMO: BSA (3alpha,11-oxo-A EIA) as antigen showed high amounts of immunoreactive substances. Therefore it was possible to use just a small amount of the supernatant of a methanolic suspension of faeces. The results correlated well with the already described method for measuring GCMs in horse faeces, i.e. analysing the samples with an EIA after a ...
True or False. Intraarticular glucocorticoids are not recommended as adjunct therapy in children and adolescents with juvenile idiopathic arthritis (JIA) and active polyarthritis, according to an American College of Rheumatology and Arthritis Foundation guideline. ...
Discount Prednisolone. Ordering Prednisolone online. Purchase Prednisolone online no prescription. Prednisolone trusted pharmacy reviews. Rx free Prednisolone. Prednisolone reviews. Where can i order Prednisolone without prescription. Kjøpe Prednisolone på nett, köpa Prednisolone online. Purchase Prednisolone for sale. Where can i buy Prednisolone online. Online buying Prednisolone. Prednisolone australia, uk, us, usa. After Prednisolone. Herbal Prednisolone. Prednisolone online cod. Prednisolone cost. Prednisolone without a prescription. Is Prednisolone safe. Prednisolone wiki. Prednisolone pharmacy. Cheap Prednisolone. Prednisolone from canadian pharmacy. Prednisolone treatment. Prednisolone coupon. Taking Prednisolone. About Prednisolone. Order Prednisolone from United States pharmacy. Prednisolone from mexico. Order Prednisolone no prescription. Prednisolone photos. Purchase Prednisolone online no prescription. Prednisolone price. Prednisolone alternatives. Prednisolone overnight. ...
This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are essential for the working of basic functionalities of the website. We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies. But opting out of some of these cookies may have an effect on your browsing experience ...
Primary FSGS is a heterogeneous entity for which evidence of effective immunosuppressive therapy is limited. Current recommendations on the use of glucocorticoids as first-line treatment are on the basis of retrospective studies using a variety of regimens (4-7). However, high-dose glucocorticoid therapy is associated with a number of adverse effects (22). The use of CNIs in primary FSGS is on the basis of clinical trials in patients deemed resistant to glucocorticoid therapy (23). No clinical trial has assessed CNIs as first-line immunosuppressive therapy in primary FSGS or directly compared CNI treatment with glucocorticoids alone. This study describes the association between choice of early therapy (including CNIs) and renal survival (ESRD) in primary FSGS, while adjusting for the most important potential confounders in this relationship between treatment and renal outcome.. Several patient and disease characteristics were potentially associated with both initiation of therapy and renal ...