Dexamethasone-induced haptoglobin release by calf liver parenchymal cells.

PubMed

Higuchi, H; Katoh, N; Miyamoto, T; Uchida, E; Yuasa, A; Takahashi, K

1994-08-01

Parenchymal cells were isolated from the liver of male calves, and monolayer cultures formed were treated with glucocorticoids to examine whether haptoglobin, appearance of which is associated with hepatic lipidosis (fatty liver) in cattle, is induced by steroid hormones. Without addition of dexamethasone, only trace amounts of haptoglobin were detected in culture medium. With addition of dexamethasone (10(-12) to 10(-4) M), considerable amounts of haptoglobin were released into the medium. Maximal release was observed at concentrations of 10(-8) to 10(-6) M dexamethasone. Haptoglobin release was similarly induced by cortisol, although the effect was less potent than that of dexamethasone. Actinomycin D (a known protein synthesis inhibitor) dose-dependently reduced amounts of haptoglobin released in response to 10(-8) M dexamethasone. Dexamethasone also induced annexin I, which is known to be synthesized in response to glucocorticoids. Dexamethasone treatment resulted in reduced protein kinase C activity in the cell cytosol, which has been shown to be an early event in dexamethasone-treated cells. Other than glucocorticoids, estradiol induced haptoglobin release, whereas progesterone was less effective. The association of haptoglobin with hepatic lipidosis can be reasonably explained by the fact that haptoglobin production by the liver is induced by glucocorticoids and estradiol, and these steroid hormones are triggers for development of hepatic lipidosis in cattle.

Death or Neurodevelopmental Impairment at 18 To 22 Months in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic Lung Disease in Extremely Low Birth Weight Infants

PubMed Central

Stark, Ann R.; Carlo, Waldemar A.; Vohr, Betty R; Papile, Lu Ann; Saha, Shampa; Bauer, Charles R.; Donovan, Edward F.; Oh, William; Shankaran, Seetha; Tyson, Jon E.; Wright, Linda L.; Poole, W. Kenneth; Das, Abhik; Stoll, Barbara J.; Fanaroff, Avroy A.; Korones, Sheldon B.; Ehrenkranz, Richard A.; Stevenson, David K.; Peralta-Carcelen, Myriam; Adams-Chapman, Ira; Wilson-Costello, Deanne E.; Bada, Henrietta S.; Heyne, Roy J.; Johnson, Yvette R.; Lee, Kimberly Gronsman; Steichen, Jean J.; Hintz, Susan R.

2014-01-01

Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18 to 22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants. Methods Evaluation of infants at 18 to 22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). NDI was defined as moderate or severe cerebral palsy, MDI or PDI less than 70, blindness, or hearing impairment. Results Death or NDI at 18 to 22 months corrected age was similar in the dexamethasone and placebo groups (65 vs 66 percent, p= 0.99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50 vs 41 percent, p=0.42 for weight less than 10th percentile). Forty nine percent of infants in the placebo group received treatment with corticosteroid compared to 32% in the dexamethasone group (p=0.02). Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group. PMID:23992673

Early response to ranibizumab predictive of functional outcome after dexamethasone for unresponsive diabetic macular oedema.

PubMed

Cicinelli, Maria Vittoria; Cavalleri, Michele; Querques, Lea; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-12-01

To analyse the effects of intravitreal dexamethasone implant in patients suffering from diabetic macular oedema (DME) on the basis of their visual and functional response to antivascular endothelial growth factor (VEGF) loading dose, in order to early shift to corticosteroids in poorly responding patients. Retrospective monocentric study. Data of patients with diabetes shifted to 0.7 mg dexamethasone implant after three injections of ranibizumab (RNB) and followed-up to 12 months were reviewed. Main outcome was the evaluation of short-term changes after dexamethasone implant injection, stratifying patients on the basis of best-corrected visual acuity (BCVA) and central macular thickness (CMT) after RNB loading dose. Secondary outcome was to investigate clinical gain maintenance at long-term follow-up. Overall, 45 eyes of 45 patients (23 males, 51.1%), mean age 69.7±9 years, were included in the analysis. After 3 injections of RNB, 30 eyes (66.7%) had a poor visual response (-4.3±10.7 letters), while 15 eyes (33.3%) disclosed good visual outcome (+13.9±9.2 letters). Patients with poor visual response were associated with limited morphological improvement (p=0.04). After 1 month from dexamethasone, only poor responders showed relevant increase in BCVA (p=0.006) and reduction in CMT (p=0.002), in comparison to good visual response patients, featuring only minor clinical effects (p=0.3). The same trend was maintained up to 12 months, after a mean of 1.9±1.1 dexamethasone administrations. Visual and anatomical responses after RNB loading dose are significant predictors of both early term and long-term visual acuity improvement after switching to corticosteroids in patients with DME unresponsive to anti-VEGF. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

PubMed

Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

2010-01-01

With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

Does Dexamethasone Helps in Meningococcal Sepsis?

PubMed Central

Tolaj, Ilir; Ramadani, Hamdi; Mehmeti, Murat; Gashi, Hatixhe; Kasumi, Arbana; Gashi, Visar; Jashari, Haki

2017-01-01

Purpose: Prompt recognition and aggressive early treatment are the only effective measures against invasive meningococcal disease (IMD). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients with IMD. The purpose of this study was to evaluate the effect of dexamethasone (DXM) as adjunctive treatment in different clinical forms of IMD, and attempt to answer if DXM should be routinely used in the treatment of IMD. Methods: In this non-interventional clinical study (NIS), 39 patients with meningococcal septicaemia with or without of meningitis were included, and compared regarding the impact of dexamethasone (DXM), as an adjunctive treatment, on the outcome of IMD. SPSS statistics is used for statistical processing of data. Results: Thirty (76.9%) patients with IMD had sepsis and meningitis, and 9 (23.1%) of them had sepsis alone. Dexamethasone was used in 24 (61.5%) cases, in both clinical groups. The overall mortality rate was 10.3%. Pneumonia was diagnosed in 6 patients (15.4%), arthritis in 3 of them (7.7%), and subdural effusion in one patient (2.6%). The data showed a significant statistical difference on the length of hospitalization, and WBC normalization in groups of patients treated with DXM. Conclusion: The use of DXM as adjunctive therapy in invasive meningococcal disease has a degree of proven benefits and no harmful effects. In fighting this very dangerous and complex infection, even a limited benefit is sufficient to recommend the use of DXM as adjunctive treatment in invasive meningococcal disease. PMID:28974828

Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma

PubMed Central

Wong, E T; Lok, E; Gautam, S; Swanson, K D

2015-01-01

Background: Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) vs chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy. Methods: Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS. Results: Patients who used dexamethasone doses >4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 vs 11.0 months respectively (χ2=34.6, P<0.0001) in the TTField-treated cohort and 6.0 vs 8.9 months respectively (χ2=10.0, P<0.0015) in the chemotherapy-treated cohort. In a single institution validation cohort treated with TTFields, the median OS of patients who used dexamethasone >4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (χ2=11.1, P=0.0009). There was a significant correlation between OS and T-lymphocyte counts. Conclusions: Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma. PMID:26125449

Adenine nucleotide translocator promotes oxidative phosphorylation and mild uncoupling in mitochondria after dexamethasone treatment.

PubMed

Arvier, Matthieu; Lagoutte, Laëtitia; Johnson, Gyasi; Dumas, Jean-François; Sion, Benoit; Grizard, Genevieve; Malthièry, Yves; Simard, Gilles; Ritz, Patrick

2007-11-01

The composition of the mitochondrial inner membrane and uncoupling protein [such as adenine nucleotide translocator (ANT)] contents are the main factors involved in the energy-wasting proton leak. This leak is increased by glucocorticoid treatment under nonphosphorylating conditions. The aim of this study was to investigate mechanisms involved in glucocorticoid-induced proton leak and to evaluate the consequences in more physiological conditions (between states 4 and 3). Isolated liver mitochondria, obtained from dexamethasone-treated rats (1.5 mg.kg(-1).day(-1)), were studied by polarography, Western blotting, and high-performance thin-layer chromatography. We confirmed that dexamethasone treatment in rats induces a proton leak in state 4 that is associated with an increased ANT content, although without any change in membrane surface or lipid composition. Between states 4 and 3, dexamethasone stimulates ATP synthesis by increasing both the mitochondrial ANT and F1-F0 ATP synthase content. In conclusion, dexamethasone increases mitochondrial capacity to generate ATP by modifying ANT and ATP synthase. The side effect is an increased leak in nonphosphorylating conditions.

ATM splicing variants as biomarkers for low dose dexamethasone treatment of A-T.

PubMed

Menotta, Michele; Biagiotti, Sara; Spapperi, Chiara; Orazi, Sara; Rossi, Luigia; Chessa, Luciana; Leuzzi, Vincenzo; D'Agnano, Daniela; Soresina, Annarosa; Micheli, Roberto; Magnani, Mauro

2017-07-05

Ataxia Telangiectasia (AT) is a rare incurable genetic disease, caused by biallelic mutations in the Ataxia Telangiectasia-Mutated (ATM) gene. Treatment with glucocorticoid analogues has been shown to improve the neurological symptoms that characterize this syndrome. Nevertheless, the molecular mechanism underlying the glucocorticoid action in AT patients is not yet understood. Recently, we have demonstrated that Dexamethasone treatment may partly restore ATM activity in AT lymphoblastoid cells by a new ATM transcript, namely ATMdexa1. In the present study, the new ATMdexa1 transcript was also identified in vivo, specifically in the PMBCs of AT patients treated with intra-erythrocyte Dexamethasone (EryDex). In these patients it was also possible to isolate new "ATMdexa1 variants" originating from canonical and non-canonical splicing, each containing the coding sequence for the ATM kinase domain. The expression of the ATMdexa1 transcript family was directly related to treatment and higher expression levels of the transcript in patients' blood correlated with a positive response to Dexamethasone therapy. Neither untreated AT patients nor untreated healthy volunteers possessed detectable levels of the transcripts. ATMdexa1 transcript expression was found to be elevated 8 days after the drug infusion, while it decreased 21 days after treatment. For the first time, the expression of ATM splicing variants, similar to those previously observed in vitro, has been found in the PBMCs of patients treated with EryDex. These findings show a correlation between the expression of ATMdexa1 transcripts and the clinical response to low dose dexamethasone administration.

[Successful treatment with a combination of lenalidomide and dexamethasone for cryoglobulinemia associated with multiple myeloma].

PubMed

Taniguchi, Hiroaki; Imaizumi, Yoshitaka; Makiyama, Junya; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Tsushima, Hideki; Hata, Tomoko; Miyazaki, Yasushi

2014-08-01

Cryoglobulinemia (Cg) in multiple myeloma (MM) is rare and no standard treatment has yet been established. Herein, we report a case of MM with Cg, successfully treated with a combination of lenalidomide and dexamethasone. A 76-year-old woman suffering from skin ulcerations, extremity pain and peripheral neuropathy was diagnosed as having IgG-kappa MM with Cg in 1992. She intermittently received conventional chemotherapy, immunosuppressant therapy and plasma exchange. Despite these treatments, Cg-related symptoms eventually became uncontrollable. She was admitted to our hospital in 2012 because of worsening skin symptoms involving both ankles. Plasmapheresis proved ineffective. Improvement of skin ulcerations and numbness was achieved with administration of lenalidomide at 25 mg daily with weekly dexamethasone, which also decreased the cryoglobulin level. The course of this patient suggests that lenalidomide plus dexamethasone is a promising treatment for MM with Cg.

Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal.

PubMed

Valenzuela, O A; Jellyman, J K; Allen, V L; Holdstock, N B; Fowden, A L

2017-01-01

Synthetic glucocorticoids are used to treat inflammatory conditions in horses. In other pregnant animals, glucocorticoids are given to stimulate fetal maturation with long-term metabolic consequences for the offspring if given preterm. However, their metabolic effects during equine pregnancy remain unknown. Thus, this study investigated the metabolic effects of dexamethasone administration on pregnant pony mares and their foals after birth. Experimental study. A total of 3 doses of dexamethasone (200 μg/kg bwt i.m.) were given to 6 pony mares at 48 h intervals beginning at ≈270 days of pregnancy. Control saline injections were given to 5 mares using the same protocol. After fasting overnight, pancreatic β cell responses to exogenous glucose were measured in the mares before, during and after treatment. After birth, pancreatic β cell responses to exogenous glucose and arginine were measured in the foals at 2 and 12 weeks. In mares during treatment, dexamethasone but not saline increased basal insulin concentrations and prolonged the insulin response to exogenous glucose. Basal insulin and glucose concentrations still differed significantly between the 2 groups 72 h post treatment. Dexamethasone treatment significantly reduced placental area but had little effect on foal biometry at birth or subsequently. Foal β cell function at 2 weeks was unaffected by maternal treatment. However, by 12 weeks, pancreatic β cell sensitivity to arginine, but not glucose, was less in foals delivered by dexamethasone- than saline-treated mares. Dexamethasone administration induced changes in maternal insulin-glucose dynamics, indicative of insulin resistance and had subtle longer term effects on post natal β cell function of the foals. The programming effects of dexamethasone in horses may be mediated partially by altered maternal metabolism and placental growth. © 2016 EVJ Ltd.

Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications

PubMed Central

Gay, Maresha S.; Li, Yong; Xiong, Fuxia; Lin, Thant; Zhang, Lubo

2015-01-01

The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner. PMID:25923220

Maternal Dexamethasone Treatment Alters Tissue and Circulating Components of the Renin-Angiotensin System in the Pregnant Ewe and Fetus

PubMed Central

Jellyman, Juanita K.; De Blasio, Miles J.; Johnson, Emma; Giussani, Dino A.; Broughton Pipkin, Fiona; Fowden, Abigail L.

2015-01-01

Antenatal synthetic glucocorticoids promote fetal maturation in pregnant women at risk of preterm delivery and their mechanism of action may involve other endocrine systems. This study investigated the effect of maternal dexamethasone treatment, at clinically relevant doses, on components of the renin-angiotensin system (RAS) in the pregnant ewe and fetus. From 125 days of gestation (term, 145 ± 2 d), 10 ewes carrying single fetuses of mixed sex (3 female, 7 male) were injected twice im, at 10–11 pm, with dexamethasone (2 × 12 mg, n = 5) or saline (n = 5) at 24-hour intervals. At 10 hours after the second injection, maternal dexamethasone treatment increased angiotensin-converting enzyme (ACE) mRNA levels in the fetal lungs, kidneys, and heart and ACE concentration in the circulation and lungs, but not kidneys, of the fetuses. Fetal cardiac mRNA abundance of angiotensin II (AII) type 2 receptor decreased after maternal dexamethasone treatment. Between the two groups of fetuses, there were no significant differences in plasma angiotensinogen or renin concentrations; in transcript levels of renal renin, or AII type 1 or 2 receptors in the lungs and kidneys; or in pulmonary, renal or cardiac protein content of the AII receptors. In the pregnant ewes, dexamethasone administration increased pulmonary ACE and plasma angiotensinogen, and decreased plasma renin, concentrations. Some of the effects of dexamethasone treatment on the maternal and fetal RAS were associated with altered insulin and thyroid hormone activity. Changes in the local and circulating RAS induced by dexamethasone exposure in utero may contribute to the maturational and tissue-specific actions of antenatal glucocorticoid treatment. PMID:26039155

A randomized controlled trial of dexamethasone as an adjunctive therapy to propylene glycol for treatment of hyperketonemia in postpartum dairy cattle.

PubMed

Tatone, Elise H; Duffield, Todd F; Capel, Michael B; DeVries, Trevor J; LeBlanc, Stephen J; Gordon, Jessica L

2016-11-01

Treatment of hyperketonemia with oral propylene glycol has proven efficacy but the cure rate remains moderate. Dexamethasone has long been suggested as a treatment for hyperketonemia, even though evidence of its efficacy is contradictory. The objective of this randomized controlled trial was to evaluate the effect of adding a single intramuscular injection of 20mg of dexamethasone to oral propylene glycol therapy for hyperketonemia [blood β-hydroxybutyrate (BHB) ≥1.2mmol/L]. All cows between 3 and 16d in milk on 4 dairy farms in New York State were tested once weekly for hyperketonemia using a handheld ketone meter. All enrolled animals received 312g (300mL) of propylene glycol orally once daily for 4d and either a single injection of dexamethasone or an equivalent volume of sterile saline. A total of 509 animals were enrolled, with 254 and 255 in the placebo and dexamethasone groups, respectively. Treatment with dexamethasone decreased the odds of being hyperketonemic in the second week posttreatment; however, the odds of hyperketonemia in the first week posttreatment only decreased in those animals that were treated at a BHB blood concentration between 1.2 and 1.5mmol/L. For the 8% of cows with blood BHB >3.2mmol/L at enrollment, receiving dexamethasone increased the odds of being hyperketonemic the following week. We detected no difference between treatment groups in the odds of postpartum disease or in milk production. For cows with initial BHB of 1.2 to 1.5mmol/L, treatment with dexamethasone tended to reduce the odds of pregnancy at first insemination. Based on the small and conditional benefits of dexamethasone and a lack of difference in milk yield or disease incidence, we do not recommend the use of dexamethasone to treat hyperketonemia. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of dexamethasone on C6 astrocytoma radiosensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lordo, C.D.; Stroude, E.C.; Del Maestro, R.F.

1989-05-01

Brain-tumor patients often undergo radiation therapy while receiving corticosteroids for the treatment of cerebral edema. Studies have demonstrated that dexamethasone is radioprotective in a number of cell lines. The C6 astrocytoma cell line is well established in vitro and is modulated by dexamethasone treatment. It has therefore been hypothesized that dexamethasone-treated C6 astrocytoma cells would be more resistant to radiation-induced damage. The present study was carried out to assess this hypothesis using both the in vitro C6 astrocytoma monolayer and three-dimensional multicellular spheroid models. Dexamethasone was inhibitory to the C6 astrocytoma cells in the monolayer preparation, increasing their doubling timemore » by 13%. In the spheroid cultures, dexamethasone treatment decreased the number of cells per spheroid by 46%. Dexamethasone did not affect the plating efficiency of either the cells from the monolayer experiment or those dissociated from spheroids, however, suggesting that the inhibitory effect was not tumoricidal. At a clinical concentration (1.94 x 10(-5) M), dexamethasone did not significantly influence plating efficiency of irradiated C6 astrocytoma cells in monolayer or three-dimensional spheroid cultures.« less

Bovine herpesvirus 1 productive infection and immediate early transcription unit 1 promoter are stimulated by the synthetic corticosteroid dexamethasone.

PubMed

Kook, Insun; Henley, Caitlin; Meyer, Florencia; Hoffmann, Federico G; Jones, Clinton

2015-10-01

The primary site for life-long latency of bovine herpesvirus 1 (BHV-1) is sensory neurons. The synthetic corticosteroid dexamethasone consistently induces reactivation from latency; however the mechanism by which corticosteroids mediate reactivation is unclear. In this study, we demonstrate for the first time that dexamethasone stimulates productive infection, in part, because the BHV-1 genome contains more than 100 potential glucocorticoid receptor (GR) response elements (GREs). Immediate early transcription unit 1 (IEtu1) promoter activity, but not IEtu2 or VP16 promoter activity, was stimulated by dexamethasone. Two near perfect consensus GREs located within the IEtu1 promoter were necessary for dexamethasone-mediated stimulation. Electrophoretic mobility shift assays and chromatin immunoprecipitation studies demonstrated that the GR interacts with IEtu1 promoter sequences containing the GREs. Although we hypothesize that DEX-mediated stimulation of IEtu1 promoter activity is important during productive infection and perhaps reactivation from latency, stress likely has pleiotropic effects on virus-infected cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Newborn lamb coronary artery reactivity is programmed by early gestation dexamethasone before the onset of systemic hypertension

PubMed Central

Roghair, Robert D.; Segar, Jeffrey L.; Sharma, Ram V.; Zimmerman, Matthew C.; Jagadeesha, D. K.; Segar, Emily M.; Scholz, Thomas D.; Lamb, Fred S.

2009-01-01

Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces organ-specific alterations in postnatal cardiovascular physiology. To determine whether early gestation corticosteroid exposure alters coronary reactivity before the development of systemic hypertension, dexamethasone (0.28 mg·kg−1 · day−1) was administered to pregnant ewes by intravenous infusion over 48 h beginning at 27 days gestation (term, 145 days). Vascular responsiveness was assessed in endothelium-intact coronary arteries isolated from 1-wk-old steroid-exposed and age-matched control lambs (N = 6). Calcium imaging was performed in fura 2-loaded primary cultures of vascular smooth muscle cells (VSMC) from the harvested coronary arteries. Early gestation steroid exposure did not significantly alter mean arterial blood pressure or coronary reactivity to KCl, thromboxane A2 mimetic U-46619, or ANG II. Steroid exposure significantly increased coronary artery vasoconstriction to acetylcholine and endothelin-1. Vasodilatation to adenosine, but not nitroprusside or forskolin, was significantly attenuated following early gestation steroid exposure. Endothelin-1 or U-46619 stimulation resulted in a comparable increase in intracellular calcium concentration ([Ca2+]i) in coronary VSMC isolated from either dexamethasone-treated or control animals. However, the ANG II- or KCl-mediated increase in [Ca2+]i in control VSMC was significantly attenuated in VSMC harvested from dexamethasone-treated lambs. Coronary expression of muscle voltage-gated l-type calcium channel α-1 subunit protein was not significantly altered by steroid exposure, whereas endothelial nitric oxide synthase expression was attenuated. These findings demonstrate that early gestation glucocorticoid exposure elicits primary alterations in coronary responsiveness before the development of systemic hypertension. Glucocorticoid-induced alterations in coronary physiology may provide a mechanistic link between an adverse

Dexamethasone treatment promotes Bcl-2-dependence in multiple myeloma resulting in sensitivity to Venetoclax

PubMed Central

Matulis, Shannon M.; Gupta, Vikas A.; Nooka, Ajay K.; Von Hollen, Hayley; Kaufman, Jonathan L.; Lonial, Sagar; Boise, Lawrence H.

2015-01-01

Venetoclax (ABT-199), a specific inhibitor of the anti-apoptotic protein Bcl-2, is currently in phase I clinical trials for multiple myeloma. Results suggest that venetoclax is only active in a small cohort of patients therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or carfilzomib produced additive or better cell death in 4 of the 5 cell lines tested. The most striking results were seen with dexamethasone. Co-treatment of human myeloma cell lines and primary patient samples, with dexamethasone and venetoclax significantly increased cell death over venetoclax alone in 4 of the 5 cell lines, and in all patient samples tested. The mechanism by which this occurs is an increase in the expression of both Bcl-2 and Bim upon addition of dexamethasone. This results in alterations in Bim binding to anti-apoptotic proteins. Dexamethasone shifts Bim binding towards Bcl-2 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with dexamethasone could be an effective therapy for a broader range of patients than would be predicted by single agent activity. PMID:26707935

Intravitreal bevacizumab and dexamethasone implant for treatment of chronic diabetic macular edema.

PubMed

Güler, Emre; Totan, Yüksel; Betül Güragaç, Fatma

2017-06-01

To evaluate anatomical and functional outcomes of intraviteal bevacizumab (IVB) in patients with chronic diabetic macular edema (DME), and the effectivity and safety of dexamethasone implant in those unresponsive to regular IVB treatment. Thirty-five eyes of 35 patients (16 male and 19 female) with chronic DME (central foveal thickness (CFT)  > 275 μm, duration  > 6 months) received three injections of 2.5 mg IVB with six-week intervals. At 18 weeks, dexamethasone implant was applied to patients unresponsive to IVB. Main outcomes were the change in best corrected visual acuity (BCVA), CFT and ocular and systemic adverse effects for both drugs. The patients responsive to IVB were followed up for 36 weeks and those patients receiving dexamethasone implant were followed up for 24 weeks postoperatively. At 18 weeks, the mean BCVA (0.68 ± 0.40 logMAR, p = 0.45) and CFT (453 ± 169 μm, p = 0.58) did not show any significant change compared to baseline (0.74 ± 0.42 logMAR and 521 ± 151 μm, respectively). In 20 patients (%57.1) responsive to IVB, the CFT was significantly improved from 12 to 36 weeks with the mean value of 295 ± 42 μ (p = 0.01). However, no significant difference was observed for BCVA during this period (p = 0.17). Dexamethasone was implanted in 15 eyes (42.8%) unresponsive to IVB at 18 weeks. Statistically significant improvements were observed in BCVA (at postoperative 4 and 12 weeks) and CFT (at postoperative 4, 12 and 24 weeks). In addition, both parameters significantly worsened at 24 weeks compared to 12 weeks (p < 0.001 and p = 0.01, respectively). Patients with chronic DME should be followed in accordance with a fixed treatment protocol combining anti-VEGF and steroid treatments.

Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury.

PubMed

Reis, Fernando Fonseca Dos; Reboredo, Maycon de Moura; Lucinda, Leda Marília Fonseca; Bianchi, Aydra Mendes Almeida; Rabelo, Maria Aparecida Esteves; Fonseca, Lídia Maria Carneiro da; Oliveira, Júlio César Abreu de; Pinheiro, Bruno Valle

2016-01-01

To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated. Avaliar os efeitos da administração de dexametasona antes da indução de lesão pulmonar induzida por ventilação mecânica (LPIVM) na evolução temporal dessa lesão. Ratos Wistar foram alocados em um dos três grupos: administração de dexametasona pr

Treatment of oral mucosal manifestations of chronic graft-versus-host disease: dexamethasone vs. budesonide.

PubMed

Zadik, Yehuda; Elad, Sharon; Shapira, Anat; Shapira, Michael Y

2017-02-01

The oral mucosa is commonly involved in chronic graft-versus-host disease (cGVHD). Oral mucosal cGVHD markedly affect individual's daily function and wellbeing. In some cases, it might become a life threating complication. Areas covered: This article describes the rationale for treatment, method of topical application in the oral cavity, evidence supporting the topical administration of dexamethasone and budesonide for oral cGVHD, and their adverse effects. Expert opinion: Evidence supports the use of topical dexamethasone and budesonide for treatment of oral cGVHD. Topical corticosteroid choice for oral cGVHD, takes into consideration the potency, bioavailability, preferred concentration, and possible adverse effects. Budesonide's pharmacological characteristics mark it as a preferable topical agent for oral cGVHD.

Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

PubMed

Snäll, Johanna; Kormi, Eeva; Lindqvist, Christian; Suominen, Anna Liisa; Mesimäki, Karri; Törnwall, Jyrki; Thorén, Hanna

2013-12-01

Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation

PubMed Central

Rocksén, D; Lilliehöök, B; Larsson, R; Johansson, T; Bucht, A

2000-01-01

Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, the anti-inflammatory effects of the anti-oxidant N-acetylcysteine (NAC) and the glucocorticoid dexamethasone were investigated in mice exposed to aerosolized endotoxin (lipopolysaccharide (LPS)). Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with NAC only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). Measurement of cytokine and chemokine expression in lung tissue revealed a significant decrease of tumour necrosis factor-alpha, IL-1α, IL-1β, IL-6, IL-12p40, and MIP-1α mRNA when mice where treated with dexamethasone but not when treated with NAC. Analysis of oxidative burst demonstrated a remarkable reduction of oxygen radicals in BALF neutrophils after treatment with dexamethasone, whereas the effect of NAC was not significantly different from that in untreated animals. In conclusion, dexamethasone exerted both anti-inflammatory and anti-oxidative effects in acute airway inflammation, probably by blocking early events in the inflammatory cascade. In contrast, treatment with NAC resulted in a weak reduction of the inflammatory response but no inhibition of proinflammatory cytokines or reduction of oxidative burst in neutrophils. These results demonstrate dramatic differences in efficiency and also indicate that the two drugs have different actions. Combined treatment with NAC and dexamethasone revealed an additive action but no synergy was observed. PMID:11091282

Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis.

PubMed

Gertz, Morie A; Lacy, Martha Q; Dispenzieri, Angela; Buadi, Francis K; Dingli, David; Hayman, Suzanne R; Kumar, Shaji K; Leung, Nelson; Lust, John; Rajkumar, S Vincent; Russell, Stephen J; Suman, Vera J; Le-Rademacher, Jennifer G; Hogan, William J

2016-07-15

Autologous stem cell transplantation (SCT) is a common management strategy for select patients with immunoglobulin light-chain amyloidosis, but no trials have documented improved overall survival. Eighty-nine patients with biopsy-proven immunoglobulin light-chain amyloidosis were allowed to select treatment with melphalan plus dexamethasone (n = 34) or SCT (n = 55); all patients were transplant eligible. Treatment preference resulted in imbalanced study arms. Patients who selected SCT were younger, more frequently had an Eastern Cooperative Oncology Group performance status score less than 2, had lower-stage amyloidosis, and had a lower incidence of cardiac amyloidosis. Patients receiving melphalan plus dexamethasone had a 3-year progression-free survival rate of 29.1% and an overall survival rate of 58.8%. Patients undergoing SCT had a 3-year progression-free survival rate of 51.7% and an overall survival rate of 83.6%. An attempt to match patients between the 2 arms in terms of risk produced 24 matched triplet sets (2 SCT patients for each melphalan-dexamethasone patient); there was no difference in hematologic response, but there was better survival after autologous SCT. A propensity score-matched analysis of the cohorts (melphalan plus dexamethasone vs SCT) showed an overall mortality hazard ratio of 2.56 (P < .01). Although the study had limitations, similar hematologic responses and improved survival were observed after SCT versus melphalan plus dexamethasone. Cancer 2016;122:2197-205. © 2016 American Cancer Society. © 2016 American Cancer Society.

Parallel increase of dolichol pathway and nucleotide pyrophosphatases in rat hepatocytes by dexamethasone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarkar, M.; Mookerjea, S.

1986-05-01

Incorporation of (/sup 14/C)-mannose to dolichol phosphate mannose, dolichol pyrophosphate oligosaccharide and N-linked glycoproteins in cultured hepatocytes was increased by dexamethasone. Nucleotide pyrophosphatases are now measured to investigate possible control of glycosylation by the nucleotide sugar pools. Dexamethasone caused about 2 fold increase of UDP-GlcNAc and GDP-Man pyrophosphatase activity which is evident as early as 4 hr and increased up to 12 hr of incubation. The K/sub m/ for UDP-GlcNAc and GDP-Man were respectively 0.43 mM and 0.47 mM in homogenate membrane and the values remained unchanged by dexamethasone treatment. However the V/sub max/ of the enzymes were increased withmore » both UDP-GlcNAc and GDP-Man. The broad pH optima of the enzymes (pH 8 to 10) indicated their alkaline nature. Mixing experiments of the cell homogenates from control and dexamethasone treated cells showed that UDP-GlcNAc and GDP-Man pyrophosphatase activities were additive which ruled out the possibility of presence of any activator or removal of any inhibitor due to dexamethasone. The parallel increase of nucleotide pyrophosphatase and dolichol linked pathway by dexamethasone does not support the possibility that stimulation of glycoprotein synthesis by dexamethasone is mediated by transfer of nucleotide sugars towards dolichol saccharides.« less

Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects.

PubMed

Bordag, Natalie; Klie, Sebastian; Jürchott, Kathrin; Vierheller, Janine; Schiewe, Hajo; Albrecht, Valerie; Tonn, Jörg-Christian; Schwartz, Christoph; Schichor, Christian; Selbig, Joachim

2015-11-03

Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.

Dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide poisoning.

PubMed

Li, Q; Song, J J; Zhang, H Y; Fu, K; Lan, H B; Deng, Y

2015-01-01

We investigated dexamethasone therapy for preventing delayed encephalopathy after carbon monoxide (CO) poisoning. Eighty healthy male rats were exposed to CO and randomly divided into four groups: hyperbaric oxygen treatment (H), treatment (D), combined hyperbaric and dexamethasone treatment (C), and a control (M) group in which the rats inhaled CO to coma in the hyperbaric oxygen chamber, then were removed without further treatment. Twelve rats were put into the hyperbaric oxygen chamber and treated with air for 60 min (N) group. An eight arm maze was used to evaluate cognitive and memory abilities of these mice. Serum myelin basic protein (MBP) levels were evaluated using ELISA, and magnetic resonance imaging was used to observe brain demyelination and morbidity associated with delayed encephalopathy. A sample of the hippocampus from each group was examined by light microscopy. Cognitive and memory functions decreased in the control group M. Three days after CO poisoning, the serum MBP level of each group increased significantly. On Day 10 after CO poisoning, the MBP levels in groups C and D decreased significantly, but returned to normal on Day 18. MBP levels in the M and H groups were elevated at all time points. Brain MRIs showed significant differences among C, D, H and control M groups. Hematoxylin & eosin staining of the hippocampus showed greater damage in the control M and H groups. Early dexamethasone treatment may be useful for preventing delayed encephalopathy after CO poisoning and may reduce serum MBP levels.

Mechanisms of Dexamethasone-Mediated Inhibition of Toll-Like Receptor Signaling Induced by Neisseria meningitidis and Streptococcus pneumoniae▿

PubMed Central

Mogensen, Trine H.; Berg, Randi S.; Paludan, Søren R.; Østergaard, Lars

2008-01-01

Excessive inflammation contributes to the pathogenesis of bacterial meningitis, which remains a serious disease despite treatment with antibiotics. Therefore, anti-inflammatory drugs have important therapeutic potential, and clinical trials have revealed that early treatment with dexamethasone significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis. The inflammatory cytokine response was dependent on Toll-like receptor signaling and was strongly inhibited by dexamethasone. Activation of the NF-κB pathway was targeted at several levels, including inhibition of IκB phosphorylation and NF-κB DNA-binding activity as well as upregulation of IκBα synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae. Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis and S. pneumoniae, which may contribute to our understanding of the clinical effect and the importance of timing with respect to corticosteroid treatment during bacterial meningitis. PMID:17938219

Randomized, Controlled, Phase 2 Trial of Povidone-Iodine/Dexamethasone Ophthalmic Suspension for Treatment of Adenoviral Conjunctivitis.

PubMed

Pepose, Jay S; Ahuja, Arjun; Liu, Wenlei; Narvekar, Abhijit; Haque, Reza

2018-05-19

To evaluate the efficacy/safety of an ophthalmic suspension of povidone-iodine (PVP-I) 0.6% and dexamethasone 0.1% in patients with acute adenoviral conjunctivitis. Multicenter, randomized, vehicle-controlled, double-masked trial. Adults with a positive Rapid Pathogen Screening Adeno-Detector Plus TM test were randomized 1:1:1 to PVP-I 0.6%/dexamethasone 0.1%, PVP-I 0.6%, or vehicle, bilaterally 4 times daily for 5 days (days 1-5). Patients were evaluated on days 3, 6, and 12 (+1-day window). Efficacy measures included clinical resolution and adenoviral eradication. Overall, 144 patients were included in the efficacy analysis (PVP-I/dexamethasone, n = 48; PVP-I, n = 50; vehicle, n = 46). The proportion of patients with clinical resolution (primary study eye with last observation carried forward [LOCF]) at the day 6 visit was higher with PVP-I/dexamethasone (31.3%) than vehicle (10.9%; P = .0158) and PVP-I (18.0%; P = nonsignificant). The proportion with adenoviral eradication (primary study eye with LOCF) was higher with PVP-I/dexamethasone than vehicle at the day 3 (35.4% vs 8.7%; P = .0019) and day 6 (79.2% vs 56.5%; P = .0186) visits and versus PVP-I (day 3 visit, 32.0%; day 6 visit, 62.0%; each P = nonsignificant). Treatment-emergent adverse events (AEs) occurred in 69.0% (vehicle), 62.7% (PVP-I), and 53.4% (PVP-I/dexamethasone) of patients in the safety dataset. Discontinuation owing to AEs occurred in 37 patients (vehicle, n = 16; PVP-I, n = 12; PVP-I/dexamethasone, n = 9). PVP-I/dexamethasone appeared safe and well tolerated, and significantly improved clinical resolution and adenoviral eradication in patients with acute adenoviral conjunctivitis. Copyright © 2018. Published by Elsevier Inc.

Supra-tarsal injection of dexamethasone in the treatment of patients with refractory vernal keratoconjunctivitis.

PubMed

Lisanework, Mulu

2003-01-01

The response to supratarsal injection of dexamethasone in severe refractory vernal keratoconjunctivitis was studied in 20 patients (14 males and 6 females) at the ophthalmology department of Menelik II Hospital, Addis Ababa in 1997. Majority of the patients were in the age range of 11-20 years with mean age of 14.6 years. Although all patients experienced relief of symptoms in the first 2 days of dexamethasone injection, symptoms recurred in the majority 16 (80%) of the patients. Cobble stone papillae and limbal signs disappeared in 2 (11%) and 5 (38%) of the patients respectively. Resolution of limbal form of the disease is more dramatic when compared to the palpebral form. This study showed that supratarsal injection of dexamethasone in severe vernal keratoconjunctivitis is effective in few, partially effective in some and ineffective in many of our patients. Further studies, particularly a randomized controlled trial is recommended prior to utilization of this new therapeutic modality as a standard form of treatment in Ethiopian patients.

Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

PubMed Central

Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

2016-01-01

Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3–16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment. PMID:27362350

Preoperative dexamethasone reduces postoperative pain, nausea and vomiting following mastectomy for breast cancer

PubMed Central

2010-01-01

Background Dexamethasone has been reported to reduce postoperative symptoms after different surgical procedures. We evaluated the efficacy of preoperative dexamethasone in ameliorating postoperative nausea and vomiting (PONV), and pain after mastectomy. Methods In this prospective, double-blind, placebo-controlled study, 70 patients scheduled for mastectomy with axillary lymph node dissection were analyzed after randomization to treatment with 8 mg intravenous dexamethasone (n = 35) or placebo (n = 35). All patients underwent standardized procedures for general anesthesia and surgery. Episodes of PONV and pain score were recorded on a visual analogue scale. Analgesic and antiemetic requirements were also recorded. Results Demographic and medical variables were similar between groups. The incidence of PONV was lower in the dexamethasone group at the early postoperative evaluation (28.6% vs. 60%; p = 0.02) and at 6 h (17.2% vs. 45.8%; p = 0.03). More patients in the placebo group required additional antiemetic medication (21 vs. 8; p = 0.01). Dexamethasone treatment significantly reduced postoperative pain just after surgery (VAS score, 4.54 ± 1.55 vs. 5.83 ± 2.00; p = 0.004), at 6 h (3.03 ± 1.20 vs. 4.17 ± 1.24; p < 0.0005) and at 12 h (2.09 ± 0.85 vs. 2.54 ± 0.98; p = 0.04). Analgesics were required in more patients of the control group (21 vs. 10; p = 0.008). There were no adverse events, morbidity or mortality. Conclusions Preoperative intravenous dexamethasone (8 mg) can significantly reduce the incidence of PONV and pain in patients undergoing mastectomy with axillary dissection for breast cancer. Trial registration number NCT01116713 PMID:21182781

Effects of dexamethasone on palate mesenchymal cell phospholipase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bulleit, R.F.; Zimmerman, E.F.

1984-09-15

Corticosteroids will induce cleft palate in mice. One suggested mechanism for this effect is through inhibition of phospholipase activity. This hypothesis was tested by measuring the effects of dexamethasone, a synthetic corticosteroid, on phospholipase activity in cultures of palate mesenchymal cells. Palate mesenchymal cells were prelabeled with (3H)arachidonic acid. The cells were subsequently treated with various concentrations of dexamethasone. Concurrently, cultures of M-MSV-transformed 3T3 cells were prepared identically. After treatment, phospholipase activity was stimulated by the addition of serum or epidermal growth factor (EGF), and radioactivity released into the medium was taken as a measure of phospholipase activity. Dexamethasone (1more » X 10(-5) or 1 X 10(-4) M) could inhibit serum-stimulated phospholipase activity in transformed 3T3 cells after 1 to 24 hr of treatment. However, no inhibition of activity was measured in palate mesenchymal cells following this period of treatment. Not until 120 hr of treatment with dexamethasone (1 X 10(-4) M) was any significant inhibition of serum-stimulated phospholipase activity observed in palate mesenchymal cells. When EGF was used to stimulate phospholipase activity, dexamethasone (1 X 10(-5) M) caused an increase in phospholipase activity in palate mesenchymal cells. These observations suggested that phospholipase in transformed 3T3 cells was sensitive to inhibition by dexamethasone. However, palate mesenchymal cell phospholipase is only minimally sensitive to dexamethasone, and in certain instances can be enhanced. These results cannot support the hypothesis that corticosteroids mediate their teratogenic effect via inhibition of phospholipase activity.« less

Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice

PubMed Central

Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.

2014-01-01

Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator–activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1–Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

PubMed

Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

2016-10-01

Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level <2.0nmol/L was considered a hypersensitive response. The neurobehavioral endpoints consisted of questionnaires regarding psychosocial and sleeping problems administered before and during the course of dexamethasone (6mg/m(2)), and dexamethasone trough levels were measured during dexamethasone treatment. Patients with a hypersensitive response to dexamethasone had more behavioral problems (N=11), sleeping problems, and/or somnolence (N=12) (P<0.05 for all three endpoints). The positive predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

PubMed

Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

2014-09-01

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

Effects of Neonatal Dexamethasone Exposure on Adult Neuropsychiatric Traits in Rats

PubMed Central

Robertson, Donald; Rodger, Jennifer; Martin-Iverson, Mathew T.

2016-01-01

The effects of early life stress in utero or in neonates has long-term consequences on hypothalamic-pituitary-adrenal (HPA) stress axis function and neurodevelopment. These effects extend into adulthood and may underpin a variety of mental illnesses and be related to various developmental and cognitive changes. We examined the potential role of neonatal HPA axis activation on adult psychopathology and dopamine sensitivity in the mature rat using neonatal exposure to the synthetic glucocorticoid receptor agonist and stress hormone, dexamethasone. We utilized a comprehensive battery of assessments for behaviour, brain function and gene expression to determine if elevated early life HPA activation is associated with adult-onset neuropsychiatric traits. Dexamethasone exposure increased startle reactivity under all conditions tested, but decreased sensitivity of sensorimotor gating to dopaminergic disruption–contrasting with what is observed in several neuropsychiatric diseases. Under certain conditions there also appeared to be mild long-term changes in stress and anxiety-related behaviours with neonatal dexamethasone exposure. Electrophysiology revealed that there were no consistent neuropsychiatric abnormalities in auditory processing or resting state brain function with dexamethasone exposure. However, neonatal dexamethasone altered auditory cortex glucocorticoid activation, and auditory cortex synchronization. Our results indicate that neonatal HPA axis activation by dexamethasone alters several aspects of adult brain function and behaviour and may induce long-term changes in emotional stress-reactivity. However, neonatal dexamethasone exposure is not specifically related to any particular neuropsychiatric disease. PMID:27936175

Phase I study evaluating the safety, tolerability and pharmacokinetics of a novel oral dissolvable film containing dexamethasone versus Fortecortin dexamethasone tablets.

PubMed

Diamant, Zuzana; Samuelsson Palmgren, Gabriella; Westrin, Bengt; Bjermer, Leif

2017-01-01

Introduction : Systemic corticosteroids are anti-inflammatory agents with dexamethasone among the most potent in the class. Within (respiratory) allergy, systemic corticosteroids are usually applied in medical emergencies. In these situations, patients may experience physical or logistic problems taking tablets. To fulfil a practical unmet need for outpatients, Dexa ODF, an oral dissolvable film containing dexamethasone, was developed. Objectives : We compared the safety, tolerability and pharmacokinetics (PK) of Dexa ODF with Fortecortin tablets in healthy subjects. Methods : Thirty subjects participated in this open label, two-way, cross-over study, consisting of two treatment visits separated by 5-10 days. On both treatment visits, subjects randomly received one single dose of Dexa ODF (one strip; 8 mg dexamethasone) or one single dose of Fortecortin (two 4 mg tablets). Safety evaluations and blood sampling for PK were conducted until 48 h post-dose and bioequivalence analysis was performed on AUC(0-t), AUC(0-∞) and Cmax. Results : All subjects were dosed. Forty-five adverse events (AEs) were reported by 17 subjects and approximately 50% were deemed 'possibly treatment related' (14 on Dexa ODF; 12 on Fortecortin) with no significant difference between treatments. For all three bioequivalence parameters the 90% CIs were within the acceptance limits of bioequivalence (0.8;1.25). Conclusion : We demonstrated good tolerability and bioequivalence of Dexa ODF (8 mg dexamethasone) compared to Fortecortin tablets (2 × 4 mg dexamethasone). Dexa ODF is currently under development as an innovative treatment for use within respiratory and allergic conditions, including emergencies.

Intravitreal dexamethasone implants for the treatment of refractory scleritis combined with uveitis in adult-onset Still's disease: a case report.

PubMed

Ahn, Seong Joon; Hwang, Sun Jin; Lee, Byung Ro

2016-11-08

Adult-onset Still's disease is a systemic inflammatory disease which presents with uveitis and scleritis in the eye. Intravitreal dexamethasone implants are used for the treatment of refractory uveitis. A 19-year-old woman diagnosed to have adult-onset Still's disease for fevers, joint pain, and a salmon-colored bumpy rash presented with scleritis and uveitis in the left eye. Topical and systemic steroids with oral methotrexate failed to control the inflammation. We performed intravitreal injections of dexamethasone implants for side effects of steroid and refractory ocular inflammation. The therapy resulted in improvements in the patient's uveitis with reductions in scleral vessel engorgement and redness. There was no recurrence of uveitis or scleritis during 4 months following treatment. Intravitreal injections of dexamethasone implants may result in clinical improvements of refractory scleritis combined with uveitis.

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jonasson, Sofia, E-mail: sofia.jonasson@foi.se; Wigenstam, Elisabeth; Department of Public Health and Clinical Medicine, Unit of Respiratory Medicine, Umeå University, Umeå

Chlorine (Cl{sub 2}) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl{sub 2}-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200 ppm Cl{sub 2} during 15 min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24 h or 14 days post-exposure. A single dose of themore » corticosteroid dexamethasone (10 or 100 mg/kg) was administered intraperitoneally 1, 3, 6, or 12 h following Cl{sub 2} exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6 h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1 h was dose-dependent; high-dose significantly reduced acute airway inflammation (100 mg/kg) but not treatment with the relatively low-dose (10 mg/kg). Both doses reduced AHR 14 days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl{sub 2} exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl{sub 2} exposure. - Highlights: • Inhalation of Cl{sub 2} may lead to a long-standing airway hyperresponsiveness. • The symptoms in Cl{sub 2}-exposed mice are similar to those described for RADS in humans. • Corticosteroids prevent delayed symptoms such as

Early treatment of chlorine-induced airway hyperresponsiveness and inflammation with corticosteroids.

PubMed

Jonasson, Sofia; Wigenstam, Elisabeth; Koch, Bo; Bucht, Anders

2013-09-01

Chlorine (Cl2) is an industrial gas that is highly toxic and irritating when inhaled causing tissue damage and an acute inflammatory response in the airways followed by a long-term airway dysfunction. The aim of this study was to evaluate whether early anti-inflammatory treatment can protect against the delayed symptoms in Cl2-exposed mice. BALB/c mice were exposed by nose-only inhalation using 200ppm Cl2 during 15min. Assessment of airway hyperresponsiveness (AHR), inflammatory cell counts in bronchoalveolar lavage, occurrence of lung edema and lung fibrosis were analyzed 24h or 14days post-exposure. A single dose of the corticosteroid dexamethasone (10 or 100mg/kg) was administered intraperitoneally 1, 3, 6, or 12h following Cl2 exposure. High-dose of dexamethasone reduced the acute inflammation if administered within 6h after exposure but treated animals still displayed a significant lung injury. The effect of dexamethasone administered within 1h was dose-dependent; high-dose significantly reduced acute airway inflammation (100mg/kg) but not treatment with the relatively low-dose (10mg/kg). Both doses reduced AHR 14days later, while lung fibrosis measured as collagen deposition was not significantly reduced. The results point out that the acute inflammation in the lungs due to Cl2 exposure only partly is associated with the long-term AHR. We hypothesize that additional pathogenic mechanisms apart from the inflammatory reactions contribute to the development of long-term airway dysfunction. By using this mouse model, we have validated early administration of corticosteroids in terms of efficacy to prevent acute lung injury and delayed symptoms induced by Cl2 exposure. Copyright © 2013 Elsevier Inc. All rights reserved.

The effects of Dexamethasone on sleep in young children with Acute Lymphoblastic Leukemia

PubMed Central

Rosen, Gerald; Harris, Anne K.; Liu, Meixia; Dreyfus, Jill; Krueger, James; Messinger, Yoav H.

2016-01-01

Purpose Corticosteroids, which are a mainstay in the treatment of acute lymphoblastic leukemia (ALL), have a well-documented adverse effect on sleep. We sought to characterize the effects of dexamethasone on sleep over an entire 28-day treatment cycle using actigraphy, an objective measure of sleep. Methods The sleep of 25 children aged 2–9 years (mean 4.5 years) with ALL treated with dexamethasone were evaluated during maintenance chemotherapy using a within-subject experimental design, actigraphy, and standardized questionnaires to assess sleep, sleep problems, and fatigue. Results During the five days of dexamethasone treatment, sleep time increased during the night (535 vs. 498 min; p = 0.004) and daytime napping increased the following day (14 vs. 0 min; p = 0.002), and the number of wake episodes during the night was lower (14 vs. 20; p = ≤ 0.001). However, when assessed individually, sleep-onset time, efficiency, and wake after sleep onset during the night were unchanged during dexamethasone treatment; when the cumulative effect of all of these factors was assessed, there was a statistically and clinically significant increase in nighttime sleep duration during dexamethasone treatment. Conclusions During the five days of treatment with dexamethasone, an increase in nighttime sleep as well as daytime napping was observed in young children with ALL. The increases in sleep duration return to baseline one day after the discontinuation of dexamethasone. PMID:25799940

Early Retinal and Choroidal Coat Thickness Changes After Intravitreal Dexamethasone Implant Injection for Diabetic Macular Edema.

PubMed

Horozoğlu, Fatih; Sever, Özkan

2018-06-05

Intravitreal steroid injection is one of the treatment choices in diabetic macular edema (DME). Dexamethasone (Dx) implant is the most novel form of intravitreal steroid therapy. Macular thickness improvement is well known effect of Dx implant however; subfoveal choroidal coat thickness (SFCT) changes need to be investigated. To evaluate the early central macular thickness (CMT) and SFCT alterations after single dose dexamethasone implant injection in DME. Retrospective cross-sectional study. We identified 29 patients with DME (29 eyes) who underwent optical coherence tomography (OCT) and fundus fluoroscein angiography (FFA). All patients received a single dose intravitreal Dx implant and were followed for CMT and SFCT alterations for the post-injection first hour, first day, first week, first month and third month. The preoperative mean CMT and SFCT measurements were 592.3±122.3 (412-879) μm and 264.8±53.7 (165-397) μm, respectively. CMT measurements significantly decreased from the first hour (p<0.050) and kept decreasing till 3 month (p<0.001); while SFCT decrement was just significant at the first day (p<0.05). When we compared the decrease in SFCT and CMT, 1 hour was similar, however not significant, 1.5% SFCT and 5% CMT decrease was, respectively (p>0.050). CMT decrease rate was significantly higher than SFCT at 1 day, 1 week, 1 month and 3 month (p<0.001). Intravitreal Dx implant has got a meaningful effect on CMT in patients with DME while SFCT decreases significantly at first hour and first day.

Effects of a glucocorticoid receptor agonist, dexamethasone, on fathead minnow reproduction, growth, and development.

PubMed

LaLone, Carlie A; Villeneuve, Daniel L; Olmstead, Allen W; Medlock, Elizabeth K; Kahl, Michael D; Jensen, Kathleen M; Durhan, Elizabeth J; Makynen, Elizabeth A; Blanksma, Chad A; Cavallin, Jenna E; Thomas, Linnea M; Seidl, Sara M; Skolness, Sarah Y; Wehmas, Leah C; Johnson, Rodney D; Ankley, Gerald T

2012-03-01

Synthetic glucocorticoids are pharmaceutical compounds prescribed in human and veterinary medicine as anti-inflammatory agents and have the potential to contaminate natural watersheds via inputs from wastewater treatment facilities and confined animal-feeding operations. Despite this, few studies have examined the effects of this class of chemicals on aquatic vertebrates. To generate data to assess potential risk to the aquatic environment, we used fathead minnow 21-d reproduction and 29-d embryo-larvae assays to determine reproductive toxicity and early-life-stage effects of dexamethasone. Exposure to 500 µg dexamethasone/L in the 21-d test caused reductions in fathead minnow fecundity and female plasma estradiol concentrations and increased the occurrence of abnormally hatched fry. Female fish exposed to 500 µg dexamethasone/L also displayed a significant increase in plasma vitellogenin protein levels, possibly because of decreased spawning. A decrease in vitellogenin messenger ribonucleic acid (mRNA) expression in liver tissue from females exposed to the high dexamethasone concentration lends support to this hypothesis. Histological results indicate that a 29-d embryo-larval exposure to 500 µg dexamethasone/L caused a significant increase in deformed gill opercula. Fry exposed to 500 µg dexamethasone/L for 29 d also exhibited a significant reduction in weight and length compared with control fry. Taken together, these results indicate that nonlethal concentrations of a model glucocorticoid receptor agonist can impair fish reproduction, growth, and development. Copyright © 2011 SETAC.

Inhibition of EGR-1 and NF-kappa B gene expression by dexamethasone during phorbol ester-induced human monocytic differentiation.

PubMed

Hass, R; Brach, M; Gunji, H; Kharbanda, S; Kufe, D

1992-10-20

The treatment of human myeloid leukemia cells (HL-60, U-937, THP-1) with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with growth arrest and appearance of a differentiated monocytic phenotype. While previous studies have reported that the glucocorticoid dexamethasone blocks phenotypic characteristics of monocytic differentiation, we demonstrated in the present work that dexamethasone delays the effects of TPA on the loss of U-937 cell proliferation. We also demonstrated that this glucocorticoid inhibits TPA-induced increases in expression of the EGR-1 early response gene. The results of nuclear run-on assays and half-life experiments indicated that this effect of dexamethasone is regulated at the post-transcriptional level. Similar studies were performed for the NF-kappa B gene. While TPA treatment was associated with transient increases in NF-kappa B mRNA levels, this induction was blocked by dexamethasone. In contrast, dexamethasone had no significant effect on the activation of pre-existing NF-kappa B protein as determined in DNA-binding assays. Taken together, these findings suggest that the activated glucocorticoid receptor inhibits signaling pathways which include expression of the EGR-1 and NF-kappa B genes and that such effects may contribute to a block in TPA-induced monocytic differentiation.

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

PubMed

Sivaprasad, S; Patra, S; DaCosta, J; Adewoyin, T; Shona, O; Pearce, E; Chong, N V

2011-01-01

To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 μg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 μm. Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 μm (±75). This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD. Copyright © 2011 S. Karger AG, Basel.

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish

PubMed Central

Wilson, K S; Tucker, C S; Al-Dujaili, E A S; Holmes, M C; Hadoke, P W F; Kenyon, C J

2016-01-01

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head–trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared ‘bolder’ than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and

Dexamethasone and Long-Term Outcome of Tuberculous Meningitis in Vietnamese Adults and Adolescents

PubMed Central

Török, M. Estée; Bang, Nguyen Duc; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Thwaites, Guy E.; Thi Quy, Hoang; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Thi Thanh Hoang, Hoang; Wolbers, Marcel; Farrar, Jeremy J.

2011-01-01

Background Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown. Methods Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability. Results 545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32). Conclusions Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM. Trial Registration ClinicalTrials.gov NCT01317654 NCT01317654?term = tuberculous+meningitis&rank = 3 PMID:22174748

Impact of dexamethasone in patients with aneurysmal subarachnoid haemorrhage.

PubMed

Czorlich, P; Sauvigny, T; Ricklefs, F; Abboud, T; Nierhaus, A; Vettorazzi, E; Reuter, D A; Regelsberger, J; Westphal, M; Schmidt, N O

2017-04-01

The role of corticosteroids in the treatment of patients with aneurysmal subarachnoid haemorrhage (SAH) has remained controversial for decades. Recent studies have suggested that the administration of corticosteroids in SAH patients is associated with favourable outcomes. Given their significant adverse effects, it is essential to identify those patients who will benefit from treatment with corticosteroids. A retrospective analysis of a prospectively collected cohort (n = 306) with SAH who were treated by microsurgical clipping or endovascular intervention was performed. The role of dexamethasone administration was analysed with regard to clinical conditions and SAH-related complications. Outcome was assessed at discharge and during follow-up using the Glasgow Outcome Scale (GOS). Patients treated with dexamethasone presented with more episodes of hyperglycaemia (P < 0.001), more overall infections (P < 0.001) and more ventriculostomy-related infections (P = 0.004). Multivariate analysis demonstrated that treatment with dexamethasone was associated with an unfavourable outcome at discharge (GOS 1-3) [odds ratio (OR) 2.814, 95% confidence interval (CI) 1.440-5.497, P = 0.002]. In the subgroup of microsurgically treated patients, dexamethasone administration was associated with a favourable outcome at follow-up (OR 0.193, 95% CI 0.06-0.621, P = 0.006). A higher risk for unfavourable outcome (OR 3.382, 95% CI 1.67-6.849, P = 0.001) at discharge was observed in endovascularly treated patients who received dexamethasone but this had no impact on the outcome at follow-up. Treatment with dexamethasone seems to be associated with a risk reduction for an unfavourable outcome in those patients who underwent microsurgical clipping. Despite an increased frequency of adverse effects, glucocorticoids may have a potential benefit in this specific surgical subgroup compared to endovascularly treated SAH patients. © 2017 EAN.

Mechanisms of dexamethasone-induced disturbed sleep and fatigue in paediatric patients receiving treatment for ALL.

PubMed

Vallance, Kelly; Liu, Wei; Mandrell, Belinda N; Panetta, John C; Gattuso, Jami S; Hockenberry, Marilyn; Zupanec, Sue; Yang, Lei; Yang, Jie; Hinds, Pamela S

2010-07-01

Dexamethasone contributes to high cure rates in paediatric acute lymphoblastic leukaemia (ALL) but significantly and adversely alters sleep and fatigue. Herein we explored three mechanisms (pharmacokinetics, serum albumin and pharmacogenetics) through which dexamethasone may cause debilitating fatigue and disrupted sleep. We enrolled 100 patients on a 10-d study: 5-d of no dexamethasone (OFF DEX) followed by 5-d of dexamethasone (ON DEX) during continuation chemotherapy. Sleep variables were collected with continuous actigraphy on days 1 through 5, both OFF DEX and ON DEX. On days 2 and 5 of each 5-d period, parents and patients 7 years of age and older completed a sleep diary and Fatigue Scale questionnaire. Blood was collected at 0 (pre-dexamethasone), 1, 2, 4 and 8 h after the first oral dexamethasone dose for pharmacokinetic analysis. Serum albumin concentration was retrospectively analysed in stored samples. Patient DNA was genotyped for 99 polymorphic loci in candidate genes associated with glucocorticoid metabolism. Dexamethasone clearance was significantly greater in younger patients than in older ones and in lower risk patients. In multiple regression models, risk group was significantly related to pharmacokinetic parameters. We found that polymorphisms in three genes (AHSG, IL6, POLDIP3) were significantly associated with sleep measures but not with fatigue. Risk group had the most significant relationship with disrupted sleep in patients while on dexamethasone. Serum albumin levels had neither a direct relationship with sleep or fatigue variables nor an indirect relationship through systemic exposure to dexamethasone. We identified candidate genes that may help explain the adverse events of disrupted sleep in paediatric patients receiving dexamethasone. Copyright 2010 Elsevier Ltd. All rights reserved.

[The effect of antiinflammatory therapy with dexamethasone and dexamethasone with pentoxifylline on the course of bacterial meningitis].

PubMed

Bociaga-Jasik, Monika; Kalinowska-Nowak, Anna; Garlicki, Aleksander; Mach, Tomasz

2003-01-01

Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high. The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF). 42 patients with the BM were analysed. They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline. Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF. However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM. In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A. Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01). Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed. In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%). Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases. In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them. Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths.

Dexamethasone treatment and prognostic factors in community-acquired bacterial meningitis: a Danish retrospective population-based cohort study.

PubMed

Bodilsen, Jacob; Dalager-Pedersen, Michael; Schønheyder, Henrik Carl; Nielsen, Henrik

2014-06-01

The morbidity and mortality in community-acquired bacterial meningitis (CABM) remain substantial and treatment outcomes and predictors of a poor prognosis must be assessed regularly. We aimed to describe the outcome of patients with CABM treated with dexamethasone and to assess the performance of the Dutch Meningitis Risk Score (DMRS). We retrospectively evaluated all adults with CABM in North Denmark Region, 1998-2012. Outcomes included in-hospital mortality and Glasgow Outcome Scale (GOS) score. A GOS score of 5 was categorized as a favourable outcome and scores of 1-4 as unfavourable. We used logistic analysis to compute relative risks (RRs) with 95% confidence intervals (CIs) for an unfavourable outcome adjusted for age, sex, and comorbidity. We identified a total of 172 cases of CABM. In-hospital mortality was unaffected by the implementation of dexamethasone in 2003 (19% vs 20%). Dexamethasone treatment was associated with a prompt diagnosis of meningitis and a statistically insignificant decrease in the risk of an unfavourable outcome (33% vs 53%; adjusted RR 0.64, 95% CI 0.41-1.01) and in-hospital mortality (15% vs 24%; adjusted RR 0.72, 95% CI 0.35-1.48). Of the risk factors included in the DMRS, we found age and tachycardia to be significantly associated with an unfavourable outcome in the multivariate analyses. Patients treated with dexamethasone were more likely to have a favourable outcome, although statistical significance was not reached. Several parameters included in the Dutch risk score were also negative predictors in our cohort, although the entire risk score could not be validated due to a lack of data.

Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study.

PubMed

Yared, J P; Starr, N J; Hoffmann-Hogg, L; Bashour, C A; Insler, S R; O'Connor, M; Piedmonte, M; Cosgrove, D M

1998-10-01

Shivering after cardiac surgery is common, and may be a result of intraoperative hypothermia. Another possible etiology is fever and chills secondary to activation of the inflammatory response and release of cytokines by cardiopulmonary bypass. Dexamethasone decreases the gradient between core and skin temperature and modifies the inflammatory response. The goal of this study was to determine whether dexamethasone can reduce the incidence of shivering. Two hundred thirty-six patients scheduled for elective coronary and/or valvular surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or placebo after the induction of anesthesia. All patients received standard monitoring and anesthetic management. After arrival in the intensive care unit (ICU), nurses unaware of the treatment groups recorded visible shivering, as well as skin and pulmonary artery temperatures. Analysis of shivering rates was performed by using chi2 tests and logistic regression analysis. Compared with placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P = 0.001). It was an independent predictor of reduced incidence of shivering and was also associated with a higher skin temperature on ICU admission and a lower central temperature in the early postoperative period. Dexamethasone is effective in decreasing the incidence of shivering. The effectiveness of dexamethasone is independent of temperature and duration of cardiopulmonary bypass. Shivering after cardiac surgery may be part of the febrile response that occurs after release of cytokines during cardiopulmonary bypass.

Dexamethasone Ophthalmic

MedlinePlus

... stopping to breast-feed if you use dexamethasone eye drops.tell your doctor if you wear soft contact lenses. If the brand of dexamethasone you are using contains benzalkonium chloride, wait at least 15 minutes after using the medicine to put in soft contact lenses.

Association between posttest dexamethasone and cortisol concentrations in the 1 mg overnight dexamethasone suppression test.

PubMed

Asvold, Bjørn O; Grill, Valdemar; Thorstensen, Ketil; Bjørgaas, Marit R

2012-11-01

It has been suggested that comparison of posttest dexamethasone and cortisol concentrations may improve the evaluation of the dexamethasone suppression test (DST) for Cushing's syndrome. In particular, this would be reasonable if posttest cortisol differs by dexamethasone levels within the range that is usually attained in the DST. Using fractional polynomial regression, we therefore studied the association between posttest 0800 h dexamethasone and cortisol levels in 53 subjects without Cushing's syndrome who were tested with the 1 mg overnight DST. Plasma dexamethasone was associated with plasma cortisol (P<0.001), and the regression line suggested a strong negative association related to dexamethasone levels <5 nmol/l. However, among the 94% of subjects with plasma dexamethasone >5.0 nmol/l, there was no association between dexamethasone and cortisol levels (P=0.55). In conclusion, subjects tested with the 1 mg overnight DST usually attain an 0800 h plasma dexamethasone >5 nmol/l, and plasma cortisol does not differ by plasma dexamethasone in these subjects. This suggests that routine comparison of dexamethasone and cortisol levels may not be a useful approach to improve the performance of the 1 mg DST. However, dexamethasone measurements may identify subjects with inadequately low plasma dexamethasone and may therefore be of value when retesting subjects with possibly false-positive DST results.

Association between posttest dexamethasone and cortisol concentrations in the 1 mg overnight dexamethasone suppression test

PubMed Central

Åsvold, Bjørn O; Grill, Valdemar; Thorstensen, Ketil; Bjørgaas, Marit R

2012-01-01

It has been suggested that comparison of posttest dexamethasone and cortisol concentrations may improve the evaluation of the dexamethasone suppression test (DST) for Cushing's syndrome. In particular, this would be reasonable if posttest cortisol differs by dexamethasone levels within the range that is usually attained in the DST. Using fractional polynomial regression, we therefore studied the association between posttest 0800 h dexamethasone and cortisol levels in 53 subjects without Cushing's syndrome who were tested with the 1 mg overnight DST. Plasma dexamethasone was associated with plasma cortisol (P<0.001), and the regression line suggested a strong negative association related to dexamethasone levels <5 nmol/l. However, among the 94% of subjects with plasma dexamethasone >5.0 nmol/l, there was no association between dexamethasone and cortisol levels (P=0.55). In conclusion, subjects tested with the 1 mg overnight DST usually attain an 0800 h plasma dexamethasone >5 nmol/l, and plasma cortisol does not differ by plasma dexamethasone in these subjects. This suggests that routine comparison of dexamethasone and cortisol levels may not be a useful approach to improve the performance of the 1 mg DST. However, dexamethasone measurements may identify subjects with inadequately low plasma dexamethasone and may therefore be of value when retesting subjects with possibly false-positive DST results. PMID:23781306

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

PubMed

Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

Dexamethasone PONV prophylaxis alters the hypothalamic-pituitary-adrenal axis after transsphenoidal pituitary surgery.

PubMed

Burkhardt, Till; Rotermund, Roman; Schmidt, Nils-Ole; Kiefmann, Rainer; Flitsch, Jörg

2014-07-01

Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 μg/L (range, 39 to 427) and a postoperative median of 87 μg/L (range, 10 to 733; P=0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 μg/L (range, 10 to 387) and postoperative levels of 273 μg/L (range, 10 to 1352; P<0.001). As early postoperative blood checks of the cortisol levels yield important information about potential pituitary sufficiency after transsphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered.

GSK-3β mediates dexamethasone-induced pancreatic β cell apoptosis

PubMed Central

Guo, Bin; Zhang, Wenjian; Xu, Shiqing; Lou, Jinning; Wang, Shuxia; Men, Xiuli

2015-01-01

Aims Glucocorticoids, such as dexamethasone, are widely used anti-inflammatory drugs. Their use is frequently associated with the development of steroid- associated diabetes. Pancreatic β-cell dysfunction has been suggested to be one of the main causes of steroid-associated diabetes. However, the mechanism is not fully understood. Glycogen synthase kinase-3β (GSK-3β) is a multifunctional serine/threonine kinase and plays an important role in energy metabolism, cell growth and apoptosis. Therefore, the contribution of GSK-3β in dexamethasone-induced pancreatic β-cell apoptosis was determined in the present study. Main Methods The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress (ROS), and the phosphorylation status of GSK-3β was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride (LiCl) on dexamethasone-induced β-cell apoptosis was also evaluated. Key Findings Dexamethasone (0.1 μM) treatment induced INS-1 apoptosis, which was associated with increased GSK-3β activation and increased NOX4-derived ROS generation. Pretreatment of INS-1 with LiCl inhibited dexamethasone induced ROS generation and INS-1 apoptosis. Significance This study provides a new mechanism of Dex induced pancreatic β cell apoptosis and may serve as a new therapeutic option for treating GCs induced diabetes. PMID:26606859

Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene

PubMed Central

Gay, Maresha S.; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela

2016-01-01

Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. PMID:27302109

Intratympanic dexamethasone versus high dosage of betahistine in the treatment of intractable unilateral Meniere disease.

PubMed

Albu, Silviu; Chirtes, Felician; Trombitas, Veronica; Nagy, Alina; Marceanu, Luigi; Babighian, Gregorio; Trabalzini, Franco

2015-01-01

The objective of our randomized, double-blind study was to compare the effectiveness of intratympanic (IT) dexamethasone versus high-dosage of betahistine in the treatment of patients with intractable unilateral Meniere disease (MD). Sixty six patients with definite unilateral MD were randomly divided in two groups: Group A received a combination of IT dexamethasone (DX) and identical-appearing placebo pills while Group B received a combination of high-dosage betahistine and IT saline. Intratympanic injections were repeated for three times with an interlude of 3days. High-dosage of betahistine entailed 144mg/day. Mean outcome measures consisted of vertigo control, pure tone average (PTA), speech discrimination score, Functional Level Score, Dizziness Handicap Inventory and Tinnitus Handicap Inventory. Fifty nine patients completed the study and were available at 12months for analysis. In Group A complete vertigo control (class A) was attained in 14 patients (46.6%) and substantial control (class B) in 7 patients (20%). In Group B, 12 patients (41%) achieved complete vertigo control (class A), 5 patients (17%) substantial control (class B). There is no statistical difference in vertigo control between the two treatment groups. In Group A hearing was unchanged in 14 patients and improved in 4 patients, while in Group B hearing was unchanged in 16 patients and improved in 2 patients. Our preliminary results demonstrate that high-dosage of betahistine achieved similar outcomes as IT dexamethasone in the control of vertigo and hearing preservation. Copyright © 2015 Elsevier Inc. All rights reserved.

Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

NASA Technical Reports Server (NTRS)

Max, Stephen R.; Konagaya, Masaaki; Konagaya, Yoko; Thomas, John W.; Banner, Carl; Vitkovic, Ljubisa

1986-01-01

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy.

The suppression of radiation-induced NF-{kappa}B activity by dexamethasone correlates with increased cell death in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Seon Young; Chung, Hee-Yong

2005-10-21

In this study, we show that dexamethasone treatment increases ionizing radiation-induced cell death by inducing the inhibitory {kappa}B{alpha} (I{kappa}B{alpha}) pathway in mice. The effect of dexamethasone on radiation-induced cell death was assessed by changes in total spleen cellularity and bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) contents after total body irradiation. While in vivo treatment of mice with dexamethasone alone (1 mg/kg/day, for 2 days) failed to elicit cell death in spleen cells, the combined treatment with dexamethasone (1 mg/kg/day, for 2 days) and {gamma}-rays (1 or 5 Gy) caused a 50-80% reduction in total cellularity in spleen and CFU-GM contents inmore » bone marrow. These results demonstrate that dexamethasone has a synergistic effect on radiation-induced cellular damages in vivo. Immunoblot analysis showed that dexamethasone treatment significantly increases I{kappa}B{alpha} expression in the spleens of irradiated mice. In addition, the dexamethasone treatment significantly reduced radiation-induced nuclear translocation of the nucleus factor-{kappa}B in the spleens of irradiated mice. These results indicate that dexamethasone treatment in vivo may increase radiation-induced cell damages by increasing I{kappa}B{alpha} expression in hematopoietic organs such as spleen and bone marrow.« less

Dexamethasone in unexplained infertility.

PubMed

Moradan, Sanam; Ghorbani, Raheb

2009-08-01

To determine if dexamethasone could be a suitable option in the treatment of patients with unexplained infertility. This study was carried out in the Obstetrics Department of Amir University Hospital, Semnan, Iran, from April 2001 to May 2008. One hundred and twenty-four cases of unexplained infertility that underwent ovulation induction and intrauterine insemination (IUI) (only one cycle) were evaluated, and divided into 2 groups. Sixteen cases were excluded, as they were unresponsive to the induction ovulation regimen. Group I (n=42) received clomiphene citrate (CC) + dexamethasone, and the control group (group II, n=66) received CC alone. These groups were the same in age, duration of infertility, and body mass index. The clinical pregnancy rates were evaluated in 2 groups by using statistical tests. The clinical pregnancy rate was 21.4% in group I, and 4.5% in group II. There was a significant statistical difference between the groups (relative risk=4.71, 95% confidence interval=1.35-16.42, p=0.0085). The pregnancy rate in women with unexplained infertility that underwent ovulation induction with CC + dexamethasone + IUI was significantly higher than those who underwent ovulation induction with CC alone + IUI.

INTRAVITREAL DEXAMETHASONE IMPLANT AS ADJUVANT TREATMENT FOR BEVACIZUMAB- AND RANIBIZUMAB-RESISTANT NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Prospective Pilot Study.

PubMed

Barikian, Anita; Salti, Haytham; Safar, Ammar; Mahfoud, Ziyad R; Bashshur, Ziad F

2017-07-01

To study the benefit of intravitreal dexamethasone implant in the management of neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. Patients with persistent macular fluid on optical coherence tomography despite monthly treatment with at least three consecutive bevacizumab injections followed by at least three ranibizumab injections were prospectively enrolled. A single dexamethasone implant was administered followed by intravitreal ranibizumab 1 week later. Ranibizumab was continued afterward on an as-needed basis. Main outcomes were improvement in central retinal thickness and best-corrected visual acuity. Nineteen patients (19 eyes) were enrolled. There was no significant change in best-corrected visual acuity over 6 months. Greatest reduction in mean central retinal thickness, from 295.2 μm to 236.2 μm, occurred 1 month after dexamethasone implant (P < 0.0001). By Month 6, mean central retinal thickness was 287.3 μm (P = 0.16). Eyes with only intraretinal fluid (13 eyes) achieved a fluid-free macula. Eyes with predominantly subretinal fluid (6 eyes) did not improve central retinal thickness and continued monthly ranibizumab. Mean baseline intraocular pressure was 13.2 mmHg, which peaked at 15.6 mmHg by Month 2 (P = 0.004). Intravitreal dexamethasone implant improved only macular intraretinal fluid in eyes with neovascular age-related macular degeneration resistant to bevacizumab and ranibizumab. However, this treatment had a limited duration.

Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma.

PubMed

Baertsch, Marc-Andrea; Schlenzka, Jana; Mai, Elias K; Merz, Maximilian; Hillengaß, Jens; Raab, Marc S; Hose, Dirk; Wuchter, Patrick; Ho, Anthony D; Jauch, Anna; Hielscher, Thomas; Kunz, Christina; Luntz, Steffen; Klein, Stefan; Schmidt-Wolf, Ingo G H; Goerner, Martin; Schmidt-Hieber, Martin; Reimer, Peter; Graeven, Ullrich; Fenk, Roland; Salwender, Hans; Scheid, Christof; Nogai, Axel; Haenel, Mathias; Lindemann, Hans W; Martin, Hans; Noppeney, Richard; Weisel, Katja; Goldschmidt, Hartmut

2016-04-25

Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and--in absence of available stem cells from earlier harvesting--undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3(rd) (arm A + B) and the 5(th) lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary

Transcriptional activation of the lipoprotein lipase gene in macrophages by dexamethasone.

PubMed

Domin, W S; Chait, A; Deeb, S S

1991-03-12

The effect of dexamethasone on lipoprotein lipase (LPL) gene expression during macrophage differentiation was investigated by using the human monocytic leukemia cell line THP-1 and human monocyte-derived macrophages. Addition of dexamethasone to THP-1 cells increased steady-state levels of LPL mRNA and LPL mass accumulation in the medium during PMA-induced differentiation by 4-fold. Studies with human monocyte-derived macrophages showed a similar effect of dexamethasone on LPL expression. Peak LPL mRNA levels were achieved 24-h post-dexamethasone addition to THP-1 cells. Optimal stimulation of LPL mRNA occurred when dexamethasone was added 24 h after induction with PMA. Thereafter, there was rapid decline in responsiveness to dexamethasone. Induction of LPL mRNA in THP-1 cells was completely blocked by actinomycin D, suggesting that induction was transcription dependent. The stability of LPL mRNA was not influenced by dexamethasone. Treatment of THP-1 cells with PMA led to a 2-fold increase in specific binding of dexamethasone and a 4-fold increase in glucocorticoid receptor mRNA within 12 h. Thus, dexamethasone stimulates LPL gene expression during differentiation of human macrophages, a process that involves induction of glucocorticoid receptor synthesis and activation.

Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

PubMed

Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

2016-08-01

Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. Copyright © 2016 by The American Society for Pharmacology and

Comparison of early dexamethasone retreatment versus standard dexamethasone regimen combined with PRN ranibizumab in diabetic macular edema.

PubMed

Arıkan Yorgun, Mücella; Toklu, Yasin; Mutlu, Melek

2017-02-01

The purpose of the study is to evaluate the efficacy and safety of as-needed dexamethasone (DEX) retreatment compared with standard DEX retreatment combined with PRN ranibizumab injections among patients with persistent diabetic macular edema (DME). Twenty-eight patients with persistent macular edema having recurrence earlier than 6 months after initial DEX implantation were included in this retrospective study. Group I consisted of 13 patients retreated using monthly PRN ranibizumab injections combined with standard 6-monthly DEX implantation; Group II consisted of 15 patients retreated with DEX implantation earlier than 6 months on an "as-needed" basis. There was no significant difference between the groups with regarding to age, gender, HbA1C levels, duration of diabetes, duration of macular edema, baseline central macular thickness (CMT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) values (p > 0.05). The mean follow-up time of the whole study population was 10.13 ± 1.75 months (range 9-15). The mean CMT values were significantly decreased in both groups compared to baseline values except for the 6th-month CMT in Group I (p < 0.05). The mean logMAR BCVA values were not statistically different between groups during the follow-up compared to baseline BCVA values (p > 0.05). However, a significant change in mean BCVA from baseline was seen at 4th, 6th, and 9th months in Group II (p ≤ 0.05). The mean number of total intravitreal treatments was 3.50 ± 0.77 in Group I and 2.53 ± 0.51 in Group II (p = 0.001). During the follow-up period, one patient in Group I and five patients in Group II had increased IOP (≥25 mmHg). Early DEX retreatment improved vision with superior anatomical improvement at 6th month and with fewer intravitreal treatments in eyes with DME. However, improvement in visual acuity is similar with standard DEX retreatment combined with PRN ranibizumab group.

The protective effect of intratympanic dexamethasone on streptomycin ototoxicity in rats.

PubMed

Gül, Aylin; Şengül, Engin; Yılmaz, Beyhan; Özkurt, Fazıl Emre; Akdağ, Mehmet; Keleş, Ayşenur; Topçu, İsmail

2017-06-01

The purpose of this experimental study was to investigate the protective role of intratympanically administered dexamethasone on the inner ears of rats that were exposed to streptomycin ototoxicity. Twenty-four adult Wistar albino rats were separated into 4 groups: Group 1 (only streptomycin), Group 2 (only intratympanic dexamethasone), Group 3 (streptomycin and intratympanic dexamethasone), and Group 4 (streptomycin and intratympanic saline). All rats were evaluated with distortion product otoacoustic emissions (DPOAE) tests before the start of treatment and on the day it ended. On the 45th day, after the final DPOAE tests, animals of all groups were sacrificed under general anesthesia. The differences between the amplitudes of DPOAE results were determined, and hearing results were statistically analyzed. Also, the cochleas of each rat were histopathologically evaluated under a light microscope with hematoxylin and eosin staining. In the intratympanic dexamethasone group it was observed that cochlear hair cells were mostly protected. No significant difference was seen between the DPOAE results before and after treatment (p >0.05). On the other hand, loss was observed in the hearing functions and hair cells of the rats that received streptomycin and streptomycin plus intratympanic saline (p <0.05). In the streptomycin plus intratympanic dexamethasone group, the cochlear hair cells were partially protected. A significant difference was observed when the DPOAE results (DP-grams) of the streptomycin plus intratypmanic dexamethasone group were compared to those of the streptomycin plus intratympanic saline group (p <0.05). After the experimental study, ototoxic effects of the administration of streptomycin and intratympanic dexamethasone were observed on the rats' cochlear hair cells. We conclude that intratympanic dexamethasone has protective effects against this cochlear damage in rats.

Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach.

PubMed

Giovannini, Alfonso; Parravano, Mariacristina; Ricci, Federico; Bandello, Francesco

2018-06-01

Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti-vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti-vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti-vascular endothelial growth factor therapy. While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.

Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia.

PubMed

Dehghan-Nayeri, Nasrin; Eshghi, Peyman; Pour, Kourosh Goudarzi; Rezaei-Tavirani, Mostafa; Omrani, Mir Davood; Gharehbaghian, Ahmad

2017-07-01

Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE-MALDI-TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which

Treatment of adenoviral keratoconjunctivitis with a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study.

PubMed

Kovalyuk, Natalya; Kaiserman, Igor; Mimouni, Michael; Cohen, Ornit; Levartovsky, Shmuel; Sherbany, Hilda; Mandelboim, Michal

2017-12-01

To determine the efficacy of combination povidone-iodine (PVP-I) 1.0% eyedrops and dexamethasone 0.1% eyedrops in the treatment of adenoviral keratoconjunctivitis. In a prospective, randomized, controlled, double-blinded clinical trial patients with recent adenoviral keratoconjunctivitis (diagnosed clinically and confirmed by PCR), we randomly divided into three treatment groups: study group - received PVP-I 1.0% and dexamethasone 0.1%, control 1 group - received dexamethasone 0.1% and control 2 group - received lubricating eyedrops (hypromellose 0.3%). The treatment was administered four times a day in each group. All patients were examined and filled a questionnaire before treatment and on the 3rd, 5th and 7th days of treatment. We included in the study 78 eyes (26 in each group). Adenovirus type 8 was the most common pathogen (83% of cases). The fastest improvement in patients red eyes, discharge, superficial punctate keratitis and pseudomembranes was observed in the study group (p < 0.001). Those patients reached a near complete recovery in 5-7 days, which was also confirmed by reduction in Adenovirus titres by PCR. The slowest improvement was in the control 2 group. Subepithelial infiltrates (SEI) were observed in 44% of the control 1 group, 20% of the control 2 group and in 0% of the study group. The rate of reduction in Adenovirus titres was the slowest in the control 1 group. The combination of PVP-I 1.0% and dexamethasone 0.1% four times a day can reduce symptoms and expedite recovery in epidemic keratoconjunctivitis patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis

PubMed Central

Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael

2014-01-01

Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc −; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage. PMID:24714627

Icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone.

PubMed

Liu, Weidong; Mao, Li; Ji, Feng; Chen, Fengli; Wang, Shouguo; Xie, Yue

2017-01-10

The potential effect of icariside II on dexamethasone-induced osteoblast cell damages was evaluated here. In MC3T3-E1 osteoblastic cells and the primary murine osteoblasts, co-treatment with icariside II dramatically attenuated dexamethasone- induced cell death and apoptosis. Icariside II activated Akt signaling, which is required for its actions in osteoblasts. Akt inhibitors (LY294002, perifosine and MK-2206) almost abolished icariside II-induced osteoblast cytoprotection against dexamethasone. Further studies showed that icariside II activated Nrf2 signaling, downstream of Akt, to inhibit dexamethasone-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary osteoblasts. On the other hand, Nrf2 shRNA knockdown inhibited icariside II-induced anti-dexamethasone cytoprotection in MC3T3-E1 cells. Finally, we showed that icariside II induced heparin-binding EGF (HB-EGF) production and EGFR trans-activation in MC3T3-E1 cells. EGFR inhibition, via anti-HB-EGF antibody, EGFR inhibitor AG1478 or EGFR shRNA knockdown, almost blocked icariside II-induced Akt-Nrf2 activation in MC3T3-E1 cells. Collectively, we conclude that icariside II activates EGFR-Akt-Nrf2 signaling and protects osteoblasts from dexamethasone. Icariside II might have translational value for the treatment of dexamethasone-associated osteoporosis/osteonecrosis.

Autoradiographic localization of specific (/sup 3/H)dexamethasone binding in fetal lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beer, D.G.; Butley, M.S.; Cunha, G.R.

1984-10-01

The cellular and subcellular localization of specific (/sup 3/H)dexamethasone binding was examined in fetal mouse lung at various stages of development and in human fetal lung at 8 weeks of gestation using a rapid in vitro steroid incubation technique followed by thaw-mount autoradiography. Competition studies with unlabeled steroids demonstrate the specificity of (/sup 3/H)dexamethasone labeling, and indicate that fetal lung mesenchyme is a primary glucocorticoid target during lung development. Autoradiographs of (/sup 3/H)dexamethasone binding in lung tissue at early stages of development demonstrate that the mesenchyme directly adjacent to the more proximal portions of the bronchiolar network is heavily labeled.more » In contrast, the epithelium which will later differentiate into bronchi and bronchioles, is relatively unlabeled. Distal portions of the growing epithelium, destined to become alveolar ducts and alveoli, do show nuclear localization of (/sup 3/H)dexamethasone. In addition, by utilizing a technique which allows the simultaneous examination of extracellular matrix components and (/sup 3/H)dexamethasone binding, a relationship is observed between extensive mesenchymal (/sup 3/H)dexamethasone binding and extensive extracellular matrix accumulation. Since glucocorticoids stimulate the synthesis of many extracellular matrix components, these results suggest a role for these hormones in affecting mesenchymal-epithelial interactions during lung morphogenesis.« less

Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up.

PubMed

Biran, N; Jacobus, S; Vesole, D H; Callander, N S; Fonseca, R; Williams, M E; Abonour, R; Katz, M S; Rajkumar, S V; Greipp, P R; Siegel, D S

2016-09-02

In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan-Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- and 5-year survival probability estimates were higher for early ASCT versus no early ASCT at 99, 93, 91, 85 and 80% versus 94, 84, 75, 65 and 57%, respectively. The median overall survival (OS) in the early versus no early ASCT group was not reached (NR) versus 5.78 years. In patients <65 years of age, median OS in the early versus no early ASCT groups was NR in both, hazard ratio 0.79, 95% confidence interval: (0.50, 0.25). In patients ⩾65 years of age, median OS in the early versus no early ASCT was NR versus 5.11 years. ASCT dropped out of statistical significance (P=0.080). Patients opting for ASCT after induction Ld/LD had a higher survival probability and improvement in OS regardless of dexamethasone dose density.

Worsened MRI findings during the early period of treatment with penicillin in a patient with general paresis.

PubMed

Zhang, She-Qing; Wan, Bo; Ma, Xiao-Long; Zheng, Hui-Min

2008-10-01

A 52-year-old man was diagnosed with general paresis, whose HIV antibodies were negative. After initiation of treatment with penicillin on the first day, no obvious clinical Jarisch-Herxheimer reaction was found. However, 6 days after treatment, the patient was found more irritable and was unable to fall asleep at night. On the seventh day, worsened magnetic resonance imaging (MRI) abnormalities in the bilateral medial and anterior temporal lobes were unexpectedly discovered. These worsened MRI abnormalities improved quickly after the addition of dexamethasone treatment. We consider that these transient and slight mental symptoms may be associated with the transiently worsening phenomenon in cerebral MRI findings during the early period of treatment with penicillin. This indicates that some nonspecific inflammatory process has happened in the early stage of treatment, which necessitates the use of corticosteroids after the occurrence of systemic or mental symptoms.

β-HYDROXY-β-METHYLBUTYRATE (HMB) PREVENTS DEXAMETHASONE-INDUCED MYOTUBE ATROPHY

PubMed Central

Aversa, Zaira; Alamdari, Nima; Castillero, Estibaliz; Muscaritoli, Maurizio; Fanelli, Filippo Rossi; Hasselgren, Per-Olof

2012-01-01

High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB. PMID:22705301

Six-month treatment with low-dose dexamethasone further reduces androgen levels in PCOS women treated with diet and lifestyle advice, and metformin.

PubMed

Vanky, E; Salvesen, K A; Carlsen, S M

2004-03-01

The purpose of this study was to investigate the effect of low-dose dexamethasone on androgen levels in women with polycystic ovary syndrome (PCOS) treated with diet and lifestyle counselling, and metformin. A prospective, randomized, double blind, placebo-controlled study was carried out. Thirty-eight women with PCOS were randomized to either dexamethasone 0.25 mg daily or placebo for 26 weeks. All received diet and lifestyle counselling at inclusion and metformin 850 mg three times daily during the whole study. Main outcome measures were: androgen levels, body mass index (BMI), insulin c-peptide, fasting glucose and serum lipids. Two-tailed t-tests and Pearson's statistics were used. Compared with the placebo, dexamethasone reduced testosterone by 27%, androstenedione by 21%, dehydroepiandrosterone sulphate by 46% and free testosterone index by 50% in women with PCOS treated with diet and lifestyle advice, and metformin. BMI, fasting glucose, insulin c-peptide and serum lipid levels were unaffected. Six-month, low-dose dexamethasone treatment further reduces androgen levels in metformin-treated PCOS women.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

PubMed

Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio

2015-01-08

Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).

Regulation of membrane-associated mucins in the human corneal epithelial cells by dexamethasone.

PubMed

Seo, Kyoung Yul; Chung, So-Hyang; Lee, Joon H; Park, Mi Young; Kim, Eung Kweon

2007-07-01

To study the influence of dexamethasone on membrane-associated mucins produced by human corneal epithelial cells. Human corneal epithelial cells were cultured in medium supplemented with various concentrations of dexamethasone (ranging from 10 to 10 M). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis using monoclonal antibodies specific for human MUC1 (HMFG-1), MUC4 (1G8), and MUC16 (OC125) were performed to evaluate the effect of dexamethasone on membrane-associated mucin expression. The effect of glucocorticoid receptor antagonist (RU38486) on dexamethasone-induced mucin expression was estimated. RT-PCR revealed that MUC1 and MUC16 gene expression were upregulated 48 hours after addition of dexamethasone and that MUC4 gene expression was downregulated in the same condition. Western blot analysis showed that MUC1 and MUC16 proteins were increased after addition of dexamethasone. However, MUC4 was not detected by anti-MUC4 monoclonal antibody (1G8) for ASGP-2 under our conditions. Treatment with RU38486 inhibited the changes of MUC1, MUC4, and MUC16 by dexamethasone; thus, the effect of dexamethasone on mucin expression is mediated by glucocorticoid receptors. This study shows that MUC1, MUC4, and MUC16 are regulated differently by dexamethasone in human corneal epithelial cells. External application of dexamethasone might affect the precorneal mucin.

Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin

PubMed Central

Liu, Chun; Croft, Quentin P. P.; Kalidhar, Swati; Brooks, Jerome T.; Herigstad, Mari; Smith, Thomas G.; Dorrington, Keith L.

2013-01-01

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure. PMID:23393065

β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

PubMed

Aversa, Zaira; Alamdari, Nima; Castillero, Estibaliz; Muscaritoli, Maurizio; Rossi Fanelli, Filippo; Hasselgren, Per-Olof

2012-07-13

High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB. Copyright © 2012 Elsevier Inc. All rights reserved.

β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

PubMed

Girón, María D; Vílchez, Jose D; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K; Rueda, Ricardo; López-Pedrosa, Jose M

2015-01-01

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

PubMed Central

Girón, María D.; Vílchez, Jose D.; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K.; Rueda, Ricardo; López-Pedrosa, Jose M.

2015-01-01

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis. PMID:25658432

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

PubMed

Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P < .001) concentrations, decreased SSGIR (HEC-II, P = .002; HEC-IV, P = .033), ISI (HEC-I, P < .015; HEC-II, P = .004), and insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P < .001). Dexamethasone decreases whole body insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Ranibizumab versus dexamethasone implant for central retinal vein occlusion: the RANIDEX study.

PubMed

Chatziralli, Irini; Theodossiadis, George; Kabanarou, Stamatina A; Parikakis, Efstratios; Xirou, Tina; Mitropoulos, Panagiotis; Theodossiadis, Panagiotis

2017-10-01

To compare intravitreal ranibizumab and dexamethasone implant in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Participants were 42 treatment naive patients with ME due to CRVO, who received either intravitreal 0.5 mg ranibizumab (n = 25) or intravitreal 0.7 mg dexamethasone implant (n = 17). The main outcomes included the mean change in best corrected visual acuity (BCVA) and central subfield thickness (CST) at month 12 compared to baseline in the two groups. At month 12, there was no statistically significant difference in BCVA and CST change between the two groups. However, there was recurrence in ME at month 5 in the dexamethasone group. Both ranibizumab and dexamethasone implant were found to be safe and effective at the 12-month follow-up in patients with ME secondary to CRVO. Since there was a recurrence in ME at month 5 in the dexamethasone group, we suggested that intravitreal injection of dexamethasone implant should be potentially administered sooner than 6 months.

Additive effects of dexamethasone and palmitate on hepatic lipid accumulation and secretion.

PubMed

Harasim-Symbor, Ewa; Konstantynowicz-Nowicka, Karolina; Chabowski, Adrian

2016-11-01

Synthetic and natural glucocorticoids are able to highly modify liver lipid metabolism, which is possibly associated with nonalcoholic fatty liver disease development. We have assessed the changes in lipid and sphingolipid contents in hepatocytes, lipid composition and saturation status as well as the expression of proteins involved in fatty acid transport after both dexamethasone and palmitate treatments. The experiments were conducted on primary rat hepatocytes, incubated with dexamethasone and/or palmitic acid during short (16 h) and prolonged (40 h) exposure. Intracellular and extracellular lipid and sphingolipid contents were assessed by gas liquid chromatography and high-performance liquid chromatography, respectively. The expression of selected proteins was estimated by Western blotting. Short and prolonged exposure to dexamethasone combined with palmitic acid resulted in increased expression of fatty acid transporters, which was subsequently reflected by excessive intracellular accumulation of triacylglycerols and ceramide. The expression of microsomal transfer protein and cassette transporter was also significantly increased after dexamethasone and palmitate treatment, which was in accordance with elevated extracellular lipid and sphingolipid contents. Our data showed additive effects of dexamethasone and palmitate on protein-dependent fatty acid uptake in primary hepatocytes, resulting in the increased accumulation of triacylglycerols and sphingolipids. Moreover, the combined treatment altered fatty acid composition and diminished triacylglycerols desaturation index. Importantly, we observed that additive effects on both increased microsomal transport protein expression as well as elevated export of triacylglycerols, which may be relevant as a liver protective mechanism. © 2016 Society for Endocrinology.

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

PubMed

Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

2006-10-01

To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p < 0.05 considered significant. A total of 166 subjects were enrolled; data for analysis were available for 44 NS-treated patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%]) tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS

Ciprofloxacin and Dexamethasone Otic

MedlinePlus

Ciprofloxacin and dexamethasone otic is used to treat outer ear infections in adults and children and acute (suddenly occurring) middle ear ... in a class of medications called quinolone antibiotics. Dexamethasone is in a class of medications called corticosteroids. ...

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

PubMed

Kastritis, E; Gavriatopoulou, M; Roussou, M; Fotiou, D; Ziogas, D C; Migkou, M; Eleutherakis-Papaiakovou, E; Panagiotidis, I; Kanellias, N; Psimenou, E; Papadopoulou, E; Pamboucas, C; Manios, E; Gakiopoulou, H; Ntalianis, A; Tasidou, A; Giannouli, S; Terpos, E; Dimopoulos, M A

2017-06-16

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

NASA Astrophysics Data System (ADS)

Kohl, Randall Lee

Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

NASA Technical Reports Server (NTRS)

Kohl, Randall Lee

1986-01-01

Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, the efficacy of dexamethasone and metyrapone is tested in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80 percent more stressful motion (P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis

PubMed Central

Zhang, Ruolin; Bo, Tao; Shen, Li; Luo, Senlin; Li, Jian

2014-01-01

OBJECTIVE: A meta-analysis of published randomized controlled trials investigating the long-term effect of dexamethasone on the nervous system of preterm infants. DATA SOURCES: Online literature retrieval was conducted using The Cochrane Library (from January 1993 to June 2013), EMBASE (from January 1980 to June 2013), MEDLINE (from January 1963 to June 2013), OVID (from January 1993 to June 2013), Springer (from January 1994 to June 2013) and Chinese Academic Journal Full-text Database (from January 1994 to June 2013). Key words were preterm infants and dexamethasone in English and Chinese. STUDY SELECTION: Selected studies were randomized controlled trials assessing the effect of intravenous dexamethasone in preterm infants. The quality of the included papers was evaluated and those without the development of the nervous system and animal experiments were excluded. Quality assessment was performed through bias risk evaluation in accordance with Cochrane Handbook 5.1.0 software in the Cochrane Collaboration. The homogeneous studies were analyzed and compared using Revman 5.2.6 software, and then effect model was selected and analyzed. Those papers failed to be included in the meta-analysis were subjected to descriptive analysis. MAIN OUTCOME MEASURES: Nervous system injury in preterm infants. RESULTS: Ten randomized controlled trials were screened, involving 1,038 subjects. Among them 512 cases received dexamethasone treatment while 526 cases served as placebo control group and blank control group. Meta-analysis results showed that the incidence of cerebral palsy, visual impairment and hearing loss in preterm infants after dexamethasone treatment within 7 days after birth was similar to that in the control group (RR = 1.47, 95%CI: 0.97–2.21; RR = 1.46, 95%CI: 0.97–2.20; RR = 0.80, 95%CI: 0.54–1.18; P > 0.05), but intelligence quotient was significantly decreased compared with the control group (MD = −3.55, 95%CI: −6.59 to −0.51; P = 0.02). Preterm

Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis.

PubMed

Zhang, Ruolin; Bo, Tao; Shen, Li; Luo, Senlin; Li, Jian

2014-03-15

A meta-analysis of published randomized controlled trials investigating the long-term effect of dexamethasone on the nervous system of preterm infants. Online literature retrieval was conducted using The Cochrane Library (from January 1993 to June 2013), EMBASE (from January 1980 to June 2013), MEDLINE (from January 1963 to June 2013), OVID (from January 1993 to June 2013), Springer (from January 1994 to June 2013) and Chinese Academic Journal Full-text Database (from January 1994 to June 2013). Key words were preterm infants and dexamethasone in English and Chinese. Selected studies were randomized controlled trials assessing the effect of intravenous dexamethasone in preterm infants. The quality of the included papers was evaluated and those without the development of the nervous system and animal experiments were excluded. Quality assessment was performed through bias risk evaluation in accordance with Cochrane Handbook 5.1.0 software in the Cochrane Collaboration. The homogeneous studies were analyzed and compared using Revman 5.2.6 software, and then effect model was selected and analyzed. Those papers failed to be included in the meta-analysis were subjected to descriptive analysis. Nervous system injury in preterm infants. Ten randomized controlled trials were screened, involving 1,038 subjects. Among them 512 cases received dexamethasone treatment while 526 cases served as placebo control group and blank control group. Meta-analysis results showed that the incidence of cerebral palsy, visual impairment and hearing loss in preterm infants after dexamethasone treatment within 7 days after birth was similar to that in the control group (RR = 1.47, 95%CI: 0.97-2.21; RR = 1.46, 95%CI: 0.97-2.20; RR = 0.80, 95%CI: 0.54-1.18; P > 0.05), but intelligence quotient was significantly decreased compared with the control group (MD = -3.55, 95%CI: -6.59 to -0.51; P = 0.02). Preterm infants treated with dexamethasone 7 days after birth demonstrated an incidence of

Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat.

PubMed Central

Leighton, B; Challiss, R A; Lozeman, F J; Newsholme, E A

1987-01-01

1. Rats were treated with dexamethasone for 4 days before measurement of the rates of lactate formation [which is an index of hexose transport; see Challiss, Lozeman, Leighton & Newsholme (1986) Biochem. J. 233, 377-381] and glycogen synthesis in response to various concentrations of insulin in isolated incubated soleus and extensor digitorum longus muscle preparations. 2. The concentration of insulin required to stimulate these processes half-maximally in soleus and extensor digitorum longus muscles isolated from control rats was about 100 muunits/ml. 3. Dexamethasone increases the concentration of insulin required to stimulate glycolysis half-maximally in soleus and extensor digitorum longus preparations to 250 and 300 muunits/ml respectively. The respective insulin concentrations necessary to stimulate glycogen synthesis half-maximally were about 430 and 370 muunits/ml for soleus and extensor digitorum longus muscle preparations isolated from steroid-treated rats. 5. Dexamethasone treatment did not change the amount of insulin bound to soleus muscle. PMID:3318810

Dexamethasone reduces side population fraction through downregulation of ABCG2 transporter in MCF-7 breast cancer cells.

PubMed

Kim, Jong Bin; Hwang, Sung Eun; Yoon, Sang-Pil

2017-07-01

Side population (SP) cells represent a rare population among breast cancer cells. SP cells have been reported to act as cancer stem‑like cells, and to participate in the development of multidrug resistance via modulating the expression of ATP-binding cassette subfamily G member 2 (ABCG2). Dexamethasone is a corticosteroid drug that has been used as an adjuvant treatment to enhance the efficacy of chemotherapeutic agents; however, its effects in breast cancer have yet to be thoroughly investigated. In the present study, the effects of dexamethasone were investigated using the human MCF‑7 breast cancer cell line, and SPs were examined in detail. Cellular proliferation, SP fractions and ABCG2 expression were examined following treatment of MCF‑7 cells with dexamethasone. Dexamethasone was revealed to cause a dose‑ and time‑dependent decrease in cancer cell proliferation, and it also decreased the size of the SP fraction of MCF‑7 cells and the expression of the ABCG2 transporter. The effects of dexamethasone on cellular proliferation, SP fraction and ABCG2 expression were abolished following the administration of the glucocorticoid antagonist RU486. These results suggested that dexamethasone may target breast cancer cell SPs and thus increase the sensitivity of tumor cells to chemotherapy. Therefore, it may be hypothesized that dexamethasone can be used as a chemosensitizer in the adjuvant treatment of patients with breast cancer.

Mitochondrial energy metabolism in a model of undernutrition induced by dexamethasone

PubMed Central

Dumas, Jean-François; Simard, Gilles; Roussel, Damien; Douay, Olivier; Foussard, Françoise; Malthiery, Yves; Ritz, Patrick

2003-01-01

This investigation was undertaken to evaluate whether mitochondrial energy metabolism is altered in a malnutrition model associated with dexamethasone treatment (1.5mg/kg/day for 5 days). Gastrocnemius and liver mitochondria were isolated from dexamethasone (DEX)-treated, pair-fed (PF) and control (CON) rats. Body weight was significantly more reduced in DEX-treated group (−16%) than in PF group (−9%). Dexamethasone increased the liver mass (+59% vs. PF and +23% vs. CON) and decreased gastrocnemius mass. Moreover, in DEX-treated rats, liver mitochondria exhibited an increased rate of non-phosphorylative oxygen consumption with all substrates (approximately +42%). There was no difference in enzymatic complex activities in liver mitochondria between rat groups. Collectively, these results suggest an increased proton leak and/or redox slipping in liver mitochondria of DEX-treated rats. In addition, dexamethasone decreased the thermodynamic coupling and efficiency of oxidative phosphorylation. We therefore suggest that this increase in the proton leak and/or of redox slip in liver is responsible for the decrease in the thermodynamic efficiency of energy conversion. In contrast, none of the determined parameters of energy metabolism were altered by dexamethasone in gastrocnemius mitochondria. Therefore, it appears that dexamethasone specifically affects mitochondrial energy metabolism in liver. PMID:14667190

Factors influencing the efficacy of round window dexamethasone protection of residual hearing post-cochlear implant surgery.

PubMed

Chang, Andrew; Eastwood, Hayden; Sly, David; James, David; Richardson, Rachael; O'Leary, Stephen

2009-09-01

To protect hearing in an experimental model of cochlear implantation by the application of dexamethasone to the round window prior to surgery. The present study examined the dosage and timing relationships required to optimise the hearing protection. Dexamethasone or saline (control) was absorbed into a pledget of the carboxymethylcellulose and hyaluronic acid and applied to the round window of the guinea pig prior to cochlear implantation. The treatment groups were 2% w/v dexamethasone for 30, 60 and 120min; 20% dexamethasone applied for 30min. Auditory sensitivity was determined pre-operatively, and at 1 week after surgery, with pure-tone auditory brainstem response audiometry (2-32kHz). Cochlear implantation was performed via a cochleostomy drilled into the basal turn of the cochlea, into which a miniature cochlear implant dummy electrode was inserted using soft-surgery techniques. ABR thresholds were elevated after cochlear implantation, maximally at 32kHz and to a lesser extent at lower frequencies. Thresholds were less elevated after dexamethasone treatment, and the hearing protection improved when 2% dexamethasone was applied to the round window for longer periods of time prior to implantation. The time that dexamethasone need be applied to achieve hearing protection could be reduced by increasing the concentration of steroid, with a 20% application for 30min achieving similar levels of protection to a 60min application of 2% dexamethasone. Hearing protection is improved by increasing the time that dexamethasone is applied to the round window prior to cochlear implantation, and the waiting time can be reduced by increasing the steroid concentration. These results suggest that the diffusion dexamethasone through the cochlea is the prime determinant of the extent of hearing protection.

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison.

PubMed

Van Sanden, Suzy; Ito, Tetsuro; Diels, Joris; Vogel, Martin; Belch, Andrew; Oriol, Albert

2018-03-01

Daratumumab (a human CD38-directed monoclonal antibody) and pomalidomide (an immunomodulatory drug) plus dexamethasone are both relatively new treatment options for patients with heavily pretreated multiple myeloma. A matching adjusted indirect comparison (MAIC) was used to compare absolute treatment effects of daratumumab versus pomalidomide + low-dose dexamethasone (LoDex; 40 mg) on overall survival (OS), while adjusting for differences between the trial populations. The MAIC method reduces the risk of bias associated with naïve indirect comparisons. Data from 148 patients receiving daratumumab (16 mg/kg), pooled from the GEN501 and SIRIUS studies, were compared separately with data from patients receiving pomalidomide + LoDex in the MM-003 and STRATUS studies. The MAIC-adjusted hazard ratio (HR) for OS of daratumumab versus pomalidomide + LoDex was 0.56 (95% confidence interval [CI], 0.38-0.83; p  = .0041) for MM-003 and 0.51 (95% CI, 0.37-0.69; p  < .0001) for STRATUS. The treatment benefit was even more pronounced when the daratumumab population was restricted to pomalidomide-naïve patients (MM-003: HR, 0.33; 95% CI, 0.17-0.66; p  = .0017; STRATUS: HR, 0.41; 95% CI, 0.21-0.79; p  = .0082). An additional analysis indicated a consistent trend of the OS benefit across subgroups based on M-protein level reduction (≥50%, ≥25%, and <25%). The MAIC results suggest that daratumumab improves OS compared with pomalidomide + LoDex in patients with heavily pretreated multiple myeloma. This matching adjusted indirect comparison of clinical trial data from four studies analyzes the survival outcomes of patients with heavily pretreated, relapsed/refractory multiple myeloma who received either daratumumab monotherapy or pomalidomide plus low-dose dexamethasone. Using this method, daratumumab conferred a significant overall survival benefit compared with pomalidomide plus low-dose dexamethasone. In the absence of head-to-head trials, these

21 CFR 522.540 - Dexamethasone solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone solution. 522.540 Section 522.540... Dexamethasone solution. (a)(1) Specifications. Each milliliter of solution contains 2 milligrams (mg) dexamethasone. (2) Sponsors. See sponsors in § 510.600(c) of this chapter: (i) Nos. 000061, 000859, and 061623...

Dexamethasone prevents hypoxia/ischemia-induced reductions in cerebral glucose utilization and high-energy phosphate metabolites in immature brain.

PubMed

Tuor, U I; Yager, J Y; Bascaramurty, S; Del Bigio, M R

1997-11-01

We examined the potential importance of dexamethasone-mediated alterations in energy metabolism in providing protection against hypoxic-ischemic brain damage in immature rats. Seven-day-old rats (n = 165) that had been treated with dexamethasone (0.1 mg/kg, i.p.) or vehicle were assigned to control or hypoxic-ischemic groups (unilateral carotid artery occlusion plus 2-3 h of 8% oxygen at normothermia). The systemic availability of alternate fuels such as beta-hydroxybutyrate, lactate, pyruvate, and free fatty acids was not altered by dexamethasone treatment, and, except for glucose, brain levels were also unaffected. At the end of hypoxia, levels of cerebral high-energy phosphates (ATP and phosphocreatine) were decreased in vehicle- but relatively preserved in dexamethasone-treated animals. The local cerebral metabolic rate of glucose utilization (lCMRgl) was decreased modestly under control conditions in dexamethasone-treated animals, whereas cerebral energy use measured in a model of decapitation ischemia did not differ significantly between groups. The lCMRgl increased markedly during hypoxia-ischemia (p < 0.05) and remained elevated throughout ischemia in dexamethasone- but not vehicle-treated groups, indicating an enhanced glycolytic flux with dexamethasone treatment. Thus, dexamethasone likely provides protection against hypoxic-ischemic damage in immature rats by preserving cerebral ATP secondary to a maintenance of glycolytic flux.

Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia

PubMed Central

Ramsey, Laura B.; Janke, Laura J.; Payton, Monique A.; Cai, Xiangjun; Paugh, Steven W.; Karol, Seth E.; Kamdem, Landry Kamdem; Cheng, Cheng; Williams, Richard T.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

2015-01-01

Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia. PMID:26252865

Intratympanic dexamethasone injections for refractory Meniere’ s disease

PubMed Central

Ren, Hongmiao; Yin, Tuanfang; Lu, Yongde; Kong, Weijia; Ren, Jihao

2015-01-01

Intratympanic injections or titration is a potential medical therapeutic strategy for patients with incurable inner ear diseases. Dexamethasone represent an attractive steroid source in intratympanic steroids strategies in the treatment of inner ear disorders. Here, we evaluated the effectiveness of intratympanic dexamethasone injections (IDI) in outpatients with refractory Meniere’s disease (MD). Vestibular function measured by Vestibular Ocular Reflex (VOR) gain and caloric test revealed that 21 outpatients out of 43 (48.8%) had complete sufficient vertigo control, while 9 (20.9%) of them were attached to fundamental manipulation. Out of the 13 remaining outpatients, 4 (9.3%) had a limit control and 9 had less modification. Therefore, 5 of 9 received re-treatment with IDI and 2 of 9 patients were administered ablative treatment with gentamicin. Meanwhile, audiology data suggested that 3 (7.0%), 4 (9.3%), 32 (74.4%), 4 (9.3%) patients were attached to the level of A, B, C, D, respectively. Furthermore, the symptom of tinnitus in 5 outpatients vanished, 21 (48.8%) diminished, 10 (23.3%) invariable, 7 (16.3%) aggravated. In 4 of 24 cases (16.7%), aural fullness disappeared after IDI, when the aural fullness was alleviated in 11 cases (45.8%) even intensive in 9 patients (37.5%). Together, our results demonstrate that intratympanic dexamethasone injection, as an effective therapeutic strategy for refractory Meniere’s disease, could either be used for cascade therapy preoperation or used for patients who couldn’t accept the surgery. PMID:26131198

Intratympanic dexamethasone injections for refractory Meniere' s disease.

PubMed

Ren, Hongmiao; Yin, Tuanfang; Lu, Yongde; Kong, Weijia; Ren, Jihao

2015-01-01

Intratympanic injections or titration is a potential medical therapeutic strategy for patients with incurable inner ear diseases. Dexamethasone represent an attractive steroid source in intratympanic steroids strategies in the treatment of inner ear disorders. Here, we evaluated the effectiveness of intratympanic dexamethasone injections (IDI) in outpatients with refractory Meniere's disease (MD). Vestibular function measured by Vestibular Ocular Reflex (VOR) gain and caloric test revealed that 21 outpatients out of 43 (48.8%) had complete sufficient vertigo control, while 9 (20.9%) of them were attached to fundamental manipulation. Out of the 13 remaining outpatients, 4 (9.3%) had a limit control and 9 had less modification. Therefore, 5 of 9 received re-treatment with IDI and 2 of 9 patients were administered ablative treatment with gentamicin. Meanwhile, audiology data suggested that 3 (7.0%), 4 (9.3%), 32 (74.4%), 4 (9.3%) patients were attached to the level of A, B, C, D, respectively. Furthermore, the symptom of tinnitus in 5 outpatients vanished, 21 (48.8%) diminished, 10 (23.3%) invariable, 7 (16.3%) aggravated. In 4 of 24 cases (16.7%), aural fullness disappeared after IDI, when the aural fullness was alleviated in 11 cases (45.8%) even intensive in 9 patients (37.5%). Together, our results demonstrate that intratympanic dexamethasone injection, as an effective therapeutic strategy for refractory Meniere's disease, could either be used for cascade therapy preoperation or used for patients who couldn't accept the surgery.

The effects of dexamethasone on post-asphyxial cerebral oxygenation in the preterm fetal sheep

PubMed Central

Lear, Christopher A; Koome, Miriam E; Davidson, Joanne O; Drury, Paul P; Quaedackers, Josine S; Galinsky, Robert; Gunn, Alistair J; Bennet, Laura

2014-01-01

Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml–1) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia. PMID:25384775

Dexamethasone Attenuates the Enhanced Rewarding Effects of Cocaine Following Experimental Traumatic Brain Injury.

PubMed

Merkel, Steven F; Andrews, Allison M; Lutton, Evan M; Razmpour, Roshanak; Cannella, Lee Anne; Ramirez, Servio H

2017-07-01

Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent preclinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay. These studies were performed in order to determine whether proinflammatory activity in the nucleus accumbens (NAc), a key brain nucleus in the reward pathway, mediates enhanced cocaine-induced CPP in adolescent animals sustaining moderate CCI-TBI. Our data reveal robust glial activation in the NAc following CCI-TBI and a significant increase in the cocaine-induced CPP of untreated CCI-TBI mice. Furthermore, our results show that dexamethasone treatment following CCI-TBI can attenuate the cocaine place preference of injured animals without producing aversion in the CPP assay. Our studies also found that dexamethasone treatment significantly reduced the expression of select immune response genes including Monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 ( ICAM-1), returning their expression to control levels, which prompted an investigation of peripheral blood monocytes in dexamethasone-treated animals. Experimental findings showed that no craniectomy/dexamethasone mice had a significant increase, while CCI-TBI/dexamethasone animals had a significant decrease in the percentage of circulating nonclassical patrolling monocytes. These results suggest that a portion of these monocytes may migrate to the brain in response to CCI-TBI, potentially sparing the development of chronic neuroinflammation in regions associated with the reward circuitry such as the NAc. Overall, our findings indicate that

Epidural Dexamethasone Influences Postoperative Analgesia after Major Abdominal Surgery.

PubMed

Hong, Jeong-Min; Kim, Kyung-Hoon; Lee, Hyeon Jeong; Kwon, Jae-Young; Kim, Hae-Kyu; Kim, Hyae-Jin; Cho, Ah-Reum; Do, Wang-Seok; Kim, Hyo Sung

2017-05-01

Epidurally administered dexamethasone might reduce postoperative pain. However, the effect of epidural administration of dexamethasone on postoperative epidural analgesia in major abdominal surgery has been doubtful. To investigate the effects and optimal dose of epidural dexamethasone on pain after major abdominal surgery. A prospective randomized, double-blind study. University hospital. One hundred twenty ASA physical status I and II men, scheduled for gastrectomy, were enrolled. Patients were randomly assigned to receive one of 3 treatment regimens (n = 40 in each group): dexamethasone 5 mg (1 mL) with normal saline (1 mL) (group D) or dexamethasone 10 mg (2 mL) (group E) or 2 mL of normal saline (group C) mixed with 8 mL of 0.375% ropivacaine as a loading dose. After the surgery, 0.2% ropivacaine - fentanyl 4 ?g/mL was epidurally administered for analgesia. The infusion was set to deliver 4 mL/hr of the PCEA solution, with a bolus of 2 mL per demand and 15 minutes lockout time. The infused volume of PCEA, intensity of postoperative pain using visual analogue scale (VAS) during rest and coughing, incidence of postoperative nausea and vomiting (PONV), usage of rescue analgesia and rescue antiemetic, and side effects such as respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, and 48 hours after the end of surgery. The resting and effort VAS was significantly lower in group E compared to group C at every time point through the study period. On the contrary, only the resting VAS in group D was lower at 2 hours and 6 hours after surgery. Total fentanyl consumption of group E was significantly lower compared to other groups. There was no difference in adverse effect such as hypotension, bradycardia, PONV, pruritis, and urinary retention among groups. Use of epidural PCA with basal rate might interrupt an accurate comparison of dexamethasone effect. Hyperglycemia and adrenal suppression were not evaluated. Epidural dexamethasone was

[Comparison of antiemesis effects of granisetron, aprepitant and dexamethasone to palonosetron, aprepitant and dexamethasone in treatment of high-emetic risk chemotherapy-induced nausea and vomiting - a retrospective study for efficacy and safety in a single institute].

PubMed

Osawa, Hiroshi; Goto, Hiroaki; Myojo, Tomohiro

2013-05-01

Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.

Dexamethasone minimizes the risk of cranial nerve injury during CEA.

PubMed

Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

2009-01-01

The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically

Head-to-head comparison of ranibizumab PRN versus single-dose dexamethasone for branch retinal vein occlusion (COMRADE-B).

PubMed

Hattenbach, Lars-Olof; Feltgen, Nicolas; Bertelmann, Thomas; Schmitz-Valckenberg, Steffen; Berk, Hüsnü; Eter, Nicole; Lang, Gabriele E; Rehak, Matus; Taylor, Simon R; Wolf, Armin; Weiss, Claudia; Paulus, Eva-Maria; Pielen, Amelie; Hoerauf, Hans

2018-02-01

To compare the efficacy and safety of ranibizumab 0.5 mg versus dexamethasone 0.7 mg according to their European labels in macular oedema secondary to branch retinal vein occlusion (BRVO) in a 6-month, phase IIIb, randomized trial. Patients received either monthly ranibizumab for 3 months followed by Pro re nata (PRN) treatment (n = 126) or a sustained-release dexamethasone implant followed by PRN sham injections (n = 118). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean changes in BCVA and foveal centre point thickness (FCPT), and adverse events (AEs). There was no difference in BCVA gains between the treatments prior to month 3. Best-corrected visual acuity (BCVA) gain with dexamethasone declined thereafter. From month 3 to month 6, mean BCVA change from baseline was significantly higher with ranibizumab than with dexamethasone [raw means (standard deviation):+16.2 (±11) letters versus +9.3 (±10.1) letters]. At month 6, the difference in BCVA gains from baseline was +17.3 letters in the ranibizumab versus +9.2 letters in the dexamethasone group. Patients in the ranibizumab group received a mean of 2.94 loading injections and 1.74 PRN retreatment injections, while those in the dexamethasone group received a single loading injection. Elevated intraocular pressure (IOP) and AEs were more frequent with dexamethasone than ranibizumab treatment. Ranibizumab PRN resulted in greater visual acuity (VA) gains in macular oedema following BRVO compared with single-dose dexamethasone over a 6-month study period, observed from month 3, when administered according to their European label. In clinical practice, retreatment with dexamethasone may be required prior to this point. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Effect of dexamethasone on expression of glucocorticoid receptor in human monocyte cell line THP-1.

PubMed

Li, Bo; Bai, Xiangjun; Wanh, Haiping

2006-01-01

The effect of dexamethasone with different concentrations and different stimulating periods on the expression of glucocorticoid receptors (GRalpha, GRbeta) protein was investigated in human monocyte cell line THP-1. The cultured human monocyte line THP-1 cells were stimulated by dexamethasone with different concentrations and different periods. The expression of GRalpha and GRbeta protein was detected by Western blotting. The results showed that the expression of GRalpha and GRbeta was detected in the THP-1 cells. The quantity of GRalpha expression was reduced by dexamethasone under the same concentration with the prolongation of the stimulating periods. The quantity of GRbeta expression was increased by dexamethasone treatment in a time- and dose-dependent manner. It was concluded that dexamethasone stimulation time-dependently reduced the GRalpha expression in THP-1 cells. Dexamethasone stimulation time- and dose-dependently increased the GRbeta expression in THP-1 cells. The expression of GRalpha and GRbeta was regulated by glucocorticoid.

Dexamethasone effects on creatine kinase activity and insulin-like growth factor receptors in cultured muscle cells

NASA Technical Reports Server (NTRS)

Whitson, Peggy A.; Stuart, Charles A.; Huls, M. H.; Sams, Clarence F.; Cintron, Nitza M.

1989-01-01

The effect of dexamethasone on the activity of creatine kinase (CK) and the insulin-like growth factor I (IGF-I) binding were investigated using skeletal- and cardiac-muscle-derived cultured cell lines (mouse, C2C12; rat, L6 and H9c2). It was found that, in skeletal muscle cells, dexamethasone treatment during differentiation of skeletal-muscle cells caused dose-dependent increases in CK activity and increases in the degree of myotube formation, whereas cardiac cells (H9c2) exhibited very low CK activity during culture or dexamethasone treatment. Results for IGF-I binding were similar in all three cell lines. The IGF-I binding to dexamethasone-treated cells (50 nM for 24 hr on the day prior to confluence) resulted in an increased number of available binding sites, with no effect on the binding affinities.

β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat

PubMed Central

Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

2014-01-01

Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy. PMID:25032690

Dexamethasone Inhibits TGF-β1–Induced Cell Migration by Regulating the ERK and AKT Pathways in Human Colon Cancer Cells Via CYR61

PubMed Central

Han, Sanghoon; Bui, Ngoc Thuy; Ho, Manh Tin; Kim, Young Mee; Cho, Moonjae; Shin, Dong Bok

2016-01-01

Purpose One of the features in cancer development is the migration of cancer cells to form metastatic lesions. CYR61 protein promotes migration and the epithelial-mesenchymal transition in several cancer cell types. Evidence suggests that CYR61 and dexamethasone are relevant to colorectal cancer. However, relationships between them and colorectal cancer are still unclear. Understanding the molecular mechanism of colorectal cancer progression related with CYR61 and dexamethasone, which is widely used for combination chemotherapy, is necessary for improved therapy. Materials and Methods We used colorectal cancer cells, HCT116, co-treated with transforming growth factor β1 (TGF-β1) and dexamethasone to examine the inhibitory migration effect of dexamethasone by migratory assay. Alternatively, both migratory pathways, expression of AKT and ERK, and the target factor CYR61 was also tested by co-treatment with TGF-β1 and dexamethasone. Results We report that dexamethasone significantly inhibited TGF-β1–induced cell migration, without affecting cell proliferation. Importantly, we observed that TGF-β1 promoted the epithelial-mesenchymal transition process and that dexamethasone co-treatment abolished this effect. ERK and AKT signaling pathways were found to mediate TGF-β1–induced migration, which was inhibited by dexamethasone. In addition, TGF-β1 treatment induced CYR61 expression whereas dexamethasone reduced it. These observations were compatible with the modulation of migration observed following treatment of HCT116 cells with human recombinant CYR61 and anti-CYR61 antibody. Our results also indicated that TGF-β1 enhanced collagen I and reduced matrix metalloproteinase 1 expression, which was reversed by dexamethasone treatment. Conclusion These findings suggested that dexamethasone inhibits AKT and ERK phosphorylation, leading to decreased CYR61 expression, which in turn blocks TGF-β1–induced migration. PMID:26693911

Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002).

PubMed

Ishido, Kenji; Higuchi, Katsuhiko; Azuma, Mizutomo; Sasaki, Tohru; Tanabe, Satoshi; Katada, Chikatoshi; Yano, Takafumi; Wada, Takuya; Koizumi, Wasaburo

2016-10-01

We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics in horses.

PubMed

Tóth, Ferenc; Frank, Nicholas; Geor, Raymond J; Boston, Raymond C

2010-01-01

To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics. 24 horses. Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration. Area under the curve for plasma glucose and serum insulin concentrations was calculated, and minimal model analyses were performed. Significant treatment-by-time effects were detected for insulin sensitivity (SI) and area under the curve for glucose and insulin in the 15-day pretreatment period. Insulin sensitivity significantly decreased over time in all treatment groups, with the largest decrease detected in the dexamethasone group. Administration of lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone and control groups, respectively, but did not affect horses in the levothyroxine group. Mean SI was the lowest in the dexamethasone group, but percentage reduction was the same for dexamethasone and control groups. Insulin sensitivity decreased during the pretreatment period in all 3 groups, indicating that hospitalization affected glucose and insulin dynamics. Dexamethasone significantly lowered SI, and endotoxemia further exacerbated insulin resistance. In contrast, there was no additional effect of endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this treatment prevented endotoxemia-induced insulin resistance.

Single Dexamethasone Intravitreal Implant in the Treatment of Noninfectious Uveitis.

PubMed

Frère, Ariane; Caspers, Laure; Makhoul, Dorine; Judice, Lia; Postelmans, Laurence; Janssens, Xavier; Lefebvre, Pierre; Mélot, Christian; Willermain, François

2017-05-01

To investigate the effect of a single intravitreal dexamethasone implant (IVT-DI; Ozurdex; Allergan, Inc.) on visual acuity, macular thickness, and intraocular pressure (IOP) in active noninfectious uveitis. Medical records of patients with noninfectious active uveitis treated by IVT-DIs were retrospectively reviewed. Uveitis etiologies, treatment indications, best corrected visual acuity (BCVA), central retinal thickness measured by ocular coherence tomography, IOP, and systemic, local, and topical treatments were collected. Parameters were analyzed before the injection of the implant, after 1.5 ± 0.8 months and 4.4 ± 0.9 months for the BCVA, after 2 ± 1.3 months and 4.6 ± 1.3 months for the ocular coherence tomography, and after 1.3 ± 0.7 months and 4.4 ± 1 months for the IOP. We included 14 patients (20 eyes, 20 implant injections) with cystoid macular edema (78%), vasculitis (7%), choroiditis (7%), and vasculitis associated with choroiditis (7%). Before the injection, mean visual acuity was 0.4 ± 0.5 logMAR (logarithm of the minimum angle of resolution) that improved to 0.3 ± 0.5 logMAR (P = 0.0002) after 1.5 ± 0.8 months and to 0.3 ± 0.5 logMAR (P = 0.005) after 4.4 ± 0.9 months. A statistically significant decrease of macular thickness was observed both at 2 ± 1.3 months and at 4.6 ± 1.3 months after IVT-DI. Mean IOP was 16 ± 5 mmHg before injections, 18 ± 6 mmHg (P = 0.13) at 1.3 ± 0.7 months, and 15 ± 4 mmHg (P = 0.65) at 4.4 ± 1 months. By Kaplan-Meier analysis, we found that after 3.3 months, 17% of the eyes still present a BCVA amelioration ≥0.3 logMAR. In our patients with active noninfectious uveitis, injection of a first single dexamethasone implant was found to improve visual acuity and decrease macular thickness without significant increase of IOP, although the effect seems limited in time.

Vitis vinifera Extract Ameliorate Hepatic and Renal Dysfunction Induced by Dexamethasone in Albino Rats

PubMed Central

Hasona, Nabil A.; Alrashidi, Ahmed A.; Aldugieman, Thamer Z.; Alshdokhi, Ali M.; Ahmed, Mohammed Q.

2017-01-01

This study was conducted to evaluate the biochemical effects of grape seed extract against dexamethasone-induced hepatic and renal dysfunction in a female albino rat. Twenty-eight adult female rats were divided randomly into four equal groups: Group 1: animals were injected subcutaneously with saline and consider as normal control one. Group 2: animals were injected subcutaneously with dexamethasone in a dose of 0.1 mg/kg body weight. Group 3: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 200 mg/kg body weight by oral gavage. Group 4: animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with a grape seed extract in a dose of 400 mg/kg body weight by oral gavage. After 4 weeks, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, albumin, uric acid, creatinine, and glucose levels were assayed. Hepatic reduced glutathione (GSH), total protein content, and catalase and glucose-6-phosphate dehydrogenase activities were also assayed. Dexamethasone administration caused elevation of serum levels of glucose, uric acid, creatinine, ALT, AST activities, and a decrease in other parameters such as hepatic glutathione, total protein levels, and catalase enzyme activity. Treatment with Vitis vinifera L. seed extract showed a significant increase in the body weight of rats in the group treated with Vitis vinifera L. seed extract orally compared with the dexamethasone control group. An increase in GSH and catalase activity in response to oral treatment with Vitis vinifera L. seed extract was observed after treatment. Grape seed extract positively affects glucocorticoid-induced hepatic and renal alteration in albino rats. PMID:29051443

Anti-inflammatory effect of intravenous immunoglobulin in comparison with dexamethasone in vitro: implication for treatment of Kawasaki disease.

PubMed

Makata, Haruyuki; Ichiyama, Takashi; Uchi, Ryutaro; Takekawa, Tsuyoshi; Matsubara, Tomoyo; Furukawa, Susumu

2006-08-01

High-dose intravenous immunoglobulin (IVIG) is a well-established standard therapy for Kawasaki disease (KD) that reduces the risk of developing coronary artery aneurysms. On the other hand, some reports have recommended an alternative therapy with steroids for KD patients. In this study we investigated the anti-inflammatory effect of IVIG in comparison with dexamethasone at clinical doses in vitro. High-dose IVIG inhibited tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB) to a greater degree than dexamethasone in human monocytic U937 cells and human coronary arterial endothelial cells (HCAEC), but not in human T lymphocytic Jurkat cells. IVIG was more potent than dexamethasone in reducing the expression of CD16 (FcgammaRIII) in human monocytic THP-1 cells stimulated with lipopolysaccharide and in Jurkat cells stimulated with dimethyl sulfoxide. In HCAEC exposed to TNF-alpha, IVIG and dexamethasone inhibited interleukin-6 production to a similar degree, whereas the expression of E-selectin was inhibited more strongly by IVIG. Our results show that high-dose IVIG inhibits the activation of monocytes/macrophages and coronary arterial endothelial cells more strongly than that of T cells, whereas dexamethasone inhibits the activation of all three cell types. These findings suggest that IVIG or dexamethasone therapy should be chosen to match the types of cells that are activated during acute KD.

Dexamethasone transcriptionally increases the expression of the pregnane X receptor and synergistically enhances pyrethroid esfenvalerate in the induction of cytochrome P450 3A23.

PubMed

Shi, Deshi; Yang, Dongfang; Yan, Bingfang

2010-10-15

The pregnane X receptor (PXR) is recognized as a key regulator for the induction of a large number of genes in drug metabolism and transport. The transactivation of PXR is enhanced by the glucocorticoid dexamethasone and the enhancement is linked to the induction of PXR in humans and rats. The present study was undertaken to determine the mechanism for the induction and ascertain the synergistic effect on the expression of CYP3A23, a rat PXR target. In primary hepatocytes, significant induction of PXR was detected as early as 2h after the treatment and the maximal induction occurred at 1 microM dexamethasone. Similar induction kinetics was observed in the hepatoma line H4-II-E-C3. The induction was abolished by actinomycin D and dexamethasone efficaciously stimulated the rat PXR promoter. In addition, dexamethasone synergized esfenvalerate (an insecticide and a PXR activator) in inducing CYP3A23 and stimulating the CYP3A23 promoter. The full promoter of CYP3A23 (-1445/+74) was activated in a similar pattern as the changes in PXR mRNA in response to dexamethasone, esfenvalerate and co-treatment. In contrast, different responding patterns were detected on the stimulation of the CYP3A23 proximal promoter. Synergistic stimulation was also observed on the CYP3A4-DP-Luc reporter, the human counterpart of CYP3A23. These findings establish that transactivation is responsible for the induction of rat PXR and the induction presents potential interactions with insecticides in a species-conserved manner. The different responding patterns among CYP3A23 reporters point to an involvement of multiple transcriptional events in the regulation of CYP3A23 expression by dexamethasone, esfenvalerate and both. Copyright 2010 Elsevier Inc. All rights reserved.

DEXAMETHASONE TRANSCRIPTIONALLY INCREASES THE EXPRESSION OF THE PREGNANE X RECEPTOR AND SYNERGISTICALLY ENHANCES PYRETHROID ESFENVALERATE IN THE INDUCTION OF CYTOCHROME P450 3A23

PubMed Central

Shi, Deshi; Yang, Dongfang; Yan, Bingfang

2010-01-01

The pregnane X receptor (PXR) is recognized as a key regulator for the induction of a large number of genes in drug metabolism and transport. The transactivation of PXR is enhanced by the glucocorticoid dexamethasone and the enhancement is linked to the induction of PXR in humans and rats. The present study was undertaken to determine the mechanism for the induction and ascertain the synergistic effect on the expression of CYP3A23, a rat PXR target. In primary hepatocytes, significant induction of PXR was detected as early as 2 h after the treatment and the maximal induction occurred at 1 μM dexamethasone. Similar induction kinetics was observed in the hepatoma line H4-II-E-C3. The induction was abolished by actinomycin D and dexamethasone efficaciously stimulated the rat PXR promoter. In addition, dexamethasone synergized esfenvalerate (an insecticide and a PXR activator) in inducing CYP3A23 and stimulating the CYP3A23 promoter. The full promoter of CYP3A23 (−1445/+74) was activated in a similar pattern as the changes in PXR mRNA in response to dexamethasone, esfenvalerate and co-treatment. In contrast, different responding patterns were detected on the stimulation of the CYP3A23 proximal promoter. Synergistic stimulation was also observed on the CYP3A4-DP-Luc reporter, the human counterpart of CYP3A23. These findings establish that transactivation is responsible for the induction of rat PXR and the induction presents potential interactions with insecticides in a species-conserved manner. The different responding patterns among CYP3A23 reporters point to an involvement of multiple transcriptional events in the regulation of CYP3A23 expression by dexamethasone, esfenvalerate and both. PMID:20599767

Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers

USDA-ARS?s Scientific Manuscript database

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers (n = 32; 209 ± 8 kg) were str...

Dexamethasone-mediated oncogenicity in vitro and in an animal model of glioblastoma.

PubMed

Luedi, Markus M; Singh, Sanjay K; Mosley, Jennifer C; Hassan, Islam S A; Hatami, Masumeh; Gumin, Joy; Andereggen, Lukas; Sulman, Erik P; Lang, Frederick F; Stueber, Frank; Fuller, Gregory N; Colen, Rivka R; Zinn, Pascal O

2018-01-12

OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort. METHODS Expression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520). RESULTS The mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of

Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol.

PubMed

Kim, Bo-Young; Son, Yonghae; Lee, Jeonga; Choi, Jeongyoon; Kim, Chi Dae; Bae, Sun Sik; Eo, Seong-Kug; Kim, Koanhoi

2017-01-01

Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol.

Dexamethasone inhibits activation of monocytes/macrophages in a milieu rich in 27-oxygenated cholesterol

PubMed Central

Kim, Bo-Young; Son, Yonghae; Lee, Jeonga; Choi, Jeongyoon; Kim, Chi Dae; Bae, Sun Sik; Eo, Seong-Kug

2017-01-01

Molecular mechanisms underlying the decreased number of macrophages and T cells in the arteries of cholesterol-fed-rabbits following dexamethasone administration are unknown. We investigated the possibility that dexamethasone could affect activation of monocytic cells induced by oxygenated derivatives of cholesterol (oxysterols) using THP-1 monocyte/macrophage cells. 27-Hydroxycholesterol (27OHChol), an oxysterol elevated with hypercholesterolemia, enhanced production of CCL2, known as MCP1, chemokine from monocytes/macrophages and migration of the monocytic cells, but the CCL2 production and the cell migration were reduced by treatment with dexamethasone. Dexamethasone inhibited superproduction of CCL2 induced by 27OHChol plus LPS and attenuated transcription of matrix metalloproteinase 9 as well as secretion of its active gene product induced by 27OHChol. The drug downregulated cellular and surface levels of CD14 and blocked release of soluble CD14 without altering transcription of the gene. Dexamethasone also inhibited expression and phosphorylation of the NF-κB p65 subunit enhanced by 27OHChol. Collectively, these results indicate that dexamethasone inhibits activation of monocytes/macrophages in response to 27OHChol, thereby leading to decreased migration of inflammatory cells in milieu rich in oxygenated derivatives of cholesterol. PMID:29236764

Pharmaceutical technology can turn a traditional drug, dexamethasone into a first-line ocular medicine. A global perspective and future trends.

PubMed

Rodríguez Villanueva, Javier; Rodríguez Villanueva, Laura; Guzmán Navarro, Manuel

2017-01-10

Dexamethasone is one of the most prescribed glucocorticoids. It is effective and safe in the treatment of a wide variety of ocular conditions, including anterior and posterior segment inflammation. However, its half-life in the vitreous humor is very short, which means that it typically requires frequent administrations, thus reducing patient adherence and causing therapeutic failure. Innovative dexamethasone delivery systems have been designed in an attempt to achieve sustained release and targeting. The FDA has approved dexamethasone implants for the treatment of macular edema secondary to retinal vein occlusion and posterior segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes, micelles and dendrimers are also proving to be adequate systems for maintaining optimal dexamethasone levels in the site of action. Pharmaceutical technology is turning a classical drug, dexamethasone, into a fashionable medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

Aerobic fitness and physical activity levels of children born prematurely following randomization to postnatal dexamethasone.

PubMed

Nixon, Patricia A; Washburn, Lisa K; Mudd, Lanay M; Webb, Heather H; O'Shea, T Michael

2011-01-01

To investigate the effects of postnatal dexamethasone treatment on aerobic fitness and physical activity levels in school-aged children born with very low birth weight (VLBW). This was a follow-up study of 65 VLBW infants who participated in a randomized controlled trial of dexamethasone (DEX) to reduce ventilator dependency. Aerobic fitness was determined from peak oxygen uptake (VO(2peak)) with a cycle ergometer. Habitual physical activity was assessed by questionnaire. A trend for a treatment with an interaction between treatment and of diagnosis of chronic lung disease (CLD) was found, with the children in the placebo group with CLD having the lowest VO(2peak) (P = .09). Reduced fitness was seen in 53% of the group treated with DEX and 48% of the group given placebo. No between-group differences in physical activity were seen. Parental reports suggested that nearly two-thirds of the children participated in < 1 hour per week of vigorous physical activity, which was explained in part by decreased large airway function (r = 0.30; P = .03). We found no adverse effect of postnatal DEX on aerobic fitness or habitual physical activity at school age. However, the reduced fitness and physical activity levels emphasize the need for closer follow-up and early interventions promoting physical activity to reduce the risk of chronic disease in this at-risk population. Copyright © 2011 Mosby, Inc. All rights reserved.

Dexamethasone facilitates fear extinction and safety discrimination in PTSD: A placebo-controlled, double-blind study.

PubMed

Michopoulos, Vasiliki; Norrholm, Seth D; Stevens, Jennifer S; Glover, Ebony M; Rothbaum, Barbara O; Gillespie, Charles F; Schwartz, Ann C; Ressler, Kerry J; Jovanovic, Tanja

2017-09-01

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone

Successful treatment of a primary gastric plasmacytoma mimicking intractable gastric ulcer by using high-dose dexamethasone therapy: a case report.

PubMed

Kang, Da-yeong; Kim, Gee-Bum; Choi, Byung-Seok; Seo, Jun-won; Lim, Hyun-Jong; Hong, Ran; Park, Sang-Gon

2016-03-31

Extramedullary plasmacytoma is a plasma cell neoplasm that presents as a solitary lesion in soft tissue. Most extramedullary plasmacytomas involve the nasopharynx or upper respiratory tract. Primary plasmacytoma of the stomach is extremely rare. A 78-year-old Korean woman presented with epigastric pain for 3 months. She had a history of an intractable gastric ulcer despite repeated endoscopic biopsies and appropriate medical therapy for the ulcer. She underwent another endoscopy and a biopsy was performed for multiple large and deep specimens. Ultimately, primary gastric plasmacytoma was confirmed. However, she and her attendant refused standard local radiotherapy or surgical resection. She came to our emergency room 3 months later with hematemesis due to a large gastric ulcer, despite management with medication for over 3 months at a local clinic. We again recommended local radiation or surgical resection. However, as she was willing to undergo only medical therapy, she was prescribed high-dose dexamethasone. Surprisingly, her ulcer completely regressed and remission was maintained for over 1 year. We report successful treatment of a rare primary gastric plasmacytoma mimicking intractable ulcer by using high-dose dexamethasone. To the best of our knowledge, this is the first reported case successfully treated with only high-dose dexamethasone.

Mechanism of dexamethasone in the context of Toxoplasma gondii infection.

PubMed

Zhang, Jing; Qin, Xin; Zhu, Y U; Zhang, Shuang; Zhang, Xue-Wei; Lu, H E

2017-09-01

Toxoplasmosis is a serious zoonoses disease and opportunistic, and can be life-threatening. Dexamethasone (DEX) is widely used in the clinic for treatment of inflammatory and autoimmune diseases. However, long-term use of DEX is often easy to lead to acute toxoplasmosis in patients, and the potential molecular mechanism is still not very clear. The aims of this study were to investigate the effect of DEX on proliferation of Toxoplasma and its molecular mechanisms, and to establish the corresponding control measures. All the results showed that dexamethasone could enhance the proliferation of Toxoplasma gondii tachyzoites. After 72 h of DEX treatment, 566 (±7) tachyzoites were found in 100 host cells, while only 86 (±8) tachyzoites were counted from the non-treated control cells (P < 0·01). Gas chromatography (GC) analysis showed changes in level and composition of fatty acids in DEX-treated host cells, and T. gondii. Fish oil was added as a modulator of lipid metabolism in experimental mice. It was found that mice fed with fish oil did not develop the disease after infection with T. gondii, and the structure of fatty acids in plasma changed significantly. The metabolism of fatty acid in the parasites was limited, and the desaturase gene expression was downregulated. These results indicate that the molecular mechanism of dexamethasone to promote the proliferation of T. gondii may be that dexamethasone induces the change of fatty acids composition of tachyzoites and host cells. Therefore, we recommend supplementation of fatty acid in immunosuppressive and immunocompromised patients in order to inhibit toxoplasmosis.

Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation.

PubMed

Wigenstam, Elisabeth; Jonasson, Sofia; Koch, Bo; Bucht, Anders

2012-11-15

Exposure to toxic alkylating mustard agents causes both acute and long-term effects to the lungs as indicated by increased number of inflammatory cells in airways, lung edema and lung tissue fibrosis. We have previously demonstrated that treatment with the corticosteroid dexamethasone 1 h after lung exposure to the nitrogen mustard analog melphalan protects mice from acute and sub-acute inflammatory responses, as well as from lung tissue fibrosis. In order to address the importance of early anti-inflammatory treatment, we investigated the therapeutic effect of dexamethasone administered 1, 2 or 6 h following exposure to melphalan. C57BL/6 mice were exposed to melphalan and treated with dexamethasone 1, 2 or 6 h after exposure. Twenty hours or 14 days post exposure mice were subjected to analysis of respiratory mechanics where the effects of incremental doses of methacholine on central and peripheral lung components were measured. We also determined the amount of inflammatory cells in the bronchoalveolar lavage fluid and measured the amount of collagen content in the lungs. Melphalan exposure increased airway hyperresponsiveness in both central and peripheral airways and induced an airway inflammation dominated by infiltration of macrophages and neutrophils. Dexamethasone given 1 h after exposure to melphalan provided better protection against airway inflammation than administration 2 or 6 h after exposure. Collagen deposition 14 days after exposure was decreased due to dexamethasone treatment. Early treatment with dexamethasone is important in order to reduce the airway hyperresponsiveness and inflammation caused by toxic alkylating mustards such as melphalan. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of Intraoperative Dexamethasone on Pain Scores and Narcotic Consumption in Patients Undergoing Total Knee Arthroplasty.

PubMed

Samona, Jason; Cook, Carrie; Krupa, Kyle; Swatsell, Krystle; Jackson, Andrew; Dukes, Chase; Martin, Sidney

2017-02-01

To examine whether the addition of intravenous dexamethasone during total knee arthroplasty (TKA) would be effective at reducing postoperative pain scores and postoperative opioid consumption. A total of 102 patients undergoing TKA were placed into two groups: 55 subjects received intraoperative dexamethasone 8 mg intravenously (treatment group) and 47 did not receive dexamethasone at any time during the perioperative period. Comparison was made using the 0-10 numeric pain rating scale and the amount of opioids used in each group. Patients who received dexamethasone required significantly less oral opioids compared to the control group. Pain scores at 24 h post-surgery were significantly less for the dexamethasone group compared to the control group. There was no difference between groups in regards to patient-controlled analgesic dose or pain scores in the post-anesthesia care unit, at 12 or 48 h post-surgery. A single dose of dexamethasone given intraoperatively significantly decreased oral narcotic consumption and decreased pain scores 24 h postoperatively. Dexamethasone appears to be a safe modality to use to control pain in patients undergoing TKA. © 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Dissociation between systemic and pulmonary anti‐inflammatory effects of dexamethasone in humans

PubMed Central

Bartko, Johann; Stiebellehner, Leopold; Derhaschnig, Ulla; Schoergenhofer, Christian; Schwameis, Michael; Prosch, Helmut

2016-01-01

Aims The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute‐phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti‐inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. Methods In this randomized, double‐blind and placebo‐controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. Results Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C‐reactive protein release. In sharp contrast, dexamethasone left the local release of acute‐phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL‐6 were only 18% lower and levels of IL‐8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. Conclusions The present study demonstrated a remarkable dissociation between the systemic anti‐inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti‐inflammatory effects in the lungs on the other. PMID:26647918

[Transcorneal and transscleral iontophoresis of the dexamethasone phosphate into the rabbit eye].

PubMed

Raiskup-Wolf, F; Eljarrat-Binstock, E; Rehák, M; Domb, A; Frucht-Pery, J

2007-09-01

To evaluate the efficiency of the dexamethasone phosphate penetration into the rabbit eye after transcorneal and transscleral iontophoresis using a drug loaded hydrogel assembled on a portable iontophoretic Mini Ion device. lontophoresis of dexamethasone phosphate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel sponges and portable iontophoretic device. Corneal iontophoretic administration was performed with electric current of 1 mAmp for 1, 2, and 4 min. In the control group, the dexamethasone was applied in drops into the conjunctival sac. Transconjunctival and transscleral iontophoresis were performed in the pars plana area, through the conjunctiva or directly on the sclera. Dexamethasone concentrations were assayed using HPLC method. To study the anatomical changes after iontophoresis application, histological examinations of corneas excised 5 minutes and 8 hours after the procedure were performed. Dexamethasone levels in the rabbits' corneas after a single transcorneal iontophoresis were up to 38 times higher compared to those obtained after topical eye drops instillation. High drug concentrations were obtained in the retina and sclera 4 hours after transscleral iontophoresis as well. There were no statistically significant differences in the drug concentration after transscleral and tranconjunctival iontophoresis. Histological examination of the corneas after the iontophoresis showed only discrete reversible changes of the epithelium and the stroma. A short, low-current, non-invasive iontophoretic treatment using the dexamethasone-loaded hydrogels has a potential clinical value in increasing the drug's penetration into the anterior and posterior segment of the eye.

21 CFR 522.542 - Dexamethasone-21-isonicotinate suspension.

Code of Federal Regulations, 2012 CFR

2012-04-01

... suspension contains 1 milligram of dexamethasone-21-isonicotinate. (b) Sponsor. No. 000010 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in the treatment of various inflammatory conditions associated with the musculoskeletal system in dogs, cats, and horses. (2) It is recommended for...

21 CFR 522.542 - Dexamethasone-21-isonicotinate suspension.

Code of Federal Regulations, 2013 CFR

2013-04-01

... suspension contains 1 milligram of dexamethasone-21-isonicotinate. (b) Sponsor. No. 000010 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in the treatment of various inflammatory conditions associated with the musculoskeletal system in dogs, cats, and horses. (2) It is recommended for...

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma

PubMed Central

Weller, Edie; Lonial, Sagar; Jakubowiak, Andrzej J.; Jagannath, Sundar; Raje, Noopur S.; Avigan, David E.; Xie, Wanling; Ghobrial, Irene M.; Schlossman, Robert L.; Mazumder, Amitabha; Munshi, Nikhil C.; Vesole, David H.; Joyce, Robin; Kaufman, Jonathan L.; Doss, Deborah; Warren, Diane L.; Lunde, Laura E.; Kaster, Sarah; DeLaney, Carol; Hideshima, Teru; Mitsiades, Constantine S.; Knight, Robert; Esseltine, Dixie-Lee; Anderson, Kenneth C.

2010-01-01

This phase 1/2 study is the first prospective evaluation of lenalidomide-bortezomib-dexamethasone in front-line myeloma. Patients (N = 66) received 3-week cycles (n = 8) of bortezomib 1.0 or 1.3 mg/m2 (days 1, 4, 8, 11), lenalidomide 15 to 25 mg (days 1-14), and dexamethasone 40 or 20 mg (days 1, 2, 4, 5, 8, 9, 11, 12). Responding patients proceeded to maintenance or transplantation. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg, and dexamethasone 20 mg. Most common toxicities included sensory neuropathy (80%) and fatigue (64%), with only 27%/2% and 32%/3% grade 2/3, respectively. In addition, 32% reported neuropathic pain (11%/3%, grade 2/3). Grade 3/4 hematologic toxicities included lymphopenia (14%), neutropenia (9%), and thrombocytopenia (6%). Thrombosis was rare (6% overall), and no treatment-related mortality was observed. Rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Twenty-eight patients (42%) proceeded to undergo transplantation. With median follow-up of 21 months, estimated 18-month progression-free and overall survival for the combination treatment with/without transplantation were 75% and 97%, respectively. Lenalidomide-bortezomib-dexamethasone demonstrates favorable tolerability and is highly effective in the treatment of newly diagnosed myeloma. This study is registered at http://clinicaltrials.gov as NCT00378105. PMID:20385792

Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma

PubMed Central

Dimopoulos, Meletios A.; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S.; Niesvizky, Ruben; Jakubowiak, Andrzej J.; San-Miguel, Jesus F.; Ludwig, Heinz; Buchanan, Jacqui; Cocks, Kim; Yang, Xinqun; Xing, Biao; Zojwalla, Naseem; Tonda, Margaret; Moreau, Philippe; Palumbo, Antonio

2016-01-01

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma. PMID:27601539

Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma.

PubMed

Stewart, A Keith; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Buchanan, Jacqui; Cocks, Kim; Yang, Xinqun; Xing, Biao; Zojwalla, Naseem; Tonda, Margaret; Moreau, Philippe; Palumbo, Antonio

2016-11-10

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Prenatal Dexamethasone Augments the Neurobehavioral Teratology of Chlorpyrifos: Significance for Maternal Stress and Preterm Labor

PubMed Central

Levin, Edward D.; Cauley, Marty; Johnson, Joshua E.; Cooper, Ellen M.; Stapleton, Heather M.; Ferguson, P. Lee; Seidler, Frederic J.; Slotkin, Theodore A.

2014-01-01

Glucocorticoids are the consensus treatment given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so human developmental coexposures to these two agents are common. This study explores how prenatal dexamethasone exposure modifies the neurobehavioral teratology of chlorpyrifos, one of the most widely used organophosphates. We administered dexamethasone to pregnant rats on gestational days 17-19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1-4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. Dexamethasone did not alter brain chlorpyrifos concentrations, nor did either agent alone or in combination affect brain thyroxine levels. Assessments were carried out from adolescence through adulthood encompassing T-maze alternation, Figure-8 maze (locomotor activity, habituation), novelty-suppressed feeding and novel object recognition tests. For behaviors where chlorpyrifos or dexamethasone individually had small effects, the dual exposure produced larger, significant effects that reflected additivity (locomotor activity, novelty-suppressed feeding, novel object recognition). Where the individual effects were in opposite directions or were restricted to only one agent, we found enhancement of chlorpyrifos’ effects by prenatal dexamethasone (habituation). Finally, for behaviors where controls displayed a normal sex difference in performance, the combined treatment either eliminated or reversed the difference (locomotor activity, novel object recognition). Combined exposure to dexamethasone and chlorpyrifos results in a worsened neurobehavioral outcome, providing a proof-of-principle that prenatal glucocorticoids can create a subpopulation with enhanced vulnerability to environmental toxicants. PMID:24177596

Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

PubMed

Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

2012-11-01

This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p < 0.05). Although piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

Dexamethasone Injection

MedlinePlus

... severe allergic reactions. It is used in the management of certain types of edema (fluid retention and ... needed for normal body functioning) and in the management of certain types of shock. Dexamethasone injection is ...

Long-term outcome of prenatal dexamethasone treatment of 21-hydroxylase deficiency.

PubMed

Lajic, Svetlana; Nordenström, Anna; Hirvikoski, Tatja

2011-01-01

Prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone (DEX) has been in use since the mid- 1980s. Its effectiveness for reducing virilization of external genitalia is well established. DEX treatment has to be started in the 6th-7th postmenstrual week and continued until the results of the prenatal diagnosis are available. Hence, the dilemma is that 7 out of 8 fetuses (boys and unaffected girls) are treated unnecessarily. Girls with CAH are treated until term. Accumulating evidence from animal studies and follow-up data has raised concerns regarding the long-term consequences of this controversial treatment. We have previously reported that direct neuropsychological assessment of children exposed to DEX and controls show normal full-scale IQ, learning and longterm memory. However, the children exposed to DEX during the first trimester had an impaired verbal working memory which was significantly associated with low self-perceived scholastic competence. In addition, the children showed increased self-rated social anxiety. The same cohort of children answered questions concerning friends, activities and gender-related behaviors. The results indicate less masculine and more neutral behavior in short-term DEX-exposed boys. These findings indicate that long-term follow-ups of this group of patients are of extreme importance and that future DEX treatment of CAH may be questioned. We therefore encourage additional studies on larger cohorts in order to draw more decisive conclusions about the safety of the treatment. Until then, it is important that the parents are thoroughly informed about the potential risks and uncertainties, as well as the benefits, of this treatment. Copyright © 2011 S. Karger AG, Basel.

Dexamethasone as an adjuvant to peripheral nerve block.

PubMed

Pehora, Carolyne; Pearson, Annabel Me; Kaushal, Alka; Crawford, Mark W; Johnston, Bradley

2017-11-09

Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone. To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia. We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery. We used standard methodological procedures expected by Cochrane. We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tewari-Singh, Neera, E-mail: Neera.Tewari-Singh@ucdenver.edu; Jain, Anil K., E-mail: Anil.Jain@ucdenver.edu; Inturi, Swetha, E-mail: Swetha.Inturi@ucdenver.edu

There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and everymore » 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost

Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B-MuD) for the treatment of relapsed multiple myeloma.

PubMed

Mangiacavalli, Silvia; Pochintesta, Lara; Pascutto, Cristiana; Cocito, Federica; Pompa, Alessandra; Cazzola, Mario; Corso, Alessandro

2013-02-01

Since multiple myeloma (MM) is still not-curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80-100 mg/m² i.v.) on day 1. The original 21-day schedule was early amended for extra-hematological toxicity and a 35-day schedule was adopted (Bortezomib 1.3 mg/m² i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty-four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m². The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression-free survival (PFS) was 19.1 months. B-MuD resulted effective in patients previous exposed to bortezomib without difference of response (P = 0.25) and PFS (P = 0.87) when compared to bortezomib-naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B-MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase. Copyright © 2012 Wiley Periodicals, Inc.

Selective Window Application of Gentamicin+ Dexamethasone in Meniere's Disease.

PubMed

Ardıç, Fazıl Necdet; Tümkaya, Funda; Aykal, Kamil; Çabuk, Burçin

2017-08-01

The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease. It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted. In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP. The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.

Effects of prenatal dexamethasone treatment on physical growth, pituitary-adrenal hormones, and performance of motor, motivational, and cognitive tasks in juvenile and adolescent common marmoset monkeys.

PubMed

Hauser, Jonas; Knapman, Alana; Zürcher, Nicole R; Pilloud, Sonia; Maier, Claudia; Diaz-Heijtz, Rochellys; Forssberg, Hans; Dettling, Andrea; Feldon, Joram; Pryce, Christopher R

2008-12-01

Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report.

PubMed

Yennurajalingam, Sriram; Williams, Janet L; Chisholm, Gary; Bruera, Eduardo

2016-03-01

Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer. We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment. A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment. The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia-cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. ©AlphaMed Press.

Clinical Efficacy and Safety of Ranibizumab Versus Dexamethasone for Central Retinal Vein Occlusion (COMRADE C): A European Label Study.

PubMed

Hoerauf, Hans; Feltgen, Nicolas; Weiss, Claudia; Paulus, Eva-Maria; Schmitz-Valckenberg, Steffen; Pielen, Amelie; Puri, Pankaj; Berk, Hüsnü; Eter, Nicole; Wiedemann, Peter; Lang, Gabriele E; Rehak, Matus; Wolf, Armin; Bertelmann, Thomas; Hattenbach, Lars-Olof

2016-09-01

To compare the efficacy and safety of the European labels of ranibizumab 0.5 mg vs dexamethasone 0.7 mg in patients with macular edema secondary to central retinal vein occlusion (CRVO). Phase IIIb, multicenter, double-masked, randomized clinical trial. Patients were randomized (1:1) to receive either monthly ranibizumab followed by pro re nata (PRN) treatment (n = 124) or 1 sustained-release dexamethasone implant followed by PRN sham injections (n = 119). Main outcomes were mean average change in best-corrected visual acuity (BCVA) from baseline to month 1 through month 6, mean change in BCVA, and adverse events (AEs). Of 243 patients, 185 (76.1%) completed the study. No difference was observed in BCVA between ranibizumab and dexamethasone at months 1 and 2. From month 3 to month 6, there was significant difference in BCVA gains in favor of ranibizumab. At month 6, mean average BCVA gain was significantly higher with ranibizumab than with dexamethasone (12.86 vs 2.96 letters; difference 9.91 letters, 95% confidence interval [6.51-13.30]; P < .0001). Mean injection number of ranibizumab was 4.52. Ocular AEs were reported in more patients in the dexamethasone than in the ranibizumab group (86.6% vs 55.6%). Using the European labels, similar efficacy was observed for ranibizumab and dexamethasone at months 1 and 2. However, ranibizumab maintained its efficacy throughout the study, whereas dexamethasone declined from month 3 onward. The main limitation of the study was that dexamethasone patients received only a single treatment during the 6-month study. In clinical practice, dexamethasone retreatment may be required earlier than 6 months. Safety findings were similar to those previously reported. Copyright © 2016 Elsevier Inc. All rights reserved.

A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats.

PubMed

Tesic, Vesna; Perovic, Milka; Zaletel, Ivan; Jovanovic, Mirna; Puskas, Nela; Ruzdijic, Sabera; Kanazir, Selma

2017-11-01

The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats. Copyright © 2017 Elsevier Inc. All rights reserved.

A diels-alder modulated approach to control and sustain the release of dexamethasone and induce osteogenic differentiation of human mesenchymal stem cells

PubMed Central

Koehler, Kenneth C.; Alge, Daniel L.; Anseth, Kristi S.; Bowman, Christopher N.

2013-01-01

We report a new approach to controlled drug release based upon exploiting the dynamic equilibrium that exists between Diels-Alder reactants and products, demonstrating the release of a furan containing dexamethasone peptide (dex-KGPQG-furan) from a maleimide containing hydrogel. Using a reaction-diffusion model, the release kinetics were tuned to achieve sustained concentrations conducive to osteogenic differentiation of human mesenchymal stem cells (hMSCs). Efficacy was first demonstrated in a 2D culture model, in which dexamethasone release induced significant increases in alkaline phosphatase (ALP) activity and mineral deposition in hMSCs compared to a dexamethasone-free treatment. The results were similar to that observed with a soluble dexamethasone treatment. More dramatic differences were observed in 3D culture, where co-encapsulation of a dexamethasone releasing hydrogel depot within an hMSC-laden extracellular matrix mimetic poly(ethylene glycol) hydrogel resulted in a local and robust osteogenic differentiation. ALP activity reached levels that were up to six times higher than the dexamethasone free treatment. Interestingly, at 5 and 10 day time points, the ALP activity exceeded the dexamethasone positive control, suggesting a potential benefit of sustained release in 3D culture. After 21 days, substantial mineralization comparable to the positive control was also observed in the hydrogels. Collectively, these results demonstrate Diels-Alder modulated release as an effective and versatile new platform for controlled drug delivery that may prove especially beneficial for sustaining the release of low molecular weight molecules in hydrogel systems. PMID:23465826

Altered calcium handling and increased contraction force in human embryonic stem cell derived cardiomyocytes following short term dexamethasone exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kosmidis, Georgios; Bellin, Milena; Ribeiro, Marcelo C.

One limitation in using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) for disease modeling and cardiac safety pharmacology is their immature functional phenotype compared with adult cardiomyocytes. Here, we report that treatment of human embryonic stem cell derived cardiomyocytes (hESC-CMs) with dexamethasone, a synthetic glucocorticoid, activated glucocorticoid signaling which in turn improved their calcium handling properties and contractility. L-type calcium current and action potential properties were not affected by dexamethasone but significantly faster calcium decay, increased forces of contraction and sarcomeric lengths, were observed in hESC-CMs after dexamethasone exposure. Activating the glucocorticoid pathway can thus contribute to mediating hPSC-CMs maturation.more » - Highlights: • Dexamethasone accelerates Ca{sup 2+} transient decay in hESC-CMs. • Dexamethasone enhances SERCA and NCX function in hESC-CMs. • Dexamethasone increases force of contraction and sarcomere length in hESC-CMs. • Dexamethasone does not alter I{sub Ca,L} and action potential characteristics in hESC-CMs.« less

Dexamethasone-conjugated DNA nanotubes as anti-inflammatory agents in vivo.

PubMed

Sellner, Sabine; Kocabey, Samet; Zhang, Tao; Nekolla, Katharina; Hutten, Saskia; Krombach, Fritz; Liedl, Tim; Rehberg, Markus

2017-07-01

The biopolymer DNA allows to create nanoscale, biocompatible structures, which can be designed in a target-specific and stimuli-responsive manner. DNA carrier systems with these characteristics hold a great potential for nanomedical applications, such as for the treatment of inflammatory diseases. Here we used a DNA-based drug carrier system for the pH-dependent delivery of the glucocorticoid dexamethasone into macrophages, a cell type with a key role in the regulation of inflammation. Dexamethasone (Dex) nanotubes were internalized within minutes by MH-S macrophages in vitro and by tissue resident macrophages in the mouse cremaster muscle in vivo and localized in their endosomes. Treatment with Dex nanotubes in vitro significantly reduced the LPS-induced TNF secretion by macrophages, as compared to equivalent amounts of free dexamethasone without affecting cell viability. Microinjection of Dex nanotubes into postischemic muscle tissue of anesthetized mice resulted in a marked reduction of ischemia-reperfusion-elicited leukocyte transmigration and diminished vascular expression of the endothelial adhesion molecules VCAM-1 and ICAM-1. Taken together, our results demonstrate that DNA nanotubes can be used as a platform for the targeted delivery of glucocorticoids and could thus foster the development of nanomedical therapeutics with reduced off-target effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dexamethasone suppression test

MedlinePlus

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

Influence of Dexamethasone on O-(2-[18F]-Fluoroethyl)-L-Tyrosine Uptake in the Human Brain and Quantification of Tumor Uptake.

PubMed

Stegmayr, Carina; Stoffels, Gabriele; Kops, Elena Rota; Lohmann, Philipp; Galldiks, Norbert; Shah, Nadim J; Neumaier, Bernd; Langen, Karl-Josef

2018-05-29

O-(2-[ 18 F]fluoroethyl)-L-tyrosine ([ 18 F]FET) is an established positron emission tomography (PET) tracer for brain tumor imaging. This study explores the influence of dexamethasone therapy on [ 18 F]FET uptake in the normal brain and its influence on the maximum and mean tumor-to-brain ratio (TBR). [ 18 F]FET PET scans of 160 brain tumor patients were evaluated (80 dexamethasone treated, 80 untreated; each group with 40 men/40 women). The standardized uptake value of [ 18 F]FET uptake in the normal brain (SUV brain ) in the different groups was compared. Nine patients were examined repeatedly with and without dexamethasone therapy. SUV brain of [ 18 F]FET uptake was significantly higher in dexamethasone-treated patients than in untreated patients (SUV brain 1.33 ± 0.1 versus 1.06 ± 0.16 in male and 1.45 ± 0.25 versus 1.31 ± 0.28 in female patients). Similar results were observed in patients with serial PET scans. Furthermore, compared to men, a significantly higher SUV brain was found in women, both with and without dexamethasone treatment. There were no significant differences between the different groups for TBR max and TBR mean , which could have been masked by the high standard deviation. In a patient with a stable brain metastasis investigated twice with and without dexamethasone, the TBR max and the biological tumor volume (BTV) decreased considerably after dexamethasone due to an increased SUV brain . Dexamethasone treatment appears to increase the [ 18 F]FET uptake in the normal brain. An effect on TBR max , TBR mean , and BTV cannot be excluded which should be considered especially for treatment monitoring and the estimation of BTV using [ 18 F]FET PET.

Effects of a docosahexaenoic acid-rich microalgae nutritional product on insulin sensitivity after prolonged dexamethasone treatment in healthy mature horses.

PubMed

Brennan, Kristen M; Graugnard, Daniel E; Spry, Malinda L; Brewster-Barnes, Tammy; Smith, Allison C; Schaeffer, Rachel E; Urschel, Kristine L

2015-10-01

To determine effects of a microalgae nutritional product on insulin sensitivity in horses. 8 healthy mature horses. PROCEDURES :Horses (n = 4/group) received a basal diet without (control diet) or with docosahexaenoic acid-rich microalgae meal (150 g/d) for 49 days (day 0 = first day of diet). On day 28, an isoglycemic hyperinsulinemic clamp procedure was performed. Horses then received dexamethasone (0.04 mg/kg/d) for 21 days. On day 49, the clamp procedure was repeated. After a 60-day washout, horses received the alternate diet, and procedures were repeated. Plasma fatty acid, glucose, and insulin concentrations and glucose and insulin dynamics during the clamp procedure were measured on days 28 and 49. Two estimates of insulin sensitivity (reciprocal of the square root of the insulin concentration and the modified insulin-to-glucose ratio for ponies) were calculated. Baseline glucose and insulin concentrations or measures of insulin sensitivity on day 28 did not differ between horses when fed the control diet or the basal diet plus microalgae meal. On day 49 (ie, after dexamethasone administration), the microalgae meal was associated with lower baseline insulin and glucose concentrations and an improved modified insulin-to-glucose ratio for ponies, compared with results for the control diet. Although the microalgae meal had no effect on clamp variables following dexamethasone treatment, it was associated with improved plasma glucose and insulin concentrations and insulin sensitivity estimates. A role for microalgae in the nutritional management of insulin-resistant horses warrants investigation.

Respiratory Support for Very Low Birth Weight Infants Receiving Dexamethasone.

PubMed

Virkud, Yamini V; Hornik, Christoph P; Benjamin, Daniel K; Laughon, Matthew M; Clark, Reese H; Greenberg, Rachel G; Smith, P Brian

2017-04-01

To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. This is an observational study of infants discharged from one of 290 neonatal intensive care units from 2003 to 2010. The cohort included very low birth weight (<1500 g birth weight) infants born at ≤32 weeks gestational age. The main outcome was respiratory support at time of exposure to dexamethasone. Significant respiratory support was defined as invasive respiratory support (conventional or high-frequency ventilation) with a fraction of inspired oxygen (FiO 2 ) > 0.3. Of 81 292 infants; 7093 (9%) received dexamethasone. At the time that dexamethasone was initiated, 4604 (65%) of infants were on significant respiratory support. In accordance with the American Academy of Pediatrics recommendations, a majority of infants were on significant respiratory support when receiving dexamethasone, yet a substantial number of infants still received dexamethasone on less than significant respiratory support. Further research on reducing dexamethasone use in premature infants is required to decrease the risk of neurodevelopmental impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of combined ovariectomy with dexamethasone on rat lumbar vertebrae.

PubMed

Ren, Hui; Liang, De; Shen, Gengyang; Yao, Zhensong; Jiang, Xiaobing; Tang, Jingjing; Cui, Jianchao; Lin, Shunxin

2016-04-01

This study investigated the effects of combined ovariectomy with dexamethasone treatment on rat lumbar vertebrae in comparison with osteoporosis induced via ovariectomy or dexamethasone alone, and analysis of the associated molecular mechanism. Sixty-two female Sprague-Dawley rats (3 months' old) were randomly divided into five treatment groups: an untreated baseline (BL) group; those receiving a sham operation (SHAM); those receiving a dexamethasone injection alone (DEXA); those undergoing bilateral ovariectomy (OVX); and those subjected to both ovariectomy and dexamethasone injection (OVX-DEXA). Animals in the BL group were euthanized at the beginning of the experiment, whereas animals in the remaining groups were euthanized at the end of the first month (M1), second month (M2), or third month (M3). Bone mineral density, bone microarchitecture, biomechanical properties of vertebrae, and serum levels of estrogen, amino-terminal propeptide of type I collagen (PINP), and β-C-telopeptide of type I collagen (β-CTX) were measured. In addition, we examined biglycan, runt-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), lipoprotein receptor-related protein-5 (LRP-5), cathepsin K (CTSK), and sclerostin mRNA expression. Bone mineral content and bone mineral density were markedly lower in the OVX-DEXA group compared with the OVX group at all time points examined. The relative bone surface (BS/TV, mm(-1), relative bone volume (BV/TV,%), and trabecular number (Tb.N, 1/mm) were markedly lower in the OVX-DEXA group compared with the remaining groups, whereas trabecular separation (Tb.Sp, mm) was markedly higher in the OVX-DEXA group compared with the remaining groups at M2 or M3. The OVX-DEXA group showed lower compressive strength and lower stiffness compared with the other groups at M2 and M3. Compressive displacement and energy absorption capacity were also markedly lower in the OVX-DEXA group compared with the OVX group at M3. Estradiol levels were markedly

Effect of Pregabalin and Dexamethasone on Postoperative Analgesia after Septoplasty

PubMed Central

Demirhan, Abdullah; Akkaya, Akcan; Tekelioglu, Umit Yasar; Apuhan, Tayfun; Bilgi, Murat; Yurttas, Veysel; Bayir, Hakan; Yildiz, Isa; Gok, Uzeyir; Kocoglu, Hasan

2014-01-01

Objectives. The aim of this study was to explore effect of a combination of pregabalin and dexamethasone on pain control after septoplasty operations. Methods. In this study, 90 patients who were scheduled for septoplasty under general anesthesia were randomly assigned into groups that received either placebo (Group C), pregabalin (Group P), or pregabalin and dexamethasone (Group PD). Preoperatively, patients received either pregabalin 300 mg one hour before surgery, dexamethasone 8 mg intravenously during induction, or placebo according to their allocation. Postoperative pain treatment included tramadol and diclofenac sodium 30 minutes before the end of the operation. Numeric rating scale (NRS) for pain assessment, side effects, and consumption of tramadol, pethidine, and ondansetron were recorded. Results. The median NRS score at the postoperative 0 and the 2nd h was significantly higher in Group C than in Group P and Group PD (P ≤ 0.004 for both). The 24 h tramadol and pethidine, consumptions were significantly reduced in Groups P and PD compared to Group C (P < 0.001 and P < 0.001). The incidence of blurred vision was significantly higher in Group PD compared to Group C within both 0–2 h and 0–24 h periods (P = 0.002 and P < 0.001, resp.). Conclusions. We conclude that administration of 300 mg pregabalin preoperatively may be an adequate choice for pain control after septoplasty. Addition of dexamethasone does not significantly reduce pain in these patients. PMID:24876957

Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

PubMed Central

Carmichael, J.; Bessell, E. M.; Harris, A. L.; Hutcheon, A. W.; Dawes, P. J.; Daniels, S.; Bessel, E. M.

1994-01-01

Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone. PMID:7981069

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

PubMed Central

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

Comparative analysis of Lacistema pubescens and dexamethasone on topical treatment of skin inflammation in a chronic disease model and side effects.

PubMed

da Silva, Josiane M; Conegundes, Jéssica L M; Pinto, Nícolas C C; Mendes, Renata F; Castañon, Maria Christina M N; Scio, Elita

2018-04-01

This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases. © 2018 Royal Pharmaceutical Society.

Dexamethasone intravitreal implant (Ozurdex) for the treatment of pediatric uveitis.

PubMed

Bratton, Monica L; He, Yu-Guang; Weakley, David R

2014-04-01

To report our experience using Ozurdex (Allergan, Irvine, CA), a biodegradable intravitreal implant containing of 0.7 mg of dexamethasone approved for use in adults with noninfectious uveitis in adults, in the treatment of pediatric uveitis. The medical records of consecutive patients with noninfectious posterior uveitis who were unresponsive to standard treatment and subsequently received the Ozurdex implant from March 2011 to March 2013 were retrospectively reviewed. A total of 14 eyes of 11 patients (mean age, 10.1 years; range 4-12) received 22 Ozurdex implants during the study period. Of the 11 patients, 7 had idiopathic intermediate or posterior uveitis, 1 had sympathetic ophthalmia, 2 had juvenile idiopathic arthritis, and 1 had sarcoidosis. All patients were uncontrolled with standard treatment, including topical or sub-Tenon's or systemic corticosteriods and/or immune-modulation. Visual acuity improved after Ozurdex implant in 5 of 8 patients (63%). Intraocular inflammation was controlled or improved after 17 of 22 of implants (12 eyes [77%]). The frequency of topical corticosteroids was decreased and/or discontinued after 18 of 22 implants (12 eyes [82%]). Complications included implant migration into the anterior chamber (4 aphakic eyes), increased intraocular pressure (5 eyes), and progression of a preexisting cataract (1 eye). The uveitis reoccurred in 57% of eyes at 4.3 months (2-7 months) after injection. The Ozurdex implant in combination with systemic immunomodulatory therapy resulted in improved visual acuity, control of intraocular inflammation, and a decrease in corticosteroid use. In the majority of eyes the uveitis reoccurred around 4 months after injection. The adverse events in our study are similar to those identified in adult studies. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Dexamethasone enhances agonist induction of tissue factor in monocytes but not in endothelial cells.

PubMed

Bottles, K D; Morrissey, J H

1993-06-01

Stimulation of monocytic cells by inflammatory agents such as bacterial lipopolysaccharide or tumour necrosis factor-alpha leads to the rapid and transient expression of tissue factor, the major cellular initiator of the extrinsic coagulation cascade in both haemostasis and tissue inflammation. In this study we investigated whether the synthetic anti-inflammatory glucocorticoid, dexamethasone, would inhibit agonist induction of tissue factor expression in both monocytes and endothelial cells. Surprisingly, dexamethasone significantly enhanced the induction of tissue factor expression by peripheral blood mononuclear cells and an established monocytic cell line, THP-1, in response to lipopolysaccharide or tumour necrosis factor-alpha. However, unlike monocytic cells, dexamethasone did not enhance agonist induction of tissue factor in endothelial cells. Synergistic enhancement of tissue factor expression by dexamethasone was also reflected in tissue factor mRNA levels in THP-1 cells, but was not the result of improved TF mRNA stability. Synergism between bacterial lipopolysaccharide and glucocorticoid in the induction of monocyte effector function is extremely unusual and may help to explain the variable outcome of glucocorticoid treatment of septic shock.

Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiation

PubMed Central

Belanto, Joseph J.; Diaz-Perez, Silvia V.; Magyar, Clara E.; Maxwell, Michele M.; Yilmaz, Yasemin; Topp, Kasey; Boso, Guney; Jamieson, Catriona H.; Cacalano, Nicholas A.; Jamieson, Christina A.M.

2010-01-01

Glucocorticoids are beneficial in many muscular dystrophies but they are ineffective in treating dysferlinopathy, a rare muscular dystrophy caused by loss of dysferlin. We sought to understand the molecular basis for this disparity by studying the effects of a glucocorticoid on differentiation of the myoblast cell line, C2C12, and dysferlin-deficient C2C12s. We found that pharmacologic doses of dexamethasone enhanced the myogenic fusion efficiency of C2C12s and increased the induction of dysferlin, along with specific myogenic transcription factors, sarcolemmal and structural proteins. In contrast, the dysferlin-deficient C2C12 cell line demonstrated a reduction in long myotubes and early induction of particular muscle differentiation proteins, most notably, myosin heavy chain. Dexamethasone partially reversed the defect in myogenic fusion in the dysferlin-deficient C2C12 cells. We hypothesize that a key therapeutic benefit of glucocorticoids may be the up-regulation of dysferlin as an important component of glucocorticoid-enhanced myogenic differentiation. PMID:20080405

Effects of thyroxine and dexamethasone on rat submandibular glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sagulin, G.B.; Roomans, G.M.

1989-08-01

Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular salivamore » was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol.« less

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin, thiabendazole, and dexamethasone solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Neomycin, thiabendazole, and dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin, thiabendazole, and dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

Effect of early handling of turkey poults on later responses to multiple dexamethasone-Escherichia coli challenge. 2. Resistance to air sacculitis and turkey osteomyelitis complex.

PubMed

Huff, G R; Huff, W E; Balog, J M; Rath, N C

2001-09-01

Dexamethasone (DEX)-induced immunosuppression facilitates Escherichia coli pathogenesis leading to lesions of air sacculitis and turkey osteomyelitis complex (TOC). The purpose of this study was to determine if early handling could affect resistance to disease in this model. Seven hundred twenty male turkey poults were handled 0, 1 (1x), or 2 (2x) times daily for the first 10 d after hatch. Handling consisted of gently catching each individual poult, holding it for 10 s, and placing it into a basket. Starting on Day 11 after hatch, half of the birds from each handling treatment were treated with three injections of 2 mg DEX/kg BW on alternating days. On the day of the third DEX treatment, duplicate pens of birds were also inoculated in the air sac with 0 or 50 cfu of E. coli. All DEX-treated birds were given a second series of DEX injections at 5 wk of age, and 10 birds per pen were necropsied 3 wk later. Surviving birds were treated with a third series of DEX injections at 10 wk of age. Two weeks later, all surviving turkeys were necropsied. All mortalities and necropsied birds were scored for air sacculitis and examined for TOC lesions. All livers, air sacs, and TOC lesions were cultured for bacteria. There was increased mortality after the first series of DEX treatments of birds handled 2x. After the second series of DEX treatments, birds handled 1x had increased mortality, incidence of air sacculitis, and recovery of E. coli from tissues, whereas 2x handled birds were identical to unhandled controls. After the third series of DEX treatments, handling 1x resulted in decreased air sacculitis scores and decreased incidence of mortality, green liver, TOC lesions, and recovery of E. coli from tissues. The effects of early handling of turkey poults were variable, depending on the number of DEX treatments and the age of the birds. These results suggest that early handling can affect the susceptibility of stressed turkeys to E. coli air sacculitis and TOC and that

Prenatal Dexamethasone Augments the Sex-Selective Developmental Neurotoxicity of Chlorpyrifos: Implications for Vulnerability after Pharmacotherapy for Preterm Labor

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Infante, Alice; Seidler, Frederic J.

2013-01-01

Glucocorticoids are routinely given in preterm labor and are also elevated by maternal stress; organophosphate exposures are virtually ubiquitous, so coexposures to these two agents are pervasive. We administered dexamethasone to pregnant rats on gestational days 17–19 at a standard therapeutic dose (0.2 mg/kg); offspring were then given chlorpyrifos on postnatal days 1–4, at a dose (1 mg/kg) that produces barely-detectable (<10%) inhibition of brain cholinesterase activity. We evaluated indices for acetylcholine (ACh) synaptic function throughout adolescence, young adulthood and later adulthood, in brain regions possessing the majority of ACh projections and cell bodies; we measured nicotinic ACh receptor binding, hemicholinium-3 binding to the presynaptic choline transporter and choline acetyltransferase activity, all known targets for the adverse developmental effects of dexamethasone and chlorpyrifos given individually. Dexamethasone did not enhance the systemic toxicity of chlorpyrifos, as evidenced by weight gain and measurements of cholinesterase inhibition during chlorpyrifos treatment. Nevertheless, it enhanced the loss of presynaptic ACh function selectively in females, who ordinarily show sparing of organophosphate developmental neurotoxicity relative to males. Females receiving the combined treatment showed decrements in choline transporter binding and choline acetyltransferase activity that were unique (not found with either treatment alone), as well as additive decrements in nicotinic receptor binding. On the other hand, males given dexamethasone showed no augmentation of the effects of chlorpyrifos. Our findings indicate that prior dexamethasone exposure could create a subpopulation that is especially vulnerable to the adverse effects of organophosphates or other developmental neurotoxicants. PMID:23416428

Inhaled budesonide and oral dexamethasone prevent acute mountain sickness.

PubMed

Zheng, Cheng-Rong; Chen, Guo-Zhu; Yu, Jie; Qin, Jun; Song, Pan; Bian, Shi-Zhu; Xu, Bai-Da; Tang, Xu-Gang; Huang, Yong-Tao; Liang, Xiao; Yang, Jie; Huang, Lan

2014-10-01

This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after acute high-altitude exposure. There were 138 healthy young male lowland residents recruited and randomly assigned to receive inhaled budesonide (200 μg, twice a day [bid]), oral dexamethasone (4 mg, bid), or placebo (46 in each group). They traveled to 3900 m altitude from 400 m by car. Medication started 1 day before high-altitude exposure and continued until the third day of exposure. Primary outcome measure was the incidence of acute mountain sickness after exposure. One hundred twenty-four subjects completed the study (42, 39, and 43 in the budesonide, dexamethasone, and placebo groups, respectively). Demographic characteristics were comparable among the 3 groups. After high-altitude exposure, significantly fewer participants in the budesonide (23.81%) and dexamethasone (30.77%) groups developed acute mountain sickness compared with participants receiving placebo (60.46%) (P = .0006 and P = .0071, respectively). Both the budesonide and dexamethasone groups had lower heart rate and higher pulse oxygen saturation (SpO2) than the placebo group at altitude. Only the budesonide group demonstrated less deterioration in forced vital capacity and sleep quality than the placebo group. Four subjects in the dexamethasone group reported adverse reactions. Both inhaled budesonide (200 μg, bid) and oral dexamethasone (4 mg, bid) were effective for the prevention of acute mountain sickness, especially its severe form, compared with placebo. Budesonide caused fewer adverse reactions than dexamethasone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Administration of dexamethasone and mortality in brain abscess patients: A Systematic Review and Meta-Analysis.

PubMed

Simjian, Thomas; Muskens, Ivo S; Lamba, Nayan; Yunusa, Ismaeel; Wong, Kristine; Veronneau, Raymond; Kronenburg, Annick; Brouwers, H Bart; Smith, Timothy R; Mekary, Rania A; Broekman, M L D

2018-04-26

Dexamethasone has been used to treat cerebral edema associated with brain abscesses. Whereas some argue that dexamethasone might aid the antibiotic treatment, others believe that because of its immune-suppressive characteristics, it might have a negative impact on outcomes. To date it is still unclear how corticosteroid use affects overall mortality of brain abscess patients. A systematic search of the literature was conducted in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane databases were utilized to identify all studies related to patients diagnosed with a brain abscess treated with dexamethasone. The main outcome of interest was mortality. Pooled effect estimates were calculated using fixed-effect (FE) and random-effects (RE) models. After removal of duplicates, 1681 articles were extracted from the literature of which 11 were included. These included 7 cohort studies and 4 case series. Indications to administer dexamethasone were either hospital brain abscess protocol or clinical presentation of cerebral edema. The seven cohort studies involving 571 patients with brain abscesses comprised of 330 patients treated with standard of care (SOC) plus dexamethasone and 241 patients treated with SOC alone, after aspiration or surgical management of the abscess in either group. Pooling results from all seven cohort studies demonstrated a non-significant mortality benefit comparing SOC and dexamethasone patients to SOC patients (RR= 0.94; 95% CI: 0.64-1.37, FE; RR=0.95; 95% CI: 049-1.82, RE; I 2 = 53.9%; P-heterogeneity = 0.04). In brain abscess patients treated with antibiotics, the use of dexamethasone was not associated with increased mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Dexamethasone effects on (/sup 125/I)albumin distribution in experimental RG-2 gliomas and adjacent brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakagawa, H.; Groothuis, D.R.; Owens, E.S.

1987-12-01

A total of 72 RG-2 transplanted gliomas were studied in 58 rats at three time points (1, 30, 240 min) after intravenous injection of (/sup 125/I)radioiodinated serum albumin ((/sup 125/I)RISA). The animals were divided into two groups: a control group that received no treatment and a second group that was treated with five doses of 1.5 mg/kg of dexamethasone over 2.5 days. Local tissue concentrations of (/sup 125/I)RISA were measured with quantitative autoradiography based on morphological features of the tumors and used to calculate the tissue distribution space. Two models were used to analyze the data. A two compartment modelmore » yielded estimates of local blood-to-tissue influx constants (K1), lower limit extracellular volumes (Ve), and plasma vascular volumes (Vp) in different tumor regions. Treatment with dexamethasone consistently reduced the RISA distribution space in the RG-2 tumors; the reduction in Ve was statistically significant in almost all tumor regions: whole tumor Ve (mean +/- SE) was reduced from 0.14 +/- 0.02 ml g-1 in control animals to 0.08 +/- 0.01 ml g-1 in dexamethasone treated animals. K1 and Vp were also decreased in all tumor regions after treatment with dexamethasone (whole tumor K1 decreased from 2.36 +/- 0.89 to 0.83 +/- 0.29 microliter g-1 min-1 and Vp decreased slightly from 0.016 +/- 0.013 to 0.010 +/- 0.005 ml g-1 after dexamethasone treatment), but these changes were not statistically significant. A comparison of the tumor influx constants in control animals and the aqueous diffusion constants of two different size molecules (RISA and aminoisobutyric acid) suggests that the ''pores'' across RG-2 capillaries are large and may not restrict the free diffusion of RISA (estimated minimum pore diameter greater than 36 nm) and that the total pore area is approximately 6.2 X 10(-5) cm2 g-1 in RG-2 tumor tissue.« less

In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

2015-02-01

Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

Effects of 2-oxoglutaric acid on bone morphometry, densitometry, mechanics, and immunohistochemistry in 9-month-old boars with prenatal dexamethasone-induced osteopenia.

PubMed

Tomaszewska, Ewa; Dobrowolski, Piotr; Bieńko, Marek; Prost, Łukasz; Szymańczyk, Sylwia; Zdybel, Adam

2015-11-01

The structural quality of the connective tissue is genetically determined and is influenced by hormonal and nutritional modification. An effect of a 2-Ox-rich diet on bone mineralization and structure and expression of non-collagenous protein in articular and growth cartilages of maternal dexamethasone-treated 9-month-old boars was considered in this study. Sows were treated i.m. with dexamethasone at the dose of 0.03 mg kg(-1) body weight every second day during the last 45 days of pregnancy. After the birth, the boars were divided into two groups: administered and not supplemented with 2-Ox for 9 months (0.4 g/kg body weight/day). Dexamethasone given during the prenatal time inhibited the growth and negatively influenced the mechanics, geometry and histomorphometrical parameters of long bones and cartilage irrespective of the diet. Moreover, maternal dexamethasone treatment resulted in expression of osteocalcin in the articular cartilage, and the diet rich in 2-Ox limited the OC expression. This study demonstrated that changes observed in adult boars initiated by dexamethasone treatment in the prenatal period were persistent and long-term use of alimentary 2-Ox supplementation can counteract only some of the destructive changes evoked by prenatal dexamethasone excess.

Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study

PubMed Central

Rosovsky, Rachel; Hong, Fangxin; Tocco, Deanna; Connell, Brendan; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Warren, Diane; Bradwin, Gary; Doyle, Mary; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul

2014-01-01

Summary In this prospective study of patients with relapsed and/or refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1–4, 9–12, and 17–21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15, and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0·05), fibrinogen (P = 0·008), plasminogen activator inhibitor-1 (P < 0·001), homocysteine (P = 0·002), and P-selectin (P < 0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin, and vascular endothelial growth factor (P < 0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach. PMID:23240658

Dexamethasone implant in silicone oil: in vitro behavior.

PubMed

Flores-Villalobos, Erick Omar; Ramírez-Estudillo, J Abel; Robles-Contreras, Atzin; Oliva-Ramírez, Jacqueline L

2018-01-01

To determine the effect of the silicone on the dexamethasone intravitreal implant. Basic, experimental, prospective and transversal study performed at the hospital "Nuestra Señora de la Luz" in Mexico City. One dexamethasone implant was placed in a test tube with 4 mL of each tamponade medium: 1000cS, 5000cS and heavy silicone oil; basic saline solution was used as the control medium. Photographs were taken weekly for 12 months. 200 µL samples were taken from each medium at 24 h, 1, 2 weeks and monthly for 12 months. ELISA test was performed to quantify dexamethasone release in every sample. An inflammatory stimulus was created and later exposed it to every sample in order to test their anti-inflammatory capacity by cytokine analysis using cytometric bead array. Statistically significant results were obtained with p < 0.05. Photographic follow-up showed disintegration of the implant in control medium. Implants in silicone oil suffered no changes during follow-up. Dexamethasone levels in control medium showed stability from month 2 to 12. Silicone oil mediums showed irregular dexamethasone release during the 1 year period. Dexamethasone in control medium had inhibitory effects on TNF-α starting at 24 h (p < 0.001) and remained stable. Dexamethasone in 1000cS silicone oil showed inhibitory effects from month 2 (p < 0.001) until month 6 (p < 0.001). Implants in denser silicone oils showed no inhibitory effects in any of the samples. Denser mediums altered the implant pharmacokinetics and showed no anti-inflammatory effects even when concentrations were quantified at levels similar to control medium in vitro.

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose

PubMed Central

Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

2017-01-01

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength (P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13–45%) decreased compared to the control (P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2

Dexamethasone Prophylaxis to Alleviate Postembolization Syndrome after Transarterial Chemoembolization for Hepatocellular Carcinoma: A Randomized, Double-Blinded, Placebo-Controlled Study.

PubMed

Yang, Hyun; Seon, Jein; Sung, Pil Soo; Oh, Jung Suk; Lee, Hae Lim; Jang, Bohyun; Chun, Ho Jong; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

2017-11-01

To test the hypothesis that prophylactic administration of dexamethasone alleviates postembolization syndrome (PES) after transarterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). This prospective, randomized, double-blinded, placebo-controlled trial was conducted in a single center from August 2015 to June 2016. A total of 88 patients with intermediate-stage HCC were enrolled. After randomization, 44 patients were assigned to the dexamethasone group and the other 44 to the control group. In the dexamethasone group, 12 mg of intravenous dexamethasone was administered before chemoembolization. Nausea, vomiting, fever, pain, and alanine aminotransferase level elevation were evaluated after chemoembolization had been performed with the use of Lipiodol and doxorubicin. The incidences of PES were 78.0% in the dexamethasone group and 97.5% in the control group (P = .008). Mean hospitalization times after chemoembolization were 2.7 days ± 1.44 in the dexamethasone group and 2.9 days ± 1.83 in the control group (P = .553). Mean doses of antiemetic and analgesic agents were lower in the dexamethasone group than the control group (0.2 ± 0.58 vs 1.0 ± 1.89 [P = .029] and 0.6 ± 0.97 vs 1.92 ± 2.54 [P = .006], respectively). Prophylactic administration of dexamethasone was a significant factor that influences PES occurrence after chemoembolization (odds ratio = 10.969, P = .027). This study demonstrates that the prophylactic administration of dexamethasone before chemoembolization is an effective way to reduce PES. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Formation of alveoli in rats: postnatal effect of prenatal dexamethasone.

PubMed

Massaro, G D; Massaro, D

1992-07-01

We administered a glucocorticosteroid (dexamethasone) or its diluent to pregnant rats on gestation days 17, 18, and 19. In male offspring we determined the lung's gas exchange surface area (S(a)), the average volume (v) of gas exchange saccules at age 2 days and alveoli at age 14 days, and their number (N) on these days. S(a), v, and N at 2 days and v at 14 days were not affected by the prenatal administration of dexamethasone. However, S(a) and N were lower in 14-day-old pups from dexamethasone-treated dams than in pups from diluent-treated dams. In separate experiments we found the responsiveness to prenatal dexamethasone, as a depressor of the postnatal increase in S(a), appeared earlier in female than male fetuses; it was present in female but not in male fetuses on days 16-18 and was found in male fetuses on days 17-19. We conclude 1) prenatal administration of dexamethasone diminishes the postnatal increase in S(a), 2) responsiveness to this action of dexamethasone occurs earlier in gestation in female than in male fetuses, and 3) prenatal dexamethasone does not effect the postnatal volume of an average alveolus but diminishes their number in male pups.

Adjunctive Dexamethasone Affects the Expression of Genes Related to Inflammation, Neurogenesis and Apoptosis in Infant Rat Pneumococcal Meningitis

PubMed Central

Blaser, Cornelia; Wittwer, Matthias; Grandgirard, Denis; Leib, Stephen L.

2011-01-01

Streptococcus pneumoniae is the most common pathogen causing non-epidemic bacterial meningitis worldwide. The immune response and inflammatory processes contribute to the pathophysiology. Hence, the anti-inflammatory dexamethasone is advocated as adjuvant treatment although its clinical efficacy remains a question at issue. In experimental models of pneumococcal meningitis, dexamethasone increased neuronal damage in the dentate gyrus. Here, we investigated expressional changes in the hippocampus and cortex at 72 h after infection when dexamethasone was given to infant rats with pneumococcal meningitis. Nursing Wistar rats were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis or were sham-infected with pyrogen-free saline. Besides antibiotics, animals were either treated with dexamethasone or saline. Expressional changes were assessed by the use of GeneChip® Rat Exon 1.0 ST Arrays and quantitative real-time PCR. Protein levels of brain-derived neurotrophic factor, cytokines and chemokines were evaluated in immunoassays using Luminex xMAP® technology. In infected animals, 213 and 264 genes were significantly regulated by dexamethasone in the hippocampus and cortex respectively. Separately for the cortex and the hippocampus, Gene Ontology analysis identified clusters of biological processes which were assigned to the predefined categories “inflammation”, “growth”, “apoptosis” and others. Dexamethasone affected the expression of genes and protein levels of chemokines reflecting diminished activation of microglia. Dexamethasone-induced changes of genes related to apoptosis suggest the downregulation of the Akt-survival pathway and the induction of caspase-independent apoptosis. Signalling of pro-neurogenic pathways such as transforming growth factor pathway was reduced by dexamethasone resulting in a lack of pro-survival triggers. The anti-inflammatory properties of dexamethasone were observed on gene and protein

The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM.

PubMed

Follin-Arbelet, Virginie; Misund, Kristine; Naderi, Elin Hallan; Ugland, Hege; Sundan, Anders; Blomhoff, Heidi Kiil

2015-08-26

We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM.

The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM

PubMed Central

Follin-Arbelet, Virginie; Misund, Kristine; Hallan Naderi, Elin; Ugland, Hege; Sundan, Anders; Kiil Blomhoff, Heidi

2015-01-01

We have previously demonstrated that activation of the cyclic adenosine monophosphate (cAMP) pathway kills multiple myeloma (MM) cells both in vitro and in vivo. In the present study we have investigated the potential of enhancing the killing of MM cell lines and primary MM cells by combining the cAMP-elevating compound forskolin with the commonly used MM therapeutic drugs melphalan, cyclophosphamide, doxorubicin, bortezomib and dexamethasone. We observed that forskolin potentiated the killing induced by all the tested agents as compared to treatment with the single agents alone. In particular, forskolin had a synergistic effect on the dexamethasone-responsive cell lines H929 and OM-2. By knocking down the proapoptotic BCL-2 family member BIM, we proved this protein to be involved in the synergistic induction of apoptosis by dexamethasone and forskolin. The ability of forskolin to maintain the killing of MM cells even at lower concentrations of the conventional agents suggests that forskolin may be used to diminish treatment-associated side effects. Our findings support a potential role of forskolin in combination with current conventional agents in the treatment of MM. PMID:26306624

The effect of phenytoin, phenobarbitone, dexamethasone and flurbiprofen on misonidazole neurotoxicity in mice.

PubMed Central

Sheldon, P. W.; Clarke, C.; Dawson, K. B.

1984-01-01

Using a quantitative cytochemical technique for measuring beta-glucuronidase activity in the peripheral nerves of mice, we have investigated the effectiveness of four potential adjuncts for reducing the dose limiting neurotoxicity of misonidazole (MISO) in the clinic. Under the conditions used, the most effective adjunct was the steroid anti-inflammatory agent dexamethasone. When given over the week previous to MISO treatment, this agent almost completely eliminated the MISO neurotoxicity as determined at week 4 after commencement of MISO dosing. The second most effective adjunct was phenytoin, the third flurbiprofen and the last adjunct, phenobarbitone, was ineffective. Dexamethasone, phenytoin and phenobarbitone all reduced the clearance half-life of MISO and hence the drug exposure dose calculated as the area under the curve of MISO tissue concentration against time. However, no correlation was evident with these parameters and MISO neurotoxicity in the mouse. Dexamethasone, whilst affording protection against MISO toxicity, did not alter the radiosensitivity of the anaplastic MT tumour. PMID:6696821

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention.

PubMed

Komane, Patrick P; Kumar, Pradeep; Marimuthu, Thashree; Toit, Lisa C du; Kondiah, Pierre P D; Choonara, Yahya E; Pillay, Viness

2018-06-10

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats.

Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations.

PubMed

Paniagua, Natalia; Lopez, Rebeca; Muñoz, Natalia; Tames, Miriam; Mojica, Elisa; Arana-Arri, Eunate; Mintegi, Santiago; Benito, Javier

2017-12-01

To determine whether 2 doses of dexamethasone is as effective as 5 days of prednisolone/prednisone therapy in improving symptoms and quality of life of children with asthma exacerbations admitted to the emergency department (ED). We conducted a randomized, noninferiority trial including patients aged 1-14 years who presented to the ED with acute asthma to compare the efficacy of 2 doses of dexamethasone (0.6 mg/kg/dose, experimental treatment) vs a 5-day course of prednisolone/prednisone (1.5 mg/kg/d, followed by 1 mg/kg/d on days 2-5, conventional treatment). Two follow-up telephone interviews were completed at 7 and 15 days. The primary outcome measures were the percentage of patients with asthma symptoms and quality of life at day 7. Secondary outcomes were unscheduled returns, admissions, adherence, and vomiting. During the study period, 710 children who met the inclusion criteria were invited to participate and 590 agreed. Primary outcome data were available in 557 patients. At day 7, experimental and conventional groups did not show differences related to persistence of symptoms (56.6%, 95% CI 50.6-62.6 vs 58.3%, 95% CI 52.3-64.2, respectively), quality of life score (80.0 vs 77.7, not significant [ns]), admission rate (23.9% vs 21.7%, ns), unscheduled ED return visits (4.6% vs 3.3%, ns), and vomiting (2.1% vs 4.4%, ns). Adherence was greater in the dexamethasone group (99.3% vs 96.0%, P < .05). Two doses of dexamethasone may be an effective alternative to a 5-day course of prednisone/prednisolone for asthma exacerbations, as measured by persistence of symptoms and quality of life at day 7. clinicaltrialsregister.eu: 2013-003145-42. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma.

PubMed

Kumar, Shaji K; Laubach, Jacob P; Giove, Thomas J; Quick, Maureen; Neuwirth, Rachel; Yung, Godwin; Rajkumar, S Vincent; Richardson, Paul G

2017-09-01

Peripheral neuropathy (PN) is the most troublesome adverse event associated with the proteasome inhibitor bortezomib. Studies suggest an inflammatory aetiology for bortezomib-induced PN (BiPN) and it has been hypothesized that reducing inflammation with concomitant dexamethasone may reduce BiPN incidence and/or severity. We retrospectively analysed PN rates from 32 studies (2697 patients with previously untreated multiple myeloma) incorporating bortezomib and differing dexamethasone schedules: partnered dosing (days of and after bortezomib), weekly dosing, and other dosing schedules (e.g. days 1-4, 8-11). Pooled overall PN rates were 45·5%, 63·9%, and 47·5%, respectively, with 5·3%, 11·0%, and 9·6% grade ≥3. Adjusting for potential confounders (age, gender, presence of thalidomide, bortezomib treatment duration), PN rates in patients on partnered dosing schedules appeared lower than in patients on weekly or other dosing schedules. Analyses conducted using patient-level data suggest that cumulative dexamethasone dose, a potential confounding factor, is unlikely to have influenced the analyses. Findings were similar in a separate pooled analysis excluding data from regimens incorporating thalidomide, when pooled overall PN rates were 50·1%, 63·9%, and 48·3%, respectively, with 4·2%, 11·0%, and 8·6% grade ≥3. These findings suggest that partnered dexamethasone dosing may result in less severe BiPN compared with alternative dexamethasone dosing schedules. © 2017 John Wiley & Sons Ltd.

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

PubMed

Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

2018-03-01

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Effective immunosuppression with dexamethasone phosphate in the Galleria mellonella larva infection model resulting in enhanced virulence of Escherichia coli and Klebsiella pneumoniae.

PubMed

Torres, Miquel Perez; Entwistle, Frances; Coote, Peter J

2016-08-01

The aim was to evaluate whether immunosuppression with dexamethasone 21-phosphate could be applied to the Galleria mellonella in vivo infection model. Characterised clinical isolates of Escherichia coli or Klebsiella pneumoniae were employed, and G. mellonella larvae were infected with increasing doses of each strain to investigate virulence in vivo. Virulence was then compared with larvae exposed to increasing doses of dexamethasone 21-phosphate. The effect of dexamethasone 21-phosphate on larval haemocyte phagocytosis in vitro was determined via fluorescence microscopy and a burden assay measured the growth of infecting bacteria inside the larvae. Finally, the effect of dexamethasone 21-phosphate treatment on the efficacy of ceftazidime after infection was also noted. The pathogenicity of K. pneumoniae or E. coli in G. mellonella larvae was dependent on high inoculum numbers such that virulence could not be attributed specifically to infection by live bacteria but also to factors associated with dead cells. Thus, for these strains, G. mellonella larvae do not constitute an ideal infection model. Treatment of larvae with dexamethasone 21-phosphate enhanced the lethality induced by infection with E. coli or K. pneumoniae in a dose- and inoculum size-dependent manner. This correlated with proliferation of bacteria in the larvae that could be attributed to dexamethasone inhibiting haemocyte phagocytosis and acting as an immunosuppressant. Notably, prior exposure to dexamethasone 21-phosphate reduced the efficacy of ceftazidime in vivo. In conclusion, demonstration of an effective immunosuppressant regimen can improve the specificity and broaden the applications of the G. mellonella model to address key questions regarding infection.

Cyclophosphamide's addition in relapsed/refractory multiple myeloma patients with biochemical progression during lenalidomide-dexamethasone treatment.

PubMed

Cesini, Laura; Siniscalchi, Agostina; Grammatico, Sara; Andriani, Alessandro; Fiorini, Alessia; De Rosa, Luca; Za, Tommaso; Rago, Angela; Caravita, Tommaso; Petrucci, Maria Teresa

2018-05-02

The aim of this study was to evaluate the addition of cyclophosphamide in relapsed-refractory multiple myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with lenalidomide and dexamethasone (Rd), to slow down the progression in active relapse. This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression. The median number of CRd cycles administered was 8 (range: 1-35). A response was observed in 9 (29%) patients. After a median observation time of 11 months, the median overall survival (OS) from the beginning of CRd was 17.7 months. The median progression-free survival (PFS) from the beginning of CRd was 13.1 months. The addition of cyclophosphamide delays the progression in patients who present a biochemical relapse during Rd treatment. The response rate and the duration of PFS obtained with minimal toxicities and low costs induced us to setting up a randomized clinical trial. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intravenous dexamethasone and perineural dexamethasone similarly prolong the duration of analgesia after supraclavicular brachial plexus block: a randomized, triple-arm, double-blind, placebo-controlled trial.

PubMed

Abdallah, Faraj W; Johnson, James; Chan, Vincent; Murgatroyd, Harry; Ghafari, Mohammad; Ami, Noam; Jin, Rongyu; Brull, Richard

2015-01-01

Perineural dexamethasone prolongs the duration of single-injection peripheral nerve block when added to the local anesthetic solution. Postulated systemic mechanisms of action along with theoretical safety concerns have prompted the investigation of intravenous dexamethasone as an alternative, with decidedly mixed results. We aimed to confirm that addition of intravenous dexamethasone will prolong the duration of analgesia after single-injection supraclavicular block compared with conventional long-acting local anesthetic alone or in combination with perineural dexamethasone for ambulatory upper extremity surgery. Seventy-five patients were randomized to receive supraclavicular block using 30-mL bupivacaine 0.5% alone (Control), with concomitant intravenous dexamethasone 8 mg (DexIV), or with perineural dexamethasone 8 mg (DexP). Duration of analgesia was designated as the primary outcome. To test our hypothesis, the superiority of DexIV was first compared with Control and then with DexP. Motor block duration, pain scores, opioid consumption, opioid-related side effects, patient satisfaction, and block-related complications were also analyzed. Twenty-five patients per group were analyzed. The duration of analgesia (mean [95% confidence interval]) was prolonged in the DexIV group(25 hours [17.6–32.4]) compared with Control (13.2 hours [11.5–15.0]; P < 0.001) but similar to the DexP group (25 hours[19.5–30.5]; P = 1). [corrected] Both DexIV and DexP had reduced pain scores, reduced postoperative opioid consumption, and improved satisfaction compared with Control. In a single-injection supraclavicular block with long-acting local anesthetic, the effectiveness of intravenous dexamethasone in prolonging the duration of analgesia seems similar to perineural dexamethasone.

The effect of perioperative dexamethasone dosing on post-tonsillectomy hemorrhage risk.

PubMed

Yiu, Yin; Mahida, Justin B; Cooper, Jennifer N; Elsey, Nicole M; Deans, Katherine J; Minneci, Peter C; Merrill, Tyler B; Tobias, Joseph D; Elmaraghy, Charles A

2017-07-01

Dexamethasone is currently recommended for routine prophylaxis against postoperative nausea and vomiting after tonsillectomy procedures. However, some studies have raised concern that dexamethasone use may lead to higher rates of post-tonsillectomy hemorrhage. Our objective was to determine whether higher doses of dexamethasone administered perioperatively during tonsillectomy procedures are associated with an increased risk of secondary post-tonsillectomy hemorrhage. We conducted a retrospective review of 9843 patients who underwent tonsillectomy and received dexamethasone at our institution from January 2010 to October 2014. We compared the dose of dexamethasone administered to patients who did and did not develop secondary post-tonsillectomy hemorrhage using Mann Whitney U tests. Multivariable logistic regression models were used to evaluate the association between dexamethasone dose and post-tonsillectomy hemorrhage after adjustment for demographic and clinical characteristics. A total of 280 (2.8%) patients developed secondary post-tonsillectomy hemorrhage. Patients who developed hemorrhage tended to be older (median (interquartile range) 7 (4-11) vs. 5 (3-8) years), p < 0.001) and had undergone tonsillectomy more often for chronic tonsillitis but less often for tonsillar or adenotonsillar hypertrophy or sleep disturbances. Dexamethasone dose was significantly lower on average in patients who experienced secondary post-tonsillectomy hemorrhage (median (interquartile range) 0.19 (0.14, 0.23) mg/kg vs. 0.21 (0.17, 0.30), p < 0.001). Multivariable modeling demonstrated that the dose of dexamethasone was not significantly associated with post-tonsillectomy hemorrhage after adjustment for age. There does not appear to be a dose-related increase in the risk of post-tonsillectomy hemorrhage for patients receiving dexamethasone during tonsillectomy procedures. Copyright © 2017 Elsevier B.V. All rights reserved.

Dexamethasone Does Not Inhibit Sugammadex Reversal After Rocuronium-Induced Neuromuscular Block.

PubMed

Buonanno, Pasquale; Laiola, Anna; Palumbo, Chiara; Spinelli, Gianmario; Servillo, Giuseppe; Di Minno, Raffaele Maria; Cafiero, Tullio; Di Iorio, Carlo

2016-06-01

Sugammadex is a relatively new molecule that reverses neuromuscular block induced by rocuronium. The particular structure of sugammadex traps the cyclopentanoperhydrophenanthrene ring of rocuronium in its hydrophobic cavity. Dexamethasone shares the same steroidal structure with rocuronium. Studies in vitro have demonstrated that dexamethasone interacts with sugammadex, reducing its efficacy. In this study, we investigated the clinical relevance of this interaction and its influence on neuromuscular reversal. In this retrospective case-control study, we analyzed data from 45 patients divided into 3 groups: dexamethasone after induction group (15 patients) treated with 8 mg dexamethasone as an antiemetic drug shortly after induction of anesthesia; dexamethasone before reversal group (15 patients) treated with dexamethasone just before sugammadex injection; and control group (15 patients) treated with 8 mg ondansetron. All groups received 0.6 mg/kg rocuronium at induction, 0.15 mg/kg rocuronium at train-of-four ratio (TOF) 2 for neuromuscular relaxation, and 2 mg/kg sugammadex for reversal at the end of the procedure at TOF2. Neuromuscular relaxation was monitored with a TOF-Watch® system. The control group had a recovery time of 154 ± 54 seconds (mean ± SD), the dexamethasone after induction group 134 ± 55 seconds, and the dexamethasone before reversal group 131 ± 68 seconds. The differences among groups were not statistically significant (P = 0.5141). Our results show that the use of dexamethasone as an antiemetic drug for the prevention of postoperative nausea and vomiting does not interfere with reversal of neuromuscular blockade with sugammadex in patients undergoing elective surgery with general anesthesia in contrast to in vitro studies that support this hypothesis.

Losartan and Dexamethasone may inhibit chemotaxis to reduce the infiltration of Th22 cells in IgA nephropathy.

PubMed

Xiao, Chenggen; Zhou, Qiaoling; Li, Xiaozhao; Li, Hui; Zhong, Yong; Meng, Ting; Zhu, Mengyuan; Sun, Hong; Liu, Shuang; Tang, Rong; Pu, Jiaxi; Xu, Yan; Xiao, Ping

2017-01-01

Angiotensin II is considered a major profibrotic factor that is involved in tissue remodeling processes, as the inhibition of Angiotensin II can halt renal inflammatory processes. Dexamethasone, an important anti-inflammatory and immunosuppressive agent, has been widely used to treat renal disease for decades. In this study, we explored the frequency of Th22 cells in a mouse model of IgA nephropathy and compared the possible effects of Losartan and Dexamethasone on Th22 cells. The experiments were performed using 6-week-old BALB/c female mice in an established IgA nephropathy model. The mice were randomly separated into 4 groups, which were administered Losartan (30mg/kg/d) or Dexamethasone (10mg/kg/d) and subjected to IgA nephropathy or the normal control treatment for 1month. The frequency of Th22 cells was measured via flow cytometry, and the relative pathological changes in renal morphology were measured with different pathological staining methods. Immunohistochemistry was performed to verify the expression of CCR10 and CCL27, which is specialized receptor on Th22 cells and its corresponding chemokine, respectively. The concentrations of CCL27 and IL-22 in renal tissue homogenates and sera were detected using ELISAs. Losartan and Dexamethasone differentially decreased the frequency of Th22 cells after 1month, and mesangial cell proliferation was also improved. Moreover, the expression of CCR10, CCL27 and IL-22 was reduced by treatment with either drug. However, significant differences between Losartan and Dexamethasone were not observed. Based on these findings, Losartan and Dexamethasone may suppress inflammatory responses by inhibiting the chemotaxis of Th22 cells in IgA nephropathy. Copyright © 2016. Published by Elsevier B.V.

A dexamethasone-regulated gene signature is prognostic for poor survival in glioblastoma patients

PubMed Central

Luedi, Markus M.; Singh, Sanjay K.; Mosley, Jennifer C.; Hatami, Masumeh; Gumin, Joy; Sulman, Erik P.; Lang, Frederick F.; Stueber, Frank; Zinn, Pascal O.; Colen, Rivka R.

2016-01-01

Background Dexamethasone is reported to induce both tumor-suppressive and tumor-promoting effects. The purpose of this study was to identify the genomic impact of dexamethasone in glioblastoma stem cell (GSC) lines and its prognostic value; furthermore, to identify drugs that can counter these side effects of dexamethasone exposure. Methods We utilized three independent GSC lines with tumorigenic potential for this study. Whole-genome expression profiling and pathway analyses were done with dexamethasone-exposed and control cells. GSCs were also co-exposed to dexamethasone and temozolomide. Risk scores were calculated for most affected genes, and their associations with survival in TCGA and REMBRANDT databases. In silico connectivity Map analysis identified camptothecin as antagonist to dexamethasone induced negative effects. Results Pathway analyses predicted an activation of dexamethasone network (z-score:2.908). Top activated canonical pathways included ‘role of BRCA1 in DNA damage response’ (p=1.07E-04). GSCs were protected against temozolomide-induced apoptosis when co-incubated with dexamethasone. Altered cellular functions included cell-movement, cell-survival, and apoptosis with z-scores of 2.815, 5.137, and −3.122 respectively. CEBPB was activated in a dose dependent manner specifically in slow-dividing ‘stem-like’ cells. CEBPB was activated in dexamethasone-treated orthotopic tumors. Patients with high risk score had significantly shorter survival. Camptothecin was validated as potential partial neutralizer of dexamethasone effects. Conclusions Dexamethasone exposure induces a genetic program and CEBPB expression in GSCs that adversely affects key cellular functions and response to therapeutics. High risk scores associated with these genes have negative prognostic value. Our findings further suggest camptothecin as a potential neutralizer of adverse dexamethasone-mediated effects. PMID:27653222

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.

PubMed

Niesvizky, Ruben; Badros, Ashraf Z; Costa, Luciano J; Ely, Scott A; Singhal, Seema B; Stadtmauer, Edward A; Haideri, Nisreen A; Yacoub, Abdulraheem; Hess, Georg; Lentzsch, Suzanne; Spicka, Ivan; Chanan-Khan, Asher A; Raab, Marc S; Tarantolo, Stefano; Vij, Ravi; Zonder, Jeffrey A; Huang, Xiangao; Jayabalan, David; Di Liberto, Maurizio; Huang, Xin; Jiang, Yuqiu; Kim, Sindy T; Randolph, Sophia; Chen-Kiang, Selina

2015-01-01

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combination therapy studies, antitumor activity was observed (phase 1). In phase 2, objective responses were achieved in 5 (20%) patients; 11 (44%) achieved stable disease. Biomarker and pharmacodynamic assessments demonstrated that palbociclib inhibited CDK4/6 and the cell cycle initially in most patients.

The induction of parturition using dexamethasone.

PubMed

Allen, J G; Herring, J

1976-10-01

Premature parturition was successfully induced with a preparation containing 2 dexamethasone esters in 709 out of 716 cows and heifers of gestational periods ranging from 3 to 8 months. A mortality rate of 38.5% was experienced among calves produced by induced cows, while only a 2.7% mortality rate occurred among 4,330 calves from normal parturitions. Approximately 50% of all treated cattle retained foetal membranes, but with apparently no ill-effect. The treatment apparently did not affect milk production, post-calving fertility, and the overall incidence of dystocias in cows and post-calving diseases. Three deaths occurred among induced cattle, but they could not be attributed to the treatment. It was concluded that the technique may prove to be of great value in dairy cattle, in seasonal milking areas.

The efficacy of dexamethasone reducing postoperative pain and emesis after total knee arthroplasty: A systematic review and meta-analysis.

PubMed

Fan, Zhengrui; Ma, Jianxiong; Kuang, Mingjie; Zhang, Lukai; Han, Biao; Yang, Baocheng; Wang, Ying; Ma, Xinlong

2018-04-01

Total knee arthroplasty (TKA) is gradually emerging as the treatment of choice for end-stage osteoarthritis. In the past, Perioperative dexamethasone treatment is still a controversial subject in total knee arthroplasty. Therefore, we write this systematic review and meta-analysis to evaluate the efficacy of dexamethasone on pain and recovery after Total knee Arthroplasty. Embase, Pubmed, and Cochrane Library were comprehensively searched. Randomized controlled trials, cohort studies were included in our meta-analysis. Eight studies that compared dexamethasone groups with placebo groups were included in our meta-analysis. The research was reported according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Randomized controlled trials were included in our meta-analysis. Our study demonstrated that the dexamethasone group was more effective than the placebo group in term of VAS score at 24 h(P < 0.00001), 48 h(P = 0.0002); Opioid consumption (P < 0.00001); postoperative nausea (P < 0.00001); and Inflammatory factors of CPR at 24 h (P = 0.003). Our meta-analysis demonstrated that dexamethasone decreased postoperative pain, the incidence of POVN, and total opioid consumption effectively which played a critical role in rapid recovery to TKA. However, we still need large sample size, high quality studies to explore the relationship between complications and dose response to give the final conclusion. Copyright © 2018. Published by Elsevier Ltd.

Prevention of relapse of Graves' disease by treatment with an intrathyroid injection of dexamethasone.

PubMed

Mao, Xiao-Ming; Li, Hui-Qin; Li, Qian; Li, Dong-Mei; Xie, Xiao-Jing; Yin, Guo-Ping; Zhang, Peng; Xu, Xiang-Hong; Wu, Jin-Dan; Chen, Song-Wang; Wang, Shu-Kui

2009-12-01

Antithyroid drugs are widely used in the treatment of Graves' disease (GD), but the relapse rate is very high after therapy withdrawal. We evaluated the reduction effects of intrathyroid injection of dexamethasone (IID) on the relapse rate of hyperthyroidism in patients with newly diagnosed GD. A total of 191 patients with GD completed the study. After 6 months of treatment with methimazole (MMI), the patients were randomly assigned to receive either MMI (96 patients) alone or MMI combined with IID (MMI+IID; 95 patients) treatment for 3 months, followed by continuing a dose of MMI that would maintain euthyroidism for the next 9 months in all of the patients. After withdrawal of the medical therapy, patients were followed for 24 months, and the relapse rate of hyperthyroidism was evaluated. No statistical difference was observed in the levels of serum FT(4), TSH, or TSH receptor antibodies (TR-Ab), the thyroid volume, or the TR-Ab positive rate between the two groups at month 6. After the next 3 months of treatment with MMI+IID or MMI alone, the levels of TSH increased significantly, and the levels of serum TR-Ab, the TR-Ab positive rate, and thyroid volume decreased significantly in the MMI+IID group compared with the MMI group. Seven patients (7.4%) experienced a relapse of overt hyperthyroidism in the MMI+IID group and 49 patients (51%) in MMI group during the 2-yr follow-up period (P < 0.001). MMI+IID treatment is helpful to prevent relapse of hyperthyroidism in GD after medical therapy withdrawal.

Effect of dexamethasone on endothelial nitric oxide synthase in experimental congenital diaphragmatic hernia

PubMed Central

Okoye, B.; Losty, P.; Fisher, M.; Wilmott, I.; Lloyd, D.

1998-01-01

AIMS—To study the effect of prenatal glucocorticoid treatment on endothelial nitric oxide synthase (eNOS) expression in rats with congenital diaphragmatic hernia (CDH).
METHODS—CDH was induced in fetal rats by the maternal administration of nitrofen on day 9.5 of gestation. Dexamethasone was administered on days 18.5 and 19.5 before delivery of the fetuses on days 20.5and 21.5. Pulmonary eNOS protein expression was studied by western immunoblotting and immunohistochemistry.
RESULTS—On day 20.5, eNOS expression was significantly reduced in CDH pups compared with normal control rats. Dexamethasone treated CDH pups had eNOS concentrations equivalent to those of normal animals. By day 21.5, however, there was no detectable difference in eNOS expression between the experimental groups.
CONCLUSIONS—eNOS is deficient in near term (day 20.5) CDH rats. Dexamethasone restores eNOS expression in these animals to that seen in normal rat lungs. At term, the precise role of eNOS in the pathophysiology of CDH remains uncertain.

 PMID:9713033

Effect of dexamethasone on the frequency of postdural puncture headache after spinal anesthesia for cesarean section: a double-blind randomized clinical trial.

PubMed

Yousefshahi, Fardin; Dahmardeh, Alireza Rahat; Khajavi, Mohammadreza; Najafi, Atabak; Khashayar, Patricia; Barkhordari, Khosro

2012-12-01

In this study, we evaluated the effect of dexamethasone used as a prophylaxis for nausea and vomiting on the incidence of postdural puncture headache (PDPH) in pregnant women receiving spinal anesthesia for cesarean section. In a prospective, randomized, double-blind, placebo-controlled study, 372 women under spinal anesthesia received 8 mg of dexamethasone or placebo intravenously just after the umbilical cord was clamped. The rate of PDPH and correlated risk factors were evaluated. The prevalence of nausea and vomiting in the dexamethasone and placebo groups was 54.4 and 51.7%, respectively. There was no statistically meaningful difference between the results (P value = 0.673). The overall incidence rate of PDPH was 10.8%, with 28 cases from the dexamethasone group compared with 11 subjects from the placebo group (P value = 0.006). This effect was most prominent on the first day (P value = 0.046) and disappeared on the second day after spinal anesthesia (P value = 0.678). Prophylactic treatment with 8 mg of dexamethasone not only increases the severity and incidence of PDPH, but is also ineffective in decreasing the prevalence of intra-operative nausea and vomiting during cesarean section. The treatment is a significant risk factor for the development of PDPH.

The activity of organic anion transporter-3: Role of dexamethasone.

PubMed

Wang, Haoxun; Liu, Chenchang; You, Guofeng

2018-02-01

Human organic anion transporter-3 (hOAT3) is richly expressed in the kidney, where it plays critical roles in the secretion, from the blood to urine, of clinically important drugs, such as anti-viral therapeutics, anti-cancer drugs, antibiotics, antihypertensives, and anti-inflammatories. In the current study, we examined the role of dexamethasone in hOAT3 transport activity in the kidney HEK293 cells. Cis-inhibition study showed that dexamethasone exhibited a concentration-dependent inhibition of hOAT3-mediated uptake of estrone sulfate, a prototypical substrate for the transporter, with IC 50 value of 49.91 μM. Dixon plot analysis revealed that inhibition by dexamethasone was competitive with a Ki = 47.08 μM. In contrast to the cis-inhibition effect of dexamethasone, prolonged incubation (6 h) of hOAT3-expressing cells with dexamethasone resulted in an upregulation of hOAT3 expression and transport activity, kinetically revealed as an increase in the maximum transport velocity V max without meaningful alteration in substrate-binding affinity K m . Such upregulation was abrogated by GSK650394, a specific inhibitor for serum- and glucocorticoid-inducible kinases (sgk). Dexamethasone also enhanced sgk1 phosphorylation. Our study demonstrated that dexamethasone exhibits dual effects on hOAT3: it is a competitive inhibitor for hOAT3-mediated transport, and interestingly, when entering the cells, it stimulates hOAT3 expression and transport activity through sgk1. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats.

PubMed

Glisić, Radmila; Koko, Vesna; Todorović, Vera; Drndarević, Neda; Cvijić, Gordana

2006-09-11

The aim of our study was to investigate the morphological, immunohistochemical and ultrastructural changes of rat serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2 mg/kg dexamethasone, rats developed diabetes similar to human diabetes type 2. Stomach, small and large intestines were examined. Large serotonin positive EC cells appeared in the corpus mucosa epithelium of D group of rats, although these cells were not present in control (C) rats. Both volume fraction and the number of EC cells per mm(2) of mucosa were significantly increased only in the duodenum. However, the number of EC cells per circular sections of both antrum and small intestine was increased, but reduced both in the ascending and descending colon in D group. The dexamethasone treatment caused a strong reduction in number of granules in the antral EC cells, while it was gradually increased beginning from the jejunum to descending colon. The mean granular content was reduced in the antral EC cells but increased in the jejunal EC cells in D group. In conclusion, the present study showed that morphological changes in gut serotonin-producing EC cells occurred in diabetic rats.

[Effect of dexamethasone contamination in drinking water on intestinal flora in mice].

PubMed

Yang, Xi; Li, Xiao-Yu; Si, Dan; Yang, Zhi-Bang; He, Zhong-Yuan; Zhang, Nan-Chen; Zhang, Shan-Shan; Shi, Zhong-Quan

2016-02-01

To evaluate the effect of water pollution with dexamethasone on intestinal flora in mice. Twenty Balb/c mice were randomly divided into control group and low-, moderate- and high-dose dexamethasone groups. The mice in dexamethasone groups were exposed to dexamethasone sodium phosphate in drinking water at doses of 0.035, 0.225, and 2.25 ng for 36 days. The changes in behaviors, fur condition, and feces of the mice were observed daily. All the mice were sacrificed at 36 days and the tissues in the ileocecal region was collected for denaturant gradient gel electrophoresis (DGGE) of 16S rDNA V6 variable regions of microbes and sequence analysis with BLAST. The mice in the 3 dexamethasone groups all showed aggressive behaviors. Cluster analysis of DGGE graph showed relatively stable floras in the ileocecal region in all the mice, but principal component analysis identified differences in the dominating flora among the groups. Diversity analysis of the flora revealed significantly increased amount and types of bacteria in the intestinal flora in all the 3 dexamethasone groups (P<0.05 or 0.01) compared with the control group. Sequence analysis of 16S rDNA V6 regions showed 15 common bacterial species and 2 differential species between the dexamethasone groups and the control group with changes in the type and proportion of the dominating bacterium in the dexamethasone groups. Lactobacillus colonization was detected in the control group but not in moderate- and high-dose dexamethasone groups, and Shigella species were found in the latter two groups. Water contamination with dexamethasone can affect the nervous system of mice, cause changes in the types and amounts of intestinal bacteria and the dominating bacteria, and inhibit the colonization of probiotics in the intestinal floras to increase the risk of invasion by intestinal pathogenic bacteria.

Dexamethasone inhibits endotoxin-induced coagulopathy in human lungs.

PubMed

Bartko, J; Schoergenhofer, C; Schwameis, M; Buchtele, N; Wojta, J; Schabbauer, G; Stiebellehner, L; Jilma, B

2016-12-01

Essentials Glucocorticoids are associated with an increased risk of thrombosis. Healthy volunteers received dexamethasone or placebo in an endotoxin lung instillation model. Dexamethasone suppressed thrombin generation in bronchoalveolar lavage. Glucocorticoids inhibit endotoxin induced pulmonary coagulopathy. Background Activation of local and systemic coagulation is a common finding in patients with pneumonia. There is evidence that glucocorticoids have procoagulant activity in the circulation, particularly in the context of inflammation. The effects of glucocorticoids on local pulmonary coagulation have not yet been investigated. Objective To use a human model of lung inflammation based on the local instillation of endotoxin in order to investigate whether glucocorticoids alter pulmonary coagulation. Methods Twenty-four healthy volunteers were randomized to receive either dexamethasone or placebo in a double-blind trial. Endotoxin was instilled via bronchoscope into right or left lung segments, followed by saline into the contralateral site. Six hours later, a bilateral bronchoalveolar lavage (BAL) was performed and coagulation parameters were measured. Results Endotoxin induced activation of coagulation in the bronchoalveolar compartment: the level of prothrombin fragment 1 + 2 (F 1 + 2 ) was increased three-fold (248 pmol L -1 , 95% confidence interval [CI] 43-454 versus 743 pmol L -1 , 95% CI 437-1050) and the level of thrombin-antithrombin complex (TATc) was increased by ~ 50% (31 μg L -1 , 95% CI 18-45 versus 49 μg L -1 , 95% CI 36-61) as compared with saline-challenged segments. Dexamethasone reduced F 1 + 2 (284 pmol L -1 , 95% CI 34-534) and TATc (9 μg L -1 , 95% CI 0.7-17) levels almost to those measured in BAL fluid from the saline-instilled segments in the placebo group. Dexamethasone even profoundly reduced F 1 + 2 levels (80%) in saline-instilled lung segments (50 pmol L -1 , 95% CI 12-87). In contrast, dexamethasone had no effect on systemic F 1

Evaluation of dexamethasone phosphate delivered by ocular iontophoresis for treating noninfectious anterior uveitis.

PubMed

Cohen, Amy E; Assang, Carol; Patane, Michael A; From, Stephen; Korenfeld, Michael

2012-01-01

Determine safe, effective, iontophoretic dose(s) of EGP-437 (dexamethasone phosphate formulated for iontophoresis) in patients with noninfectious anterior uveitis; evaluate systemic drug exposures. Prospective, phase I/II, multicenter, double-masked, parallel group, randomized clinical trial. Forty outpatients with anterior uveitis. Forty of 42 randomized patients received an iontophoresis treatment in 1 qualifying eye and completed the study. Patients were randomized into 1 of 4 iontophoresis dose groups (1.6, 4.8, 10.0, or 14.0 mA-min), treated with EGP-437 via the EyeGate II Delivery System (EGDS), and followed until day 28. The main outcome measures were anterior chamber cell (ACC) scores at days 14 and 28; time to ACC score of zero; proportion of patients with an ACC score reduction from baseline of ≥ 0.5 at day 28; mean change from baseline in ACC score at day 28; and the systemic exposures of dexamethasone and dexamethasone phosphate after EGP-437 treatment with the EGDS. After a single EGP-437 treatment, 19 of 40 patients (48%) achieved an ACC score of zero at day 14. By day 28, 24 of 40 patients (60%) achieved an ACC score of zero. A Kaplan-Meier analysis demonstrated that the 1.6 mA-min dose was the most effective and revealed an inverse dose response; median days to an ACC score of zero were 11.5 days in the 1.6 mA-min group versus 31 days in the 14.0 mA-min group. Twenty-six patients (65%) had an ACC score reduction from baseline of ≥ 0.5 at day 28. The mean change in ACC score from baseline to day 28 was -2.14 with a median of -2.00. Throughout the study, the mean intraocular pressure remained within normal range and mean best-corrected visual acuity at 4 meters remained relatively stable. Most adverse events were mild; no serious adverse events were reported. Pharmacokinetics results showed low short-term systemic exposure to dexamethasone after iontophoresis; no nonocular systemic corticosteroid-mediated effects were observed. Approximately two

Laponite as carrier for controlled in vitro delivery of dexamethasone in vitreous humor models.

PubMed

Fraile, José M; Garcia-Martin, Elena; Gil, Cristina; Mayoral, José A; Pablo, Luis E; Polo, Vicente; Prieto, Esther; Vispe, Eugenio

2016-11-01

Laponite clay is able to retain dexamethasone by simple physisorption, presumably accomplished by hydrogen bonding formation and/or complexation with sodium counterions, as shown by solid state NMR. The physisorption can be somehow modulated by changing the solvent in the adsorption process. This simple system is able to deliver dexamethasone in a controlled manner to solutions used as models for vitreous humor. The proven biocompatibility of laponite as well as its transparency in the gel state, together with the simplicity of the preparation method, makes this system suitable for future in vivo tests of ophthalmic treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical and Antiviral Efficacy of an Ophthalmic Formulation of Dexamethasone Povidone-Iodine in a Rabbit Model of Adenoviral Keratoconjunctivitis

PubMed Central

Clement, Christian; Capriotti, Joseph A.; Kumar, Manish; Hobden, Jeffery A.; Foster, Timothy P.; Bhattacharjee, Partha S.; Thompson, Hilary W.; Mahmud, Rashed; Liang, Bo

2011-01-01

Purpose. To determine the efficacy of a new formulation of topical dexamethasone 0.1%/povidone-iodine 0.4% (FST-100) in reducing clinical symptoms and infectious viral titers in a rabbit model of adenoviral keratoconjunctivitis. Methods. Rabbit corneas were inoculated bilaterally with 2 × 106 plaque-forming-units (PFU) of adenovirus type 5 (Ad5) after corneal scarification. Animals were randomized 1:1:1:1 (five rabbits per group) to FST-100, 0.5% cidofovir, tobramycin/dexamethasone (Tobradex; Alcon Laboratories, Fort Worth, TX) ophthalmic suspension, and balanced salt solution (BSS; Alcon Laboratories). Treatment began 12 hours after viral inoculation and continued for 7 consecutive days. The eyes were clinically scored daily for scleral inflammation (injection), ocular neovascularization, eyelid inflammation (redness), friability of vasculature, inflammatory discharge (pus), and epiphora (excessive tearing). Eye swabs were collected daily before treatment for the duration of the study. Virus was eluted from the swabs and PFU determined by titration on human A549 cells, according to standard procedures. Results. The FST-100 treatment resulted in significantly lower clinical scores (P < 0.05) than did the other treatments. The 0.5% cidofovir exhibited the most ocular toxicity compared with FST-100, tobramycin/dexamethasone, and balanced salt solution treatments. FST-100 and 0.5% cidofovir significantly (P < 0.05) reduced viral titers compared with tobramycin/dexamethasone or balanced salt solution. Conclusions. FST-100 was the most efficacious in minimizing the clinical symptoms of adenovirus infection in rabbit eyes. FST-100 and 0.5% cidofovir were both equally effective in reducing viral titers and decreasing the duration of viral shedding. By providing symptomatic relief in addition to reducing infectious virus titers, FST-100 should be a valuable addition to treatment of epidemic adenoviral keratoconjunctivitis. PMID:20702820

Improvement of dexamethasone sensitivity by chelation of intracellular Ca2+ in pediatric acute lymphoblastic leukemia cells through the prosurvival kinase ERK1/2 deactivation.

PubMed

Abdoul-Azize, Souleymane; Dubus, Isabelle; Vannier, Jean-Pierre

2017-04-18

Previous studies have demonstrated that glucocorticoid hormones, including dexamethasone, induced alterations in intracellular calcium homeostasis in acute lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular calcium homeostasis participates in dexamethasone sensitivity and resistance on ALL cells remains elusive. Here, we found that treatment of cells with dexamethasone resulted in increased intracellular calcium concentrations through store-operated calcium entry stimulation, which was curtailed by store-operated calcium channel blockers. We show that BAPTA-AM, an intracellular Ca2+ chelator, synergistically enhances dexamethasone lethality in two human ALL cell lines and in three primary specimens. This effect correlated with the inhibition of the prosurvival kinase ERK1/2 signaling pathway. Chelating intracellular calcium with Bapta-AM or inhibiting ERK1/2 with PD98059 significantly potentiated dexamethasone-induced mitochondrial membrane potential collapse, reactive oxygen species production, cytochrome c release, caspase-3 activity, and cell death. Moreover, we show that thapsigargin elevates intracellular free calcium ion level, and activates ERK1/2 signaling, resulting in the inhibition of dexamethasone-induced ALL cells apoptosis. Together, these results indicate that calcium-related ERK1/2 signaling pathway contributes to protect cells from dexamethasone sensitivity by limiting mitochondrial apoptotic pathway. This report provides a novel resistance pathway underlying the regulatory effect of dexamethasone on ALL cells.

Improvement of dexamethasone sensitivity by chelation of intracellular Ca2+ in pediatric acute lymphoblastic leukemia cells through the prosurvival kinase ERK1/2 deactivation

PubMed Central

Abdoul-Azize, Souleymane; Dubus, Isabelle; Vannier, Jean-Pierre

2017-01-01

Previous studies have demonstrated that glucocorticoid hormones, including dexamethasone, induced alterations in intracellular calcium homeostasis in acute lymphoblastic leukemia (ALL) cells. However, the mechanism by which intracellular calcium homeostasis participates in dexamethasone sensitivity and resistance on ALL cells remains elusive. Here, we found that treatment of cells with dexamethasone resulted in increased intracellular calcium concentrations through store-operated calcium entry stimulation, which was curtailed by store-operated calcium channel blockers. We show that BAPTA-AM, an intracellular Ca2+ chelator, synergistically enhances dexamethasone lethality in two human ALL cell lines and in three primary specimens. This effect correlated with the inhibition of the prosurvival kinase ERK1/2 signaling pathway. Chelating intracellular calcium with Bapta-AM or inhibiting ERK1/2 with PD98059 significantly potentiated dexamethasone-induced mitochondrial membrane potential collapse, reactive oxygen species production, cytochrome c release, caspase-3 activity, and cell death. Moreover, we show that thapsigargin elevates intracellular free calcium ion level, and activates ERK1/2 signaling, resulting in the inhibition of dexamethasone-induced ALL cells apoptosis. Together, these results indicate that calcium-related ERK1/2 signaling pathway contributes to protect cells from dexamethasone sensitivity by limiting mitochondrial apoptotic pathway. This report provides a novel resistance pathway underlying the regulatory effect of dexamethasone on ALL cells. PMID:28423696

Granistron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children.

PubMed

Fujii, Y; Tanaka, H; Toyooka, H

1996-12-01

Dexamethasone decreases chemotherapy-induced emesis when added to antiemetic regimens. This study was designed to compare the effectiveness of granisetron and dexamethasone with granisetron alone in the prevention of post-operative vomiting after strabismus repair, tonsillectomy with or without adenoidectomy in children. In a randomized, double-blind study, 60 healthy children, 4-10 yr of age, received either granisetron 40 micrograms.kg-1 and saline (Group S) or granisetron 40 micrograms.kg-1 and dexamethasone 4 mg (Group D) iv immediately after the induction of anaesthesia. All subjects received anaesthetics consisting of sevoflurane and nitrous oxide in oxygen Postoperative pain was treated with acetaminophen pr or pentazocine iv. Postoperatively, during the first 24 hr after anaesthesia, the frequencies of retching and vomiting, and the incidence of adverse events were recorded by nursing staff. There were no differences between the treatment groups with regard to demographics, surgical procedure, anaesthetic administered or analgesics used for postoperative pain. The frequency of the symptoms was 27% and 7% in Groups S and D, respectively (P < 0.05). The incidence of adverse events was comparable in the two groups. The prophylactic administration of granisetron and dexamethasone was more effective than granisetron alone in the prevention of postoperative vomiting in paediatric subjects undergoing strabismus repair, tonsillectomy and adenoidectomy.

Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial.

PubMed

San-Miguel, Jesús F; Hungria, Vania T M; Yoon, Sung-Soo; Beksac, Meral; Dimopoulos, Meletios A; Elghandour, Ashraf; Jedrzejczak, Wieslaw W; Günther, Andreas; Nakorn, Thanyaphong N; Siritanaratkul, Noppadol; Schlossman, Robert L; Hou, Jian; Moreau, Philippe; Lonial, Sagar; Lee, Jae H; Einsele, Hermann; Sopala, Monika; Bengoudifa, Bourras-Rezki; Binlich, Florence; Richardson, Paul G

2016-11-01

Panobinostat plus bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial. PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments. Patients were randomly assigned (1:1) to receive panobinostat (20 mg orally) or placebo, with bortezomib (1·3 mg/m 2 intravenously) and dexamethasone (20 mg orally), over two distinct treatment phases. In treatment phase 1 (eight 3-week cycles), patients received: panobinostat or placebo on days 1, 3, 5, 8, 10, and 12; bortezomib on days 1, 4, 8, and 11; and dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. During treatment phase 2 (four 6-week cycles with a 2 weeks on, 1 week off schedule), panobinostat or placebo was given three times a week, bortezomib was administered once a week, and dexamethasone was given on the days of and following bortezomib administration. The primary endpoint was progression-free survival; overall survival was a key secondary endpoint. This study is registered at ClinicalTrials.gov, NCT01023308. Between Jan 21, 2010, and Feb 29, 2012, 768 patients were enrolled into the study and randomly assigned to receive either panobinostat (n=387) or placebo (n=381), plus bortezomib and dexamethasone. At data cutoff (June 29, 2015), 415 patients had died. Median overall survival was 40·3 months (95% CI 35·0-44·8) in those who received panobinostat, bortezomib, and dexamethasone versus 35·8 months (29·0-40·6) in those who received placebo, bortezomib, and dexamethasone (hazard ratio [HR] 0·94, 95% CI 0·78-1·14; p=0·54). Of patients who had received at least two previous regimens including bortezomib and an immunomodulatory drug, median overall survival was 25·5 months (95% CI 19·6-34·3) in 73

Prevention of Acute Mountain Sickness by Dexamethasone,

DTIC Science & Technology

1983-07-27

Circ Res 1966; 19:274-82. 15. Lassen NA, Harper AM. High- altitude cerebral oedema . Lancet 1975; 2:1154. 16. Houston CS, Dickinson 3. Cerebral form of...individuals rapidly ascend to hign altitude . It is postulated that cerebral edema causes the symptoms of AMS. Since dexamethasone is useful in treating some...to a simulated altitude of 4570 m (15,000 ft) on two occasions. On S one occasion, they received dexamethasone (4 mg every 6 h) for 36 h before and

Polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate to prevent cisplatin-induced ototoxicity.

PubMed

Martín-Saldaña, Sergio; Palao-Suay, Raquel; Aguilar, María Rosa; Ramírez-Camacho, Rafael; San Román, Julio

2017-04-15

The aim of this work is the development of highly protective agents to be administered locally within the middle ear to avoid cisplatin-induced ototoxicity, which affects to 100% of the clinical patients at ultra-high concentrations (16mg/kg). The protective agents are based on polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate as anti-inflammarory and anti-apoptotic molecules. Dexamethasone and α-tocopheryl succinate are poorly soluble in water and present severe side effects when systemic administered during long periods of time. Their incorporation in the hydrophobic core of nanoparticles with the appropriate hydrodynamic properties provides the desired effects in vitro (lower cisplatin-induced toxicity, decreasing of caspase 3/7 activity, and lower IL-1β release) and in vivo (reducing the hearing loss at the local level). The local administration of the nanoparticles by bullostomy provides an adequate dose of drug without systemic interference with the chemotherapeutic effect of cisplatin. 100% of the cancer patients receiving ultra-high doses of CDDP (16mg/kg) suffer severe hearing loss, being a limiting factor in antineoplastic treatments. In this paper we describe the application of polymeric nanoparticles loaded with dexamethasone or α-tocopheryl succinate to palliate the cisplatin ototoxicity derived from chemotherapy treatment. These new nanoparticles, that encapsulate, transport, and deliver dexamethasone or α-tocopheryl succinate in the middle ear, are able to partially prevent ototoxicity derived from high doses of CDDP. This is an interdisciplinary study in which in vitro and in vivo experiments are described and extensively discussed. The importance of the results opens an excellent opportunity to the translation to the clinic. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Dexamethasone upregulates ANP C-receptor protein in human mesangial cells without affecting mRNA.

PubMed

Ardaillou, N; Blaise, V; Placier, S; Amestoy, F; Ardaillou, R

1996-03-01

The objective of this study was to examine the role of dexamethasone on the expression of natriuretic peptide B-type and C-type receptors (ANPR-B and ANPR-C) in cultured human mesangial cells, which only possess these two subtypes. Dexamethasone caused concentration- and time-dependent increases in 125I-labeled ANP binding, which were prevented by glucocorticoid receptor inhibition with RU-38486. A lag time of 24 h and a concentration of dexamethasone of at least 1 nmol/l were necessary for this effect to occur. Dexamethasone-induced upregulation of 125I-ANP binding resulted from increased receptor density. No change in dissociation constant (Kd) was observed. Only ANPR-C were affected by dexamethasone. Indeed, dexamethasone did not modify C-type natriuretic peptide (i.e., CNP)-dependent cGMP production by mesangial cells. Moreover, dexamethasone upregulated ANPR-C protein expression as shown by Western blot analysis and by an increase in ANPR-C immunoreactivity at the cell surface. In contrast, dexamethasone did not modify ANPR-C mRNA expression. In conclusion, glucocorticoids increase ANPR-C density on mesangial cells through a mechanism implying, successively, interaction with the glucocorticoid receptor and increase of ANPR-C protein synthesis at a posttranscriptional stage. Thus dexamethasone may influence availability of natriuretic peptides at their glomerular target sites.

Evaluation of best corrected visual acuity and central macular thickness after intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome: A retrospective study of six cases.

PubMed

Keilani, Chafik; Halalchi, Aziz; Wakpi Djeugue, Désiré; Regis, Anne; Abada, Samir

2016-10-01

Irvine-Gass syndrome is a macular edema (ME) that specifically occurs after cataract surgery. Its incidence varies from 0.2-2%. The purpose of this study is to evaluate the effectiveness of intravitreal dexamethasone implant injections in patients with Irvine-Gass syndrome. Patients with ME secondary to cataract surgery who underwent intravitreal injections of dexamethasone implant between December 2011 to October 2014 at François-Quesnay hospital (Mantes-la-Jolie, France) were retrospectively reviewed. The patients were followed for at least 10 months. All the patients were handled by intravitreal injection of dexamethasone in the eye of study among which some resisted to a preliminary treatment by non-steroidal anti-inflammatory drug (NSAID) and acetazolamide. The patients were examined each month. The patients were again handled by intravitreal injection of dexamethasone if they presented a recurrence. The primary endpoint of the study was determined on best corrected visual acuity (BCVA) using early diabetic retinopathy study (ETDRS) scale and central macular thickness (CMT) [μm] using optical coherence tomography (OCT) 3 and 6 months after the first injection. Secondary endpoints were the number of recurrences, the number of injections, the duration average before the first recurrence, the BCVA 10 months after the first injection and the tolerance. Six eyes of six patients were studied. At baseline, the mean (standard deviation [SD]) of the BCVA was 59.8±11. Three months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72.2±8.6 (P=0.03). Six months after the first injection, the mean (SD) of the BCVA showed a statistically significant increase to 72±11.8 (P=0.03). Concerning the CMT, the mean (SD) was 495.6±135.2 before treatment. Three months after the first injection, the mean (SD) of the CMT showed a statistically significant decrease to 268.6±57.8 (P=0.03). Six months after the first injection, the

Intravitreal Controlled Release of Dexamethasone from Engineered Microparticles of Porous Silicon Dioxide

PubMed Central

Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R.; Cheng, Lingyun

2014-01-01

Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterificaion Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

Is Misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, D.F.; Gillespie, B.W.; Diener, M.D.

1984-09-01

An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. CNS toxicity and ototoxicity rates were no different between treatment groups with overall rates of 2.7 and 1.1%, respectively. Phenytoin did not significantly alter CNS and peripheral neuropathy (PN) toxicity rates. All ototoxicities occurred in patients not on phenytoin. There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence ofmore » (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.« less

Evaluation of ocular and general safety following repeated dosing of dexamethasone phosphate delivered by transscleral iontophoresis in rabbits.

PubMed

Patane, Michael A; Schubert, William; Sanford, Thomas; Gee, Raymond; Burgos, Melissa; Isom, William P; Ruiz-Perez, Begona

2013-10-01

, anemia, decreased leukocyte and lymphocyte counts, compromised liver function, enlarged liver, and reduced spleen weight were consistent with systemic corticosteroid-mediated pharmacology, repeated use of anesthesia, stress, and sedentariness, and unlikely to be related to iontophoresis application. The results of this investigation suggest that repeated transscleral iontophoresis with dexamethasone phosphate may be safe for use as a treatment for inflammatory ocular disorders that require prolonged and/or repeated corticosteroid therapy.

The Combination of IV and Perineural Dexamethasone Prolongs the Analgesic Duration of Intercostal Nerve Blocks Compared with IV Dexamethasone Alone.

PubMed

Maher, Dermot P; Serna-Gallegos, Derek; Mardirosian, Rodney; Thomas, Otto J; Zhang, Xiao; McKenna, Robert; Yumul, Roya; Zhang, Vida

2017-06-01

 The use of multiple-level, single-injection intercostal nerve blocks for pain control following video-assisted thorascopic surgery (VATS) is limited by the analgesic duration of local anesthetics. This study examines whether the combination of perineural and intravenous (IV) dexamethasone will prolong the duration of intraoperatively placed intercostal nerve blocks following VATS compared with IV dexamethasone and a perineural saline placebo.  Prospective, double-blind, randomized placebo-controlled trial.  Single level-1 academic trauma center.  Forty patients undergoing a unilateral VATS under the care of a single surgeon.  Patients were randomly assigned to two groups and received an intercostal nerve block containing 1) 0.5% bupivacaine with epinephrine and 1 ml of 0.9% saline or 2) 0.5% bupivacaine with epinephrine and 1 ml of a 4 mg/ml dexamethasone solution. All patients received 8 mg of IV dexamethasone.  Group 2 had lower NRS-11 scores at post-operative hours 8 (5.05, SD = 2.13 vs 3.50, SD = 2.50; p  = 0.04), 20 (4.30, SD = 2.96 vs 2.26, SD = 2.31; p  = 0.02), and 24 (4.53, SD = 1.95 vs 2.26, SD = 2.31; p  = 0.02). Equianalgesic opioid requirement was decreased in group 2 at 32 hours (5.78 mg, SD = 5.77 vs 1.67 mg, SD = 3.49; p  = 0.02). Group 2 also had greater FEV1 measured at 8, 12, 24, and 44 hours; greater FVC at 24 hours; greater PEF at 28 through 48 hours; and greater FEV1/FVC at 8 and 36 hours.  The combination of IV and perineural dexamethasone prolonged the duration of a single-injection bupivacaine intercostal nerve block as measured by NRS-11 compared with IV dexamethasone alone at 24 hours. Reduced NRS-11 at other times, reduced opioid requirements, and increased PFTs were observed in group 2. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model

PubMed Central

Ali, Hazem; Kalashnikova, Irina; White, Mark Andrew; Sherman, Michael; Rytting, Erik

2013-01-01

The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140–298 nm, and encapsulation efficiency ranging from 52–89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently-labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia. PMID:23850397

Progression of diabetic retinopathy severity after treatment with dexamethasone implant: a 24-month cohort study the 'DR-Pro-DEX Study'.

PubMed

Iglicki, Matias; Zur, Dinah; Busch, Catharina; Okada, Mali; Loewenstein, Anat

2018-06-01

Intravitreal anti-vascular endothelial growth factor agents have been shown to reduce diabetic retinopathy (DR) progression; data on the effects of intravitreal corticosteroids on modifying disease severity are limited. This study evaluates the long-term effect of intravitreal dexamethasone implant (DEX) on the severity and progression of non-proliferative DR (NPDR). This was a retrospective cohort study. Sixty eyes from 60 consecutive patients with NPDR and diabetic macular edema (DME) treated with dexamethasone implant (DEX group) and 49 eyes from consecutive 49 patients without DME requiring observation only. Fundus angiography images from baseline and after 24 months were graded by two masked assessors into mild, moderate and severe NPDR and PDR, according to the ETDRS classification. Patients were followed up 1-3 and 4-6 months after each DEX implant. Re-treatment with DEX implant was on a pro re nata basis. Records were reviewed for performance of panretinal photocoagulation. Main outcome was as follows: change of DR ≥ 1 grade and progression to proliferative diabetic retinopathy (PDR). Three eyes (5%) in the DEX group and 43 (87.8%) eyes in the control group progressed to PDR (P < 0.0001). Twenty-five eyes (41.7%) in the DEX group but none in the control group demonstrated an improvement in DR severity (P < 0.0001). This study provides the first long-term evidence that DEX implant has the potential to not only delay progression of DR and PDR development, but may also improve DR severity over 24 months. Better understanding of the effects of corticosteroids will help guide its use in the treatment pathway of DR.

The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

PubMed

Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

2016-12-01

Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P < 0.0001) and at the end of surgery (P < 0.0001) showed significantly higher glucose levels in the dexamethasone group. Impaired wound healing was not observed in either group. A single low-dose of dexamethasone prevents intraoperative vomiting for awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

Dexamethasone injection into the pterygomandibular space in lower third molar surgery.

PubMed

Boonsiriseth, K; Latt, M M; Kiattavorncharoen, S; Pairuchvej, V; Wongsirichat, N

2017-07-01

The objective of this study was to evaluate the effects of 8mg dexamethasone injection into the pterygomandibular space on the postoperative sequelae of lower third molar surgery. A prospective, randomized, controlled, split-mouth study was designed involving 62 lower third molar extractions (31 patients). Prior to surgery, the study group received 2ml of 4mg/ml (8mg) dexamethasone injection through the pterygomandibular space following local anaesthesia; the control group received 2ml normal saline injection. Facial swelling, mouth opening, pain on a visual analogue scale (VAS), and the number of analgesics consumed were assessed. Descriptive statistics and the independent-samples t-test were used to compare the two groups at P<0.05. There was a significant reduction in swelling on day 2 postoperative in the dexamethasone group. Mouth opening was also significantly greater on day 2 in the dexamethasone group. The VAS pain score was significantly lower on the day of the operation and first postoperative day in the dexamethasone group, but did not differ significantly between the groups on the other postoperative days. The injection of 8mg dexamethasone into the pterygomandibular space was effective in reducing postoperative swelling, limited mouth opening, and pain following impacted lower third molar extraction. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Dexamethasone nanowafer as an effective therapy for dry eye disease.

PubMed

Coursey, Terry G; Henriksson, Johanna Tukler; Marcano, Daniela C; Shin, Crystal S; Isenhart, Lucas C; Ahmed, Faheem; De Paiva, Cintia S; Pflugfelder, Stephen C; Acharya, Ghanashyam

2015-09-10

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500 nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye. Copyright © 2015 Elsevier B.V. All rights reserved.

Glucose-dependent insulinotropic polypeptide-producing K cells in dexamethasone-treated rats.

PubMed

Koko, V; Glisic, R; Todorovic, V; Drndarevic, N; Mitrovic, O

2008-12-01

Some studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulin-dependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg(-1) dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP-producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIP-secreted but also of insulin-secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP-producing K cells to insulin-synthesizing cells.

Omega-3 Polyunsaturated Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid Enhance Dexamethasone Sensitivity in Multiple Myeloma Cells by the p53/miR-34a/Bcl-2 Axis.

PubMed

Dai, Xianping; Li, Mengshun; Geng, Feng

2017-07-01

Dexamethasone is widely used in multiple myeloma (MM) for its cytotoxic effects on lymphoid cells. However, many MM patients are resistant to dexamethasone, although some can benefit from dexamethasone treatment. In this study, we noted that ω-3 polyunsaturated fatty acids (PUFAs) enhanced the dexamethasone sensitivity of MM cells by inducing cell apoptosis. q-PCR analysis revealed that miR-34a could be significantly induced by PUFAs in U266 and primary MM cells. Transfection with miR-34a antagonist or miR-34a agomir could restore or suppress the dexamethasone sensitivity in U266 cells. Both luciferase reporter assay and Western blot showed that Bcl-2 is the direct target of miR-34a in MM cells. In addition, we observed that PUFAs induced p53 protein expression in MM cells under dexamethasone administration. Furthermore, suppressing p53 by its inhibitor, Pifithrin-α, regulated the miR-34a expression and modulated the sensitivity to dexamethasone in U266 cells. In summary, these results suggest that PUFAs enhance dexamethasone sensitivity to MM cells through the p53/miR-34a axis with a likely contribution of Bcl-2 suppression.

Paradoxical response to dexamethasone and spontaneous hypocortisolism in Cushing's disease

PubMed Central

Lila, Anurag R; Sarathi, Vijaya; Bandgar, Tushar R; Shah, Nalini S

2013-01-01

Paradoxical response to dexamethasone and spontaneous development of hypocortisolism are rare features of Cushing's disease. We report a 13-year-old boy with Cushing's disease owing to a pituitary macroadenoma. On initial evaluation, he had partial suppression of serum cortisol by dexamethasone. He developed transient hypocortisolism after first adenomectomy, but the disease recurred after 1 year. Repeat evaluation showed recurrent hypercortisolism and paradoxical response to dexamethasone. He underwent second surgery and, postoperatively, hypercostisolism persisted even after 2 years of surgery. Repeat evaluations after 8 years of second surgery revealed persistent hypocortisolism despite residual tumour of same size and similar plasma adrenocorticotropic hormone (ACTH) levels. We have also shown that the paradoxical increase in serum cortisol was preceded by a paradoxical increase in ACTH. The paradoxical response persisted despite hypocortisolism. This patient with Cushing's disease had two very rare features: paradoxical response to dexamethasone and spontaneous development of hypocortisolism. PMID:23365169

Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonin, Camila P., E-mail: mila_bonin@yahoo.com.br; Baccarin, Raquel Y.A., E-mail: baccarin@usp.br; Nostell, Katarina, E-mail: katarina.nostell@slu.se

2013-03-08

Highlights: ► Chimpanzees, horses and humans have regions of similarity on TLR4 and MD2 promoters. ► Rodents have few regions of similarity on TLR4 promoter when compared to primates. ► Conserved NFkB binding sites were found in the promoters of TLR4 and MD2. ► LPS-induced inhibition of TLR4 transcription is reversed by dexamethasone. ► LPS-induced transcription of MD2 is inhibited by dexamethasone. -- Abstract: Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explainingmore » these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.« less

Combined application of dexamethasone and hyperbaric oxygen therapy yields better efficacy for patients with delayed encephalopathy after acute carbon monoxide poisoning.

PubMed

Xiang, Wenping; Xue, Hui; Wang, Baojun; Li, Yuechun; Zhang, Jun; Jiang, Changchun; Liang, Furu; Pang, Jiangxia; Yu, Lehua

2017-01-01

Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) commonly occurs after recovering from acute CO poisoning. This study was performed to assess the efficacy of the combined application of dexamethasone and hyperbaric oxygen (HBO) therapy in patients with DEACMP. A total of 120 patients with DEACMP were recruited and randomly assigned into the experimental group (receiving dexamethasone 5 mg/day or 10 mg/day plus HBO therapy) and control group (HBO therapy as monotherapy). Meanwhile, the conventional treatments were provided for all the patients. We used the Mini-Mental State Examination (MMSE) scale to assess the cognitive function, the National Institutes of Health Stroke Scale (NIHSS) to assess the neurological function and the remission rate (RR) to assess the clinical efficacy. Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) was also measured. After 4 weeks of treatment, compared to the control group, the experimental group had a significantly higher remission rate ( P =0.032), a significantly higher average MMSE score ( P =0.037) and a significantly lower average NIHSS score ( P =0.002). Meanwhile, there was a trend toward better improvement with dexamethasone 10 mg/day, and the level of MBP in the CSF of patients was significantly lower in the experimental group than in the control group ( P <0.0001). The addition of dexamethasone did not significantly increase the incidence of adverse events. These results indicate that the combined application of dexamethasone and HBO therapy could yield better efficacy for patients with DEACMP and should be viewed as a potential new therapy.

Dexamethasone inhibits inflammatory response via down regulation of AP-1 transcription factor in human lung epithelial cells.

PubMed

Patil, Rajeshwari H; Naveen Kumar, M; Kiran Kumar, K M; Nagesh, Rashmi; Kavya, K; Babu, R L; Ramesh, Govindarajan T; Chidananda Sharma, S

2018-03-01

The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Activator protein-1 is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 cells to examine the effect of dexamethasone on the phorbol ester (PMA)/Lipopolysaccharide (LPS) induced pro-inflammatory cytokines and AP-1 factors. A549 cells were treated with and without PMA or LPS or dexamethasone and the cell viability and nitric oxide production was measured by MTT assay and Griess reagent respectively. Expression of pro-inflammatory cytokines and AP-1 factors mRNA were measured using semi quantitative RT-PCR. The PMA/LPS treated cells show significant 2-3 fold increase in the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8 and TNF-α), cyclo‑oxygenase-2 (COX-2) and specific AP-1 factors (c-Jun, c-Fos and Jun-D). Whereas, pretreatment of cells with dexamethasone significantly inhibited the LPS induced nitric oxide production and PMA/LPS induced mRNAs expression of above pro-inflammatory cytokines, COX-2 and AP-1 factors. Cells treated with dexamethasone alone at both the concentrations inhibit the mRNAs expression of IL-1β, IL-6 and TNF-α compared to control. Our study reveals that dexamethasone decreased the mRNAs expression of c-Jun and c-Fos available for AP-1 formation suggested that AP-1 is the probable key transcription factor involved in the anti-inflammatory activity of dexamethasone. This may be an important molecular mechanism of steroid action in asthma and other chronic inflammatory lung diseases which may be useful for treatment of lung inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle Dogs.

PubMed

Blizzard, Charles; Desai, Ankita; Driscoll, Arthur

2016-11-01

To examine the pharmacokinetic characteristics of sustained-release dexamethasone depots in two separate canine studies. Dexamethasone depots loaded with a clinically representative (0.4 mg) dose (DEXTENZA™; Ocular Therapeutix) or an elevated (0.7 mg) dose were inserted into the canaliculi of beagle eyes (n = 37 and n = 34, respectively). Tear fluid was collected for pharmacokinetic analysis of dexamethasone in both studies at predetermined time points. Explanted 0.4 mg depots were collected weekly to measure remaining drug level. Clinical observations and ophthalmic examinations were performed in both studies at each visit. The 0.4 mg depots released a median 308 μg by day 15 and tapered to complete drug release by day 28. Median dexamethasone tear fluid concentrations in the 0.4 mg study group decreased from 2,805 ng/mL at day 7 to 0 ng/mL on day 28. Median dexamethasone tear fluid concentrations in the 0.7 mg study group decreased from 4,370 ng/mL at 6 h post insertion to 830 ng/mL on day 35. Mean ± standard deviation intraocular pressures in the 0.4 and 0.7 mg study groups were 20.7 ± 2.8 and 19.0 ± 4.1 mmHg at baseline, respectively, and demonstrated no meaningful change (20.5 ± 3.0 and 20.6 ± 2.9 mmHg, respectively) over the studies' durations. No ocular toxicities were attributed to the dexamethasone depot. Sustained-release dexamethasone produced no identifiable ocular toxicity in this animal model, and pharmacokinetics demonstrated a sustained and tapered drug release over 28 days at a 0.4 mg dose and exceeded 35 days at a 0.7 mg dose.

Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia

PubMed Central

Kawedia, Jitesh D.; Liu, Chengcheng; Pei, Deqing; Cheng, Cheng; Fernandez, Christian A.; Howard, Scott C.; Campana, Dario; Panetta, John C.; Bowman, W. Paul; Evans, William E.; Pui, Ching-Hon

2012-01-01

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia. Whether interpatient pharmaco-kinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti–asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for acute lymphoblastic leukemia and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (mean ± SD) was higher (P = 3 × 10−8) in patients whose sera was positive (17.7 ± 18.6 L/h per m2) versus nega-tive (10.6 ± 5.99 L/h per m2) for anti–asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (P = .01) and of central nervous system relapse (P = .014). Central nervous system relapse was also more common in patients with anti–asparaginase antibodies (P = .019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti–asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse. PMID:22117041

Preventing hearing damage using topical dexamethasone during reversible cochlear ischemia: an animal model.

PubMed

Morawski, Krzysztof; Telischi, Fred F; Bohorquez, Jorge; Niemczyk, Kazimierz

2009-09-01

Local application of dexamethasone to the round window (RW) niche prevents cochlear damage caused by local reversible ischemia. Cochlear ischemia induced by internal auditory artery (IAA) compression/stretching is thought to cause postoperative sensory hearing loss after attempted hearing preservation removal of acoustic neuroma tumors. Dexamethasone administered to the RW niche traveling through the membrane to the cochlear fluids may prevent ischemic damage. Ten young albino rabbits were used for this study. Ischemic episodes were induced by compressing the IAA. Laser Doppler cochlear blood flow was measured using a probe positioned at the RW niche. Transtympanic electrocochleography was measured at 4, 8, and 12 kHz. In 5 test ears, dexamethasone was administered topically at the RW for approximately 50 minutes before the IAA compressions, whereas in 5 control ears, saline was applied in the same way. Each ear underwent one 10-minute IAA compression with a 60-minute postischemic period of transtympanic electrocochleography monitoring. In both control- and dexamethasone-treated ears, ischemic episodes measured by Laser Doppler cochlear blood flow were comparable. Fifty minutes after IAA decompression, in dexamethasone-pretreated ears, cochlear microphonic and compound action potential amplitudes at all test frequencies were 10 to 15% less reduced than those in control ears. Compound action potential latencies in dexamethasone-pretreated ears resulted in shorter latency delay than in control ears. The RW seems to be an efficacious route for the administration of dexamethasone into the inner ear. Dexamethasone showed a protective effect on cochlear function after local ischemia. Transtympanic electrocochleography was found to be a sufficient and effective tool in monitoring hearing.

Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

PubMed Central

An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

2015-01-01

Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone

Epidural Dexamethasone for Postoperative Analgesia in Patients Undergoing Unilateral Inguinal Herniorrhaphy: A Comparative Study

PubMed Central

Razavizadeh, M. R.; Heydarian, N.; Atoof, F.

2017-01-01

Background. This study was designed to evaluate the effect of adding dexamethasone to epidural bupivacaine on postoperative analgesia in unilateral inguinal herniorrhaphy. Methods. Forty-four patients were enrolled in this double-blind, clinical trial study. Patients were randomly allocated into dexamethasone or control group. In the dexamethasone group, patients received 18 ml of bupivacaine 0.5% and 2 ml (8 mg) of dexamethasone; in the control group, patients received 18 ml of bupivacaine 0.5% and 2 ml of normal saline. The onset of sensory block and its duration and incidence of nausea and vomiting were recorded. Results. The onset of epidural anesthesia was significantly more rapid in the dexamethasone group than in the control group (P < 0.001). Duration of analgesia was markedly prolonged in the dexamethasone group than in the control group (P < 0.001). Five patients (22.7%) in the control group had nausea in the first hour after the procedure (P = 0.048). None of the patients in the dexamethasone group had nausea. None of our patients had vomiting in the two groups. Conclusions. This study showed that adding dexamethasone to bupivacaine significantly prolongs the duration of postoperative analgesia. This trial is registered with Iranian Registry of Clinical Trials (IRCT) number IRCT2012062910137N1. PMID:28348504

A case of aminoglycosides induced retinal toxicity treated with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex(®)).

PubMed

Hernández Pardines, F; Tapia-Quijada, H; Hueso-Abancens, J R

2016-06-01

The case is described of a patient who had a sudden loss of vision in her right eye after glaucoma surgery. A diagnosis of retinal toxicity due to tobramycin (an aminoglycoside) was reached, which was characterised by retinal whitening with a red cherry stain, macular oedema, and vasculitis that progressed to papillary and macular atrophy with arteriolar sclerosis. Given the severity of symptoms an early attempt was made with megadoses of steroids and an intravitreal dexamethasone implant (Ozurdex®, Allergan S.A.), without response. Aminoglycoside toxicity is a rare, idiosyncratic, very serious complication for which there is no effective treatment. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Early clinical outcomes following laparoscopic inguinal hernia repair.

PubMed

Tolver, Mette Astrup

2013-07-01

Laparoscopic inguinal hernia repair (TAPP) has gained increasing popularity because of less post-operative pain and a shorter duration of convalescence compared with open hernia repair technique (Lichtenstein). However, investigation of duration of convalescence with non-restrictive recommendations, and a procedure-specific characterization of the early clinical outcomes after TAPP was lacking. Furthermore, optimization of the post-operative period with fibrin sealant versus tacks for fixation of mesh, and the glucocorticoid dexamethasone versus placebo needed to be investigated in randomized clinical trials. The objective of this PhD thesis was to characterize the early clinical outcomes after TAPP and optimize the post-operative period. The four studies included in this thesis have investigated duration of convalescence and procedure-specific post-operative pain and other early clinical outcomes after TAPP. Furthermore, it has been shown that fibrin sealant can improve the early post-operative period compared with tacks, while dexamethasone showed no advantages apart from reduced use of antiemetics compared with placebo. Based on these findings, and the existing knowledge, 3-5 days of convalescence should be expected when 1 day of convalescence is recommended and future studies should focus on reducing intraabdominal pain after TAPP. Fibrin sealant can optimize the early clinical outcomes but the risk of hernia recurrence and chronic pain needs to be evaluated. Dexamethasone should be investigated in higher doses.

Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children.

PubMed

Tseng, Wan-Ning; Chen, Chih-Cheng; Yu, Hong-Ren; Huang, Li-Tung; Kuo, Ho-Chang

2016-12-03

Background: Antenatal steroid administration may benefit fetal lung maturity in preterm infants. Although some studies have shown that this treatment may increase asthma in childhood, the correlation between antenatal dexamethasone exposure and allergic diseases remains unclear. The purpose of this study is to investigate the association between antenatal dexamethasone and T cell expression in childhood allergic diseases. Methods: We recruited a cohort of preterm infants born at Kaohsiung Chang Gung Memorial Hospital between 2007 and 2010 with a gestational age of less than 35 weeks and body weight at birth of less than 1500 g. The status of antenatal exposure to steroids and allergic diseases were surveyed using a modified ISAAC questionnaire for subjects aged 2-5 years old. We analyzed Th1/Th2/Th17 expression of mRNA, cytokines (using the Magpix ® my-system), and mental development index (MDI). Results: Among the 40 patients that were followed, the data showed that the antenatal dexamethasone exposure group ( N = 24) had a significantly higher incidence of allergic diseases (75.0% vs. 18.8%, p < 0.0001) when compared to the non-dexamethasone exposure group ( N = 16), especially with regard to asthma (41.7% vs. 0.0%, p = 0.003) and allergic rhinitis (58.3% vs. 18.8%, p = 0.013), but not atopic dermatitis. No statistical difference was observed in the mRNA expression levels of total white blood cell count between the dexamethasone exposure and non-exposure groups ( p > 0.05). However, the asthma group had higher IL-5 levels ( p = 0.009), and the MDI was shown to be significantly higher in the dexamethasone exposure group (90.38 ± 3.31 vs. 79.94 ± 3.58, p = 0.043) while no significant difference was found between the PDI of the two groups. Conclusions: Exposure to antenatal dexamethasone in preterm infants will increase their susceptibility to allergic diseases, particularly asthma and allergic rhinitis. Preterm infants' exposure to antenatal dexamethasone also

Treatment of early Parkinson's disease.

PubMed

Pahwa, Rajesh; Lyons, Kelly E

2014-08-01

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease. The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease. Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

Prenatal Dexamethasone, as Used in Preterm Labor, Worsens the Impact of Postnatal Chlorpyrifos Exposure on Serotonergic Pathways

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

2014-01-01

This study explores how glucocorticoids sensitize the developing brain to the organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard therapeutic dose (0.2 mg/kg) of dexamethasone on gestational days 17–19; pups were given subtoxic doses of chlorpyrifos on postnatal days 1–4, (1 mg/kg, <10% cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from postnatal day 30 to day 150, assessing the expression of 5HT receptors and the 5HT transporter, along with 5HT turnover (index of presynaptic impulse activity) in brain regions encompassing all the 5HT projections and cell bodies. These parameters are known targets for neurodevelopmental effects of dexamethasone and chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in the expression of 5HT synaptic proteins, with a progressive increase from adolescence to adulthood; this effect was attenuated by prenatal dexamethasone treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT turnover, indicating that the receptor upregulation was an adaptive response to deficient presynaptic activity. Turnover deficiencies were magnified by dexamethasone pretreatment, worsening the functional impairment caused by chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected relative sparing of adverse effects compared to males. Nevertheless, prenatal dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor expression in females, demonstrating the same adverse interaction. Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in maternal stress; accordingly, our results indicate that this group represents a large subpopulation that may have heightened vulnerability to developmental neurotoxicants such as the organophosphates. PMID:24280657

Ischemic index changes in diabetic retinopathy after intravitreal dexamethasone implant using ultra-widefield fluorescein angiography: a pilot study.

PubMed

Querques, Lea; Parravano, Mariacristina; Sacconi, Riccardo; Rabiolo, Alessandro; Bandello, Francesco; Querques, Giuseppe

2017-08-01

To investigate the effect of dexamethasone intravitreal implant on peripheral ischemia in patients affected by diabetic macular edema (DME). Patients with treatment-naïve diabetic retinopathy (DR) undergoing intravitreal dexamethasone implant for DME between October 2015 and March 2017 were enrolled. Patients underwent a comprehensive ocular examination at baseline (<2 weeks before treatment) and 10 ± 2 weeks after dexamethasone implant including best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography, ultra-widefield (UWF) retinography and UWF fluorescein angiography (UWFA). Nine eyes of seven consecutive patients (five males; mean age 66.4 ± 6.7 years) were enrolled. Mean duration of DR was 12.3 ± 8.4 years. Mean interval between UWFA acquisitions was 12.1 ± 2.1 weeks, and the mean interval between intravitreal injection and UWFA acquisition was 11.0 ± 1.6 weeks. Mean pre- and post-injection BCVA was 0.30 ± 0.20 and 0.21 ± 0.14 logMAR (p = 0.06), respectively. Mean pre- and post-injection central macular thickness was 449.8 ± 92.5 and 356.3 ± 52.4 μm (p = 0.03), respectively. Mean pre- and post-injection ischemic index was 24.0 ± 25.0 and 9.8 ± 12.1% (p = 0.0427), respectively. Intravitreal dexamethasone implant reduces peripheral retina ischemia in patients with DR.

Dexamethasone and sex regulate placental glucocorticoid receptor isoforms in mice.

PubMed

Cuffe, James S M; Saif, Zarqa; Perkins, Anthony V; Moritz, Karen M; Clifton, Vicki L

2017-08-01

Maternal dexamethasone exposure in the mouse impairs placental development and programs adult disease in a sexually dimorphic manner. Glucocorticoids bind to different glucocorticoid receptor (GR) isoforms to regulate gene transcription and cellular signaling. We hypothesized that sexually dimorphic placental responses to glucocorticoids are due to differences in GR isoforms present in the placenta. Pregnant C57Bl6 mice were exposed to saline or dexamethasone from E12.5 until E14.5 (1 µg/kg/h) before the collection of placentae. Cytoplasmic and nuclear protein fractions were extracted from placentae of male and female fetuses for Western blot analysis of GR isoforms. Eight known isoforms of the GR were detected in the mouse placenta including the translational isoforms GRα-A, B, C and D1-3 and the splice variants GRA and GRP. The expression of GRA, GRP and each of the GRα isoforms were altered by dexamethasone in relation to fetal sex and cellular location. Placentae of female fetuses had higher GRα-A and GRP expression in the cytoplasm than males, and GRα-C was more highly expressed in the nucleus of females than that in males. Dexamethasone significantly increased the cytoplasmic expression of GRα-A, but reduced the expression of GRα-C in placentae of males. Dexamethasone increased the expression of the GRα-C-regulated genes Sgk1 and Bcl2l11 , particularly in females. The cleaved caspase-3 staining in placental sections indicated GRα-C may mediate sex differences in dexamethasone-induced apoptosis. These findings may underlie the sex-specific placental adaptations that regulate different growth profiles in males and females and different risks for programmed disease outcomes in offspring. © 2017 Society for Endocrinology.

Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit.

PubMed

Papangkorn, Kongnara; Prendergast, Eri; Higuchi, John W; Brar, Balbir; Higuchi, William I

2017-12-01

To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis. Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology. The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response. All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

Coronary endothelial function and vascular smooth muscle proliferation are programmed by early-gestation dexamethasone exposure in sheep

PubMed Central

Volk, Kenneth A.; Roghair, Robert D.; Jung, Felicia; Scholz, Thomas D.; Lamb, Fred S.

2010-01-01

Exposure of the early-gestation ovine fetus to exogenous glucocorticoids induces changes in postnatal cardiovascular physiology. We sought to characterize coronary artery vascular function in this model by elucidating the contribution of nitric oxide and reactive oxygen species to altered coronary vascular reactivity and examining the proliferative potential of coronary artery vascular smooth muscle cells. Dexamethasone (dex, 0.28 mg·kg−1·day−1 for 48 h) was administered to pregnant ewes at 27–28-day gestation (term 145 days). Coronary arteries were isolated from 1- to 2-wk-old dex-exposed offspring and aged-matched controls. Compared with controls, coronary arteries from dex-exposed lambs demonstrated enhanced vasoconstriction to endothelin-1 and ACh that was abolished by endothelial removal or preincubation with the nitric oxide synthase inhibitor l-NNA, membrane-permeable superoxide dismutase + catalase, or apamin + charybdotoxin, but not indomethacin. The rate of coronary vascular smooth muscle cell (VSMC) proliferation was also significantly greater in dex-exposed lambs. Protein levels of the proliferating cell nuclear antigen were increased and α-smooth muscle actin decreased in dex-exposed coronary VSMC, consistent with a proliferative state. Finally, expression of the NADPH oxidase Nox 4, but not Nox 1, mRNA was also decreased in coronary VSMC from dex-exposed lambs. These findings suggest an important interaction exists between early-gestation glucocorticoid exposure and reactive oxygen species that is associated with alterations in endothelial function and coronary VSMC proliferation. These changes in coronary physiology are consistent with those associated with the development of atherosclerosis and may provide an important link between an adverse intrauterine environment and increased risk for coronary artery disease. PMID:20335378

Minimal extracorporeal circulation (MECC) does not result in less hypertrophic scar formation as compared to conventional extracorporeal circulation (CECC) with dexamethasone.

PubMed

Soykan, E A; Butzelaar, L; de Kroon, T L; Beelen, R H J; Ulrich, M M W; Mink van der Molen, A B; Niessen, F B

2014-05-01

Cardiopulmonary bypass surgery is associated with a systemic inflammatory response through the interaction of air, blood and synthetic components in the bypass system and the physical trauma of surgery. An alternative cardiopulmonary bypass system, minimal extracorporeal circulation (MECC), has shown promising results in terms of reducing the inflammatory response. We hypothesized that this system may reduce pathological excessive scarring. To study this assumption, the effects of MECC and the effects of conventional extracorporeal circulation (CECC) with dexamethasone on skin scarring were compared in a standardized wound-healing model. Pre-sternal scars were evaluated prospectively at four and 12 months postoperatively. The height and width of the scars were measured, using a slide caliper and sonography. The scars were scored using the validated Patient and Observer Scar Assessment Scale. Additional risk factors for hypertrophic scar formation were identified by means of a questionnaire. During surgery, MECC was used in 45 patients and CECC/dexamethasone in 42 patients. Four months postoperatively, 22 patients of the MECC group (49%) and 18 patients in the CECC/dexamethasone group (43%) had developed hypertrophic scars. Twelve months postoperatively, the hypertrophic scars in four patients of the MECC group and in two patients of the CECC/dexamethasone group had become normotrophic. In 18 patients of the MECC group (38%) and 16 patients of the CECC group (41%) the scars remained hypertrophic at 12 months. These differences between the two groups were not statistically significant. MECC does not reduce hypertrophic scar formation compared with CECC with dexamethasone, but its use is more beneficial than the use of CECC/dexamethasone because of the circulatory and immunological advantages and because treatment with dexamethasone can be omitted.

Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis.

PubMed

Kishore, K; Conway, M D; Peyman, G A

2001-01-01

To present a new method for the management of toxoplasmic retinochoroiditis (TRC). The patients were females ranging in age from 10 to 61 years (average 26.5). Four eyes of 4 patients were treated with intravitreal injections of 1.0 mg clindamycin in 0.1 mL and 1.0 mg of dexamethasone in 0.1 mL. The injections were given under general or peribulbar anesthesia. Three patients continued one systemic drug. Follow-up ranged from 11 to 26 months (mean 17.5). A favorable response was noted in each eye within two weeks after the intravitreal injections. All patients required 2 to 4 intravitreal injections in the affected eye for the control of TRC. Visual acuity improved in each eye. The disc and macula were preserved in all eyes. Recurrence was noted in one case, which responded to a repeated intravitreal injection of clindamycin and dexamethasone. Intravitreal injections of clindamycin and dexamethasone are well tolerated and may offer an additional strategy to treat TRC in patients who are unable to afford or tolerate systemic therapy, or whose disease progresses despite systemic therapy.

Upper and lower respiratory tract microbiota in horses: bacterial communities associated with health and mild asthma (inflammatory airway disease) and effects of dexamethasone.

PubMed

Bond, Stephanie L; Timsit, Edouard; Workentine, Matthew; Alexander, Trevor; Léguillette, Renaud

2017-08-23

The microbial composition of the equine respiratory tract, and differences due to mild equine asthma (also called Inflammatory Airway Disease (IAD)) have not been reported. The primary treatment for control of IAD in horses are corticosteroids. The objectives were to characterize the upper and lower respiratory tract microbiota associated with respiratory health and IAD, and to investigate the effects of dexamethasone on these bacterial communities using high throughput sequencing. The respiratory microbiota of horses was dominated by four major phyla, Proteobacteria (43.85%), Actinobacteria (21.63%), Firmicutes (16.82%), and Bacteroidetes (13.24%). Fifty genera had a relative abundance > 0.1%, with Sphingomonas and Pantoea being the most abundant. The upper and lower respiratory tract microbiota differed in healthy horses, with a decrease in richness in the lower airways, and 2 OTUs that differed in abundance. There was a separation between bacterial communities in the lower respiratory tract of healthy and IAD horses; 6 OTUs in the tracheal community had different abundance with disease status, with Streptococcus being increased in IAD horses. Treatment with dexamethasone had an effect on the lower respiratory tract microbiota of both heathy and IAD horses, with 8 OTUs increasing in abundance (including Streptococcus) and 1 OTU decreasing. The lower respiratory tract microbiota differed between healthy and IAD horses. Further research on the role of Streptococcus in IAD is warranted. Dexamethasone treatment affected the lower respiratory tract microbiota, which suggests that control of bacterial overgrowth in IAD horses treated with dexamethasone could be part of the treatment strategy.

Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system.

PubMed

Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S; Philipp, Mario T

2017-02-02

Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals. In contrast, these signs were evident in the infected animals that were left untreated or in those that were treated with meloxicam, a non-steroidal anti-inflammatory drug. To address the differential anti-inflammatory effects of dexamethasone and meloxicam in the central nervous system (CNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in culture supernatants of rhesus frontal cortex (FC) explants, primary rhesus astrocytes and microglia, and human oligodendrocytes. We also ascertained the potential of dexamethasone to modulate Bb-induced apoptosis in rhesus FC explants. As meloxicam is a known COX-2 inhibitor, we evaluated whether meloxicam altered the levels of COX-2 as induced by live Bb in cell lysates of primary rhesus astrocytes and microglia. Dexamethasone but not meloxicam significantly reduced the levels of several Bb-induced immune mediators in culture supernatants of FC explants, astrocytes, microglia, and oligodendrocytes. Dexamethasone also had a protective effect on Bb-induced neuronal and oligodendrocyte apoptosis in rhesus FC explants. Further, meloxicam significantly reduced the levels of Bb-induced COX-2 in microglia, while both Bb and meloxicam were unable to alter the constitutive levels of COX-2 in astrocytes. These data indicate that dexamethasone and meloxicam have differential anti-inflammatory effects on Bb-induced inflammation in glial and neuronal cells

Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo.

PubMed

Akhter, S R; Ikezaki, H; Gao, X P; Rubinstein, I

1999-05-01

The purpose of this study was to determine whether dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux from the in situ hamster cheek pouch and, if so, whether this response is specific. By using intravital microscopy, we found that an aqueous extract of grain sorghum dust elicited significant, concentration-dependent leaky site formation and increase in clearance of FITC-labeled dextran (FITC-dextran; mol mass, 70 kDa) from the in situ hamster cheek pouch (P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated substance P-induced leaky site formation and increase in clearance of FITC-dextran from the cheek pouch but had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on arteriolar diameter in the cheek pouch. On balance, these data indicate that dexamethasone attenuates grain sorghum dust extract- and substance P-induced increases in macromolecular efflux from the in situ hamster cheek pouch in a specific fashion.

Ondansetron, granisetron, and dexamethasone compared for the prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy : A randomized placebo-controlled study.

PubMed

Erhan, Yamac; Erhan, Elvan; Aydede, Hasan; Yumus, Okan; Yentur, Alp

2008-06-01

Laparoscopic cholecystectomies are associated with an appreciably high rate of postoperative nausea and vomiting (PONV). This study was designed to compare the effectiveness of ondansetron, granisetron, and dexamethasone for the prevention of PONV in patients after laparoscopic cholecystectomy. A total of 80 American Society of Anesthesiologists (ASA) physical class I-II patients scheduled for laparoscopic cholecystectomy were included in this randomized, double blind, placebo-controlled study. All patients received a similar standardized anesthesia and operative treatment. Patients were randomly divided into four groups (n = 20 each). Group 1, consisting of control patients, received 0.9% NaCl; group 2 patients received ondansetron 4 mg i.v.; group 3 patients received granisetron 3 mg i.v.; and group 4 patients received dexamethasone 8 mg i.v., all before the induction of anesthesia. Both nausea and vomiting were assessed during the first 24 h after the procedure. The total incidence of PONV was 75% with placebo, 35% with ondansetron, 30% with granisetron, and 25% with dexamethasone. The incidence of PONV was significantly less frequent in groups receiving antiemetics (p < 0.05). The differences between dexamethasone, granisetron, and ondansetron were not significant. Prophylactic dexamethasone 8 mg i.v. significantly reduced the incidence of PONV in patients undergoing laparoscopic cholecystectomy. Dexamethasone 8 mg was as effective as ondansetron 4 mg and granisetron 3 mg, and it was more effective than placebo.

Isolation and characterization of dexamethasone-resistant mutants from human lymphoid cell line CEM-C7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, J.M.; Thompson, E.B.

1981-06-01

Fifty-four independent dexamethasone-resistant clones were isolated from the clonal, glucocorticoid-sensitive human leukemic T-cell line CEM-C7. Resistance to 1 ..mu..M dexamethasone was acquired spontaneously at a rate of 2.6 x 10/sup -5/ per cell per generation as determined by fluctuation analysis. After mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the phenotypic expression time for dexamethasone resistance was determined to be 3 days. The mutagens ICR 191 and MNNG were effective in increasing the dexamethasone-resistant fraction of cells in mutagenized cultures; ICR 191 produced a 35.6-fold increase, and MNNG produced an 8.5-fold increase. All the spontaneous dexamethasone-resistant clones contained glucocorticoid receptors, usually less than halfmore » of the amount found in the parental clone. They are therefore strikingly different from dexamethasone-resistant clones derived from the mouse cell lines S49 and W7. Dexamethasone-resistant clones isolated after mutagenesis of CEM-C7 contained, on the average, lower concentrations of receptor than did those isolated spontaneously, and one clone contained no detectable receptor. These results are consistent with a mutational origin for dexamethasone resistance in these human cells at a haploid or functionally hemizygous locus. They also suggest that this is a useful system for mutation assay.« less

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

PubMed

Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Study of the protective effect of dexamethasone on cisplatin-induced ototoxicity in rats.

PubMed

Capelo, Isabelle Oliveira Jatai; Batista, Avner Marcos Alves; Brito, Yuri Neyson Ferreira; Diniz, Krissia Braga; Brito, Gerly Anne de Castro; Freitas, Marcos Rabelo de

2017-10-01

To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide

PubMed Central

Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T.; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry

2015-01-01

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients’ health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. PMID:25769541

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

PubMed

Delforge, Michel; Minuk, Leonard; Eisenmann, Jean-Claude; Arnulf, Bertrand; Canepa, Letizia; Fragasso, Alberto; Leyvraz, Serge; Langer, Christian; Ezaydi, Yousef; Vogl, Dan T; Giraldo-Castellano, Pilar; Yoon, Sung-Soo; Zarnitsky, Charles; Escoffre-Barbe, Martine; Lemieux, Bernard; Song, Kevin; Bahlis, Nizar Jacques; Guo, Shien; Monzini, Mara Silva; Ervin-Haynes, Annette; Houck, Vanessa; Facon, Thierry

2015-06-01

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for their perceived clinical relevance. Lenalidomide and low-dose dexamethasone, and melphalan, prednisone, thalidomide improved patients' health-related quality-of-life from baseline over the duration of the study across all pre-selected domains of the QLQ-C30 and EQ-5D. In the QLQ-MY20, lenalidomide and low-dose dexamethasone demonstrated a significantly greater reduction in the Disease Symptoms domain compared with melphalan, prednisone, thalidomide at Month 3, and significantly lower scores for QLQ-MY20 Side Effects of Treatment at all post-baseline assessments except Month 18. Linear mixed-model repeated-measures analyses confirmed the results observed in the cross-sectional analysis. Continuous lenalidomide and low-dose dexamethasone delays disease progression versus melphalan, prednisone, thalidomide and has been associated with a clinically meaningful improvement in health-related quality-of-life. These results further establish continuous lenalidomide and low-dose dexamethasone as a new standard of care for initial therapy of myeloma by demonstrating superior health-related quality-of-life during treatment, compared with melphalan, prednisone, thalidomide. Copyright© Ferrata Storti Foundation.

Creation of Lung-Targeted Dexamethasone Immunoliposome and Its Therapeutic Effect on Bleomycin-Induced Lung Injury in Rats

PubMed Central

Li, Nan; Hu, Yang; Zhang, Yuan; Xu, Jin-Fu; Li, Xia; Ren, Jie; Su, Bo; Yuan, Wei-Zhong; Teng, Xin-Rong; Zhang, Rong-Xuan; Jiang, Dian-hua; Mulet, Xavier; Li, Hui-Ping

2013-01-01

Objective Acute lung injury (ALI), is a major cause of morbidity and mortality, which is routinely treated with the administration of systemic glucocorticoids. The current study investigated the distribution and therapeutic effect of a dexamethasone(DXM)-loaded immunoliposome (NLP) functionalized with pulmonary surfactant protein A (SP-A) antibody (SPA-DXM-NLP) in an animal model. Methods DXM-NLP was prepared using film dispersion combined with extrusion techniques. SP-A antibody was used as the lung targeting agent. Tissue distribution of SPA-DXM-NLP was investigated in liver, spleen, kidney and lung tissue. The efficacy of SPA-DXM-NLP against lung injury was assessed in a rat model of bleomycin-induced acute lung injury. Results The SPA-DXM-NLP complex was successfully synthesized and the particles were stable at 4°C. Pulmonary dexamethasone levels were 40 times higher with SPA-DXM-NLP than conventional dexamethasone injection. Administration of SPA-DXM-NLP significantly attenuated lung injury and inflammation, decreased incidence of infection, and increased survival in animal models. Conclusions The administration of SPA-DXM-NLP to animal models resulted in increased levels of DXM in the lungs, indicating active targeting. The efficacy against ALI of the immunoliposomes was shown to be superior to conventional dexamethasone administration. These results demonstrate the potential of actively targeted glucocorticoid therapy in the treatment of lung disease in clinical practice. PMID:23516459

BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

PubMed

Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

2008-02-01

This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy individuals.

PubMed

Wingenfeld, K; Wolf, S; Kunz, M; Krieg, J-C; Lautenbacher, S

2015-07-01

There is some evidence that stress-induced cortisol increase leads to a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but no study has yet investigated both pharmacological enhancement and reduction of cortisol levels in the same individuals. Firstly, we tested in 16 healthy individuals whether the treatment with hydrocortisone and dexamethasone, respectively, results in altered pain thresholds. Secondly, we aimed to test whether hormone effects are different across the pain range by using ratings for pain stimuli with varying intensity; and thirdly, we tested whether cortisol levels influence the discrimination ability for painful stimuli. Despite substantial effects of dexamethasone and hydrocortisone administration on cortisol levels, no effect of these drugs was seen in terms of pain sensitivity (pain threshold, pain rating, pain discrimination ability), although comprehensively examined. However, in the placebo condition, a significant negative correlation between cortisol and pain thresholds was seen. Similarly, there were also strong negative associations between cortisol levels in the placebo condition and pain thresholds after drug treatment (especially after hydrocortisone). These findings suggest that short-term variations of cortisol do not influence pain sensitivity whereas, in general, high levels of cortisol are associated with increased pain sensitivity, at least for weak to moderate stimuli. © 2014 European Pain Federation - EFIC®

Hydrocortisone as an Intervention for Dexamethasone-Induced Adverse Effects in Pediatric Patients With Acute Lymphoblastic Leukemia: Results of a Double-Blind, Randomized Controlled Trial.

PubMed

Warris, Lidewij T; van den Heuvel-Eibrink, Marry M; Aarsen, Femke K; Pluijm, Saskia M F; Bierings, Marc B; van den Bos, Cor; Zwaan, Christian M; Thygesen, Helene H; Tissing, Wim J E; Veening, Margreet A; Pieters, Rob; van den Akker, Erica L T

2016-07-01

Dexamethasone is a key component in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious adverse effects. Recent studies have led to the hypothesis that neuropsychological adverse effects may be a result of cortisol depletion of the cerebral mineralocorticoid receptors. We examined whether including a physiologic dose of hydrocortisone in dexamethasone treatment can reduce neuropsychologic and metabolic adverse effects in children with ALL. We performed a multicenter, double-blind, randomized controlled trial with a crossover design. Of 116 potentially eligible patients (age 3 to 16 years), 50 were enrolled and were treated with two consecutive courses of dexamethasone in accordance with Dutch Childhood Oncology Group ALL protocols. Patients were randomly assigned to receive either hydrocortisone or placebo in a circadian rhythm (10 mg/m(2)/d) during both dexamethasone courses. Primary outcome measure was parent-reported Strength and Difficulties Questionnaire in Dutch, which assesses psychosocial problems. Other end points included questionnaires, neuropsychological tests, and metabolic parameters. Of 48 patients who completed both courses, hydrocortisone had no significant effect on outcome; however, a more detailed analysis revealed that in 16 patients who developed clinically relevant psychosocial adverse effects, addition of hydrocortisone substantially reduced their Strength and Difficulties Questionnaire in Dutch scores in the following domains: total difficulties, emotional symptoms, conduct problems, and impact of difficulties. Moreover, in nine patients who developed clinically relevant, sleep-related difficulties, addition of hydrocortisone reduced total sleeping problems and disorders of initiating and maintaining sleep. In contrast, hydrocortisone had no effect on metabolic parameters. Our results suggest that adding a physiologic dose of hydrocortisone to dexamethasone treatment can reduce the occurrence of serious

A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

PubMed Central

Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

1994-01-01

We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

Dexamethasone, all trans retinoic acid and interferon alpha 2a in patients with refractory multiple myeloma.

PubMed

Avilés, A; Rosas, A; Huerta-Guzmán, J; Talavera, A; Cleto, S

1999-02-01

Few effective regimen are available for patients with refractory multiple myeloma (RMM). Generally, responses are scarce and disease free survival is very short. We developed a new therapeutic option in these patients using dexamethasone (40 mg/m2, i.v., daily, days 1 to 4), all-trans retinoic acid (45 mg/m2, po, daily, days 5 to 14) and interferon alpha 2a (9.0 MU, daily, subcutaneously, days 5 to 14). The treatment was administered every 21 days for 6 cycles. In a pilot study, 12 patients, heavily treated with chemotherapy and radiotherapy and in some cases with interferon, were allocated to receive the afore mentioned treatment. Response was observed in 10 patients (83%). With a median follow-up of 36.1 months (range 27 to 41), seven patients remain alive and disease-free without any treatment. Two patients were failures and have died due to tumor progression. Toxicity was mild and all patients received treatment according to the planned doses of drugs. The use of biological modifiers in combination with dexamethasone offer a safe and effective therapeutic option in patients with refractory multiple myeloma. More studies are warranted to define the role of this type of treatment.

Age-related effects of dexamethasone administration in adrenal zona reticularis.

PubMed

Almeida, Henrique; Matos, Liliana; Ferreira, Jorge; Neves, Delminda

2006-05-01

Suppression of adrenocorticotropic hormone results in reduced adrenal steroid output, adrenocortical cell atrophy, and apoptosis in young rats. To verify such effects during aging, dexamethasone was injected into rats for 3 days at five different ages; at day 4, adrenals and blood were collected for morphologic and corticosterone assay. Adrenal structure was similar at all ages, but in dexamethasone-injected animals there were ultrastructural features of apoptosis and a higher percentage of TUNEL and caspase-3-labeled nuclei and cytoplasm; their corticosterone decreased significantly. In both groups, there was age-related decrease in the percentage of apoptotic cells, significant only in dexamethasone-injected rats. The data suggest that aged adrenocortical cells are less susceptible to the lack of adrenocorticotropic hormone (ACTH), possibly as a result of their decreased functional ability.

Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain.

PubMed

Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

2018-01-01

The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O 2 sat were recorded 1, 3, 5, and 10 min after propofol injection. The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 ( P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 ( P = 0.001). There were no differences in either mean arterial pressure or O 2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser ( P = 0.04). Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection.

Comparison the Effect of Granisetron and Dexamethasone on Intravenous Propofol Pain

PubMed Central

Adinehmehr, Leili; Salimi, Sohrab; Sane, Shahryar; Sina, Venous; Najafizadeh, Rana

2018-01-01

Background: The incidence of propofol injection pain during induction of general anesthesia varies from 28% to 90%. This prospective, randomized, double-blind, placebo-controlled study evaluated the effect of dexamethasone and granisetron for reducing the incidence and severity of propofol injection pain. Materials and Methods: A total of 227 female subjects received 5 mL of preservative-free saline, 1 mg granisetron (5 ml), or 0.15 mg/kg of dexamethasone (5 ml), intravenously, following exsanguination and occlusion of the veins of the arm. This was followed by a 0.5 mg/kg injection of propofol. Pain scores and intensity of pain recorded immediately following the injection of propofol. Hemodynamic parameters and O2 sat were recorded 1, 3, 5, and 10 min after propofol injection. Results: The incidence pain following the injection of propofol was significantly decreased with both granisetron and dexamethasone (50.7% and 49.4%). Mean pain score in granisetron group was 3.16 ± 1.23, dexamethasone was 2.73 ± 1.03, and in saline group was 4.82 ± 1.73 (P = 0.001). Mean pain intensity in granisetron group was 1.16 ± 0.18, dexamethasone was 1.26 ± 0.14, and in saline group was 2.2 ± 0.99 (P = 0.001). There were no differences in either mean arterial pressure or O2 Sate at any time point after drugs injection among the groups. There was a significant difference in pulse rate in third minutes between three groups and in the group who received granisetron was lesser (P = 0.04). Conclusion: Pretreatment with intravenous granisetron (1 mg) and dexamethasone (0.15 mg/kg) before injection of propofol is effective and safe in reducing the incidence and severity of pain due to propofol injection. PMID:29862223

Effectiveness of Dexamethasone Iontophoresis for Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis

PubMed Central

Mina, Rina; Melson, Paula; Powell, Stephanie; Rao, Marepalli; Hinze, Claas; Passo, Murray; Graham, T. Brent; Brunner, Hermine I.

2011-01-01

Objective Temporomandibular joint (TMJ) involvement is common in Juvenile Idiopathic Arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP. Methods Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997 to 2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal inter-incisor opening (MIOTMJ) and the maximal lateral excursion (MLETMJ) before and after treatment. Results Twenty-eight patients (ages 2– 21 years) who received an average of eight DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIOTMJ (p< 0.0001) was observed in 68%. The median MLETMJ (p= 0.03) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIOTMJ, lower MLETMJ, and absence of TMJ crepitus at baseline. Conclusion In this pilot study DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed. PMID:22034112

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study

PubMed Central

Bergsten, Elisabet; Horne, AnnaCarin; Aricó, Maurizio; Astigarraga, Itziar; Egeler, R. Maarten; Filipovich, Alexandra H.; Ishii, Eiichi; Janka, Gritta; Ladisch, Stephan; Lehmberg, Kai; McClain, Kenneth L.; Minkov, Milen; Montgomery, Scott; Nanduri, Vasanta; Rosso, Diego

2017-01-01

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. In the HLH-94 study, with an estimated 5-year probability of survival (pSu) of 54% (95% confidence interval, 48%-60%), systemic therapy included etoposide, dexamethasone, and, from week 9, cyclosporine A (CSA). Hematopoietic stem cell transplantation (HSCT) was indicated in patients with familial/genetic, relapsing, or severe/persistent disease. In HLH-2004, CSA was instead administered upfront, aiming to reduce pre-HSCT mortality and morbidity. From 2004 to 2011, 369 children aged <18 years fulfilled HLH-2004 inclusion criteria (5 of 8 diagnostic criteria, affected siblings, and/or molecular diagnosis in FHL-causative genes). At median follow-up of 5.2 years, 230 of 369 patients (62%) were alive (5-year pSu, 61%; 56%-67%). Five-year pSu in children with (n = 168) and without (n = 201) family history/genetically verified FHL was 59% (52%-67%) and 64% (57%-71%), respectively (familial occurrence [n = 47], 58% [45%-75%]). Comparing with historical data (HLH-94), using HLH-94 inclusion criteria, pre-HSCT mortality was nonsignificantly reduced from 27% to 19% (P = .064 adjusted for age and sex). Time from start of therapy to HSCT was shorter compared with HLH-94 (P = .020 adjusted for age and sex) and reported neurological alterations at HSCT were 22% in HLH-94 and 17% in HLH-2004 (using HLH-94 inclusion criteria). Five-year pSu post-HSCT overall was 66% (verified FHL, 70% [63%-78%]). Additional analyses provided specific suggestions on potential pre-HSCT treatment improvements. HLH-2004 confirms that a majority of patients may be rescued by the etoposide/dexamethasone combination but intensification with CSA upfront, adding corticosteroids to intrathecal therapy, and reduced time to HSCT did not improve outcome significantly. PMID:28935695

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Dexamethasone exacerbates cerebral edema and brain injury following lithium-pilocarpine induced status epilepticus☆

PubMed Central

Duffy, B.A.; Chun, K.P.; Ma, D.; Lythgoe, M.F.; Scott, R.C.

2014-01-01

Anti-inflammatory therapies are the current most plausible drug candidates for anti-epileptogenesis and neuroprotection following prolonged seizures. Given that vasogenic edema is widely considered to be detrimental for outcome following status epilepticus, the anti-inflammatory agent dexamethasone is sometimes used in clinic for alleviating cerebral edema. In this study we perform longitudinal magnetic resonance imaging in order to assess the contribution of dexamethasone on cerebral edema and subsequent neuroprotection following status epilepticus. Lithium-pilocarpine was used to induce status epilepticus in rats. Following status epilepticus, rats were either post-treated with saline or with dexamethasone sodium phosphate (10 mg/kg or 2 mg/kg). Brain edema was assessed by means of magnetic resonance imaging (T2 relaxometry) and hippocampal volumetry was used as a marker of neuronal injury. T2 relaxometry was performed prior to, 48 h and 96 h following status epilepticus. Volume measurements were performed between 18 and 21 days after status epilepticus. Unexpectedly, cerebral edema was worse in rats that were treated with dexamethasone compared to controls. Furthermore, dexamethasone treated rats had lower hippocampal volumes compared to controls 3 weeks after the initial insult. The T2 measurements at 2 days and 4 days in the hippocampus correlated with hippocampal volumes at 3 weeks. Finally, the mortality rate in the first week following status epilepticus increased from 14% in untreated rats to 33% and 46% in rats treated with 2 mg/kg and 10 mg/kg dexamethasone respectively. These findings suggest that dexamethasone can exacerbate the acute cerebral edema and brain injury associated with status epilepticus. PMID:24333865

Intra-ocular lens optical changes resulting from the loading of dexamethasone.

PubMed

Artigas, José M; García-Domene, M Carmen; Navea, Amparo; Botella, Pablo; Fernández, Eduardo

2017-10-01

To study the optical changes on hydrogel-silicone intraocular lenses (IOLs) resulting from loading them with dexamethasone. We used prototype hydrogel(pHEMA)-silicone IOLs and loaded the matrices with an anti-inflammatory drug (dexamethasone). The optical properties we analyzed experimentally were a) modulation transfer function (MTF); b) spectral transmission; c) diopter power. These determinations were performed on drug-loaded IOLs, IOLs that had released the drug, and IOLs that had not been drug-loaded. Loading a hydrogel-silicone IOL with dexamethasone results in impairment of its optical qualities, in particular its MTF and spectral transmission, but not dioptric power. However, once the drug has been released, it almost recovers its initial optical properties.

Intra-ocular lens optical changes resulting from the loading of dexamethasone

PubMed Central

Artigas, José M.; García-Domene, M. Carmen; Navea, Amparo; Botella, Pablo; Fernández, Eduardo

2017-01-01

To study the optical changes on hydrogel-silicone intraocular lenses (IOLs) resulting from loading them with dexamethasone. We used prototype hydrogel(pHEMA)-silicone IOLs and loaded the matrices with an anti-inflammatory drug (dexamethasone). The optical properties we analyzed experimentally were a) modulation transfer function (MTF); b) spectral transmission; c) diopter power. These determinations were performed on drug-loaded IOLs, IOLs that had released the drug, and IOLs that had not been drug-loaded. Loading a hydrogel-silicone IOL with dexamethasone results in impairment of its optical qualities, in particular its MTF and spectral transmission, but not dioptric power. However, once the drug has been released, it almost recovers its initial optical properties. PMID:29082089

Inhibition of Dexamethasone-induced Fatty Liver Development by Reducing miR-17-5p Levels

PubMed Central

Du, William W; Liu, Fengqiong; Shan, Sze Wan; Ma, Xindi Cindy; Gupta, Shaan; Jin, Tianru; Spaner, David; Krylov, Sergey N; Zhang, Yaou; Ling, Wenhua; Yang, Burton B

2015-01-01

Steatosis is a pivotal event in the initiation and progression of nonalcoholic fatty liver disease (NAFLD) which can be driven by peroxisome proliferator-activated receptor-α (PPAR-α) dysregulation. Through examining the effect of PPAR-α on fatty liver development, we found that PPAR-α is a target of miR-17-5p. Transgenic mice expressing miR-17 developed fatty liver and produced higher levels of triglyceride and cholesterol but lower levels of PPAR-α. Ectopic expression of miR-17 enhanced cellular steatosis. Gain-of-function and loss-of-function experiments confirmed PPAR-α as a target of miR-17-5p. On the other hand, PPAR-α bound to the promoter of miR-17 and promoted its expression. The feed-back loop between miR-17-5p and PPAR-α played a key role in the induction of steatosis and fatty liver development. Mice with high levels of miR-17-5p were sensitive to Dexamethasone-induced fatty liver formation. Inhibition of miR-17-5p suppressed this process and enhanced PPAR-α expression in mice treated with Dexamethasone. Clofibrate, Ciprofibrate, and WY-14643: three agents used for treatment of metabolic disorders, were found to promote PPAR-α expression while decreasing miR-17-5p levels and inhibiting steatosis. Our studies show that miR-17-5p inhibitor and agents used in metabolic disorders may be applied in combination with Dexamethasone in the treatment of anti-inflammation, immunosuppression, and cancer patients. PMID:25896250

Atrial natriuretic peptide: a possible mediator involved in dexamethasone's inhibition of cell proliferation in multiple myeloma.

PubMed

Ding, Jiang-Hua; Chang, Yu-Sui

2012-08-01

Atrial natriuretic peptide (ANP) has been recognized for several decades for its role of regulating blood pressure. Recently, cumulating evidences show that ANP plays an anticancer role in various solid tumors via blocking the kinase cascade of Ras-MEK1/2-ERK1/2 with the result of inhibition of DNA synthesis. ANP, as well as its receptors (NPR-A and NPR-C) has been identified present in the embryonic stem cell and a wide range of cancer cells. Various lymphoid organs, such as lymph nodes, have been detected the presence of ANP. Multiple myeloma (MM), though the therapies have evolved significantly, is still an incurable disease as B lymphocyte cell neoplasm. Dexamethasone is the cornerstone in treatment of MM via inactivation of Ras-MEK1/2-ERK1/2 cascade reaction. Coincidently, dexamethasone can increase the expression of ANP markedly. Nevertheless, the role of ANP in MM is unclear. Based on these results above, we raise the hypothesis that ANP is involved in mediating dexamethasone's inhibition of proliferation in MM cells, which suggests that ANP may be a potential agent to treat MM. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Enhancing Continuous Online Microdialysis Using Dexamethasone: Measurement of Dynamic Neurometabolic Changes during Spreading Depolarization.

PubMed

Varner, Erika L; Leong, Chi Leng; Jaquins-Gerstl, Andrea; Nesbitt, Kathryn M; Boutelle, Martyn G; Michael, Adrian C

2017-08-16

Microdialysis is well established in chemical neuroscience as a mainstay technology for real time intracranial chemical monitoring in both animal models and human patients. Evidence shows that microdialysis can be enhanced by mitigating the penetration injury caused during the insertion of microdialysis probes into brain tissue. Herein, we show that retrodialysis of dexamethasone in the rat cortex enhances the microdialysis detection of K + and glucose transients induced by spreading depolarization. Without dexamethasone, quantification of glucose transients was unreliable by 5 days after probe insertion. With dexamethasone, robust K + and glucose transients were readily quantified at 2 h, 5 days, and 10 days after probe insertion. The amplitudes of the K + transients declined day-to-day following probe insertion, and the amplitudes of the glucose transients exhibited a decreasing trend that did not reach statistical significance. Immunohistochemistry and fluorescence microscopy confirm that dexamethasone is highly effective at preserving a healthy probe-brain interface for at least 10 days even though retrodialysis of dexamethasone ceased after 5 days.

Dexamethasone treatment promotes Bcl-2 dependence in multiple myeloma resulting in sensitivity to venetoclax.

PubMed

Matulis, S M; Gupta, V A; Nooka, A K; Hollen, H V; Kaufman, J L; Lonial, S; Boise, L H

2016-05-01

Venetoclax (ABT-199), a specific inhibitor of the anti-apoptotic protein Bcl-2, is currently in phase I clinical trials for multiple myeloma. The results suggest that venetoclax is only active in a small cohort of patients therefore we wanted to determine its efficacy when used in combination. Combining venetoclax with melphalan or carfilzomib produced additive or better cell death in four of the five cell lines tested. The most striking results were seen with dexamethasone (Dex). Co-treatment of human myeloma cell lines and primary patient samples, with Dex and venetoclax, significantly increased cell death over venetoclax alone in four of the five cell lines, and in all patient samples tested. The mechanism by which this occurs is an increase in the expression of both Bcl-2 and Bim upon addition of Dex. This results in alterations in Bim binding to anti-apoptotic proteins. Dex shifts Bim binding towards Bcl-2 resulting in increased sensitivity to venetoclax. These data suggest that knowledge of drug-induced alterations of Bim-binding patterns may help inform better combination drug regimens. Furthermore, the data indicate combining this novel therapeutic with Dex could be an effective therapy for a broader range of patients than would be predicted by single-agent activity.

Dexamethasone enhances interaction of endogenous annexin 1 with L-selectin and triggers shedding of L-selectin in the monocytic cell line U-937.

PubMed

de Coupade, Catherine; Solito, Egle; Levine, Jon D

2003-09-01

(1) L-selectin, constitutively expressed by leukocytes, is involved in the initial binding of leukocytes to activated endothelium. Anti-inflammatory drugs like glucocorticoids can induce shedding of L-selectin, but the mechanism is still unknown. Annexin 1, a protein whose synthesis and externalization/secretion are induced during the inflammatory response, has been proposed as a mediator of the anti-inflammatory actions of glucocorticoids. (2) The monocytic cell line U-937 strongly expresses Annexin 1 after 24 h of phorbol 12-myristate 13-acetate (PMA, 1 nm) treatment and externalizes/releases the protein after additional 16 h of dexamethasone (1 microm) treatment. (3) This study investigated the possible regulation of cell surface L-selectin shedding by endogenous Annexin 1, and its role in glucocorticoid-induced L-selectin shedding in the U-937 cell line. (4) PMA- and dexamethasone treatment-induced L-selectin shedding was potentially mediated by Annexin 1, since neutralizing antibodies against Annexin 1 reduced dexamethasone- and Annexin 1-induced shedding. (5) Immunoprecipitation and binding assays provided support for the suggestion that this effect could be mediated by an interaction between externalized Annexin 1 and L-selectin. Such interaction involved the N-terminal domain of Annexin 1 and was calcium-dependent. Confocal microscopy studies demonstrated increased colocalization of Annexin 1 and L-selectin on the cell surface. (6) Overall, our study provides new insights into the potential role of endogenous ANXA1 as a mediator of dexamethasone-induced L-selectin shedding, which may contribute to the anti-inflammatory activity of glucocorticoids.

Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

PubMed

Nishiwaki, Satoshi; Nakayama, Takayuki; Murata, Makoto; Nishida, Tetsuya; Terakura, Seitaro; Saito, Shigeki; Kato, Tomonori; Mizuno, Hiroki; Imahashi, Nobuhiko; Seto, Aika; Ozawa, Yukiyasu; Miyamura, Koichi; Ito, Masafumi; Takeshita, Kyosuke; Kato, Hidefumi; Toyokuni, Shinya; Nagao, Keisuke; Ueda, Ryuzo; Naoe, Tomoki

2014-01-01

Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.

Roles for the Mitogen-activated Protein Kinase (MAPK) Phosphatase, DUSP1, in Feedback Control of Inflammatory Gene Expression and Repression by Dexamethasone*

PubMed Central

Shah, Suharsh; King, Elizabeth M.; Chandrasekhar, Ambika; Newton, Robert

2014-01-01

Glucocorticoids act on the glucocorticoid receptor (NR3C1) to repress inflammatory gene expression. This is central to their anti-inflammatory effectiveness and rational improvements in therapeutic index depend on understanding the mechanism. Human pulmonary epithelial A549 cells were used to study the role of the mitogen-activated protein kinase (MAPK) phosphatase, dual-specificity phosphatase 1 (DUSP1), in the dexamethasone repression of 11 inflammatory genes induced, in a MAPK-dependent manner, by interleukin-1β (IL1B). Adenoviral over-expression of DUSP1 inactivated MAPK pathways and reduced expression of all 11 inflammatory genes. IL1B rapidly induced DUSP1 expression and RNA silencing revealed a transient role in feedback inhibition of MAPKs and inflammatory gene expression. With dexamethasone, which induced DUSP1 expression, plus IL1B (co-treatment), DUSP1 expression was further enhanced. At 1 h, this was responsible for the dexamethasone inhibition of IL1B-induced MAPK activation and CXCL1 and CXCL2 mRNA expression, with a similar trend for CSF2. Whereas, CCL20 mRNA was not repressed by dexamethasone at 1 h, repression of CCL2, CXCL3, IL6, and IL8 was unaffected, and PTGS2 repression was partially affected by DUSP1 knockdown. At later times, dexamethasone repression of MAPKs was unaffected by DUSP1 silencing. Likewise, 6 h post-IL1B, dexamethasone repression of all 11 mRNAs was essentially unaffected by DUSP1 knockdown. Qualitatively similar data were obtained for CSF2, CXCL1, IL6, and IL8 release. Thus, despite general roles in feedback inhibition, DUSP1 plays a transient, often partial, role in the dexamethasone-dependent repression of certain inflammatory genes. Therefore this also illustrates key roles for DUSP1-independent effectors in mediating glucocorticoid-dependent repression. PMID:24692548

Dexamethasone, ondansetron, and their combination and postoperative nausea and vomiting in children undergoing strabismus surgery: a meta-analysis of randomized controlled trials.

PubMed

Shen, Yun-Dun; Chen, Chien-Yu; Wu, Chih-Hsiung; Cherng, Yih-Giun; Tam, Ka-Wai

2014-05-01

Postoperative nausea and vomiting (PONV) is a common complication after pediatric strabismus surgery. Steroids and ondansetron (a 5-HT3 antagonist) can effectively reduce nausea, vomiting, and pain and thus might be useful agents for the prevention of PONV in pediatric patients. The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the prophylactic effects of dexamethasone and ondansetron on PONV after strabismus surgery in pediatric patients. A comprehensive literature search was conducted to identify RCTs that investigated the efficacy and safety of intravenous dexamethasone or ondansetron on PONV in pediatric strabismus surgical patients. The primary outcome was the incidence of PONV during the initial 24 postoperative hours. The secondary outcomes were number of patients requiring a rescue antiemetic and complications. We included 13 RCTs that evaluated 2006 patients. In the two studies that compared dexamethasone and placebo treatments, POV occurred in 34.3% (23/67) of the patients in the dexamethasone group and in 68.2% (45/66) of the patients in the placebo group. The difference between the two groups was significant (RR 0.50; 95% confidence interval (CI) 0.34-0.72). Similarly, seven studies that compared ondansetron and a placebo identified a relatively lower incidence of PONV in the ondansetron group (103/277, 37.2%) than in the placebo group (177/270, 65.6%). The difference between the two groups was also significant (RR 0.58; 95% CI 0.43-0.79). The combination of dexamethasone and ondansetron was significantly more effective at reducing the incidence of POV than dexamethasone or ondansetron alone. In all included RCTs, experimental drug-related complications, such as facial flushing and headache, were limited. Surgeons and anesthesiologists are recommended to administer the combination of dexamethasone and ondansetron to pediatric patients undergoing strabismus surgery. © 2014 John

Comparison of the efficacy of liraglutide with pioglitazone on dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycaemia in albino rats.

PubMed

Vinodraj, K; Nagendra Nayak, I M; Rao, J Vikram; Mathai, Paul; Chandralekha, N; Nitasha, B; Rajesh, D; Chethan, T K

2015-01-01

To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats. There were four groups of six rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received liraglutide 1.8 mg/kg subcutaneously 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load were measured. Liver weight, liver volume, and histopathological analysis were done. Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and liraglutide significantly reduced hepatomegaly, dyslipidemia and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone when compared with liraglutide (P < 0.01). Liraglutide has comparable efficacy to pioglitazone in prevention of dexamethasone induced hepatomegaly, dyslipidemia and fasting hyperglycemia.

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

PubMed

Brown, Sarah; Hinsley, Samantha; Ballesteros, Mónica; Bourne, Sue; McGarry, Paul; Sherratt, Debbie; Flanagan, Louise; Gregory, Walter; Cavenagh, Jamie; Owen, Roger; Williams, Cathy; Kaiser, Martin; Low, Eric; Yong, Kwee

2016-01-01

Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than

Role of lipocortin-1 in the anti-hyperalgesic actions of dexamethasone

PubMed Central

Ferreira, S H; Cunha, F Q; Lorenzetti, B B; Michelin, M A; Perretti, M; Flower, R J; Poole, S

1997-01-01

The effect of dexamethasone, lipocorton-12–26 and an antiserum to lipocortin-12–26 (LCPS1) upon the hyperalgesic activities in rats of carrageenin, bradykinin, tumour necrosis factor α (TNFα), interleukin-12, interleukin-6 (IL-6), interleukin-8 (IL-8), prostaglandin Eβ (PGE2) and dopamine were investigated in a model of mechanical hyperalgesia. Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin (100 μg), bradykinin (500 ng), TNFα (2.5 pg), IL-1β (0.5 pg), and IL-6 (1.0 ng), but not responses to IL-8 (0.1 ng), PGE2 (100 ng) and dopamine (10 μg), were inhibited by pretreatment with dexamethasone (0.5 mg kg−1, subcutaneously, s.c., or 0.04–5.0 μg/paw). Inhibition of hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng) and IL-1β (0.5 pg) by dexamethasone (0.5 mg kg−1, s.c.) was reversed by LCPS1 (0.5 ml kg−1, injected s.c., 24 h and 1 h before hyperalgesic substances) and hyperalgesic responses to injections (i.pl.) of bradykinin (500 ng), TNFα (2.5 pg) and IL-1β (0.5 pg), but not responses to PGE2 (100 ng), were inhibited by pretreatment with lipocortin-12–26 (100 μg/paw). Also, lipocortin-12–26 (30 and 100 μg ml−1) and dexamethasone (10 μg ml−1) inhibited TNFα release by cells of the J774 (murine macrophage-like) cell-line stimulated with LPS (3 μg ml−1), and LCPS1 partially reversed the inhibition by dexamethasone. These data are consistent with an important role for endogenous lipocortin-12–26 in mediating the anti-hyperalgesic effect of dexamethasone, with inhibiton of TNFα production by lipocortin-12–26 contributing, in part, to this role. Although arachidonic acid by itself was not hyperalgesic, the hyperalgesic response to IL-1β (0.25 pg, i.pl.) was potentiated by arachidonic acid (50 μg) and the potentiated response was inhibited by dexamethasone (50 μg, i.pl.) and lipocortin-12–26 (100 μg, i.pl.). Also

Recovery of hearing in Cisplatin-induced ototoxicity in the Guinea pig with intratympanic dexamethasone.

PubMed

Calli, Caglar; Pinar, Ercan; Oncel, Semih; Alper Bagriyanik, H; Umut Sakarya, E

2012-03-01

The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a therapeutic agent against cisplatin-induced ototoxicity. Animals were randomly divided into three groups. Group one received intraperitoneal cisplatin alone, group two, received intratympanic dexamethasone after cisplatin ototoxicity had been demonstrated. Group three, which is control group, received intratympanic dexamethasone.Then we made three measurements. First we measured the baseline distortion product otoacustic emission (DPOAEs) of all the guine pigs. Second we injected cisplatin intraperitoneal group one and two the same day. Third we measured DPOAEs after 72 h of group one and two. Moreover DPOAEs were measured at the end of the first and second week only in group two. Cochleae were harvested and processed for electron microscopy after then. Values of The DPOAEs amplitudes and signal-to-noise ratio (SNR) at 1-6 kHz frequencies for group 1 after the injections significantly decreased over those before injections (P < 0.05). In group 3, there were no significant differences in DPOAE amplitude and SNR values When they are compare before and after their intratympanic dexamethasone injections (P > 0.05). In group 2, the DPOAEs measurements were close to significance at the end of the second week (P = 0.056). Intratympanic dexamethasone injection did not cause any ototoxic effect. Although intratympanic dexamethasone did not reach the statistically significant results, the measurements were close to significance. Intratympanic dexamethasone might have a significant therapeutic effect after cisplatin ototoxicity with different dose and application regimens.

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma.

PubMed

Martin, Thomas; Baz, Rachid; Benson, Don M; Lendvai, Nikoletta; Wolf, Jeffrey; Munster, Pamela; Lesokhin, Alexander M; Wack, Claudine; Charpentier, Eric; Campana, Frank; Vij, Ravi

2017-06-22

This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and pharmacokinetics of anti-CD38 monoclonal antibody isatuximab given in 2 schedules (3, 5, or 10 mg/kg every other week [Q2W] or 10 or 20 mg/kg weekly [QW] for 4 weeks and then Q2W thereafter [QW/Q2W]), in combination with lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (QW), in patients with relapsed/refractory multiple myeloma (RRMM). Patients received 28-day treatment cycles; the primary objective was to determine the maximum tolerated dose (MTD) of isatuximab with lenalidomide and dexamethasone. Fifty-seven patients (median 5 [range 1-12] prior regimens; 83% refractory to previous lenalidomide therapy) were treated. Median duration of dosing was 36.4 weeks; 15 patients remained on treatment at data cutoff. Isatuximab-lenalidomide-dexamethasone was generally well tolerated with only 1 dose-limiting toxicity reported (grade 3 pneumonia at 20 mg/kg QW/Q2W); the MTD was not reached. The most common isatuximab-related adverse events were infusion-associated reactions (IARs) (56%), which were grade 1/2 in 84% of patients who had an IAR and predominantly occurred during the first infusion. In the efficacy-evaluable population, the overall response rate (ORR) was 56% (29/52) and was similar between the 10 mg/kg Q2W and 10 and 20 mg/kg QW/Q2W cohorts. The ORR was 52% in 42 evaluable lenalidomide-refractory patients. Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide pharmacokinetic parameters appeared independent. These data suggest that isatuximab combined with lenalidomide and dexamethasone is active and tolerated in heavily pretreated patients with RRMM. This trial was registered at www.clinicaltrials.gov as #NCT01749969. © 2017 by The American Society of Hematology.

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

PubMed Central

Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

2016-01-01

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

Treatment of refractory uveitic macular edema: results of a first and second implant of long-acting intravitreal dexamethasone

PubMed Central

Zola, Marta; Briamonte, Cristina; Lorenzi, Umberto; Machetta, Federica; Grignolo, Federico M; Fea, Antonio M

2017-01-01

Purpose The purpose of this study was to report the functional and anatomical outcomes of a prospective study resulting from repeated dexamethasone intravitreal implants in patients with uveitic refractory macular edema. Methods Twelve eyes of 9 patients with intermediate and posterior noninfectious inflammatory uveitis complicated with refractory macular edema were regularly reviewed after a dexamethasone intravitreal implant. Patients were examined at baseline, 30, 90, 135, and 180 days with best-corrected visual acuity (BCVA), complete slit-lamp examination, intraocular pressure (IOP), optical coherence tomography, and fluorescein angiography. After 6 months of follow-up, eyes were reassessed to receive a second implant. Results BCVA significantly improved when comparing the baseline values after the first and second implant (16.2 and 25.8 letters, respectively, 9.6 letters improvements, p<0.05). BCVA was better after the second implant compared to the first one throughout the follow-up, but without statistical significance. Mean central macular thickness (CMT) was 446.3±129.9 μm at baseline and was significantly reduced until day 135 (p<0.05). CMT reductions after the second injection showed a similar pattern, though differences were not statistically significant. Cataract progression was observed in 4 of 8 phakic eyes (50%) after the first implant, and in 2 of 3 phakic eyes following the second implant, with 1 eye requiring cataract surgery. One eye developed an IOP >30 mmHg 30 days after the second implant, treated topically. Conclusion Repeated dexamethasone intravitreal implants in uveitic patients with refractory macular edema can be used effectively in a clinical setting with an acceptable safety profile. PMID:29184384

Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit.

PubMed

Huang, Xuetao; Liu, Shaogang; Yang, Yezhen; Duan, Yiqin; Lin, Ding

2017-11-01

Corticosteroids have been used for treatment of posterior segment eye diseases, but the delivery of drug to the posterior segments is still a problem to resolve. In our study, we explore the feasibility of Sub-tenon's Controllable Continuous Drug Delivery to ocular posterior segment. Controllable continuous sub-tenon drug delivery (CCSDD) system, intravenous injections (IV) and sub-conjunctival injections (SC) were used to deliver dexamethasone disodium phosphate (DEXP) in rabbits, the dexamethasone concentration was measured in the ocular posterior segment tissue by Shimadzu LC-MS 2010 system at different time points in 24 h after first dose injection. Levels of dexamethasone were significantly higher at 12, 24 h in CCSDD than two other approaches, and at 3, 6 h in CCSDD than IV in vitreous body (p < 0.01); at 6, 12, 24 h in CCSDD than two other approaches, and at 1, 3 h in CCSDD than IV in retinal/choroidal compound (p < 0.01); at 3, 6, 12, 24 h in CCSDD than two other approaches, and at 1 h in CCSDD than IV in sclera (p < 0.05). The AUC 0-24 in CCSDD group is higher than two other groups in all ocular posterior segment tissue. Our results demonstrated that dexamethasone concentration could be sustained moderately higher in the posterior segment by CCSDD than SC and IV, indicating that CCSDD might be a therapeutic alternative to treat a variety of intractable posterior segment diseases.

Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo study

PubMed Central

2014-01-01

Background The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye. Methods An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases. For this study, an eye cup filled with dexamethasone sodium phosphate was placed on the cornea. Ultrasound was applied at intensity of 0.8 W/cm2 and frequency of 400 or 600 kHz for 5 min. The drug concentration in aqueous humor samples, collected 90 min after the treatment, was determined using chromatography methods. Light microscopy observations were done to determine the structural changes in the cornea as a result of ultrasound application. Results An increase in drug concentration in aqueous humor samples of 2.8 times (p < 0.05) with ultrasound application at 400 kHz and 2.4 times (p < 0.01) with ultrasound application at 600 kHz was observed as compared to sham-treated samples. Histological analysis showed that the structural changes in the corneas exposed to ultrasound predominantly consisted of minor epithelial disorganization. Conclusions Ultrasound application enhanced the delivery of an anti-inflammatory ocular drug, dexamethasone sodium phosphate, through the cornea in vivo. Ultrasound-enhanced ocular drug delivery appears to be a promising area of research with a potential future application in a clinical setting. PMID:24921047

Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate.

PubMed

Ekstrand, C; Bondesson, U; Gabrielsson, J; Hedeland, M; Kallings, P; Olsén, L; Ingvast-Larsson, C

2015-06-01

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03 mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 ± 2.9 days (LLOQ: 0.025 μg/L) and in urine for 9.8 ± 3.1 days (LLOQ: 0.15 μg/L). Maximum observed dexamethasone concentration in plasma was 0.61 ± 0.12 μg/L and in urine 4.2 ± 0.9 μg/L. Terminal plasma half-life was 38.7 ± 19 h. Hydrocortisone was significantly suppressed for 140 h. The plasma half-life of hydrocortisone was 2.7 ± 1.3 h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 ± 0.04 μg/L, 0.95 ± 0.04 and 6.2 ± 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone. © 2014 John Wiley & Sons Ltd.

Hyponatremia due to Secondary Adrenal Insufficiency Successfully Treated by Dexamethasone with Sodium Chloride

PubMed Central

Kazama, Itsuro; Tamada, Tsutomu; Nakajima, Toshiyuki

2015-01-01

Patient: Female, 60 Final Diagnosis: Hyponatremia due to secondary adrenal insufficiency Symptoms: prolonged general fatigue and anorexia Medication: — Clinical Procedure: Successfully treated by dexamethasone with sodium chloride Specialty: Nephrology Objective: Rare co-existance of disease or pathology Background: Patients who were surgically treated for Cushing’s syndrome postoperatively surrender to “primary” adrenal insufficiency. However, the preoperative over-secretion of cortisol or the postoperative administration of excessive glucocorticoids can cause “secondary” adrenal insufficiency, in which the prevalence of hyponatremia is usually lower than that of primary adrenal insufficiency. Case Report: A 60-year-old woman with a past medical history of Cushing’s syndrome developed hyponatremia with symptoms of acute glucocorticoid deficiency, such as prolonged general fatigue and anorexia, after upper respiratory tract infection. A decrease in the serum cortisol level and the lack of increase in the ACTH level, despite the increased demand for cortisol, enabled a diagnosis of “secondary” adrenal insufficiency. Although the initial fluid replacement therapy was not effective, co-administration of dexamethasone and sodium chloride quickly resolved her symptoms and ameliorated the refractory hyponatremia. Conclusions: In this case, the hypothalamic-pituitary axis of the patient was thought to have become suppressed long after the surgical treatment for Cushing’s syndrome. This case suggested a mechanism of refractory hyponatremia caused by secondary adrenal insufficiency, for which the administration of dexamethasone and sodium chloride exerted additional therapeutic efficacy. PMID:26319655

Adventitial Drug Delivery of Dexamethasone to Improve Primary Patency in the Treatment of Superficial Femoral and Popliteal Artery Disease: 12-Month Results From the DANCE Clinical Trial.

PubMed

Razavi, Mahmood K; Donohoe, Dennis; D'Agostino, Ralph B; Jaff, Michael R; Adams, George

2018-05-28

This study was designed to evaluate outcomes of adventitial dexamethasone delivery adjunctive to standard endovascular revascularization in femoropopliteal peripheral artery disease. Drug-coated balloons and drug-eluting stents improve patency of endovascular interventions with passive diffusion of antiproliferative drugs. Adventitial dexamethasone delivery targets the initial triggers of the inflammatory reaction to injury, thus potentially providing a potent antirestenotic strategy. The single-arm DANCE (Dexamethasone to the Adventitia to Enhance Clinical Efficacy After Femoropopliteal Revascularization) trial enrolled 262 subjects (283 limbs) with symptomatic peripheral artery disease (Rutherford category 2 to 4) receiving percutaneous transluminal angioplasty (PTA) (n = 124) or atherectomy (ATX) (n = 159) in femoropopliteal lesions ≤15 cm in length. A mixture of dexamethasone/contrast medium (80%/20%) was delivered to the adventitia and perivascular tissues surrounding target lesions in all subjects. Thirty-day assessments included major adverse limb events (MALE) and post-operative death. Twelve-month assessments included primary patency, freedom from clinically driven target lesion revascularization (CD-TLR), Rutherford scoring, and walking impairment questionnaire. At 12 months, primary patency rates in DANCE-ATX and -PTA per-protocol populations were 78.4% (74.8% intent-to-treat [ITT]) and 75.5% (74.3% ITT), respectively. Rates of CD-TLR in DANCE-ATX and -PTA subjects were 10.0% (13.1% ITT) and 11.0% (13.7% ITT), respectively. There were no 30-day MALE + post-operative death events nor 12-month device- or drug-related deaths or MALE. Direct adventitial delivery of dexamethasone appears to be an effective and safe therapy to prevent restenosis. Randomized studies are needed to further test this possibility. (Dexamethasone to the Adventitia to Enhance Clinical Efficacy After Femoropopliteal Revascularization [DANCE]; NCT01983449). Copyright © 2018

Evidence-based practice guidelines: a survey of subcutaneous dexamethasone administration.

PubMed

Walker, Jackie; Lane, Pauline; McKenzie, Clare

2010-10-01

Searching for good evidence to develop clinical practice guidelines can be challenging, as research may not be published or available. A simple question set the authors on a journey to find evidence related to the nursing administration of subcutaneous dexamethasone in the palliative setting. This article outlines the search for evidence and discusses the survey results to gather expert opinion about the nursing administration of dexamethasone. Survey results indicated that only 39% of community services gave dexamethasone via a bolus injection and 88% gave it via a continuous infusion, mainly for site preservation. The diluents used were water for injection or normal saline. Many procedural aspects were supported by current guidelines, with several services using the New Zealand Waitemata District Health Board's (2008) clinical guidelines. Developing and implementing procedural recommendations for nurses to administer this subcutaneous medication will form the next stage of the project.

A Comparative Study on the Efficacy of Submucosal Injection of Dexamethasone Versus Methylprednisolone in Reducing Postoperative Sequelae After Third Molar Surgery.

PubMed

Lim, Daniel; Ngeow, Wei Cheong

2017-11-01

To compare the efficacy of preoperative submucosal injection of 4 mg of dexamethasone versus 40 mg of methylprednisolone in reducing postoperative sequelae after surgical removal of impacted mandibular third molars. This prospective, randomized, double-blind study included 65 patients who required surgical removal of impacted mandibular third molars with Class II or position B impaction (Pell and Gregory classification). Patients were randomly assigned to 1 of 3 groups: dexamethasone, methylprednisolone, or placebo (control). Surgery was performed with patients under local anesthesia. Baseline measurements were obtained preoperatively, and subsequent assessments were made on postoperative day 1, 2, 5, and 7 to measure postoperative facial swelling by use of 2 linear measurements: interincisal mouth opening width and visual analog scale score for pain. The amount of analgesics consumed was recorded. Wound healing also was assessed on postoperative day 7. Descriptive and multivariate statistics were computed, and significance was set at P < .05. Both methylprednisolone and dexamethasone significantly reduced swelling and trismus (P < .05, Kruskal-Wallis test), whereas the methylprednisolone group had significantly less pain (P < .05, Kruskal-Wallis test) and consumed a lower amount of analgesics (P < .05, χ 2 test) during the early postoperative days. The study findings suggest that a single preoperative dose of dexamethasone versus methylprednisolone was equally effective in reducing postoperative swelling and trismus. Pain control by these corticosteroids, however, was variable. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons.

PubMed

Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

2016-12-01

Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Dexamethasone-immunosuppressed male mice (6-8weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (P<0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45+ and CD8+ inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Suppression of dexamethasone-stimulated DNA synthesis in an oncogene construct containing rat cell line by a DNA site-oriented ligand of poly-ADP-ribose polymerase: 6-amino-1,2-benzopyrone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirsten, E.; Bauer, P.I.; Kun, E.

1991-03-01

The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethansone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. AT a nontoxic concentration 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone-stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the levelmore » of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically.« less

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.

PubMed

Dimopoulos, Meletios A; Oriol, Albert; Nahi, Hareth; San-Miguel, Jesus; Bahlis, Nizar J; Usmani, Saad Z; Rabin, Neil; Orlowski, Robert Z; Komarnicki, Mieczyslaw; Suzuki, Kenshi; Plesner, Torben; Yoon, Sung-Soo; Ben Yehuda, Dina; Richardson, Paul G; Goldschmidt, Hartmut; Reece, Donna; Lisby, Steen; Khokhar, Nushmia Z; O'Rourke, Lisa; Chiu, Christopher; Qin, Xiang; Guckert, Mary; Ahmadi, Tahamtan; Moreau, Philippe

2016-10-06

Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P<0.001 by stratified log-rank test). The Kaplan-Meier rate of progression-free survival at 12 months was 83.2% (95% CI, 78.3 to 87.2) in the daratumumab group, as compared with 60.1% (95% CI, 54.0 to 65.7) in the control group. A significantly higher rate of overall response was observed in the daratumumab group than in the control group (92.9% vs. 76.4%, P<0.001), as was a higher rate of complete response or better (43.1% vs. 19.2%, P<0.001). In the daratumumab group, 22.4% of the patients had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells), as compared with 4.6% of those in the control group (P<0.001); results below the threshold for minimal residual disease were associated with improved outcomes. The most common adverse events of grade 3 or 4 during treatment were neutropenia (in 51.9% of the patients in the daratumumab group vs. 37.0% of those in the control group), thrombocytopenia (in 12.7% vs. 13.5%), and anemia (in 12.4% vs. 19.6%). Daratumumab-associated infusion-related reactions occurred in 47.7% of the patients and were mostly of grade 1 or 2. The addition of daratumumab to lenalidomide and dexamethasone significantly lengthened

The efficacy of dexamethasone on reduction in the reoperation rate of chronic subdural hematoma – the DRESH study: straightforward study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Chronic subdural hematoma (cSDH) is a common neurosurgical disease. It is often considered to be a rather benign entity. In spite of well established surgical procedures cSDH is complicated by a recurrence rate up to 30%. Since glucocorticoids have been used for treatment of cSDH in 1962 their role is still discussed controversially in lack of evident data. On the basis of the ascertained inflammation cycle in cSDH dexamethasone will be an ideal substance for a short lasting, concomitant treatment protocol. Objective: to test the efficacy of dexamethasone on reduction inthe reoperation rate of cSDH. Methods/Design The study is designed as a double-blind randomized placebo-controlled trial 820 patients who are operated for cSDH and from the age of 25 years are included after obtaining informed consent. They are randomized for administration of dexamethasone (16-16-12-12-8-4 mg/d) or placebo (maltodextrin) during the first 48 hours after surgery. The type I error is 5% and the type II error is 20%. The primary endpoint is the reoperation within 12 weeks postoperative. Discussion This study tests whether dexamethasone administered over 6 days is a safe and potent agent in relapse prevention for evacuated cSDH. Trial registration EudraCT 201100354442 PMID:24393328

Dexamethasone in head and neck cancer patients with microvascular reconstruction: No benefit, more complications.

PubMed

Kainulainen, S; Törnwall, J; Koivusalo, A M; Suominen, A L; Lassus, P

2017-02-01

Glucocorticoids are widely used in association with major surgery of the head and neck to improve postoperative rehabilitation, shorten intensive care unit and hospital stay, and reduce neck swelling. This study aimed to clarify whether peri- and postoperative use of dexamethasone in reconstructive head and neck cancer surgery is associated with any advantages or disadvantages. This prospective double-blind randomized controlled trial comprised 93 patients. A total dose of 60mg of dexamethasone was administered to 51 patients over three days peri- and postoperatively. The remaining 42 patients served as controls. The main primary outcome variables were neck swelling, length of intensive care unit and hospital stay, duration of intubation or tracheostomy, and delay to start of possible radiotherapy. Complications were also recorded. No statistical differences emerged between the two groups in any of the main primary outcome variables. However, there were more major complications, especially infections, needing secondary surgery within three weeks of the operation in patients receiving dexamethasone than in control patients (27% vs. 7%, p=0.012). The use of dexamethasone in oral cancer patients with microvascular reconstruction did not provide a benefit. More major complications, especially infections, occurred in patients receiving dexamethasone. Our data thus do not support the use of peri- and postoperative dexamethasone in oropharyngeal cancer patients undergoing microvascular reconstruction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone

PubMed Central

dos Anjos, Isabelle Valle; Chalkidis, Hipocrates de Menezes; Mourão, Rosa Helena Veras; Moura-da-Silva, Ana Maria; Sano-Martins, Ida Sigueko; Gonçalves, Luis Roberto de Camargo

2017-01-01

Bothrops atrox snakes are the leading cause of snake bites in Northern Brazil. The venom of this snake is not included in the antigen pool used to obtain the Bothrops antivenom. There are discrepancies in reports on the effectiveness of this antivenom to treat victims bitten by B. atrox snakes. However, these studies were performed using a pre-incubation of the venom with the antivenom and, thus, did not simulate a true case of envenomation treatment. In addition, the local lesions induced by Bothrops venoms are not well resolved by antivenom therapy. Here, we investigated the efficacy of the Bothrops antivenom in treating the signs and symptoms caused by B. atrox venom in mice and evaluated whether the combination of dexamethasone and antivenom therapy enhanced the healing of local lesions induced by this envenomation. In animals that were administered the antivenom 10 minutes after the envenomation, we observed an important reduction of edema, dermonecrosis, and myonecrosis. When the antivenom was given 45 minutes after the envenomation, the edema and myonecrosis were reduced, and the fibrinogen levels and platelet counts were restored. The groups treated with the combination of antivenom and dexamethasone had an enhanced decrease in edema and a faster recovery of the damaged skeletal muscle. Our results show that Bothrops antivenom effectively treats the envenomation caused by Bothrops atrox and that the use of dexamethasone as an adjunct to the antivenom therapy could be useful to improve the treatment of local symptoms observed in envenomation caused by Bothrops snakes. PMID:28306718

Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression

PubMed Central

Murray, Megan Y.; Rushworth, Stuart A.; Zaitseva, Lyubov; Bowles, Kristian M.; MacEwan, David J.

2013-01-01

Dexamethasone is a key front-line chemotherapeutic for B-cell malignant multiple myeloma (MM). Dexamethasone modulates MM cell survival signaling but fails to induce marked cytotoxicity when used as a monotherapy. We demonstrate here the mechanism behind this insufficient responsiveness of MM cells toward dexamethasone, revealing in MM a dramatic anti-apoptotic role for microRNA (miRNA)-125b in the insensitivity toward dexamethasone-induced apoptosis. MM cells responding to dexamethasone exhibited enhanced expression of oncogenic miR-125b. Dexamethasone also induced expression of miR-34a, which acts to suppress SIRT1 deacetylase, and thus allows maintained acetylation and inactivation of p53. p53 mRNA is also suppressed by miR-125b targeting. Reporter assays showed that both these dexamethasone-induced miRNAs act downstream of their target genes to prevent p53 tumor suppressor actions and, ultimately, resist cytotoxic responses in MM. Use of antisense miR-125b transcripts enhanced expression of pro-apoptotic p53, repressed expression of anti-apoptotic SIRT1 and, importantly, significantly enhanced dexamethasone-induced cell death responses in MM. Pharmacological manipulations showed that the key regulation enabling complete dexamethasone sensitivity in MM cells lies with miR-125b. In summary, dexamethasone-induced miR-125b induces cell death resistance mechanisms in MM cells via the p53/miR-34a/SIRT1 signaling network and provides these cells with an enhanced level of resistance to cytotoxic chemotherapeutics. Clearly, such anti-apoptotic mechanisms will need to be overcome to more effectively treat nascent, refractory and relapsed MM patients. These mechanisms provide insight into the role of miRNA regulation of apoptosis and their promotion of MM cell proliferative mechanisms. PMID:23759586

Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States.

PubMed

Jakubowiak, Andrzej J; Houisse, Ivan; Májer, István; Benedict, Ágnes; Campioni, Marco; Panjabi, Sumeet; Ailawadhi, Sikander

2017-12-01

We assessed the economic value of carfilzomib 56 mg/m 2 and dexamethasone (Kd56) vs. bortezomib and dexamethasone (Vd) for relapsed/refractory multiple myeloma (R/RMM) using ENDEAVOR trial results. Cost-effectiveness of Kd56 vs. Vd was assessed using a partitioned survival model by estimating progression-free survival, overall survival, and direct costs over a lifetime horizon. Surveillance Epidemiology and End Results (SEER) survival data were extrapolated after matching registry and ENDEAVOR patients. Utilities were sourced from the literature and mapped from patient-reported quality of life in ENDEAVOR to estimate quality-adjusted life-years (QALYs) from life-years (LYs). The model predicted an average gain of 1.66 LYs and 1.50 QALYs with Kd56 vs. Vd, and lifetime additional costs of $182,699, resulting in an incremental cost-effectiveness ratio (ICER) of $121,828/QALY gained. The ICER was $114,793/QALY in patients with 1 prior treatment; $99,263/QALY in those not transplanted, and <$150,000/QALY up to an 85% discount in bortezomib price. Kd56 is cost-effective for patients with R/RMM at a willingness-to-pay threshold of $150,000/QALY. Trial data in the model may limit generalizability; however, SEER registry data mitigates this challenge. Kd56 provides additional value in key subgroups, and remains cost-effective after steep comparator discounts.

Feasibility of metronomic chemotherapy with tegafur-uracil, cisplatin, and dexamethasone for docetaxel-refractory prostate cancer

PubMed Central

Kubota, Hiroki; Fukuta, Katsuhiro; Yamada, Kenji; Hirose, Masahito; Naruyama, Hiromichi; Yanai, Yoshimasa; Yamada, Yasuyuki; Watase, Hideki; Kawai, Noriyasu; Tozawa, Keiichi; Yasui, Takahiro

2017-01-01

Objectives: To evaluate the efficacy of tegafur–uracil (UFT), a prodrug of 5-fluorouracil, plus cisplatin and dexamethasone in patients with docetaxel-refractory prostate cancers. Methods: Twenty-five patients with docetaxel-refractory prostate cancer were administered oral UFT plus intravenous cisplatin (UFT-P therapy) and dexamethasone. Treatment responses were assessed monthly via prostate-specific antigen (PSA) level measurements. Treatment-related adverse events and overall survival were also assessed. Results: UFT-P therapy resulted in decreased PSA levels in 14 (56%) patients and increased PSA levels in 11 (44%). In patients with increased PSA levels, 7 (64%) of the 11 patients displayed decreased PSA doubling times. The UFT-P therapy response rate was 84% (21/25 patients). Imaging studies revealed that tumor shrinkage during UFT-P therapy occurred in 1 patient in whom bilateral hydronephrosis caused by lymph node metastasis improved. The median survival time from docetaxel initiation was 36 months. In UFT-P-treated patients, the median PSA progression and overall survival times were 6 and 14 months, respectively. UFT-P treatment-related adverse events were mild diarrhea, general fatigue, and anorexia. Treatment was not discontinued for any of the patients. UFT-P therapy did not cause serious hepatic or renal dysfunction or pancytopenia. Conclusions: UFT-P therapy is a safe and effective treatment for patients with docetaxel-refractory prostate cancer, although large-scale, multicenter, prospective studies are needed to validate these findings. PMID:29255528

Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study.

PubMed

Badie, B; Schartner, J M; Paul, J; Bartley, B A; Vorpahl, J; Preston, J K

2000-10-01

Commonly used for management of cerebral edema in patients with brain tumors, steroid medications also have immunosuppressive functions. To characterize the effects of steroids on the central nervous system's response to tumors more clearly, flow cytometry was used to quantify the extent of inflammatory cell infiltration in an immunogenic rat glioma model. Freshly prepared 11-day-old intracranial C6 tumors that had been excised from dexamethasone-treated and untreated rats were labeled ex vivo with monoclonal antibodies against CD 11b/c, CD45, and CD8a antigens. The extent of microglia (CD11b/c-highly positive, CD45-slightly positive cell), macrophage (CD11b/c-highly positive, CD45-highly positive cell), lymphocyte (CD11b/c-negative, CD45-highly positive cell), and cytotoxic T-cell (CD8a-positive cell) infiltration into each rat's tumor, tumor periphery, and contralateral tumor-free hemisphere was analyzed using flow cytometry. Microglia and lymphocytes constituted a significant component of infiltrating cells in this model, comprising 23 +/- 3% and 33 +/- 5% of viable cells, respectively. Macrophages, on the other hand, accounted for only 9 +/- 1% of infiltrating cells. Treatment of rats with a 7-day course of low-dose dexamethasone (0.1 mg/kg/day) resulted in a greater than 50% inhibition of microglia (p = 0.03) and lymphocyte (p = 0.001) infiltration into tumors. Increasing the dexamethasone dose to 1 mg/kg/day further abolished lymphocyte infiltration (89% inhibition, p = 0.001) but had no additional inhibitory effect on microglia invasion. Macrophage infiltration of tumors was not inhibited at the dexamethasone doses used in this study (p = 0.42). Flow cytometry is a valuable technique for characterizing tumor-associated inflammatory cells in gliomas. Even at low doses, dexamethasone was found to inhibit significantly the infiltration of brain tumors by lymphocytes and microglia. These findings should be considered when experimental immunotherapeutic

Clinical effectiveness analysis of dextran 40 plus dexamethasone on the prevention of fat embolism syndrome.

PubMed

Liu, Xi-Ming; Huang, Jin-Cheng; Wang, Guo-Dong; Lan, Sheng-Hui; Wang, Hua-Song; Pan, Chang-Wu; Zhang, Ji-Ping; Cai, Xian-Hua

2014-01-01

This study aims to investigate the clinical efficacy of Dextran 40 plus dexamethasone on the prevention of fat embolism syndrome (FES) in high-risk patients with long bone shaft fractures. According to the different preventive medication, a total of 1837 cases of long bone shaft fracture patients with injury severity score (ISS) > 16 were divided into four groups: dextran plus dexamethasone group, dextran group, dexamethasone group and control group. The morbidity and mortality of FES in each group were analyzed with pairwise comparison analysis. There were totally 17 cases of FES and 1 case died. The morbidity of FES was 0.33% in dextran plus dexamethasone group and significantly lowers than that of other groups (P < 0.05). There was no significant difference among other groups (P > 0.05). Conclusion from our data is dextran 40 plus dexamethasone can effectively prevent long bone shaft fractures occurring in high-risk patients with FES.

Antenatal dexamethasone after asphyxia increases neural injury in preterm fetal sheep.

PubMed

Koome, Miriam E; Davidson, Joanne O; Drury, Paul P; Mathai, Sam; Booth, Lindsea C; Gunn, Alistair Jan; Bennet, Laura

2013-01-01

Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain. Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach. Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290 ± 76 vs 484 ± 98 neurons/mm(2), mean ± SEM, P<0.05) and basal ganglia (putamen, 538 ± 112 vs 814 ± 34 neurons/mm(2), P<0.05) compared to asphyxia-saline, and with greater loss of both total (913 ± 77 vs 1201 ± 75/mm(2), P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66 ± 8 vs 114 ± 12/mm(2), P<0.05, vs sham controls 165 ± 10/mm(2), P<0.001). This was associated with transient hyperglycemia (peak 3.5 ± 0.2 vs. 1.4 ± 0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum -1.5 ± 1.2 dB vs. -5.0 ± 1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures. In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage.

A randomized trial of dexamethasone and acetazolamide for acute mountain sickness prophylaxis.

PubMed

Ellsworth, A J; Larson, E B; Strickland, D

1987-12-01

Forty-seven climbers participated in a double-blind, randomized trial comparing acetazolamide 250 mg, dexamethasone 4 mg, and placebo every eight hours as prophylaxis for acute mountain sickness during rapid, active ascent of Mount Rainier (elevation 4,392 m). Forty-two subjects (89.4 percent) achieved the summit in an average of 34.5 hours after leaving sea level. At the summit or high point attained above base camp, the group taking dexamethasone reported less headache, tiredness, dizziness, nausea, clumsiness, and a greater sense of feeling refreshed (p less than or equal to 0.05). In addition, they reported fewer problems of runny nose and feeling cold, symptoms unrelated to acute mountain sickness. The acetazolamide group differed significantly (p less than or equal to 0.05) from other groups at low elevations (1,300 to 1,600 m), in that they experienced more feelings of nausea and tiredness, and they were less refreshed. These drug side effects probably obscured the previously established prophylactic effects of acetazolamide for acute mountain sickness. Separate analysis of an acetazolamide subgroup that did not experience side effects at low elevations revealed a prophylactic effect of acetazolamide similar in magnitude to the dexamethasone effect but lacking the euphoric effects of dexamethasone. This study demonstrates that prophylaxis with dexamethasone can reduce the symptoms associated with acute mountain sickness during active ascent and that acetazolamide can cause side effects that may limit its effectiveness as prophylaxis against the disease.

Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

PubMed Central

Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

2013-01-01

Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

Randomized, Controlled Trial of Dexamethasone Versus Dexamethasone Plus Hydrocortisone as Prophylaxis for Hypersensitivity Reactions Due to Paclitaxel Treatment for Gynecologic Cancer.

PubMed

Jeerakornpassawat, Dhammapoj; Suprasert, Prapaporn

2017-10-01

The aim of this study was to assess intravenous hydrocortisone (HCT) added to standard dexamethasone (DXM) prophylaxis for paclitaxel-associated hypersensitivity reactions (HSRs). Paclitaxel naives scheduled for 6 cycles of paclitaxel (plus platinum) were randomized to DXM alone (20 mg intravenously [IV]) versus DXM plus HCT (100 mg IV) as premedication including chlorpheniramine (10 mg IV), diphenhydramine (25 mg orally), and ranitidine (50 mg IV) 30 minutes before infusion. Clinic nurses observed for HSRs. Groups were well balanced for cancer type, stage, drug allergy, chemotherapy naivete, mean age, body mass index, and paclitaxel dose. The 44 DXM controls underwent 213 cycles and the 42 investigational DXM plus HCT group 192 per protocol cycles. Hypersensitivity reactions were observed among 9 (4.2%) DXM only cycles compared with 1 (0.5%) among DXM plus HCT cycles (P = 0.022). Hypersensitivity reactions occurred in 8 (18%) DXM only patients and in 1 (2.4%) among those correctly receiving DXM plus HCT (P = 0.030). All HSRs occurred in cycles 1 to 3, within 10 to 40 minutes after infusion initiation, and peaked in cycle 2 (5/39) for DXM recipients and in cycle 3 (1/30) for DXM plus HCT. Hypersensitivity reaction severity was grade 1 in 3 DXM only recipients and grade 2 in 6 DXM and 1 DXM plus HCT. A sole grade 3 HSR was in an intention-to-treat DXM-HCT patient, who erroneously received no HCT. Hypersensitivity reaction symptoms were facial flushing (8 episodes), dyspnea (7), palmar rash (1), and transient hypotension (1). Paclitaxel infusion was suspended for treatment of HSRs; in all cases, symptoms mitigated and infusion successfully restarted for the remaining dose. Adding HCT to routine DXM prophylaxis significantly decreased paclitaxel HSR frequency.

Growth hormone and early treatment.

PubMed

Antoniazzi, F; Cavarzere, P; Gaudino, R

2015-06-01

Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.

Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549).

PubMed

Coyne, Cody P; Narayanan, Lakshmi

2016-01-01

Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively "target" delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10(-9) M and 10(-5) M. Rapid increases in

Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses.

PubMed

Haspel, A D; Giguère, S; Hart, K A; Berghaus, L J; Davis, J L

2018-01-01

Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. Randomised crossover experiment. Dexamethasone sodium phosphate was administered to six healthy adult horses at a dose of 5 mg q. 24 h for 5 days via nebulised, or intravenous (i.v.) routes. Plasma dexamethasone concentrations were measured by UPLC/MS-MS to calculate bioavailability. Cytological examination of bronchoalveolar fluid was performed at baseline and after the last dose of DSP. A validated chemiluminescent immunoassay was used to measure basal serum cortisol concentrations. After nebulisation to adult horses, dexamethasone had a mean (±s.d.) maximum plasma concentration of 0.774 ± 0.215 ng/mL and systemic bioavailability of 4.3 ± 1.2%. Regardless of route of administration, there was a significant decrease in the percentage of neutrophils in bronchoalveolar lavage fluid over time. During i.v. administration, basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, basal serum cortisol concentration did not change significantly during administration via nebulisation. Small sample size and short period of drug administration. Dexamethasone sodium phosphate administered via nebulisation had minimal systemic bioavailability and did not induce lower airway inflammation or HPA axis suppression in healthy horses. © 2017 EVJ Ltd.

Evaluation of the effects and adverse drug reactions of low-dose dexamethasone premedication with weekly docetaxel.

PubMed

Kang, Rae Young; Yoo, Kyung Sook; Han, Hyeon Ju; Lee, Ju-Yeun; Lee, Se-Hoon; Kim, Dong-Wan; Lee, Yu Jeung

2017-02-01

A weekly docetaxel regimen had comparable efficacy with a tri-weekly schedule and caused significantly less severe neutropenia and febrile neutropenia. Therefore, a weekly docetaxel regimen has become increasingly common in cancer treatment. Premedication with corticosteroids can effectively prevent or reduce the severity of hypersensitivity and fluid retention. However, no recommended steroid dosage for a weekly docetaxel regimen has been established to date. The aim of this study is to compare the efficacy and complications of two different weekly docetaxel premedication protocols. We retrospectively compared the hypersensitivity, hyperglycemia, and infection incidence associated with two weekly docetaxel premedication protocols. The control group (dexamethasone 10 mg intravenously and 4 mg orally every 12 h for four doses, starting 1 h before docetaxel administration) patients started weekly docetaxel chemotherapy between May 2012 and April 2013 at Seoul National University Hospital, and the experimental group (dexamethasone 10 mg intravenously 1 h prior to each docetaxel administration) patients started weekly docetaxel chemotherapy between May 2013 and April 2014. In total, 109 patients in the control group and 97 patients in the experimental group were included in this study, and there were no statistically significant differences in baseline characteristics between the two groups. The incidence of hypersensitivity and hyperglycemia were similar, but infections were observed significantly less in the experimental group (p = 0.020, OR = 0.408, 0.0190-0.0879). A low-dose dexamethasone premedication protocol has comparable efficacy in the prevention of docetaxel hypersensitivity with fewer infection complications. Therefore, we recommend a low-dose dexamethasone premedication protocol for weekly docetaxel regimens.

Dexamethasone and perioperative blood glucose in patients undergoing total joint arthroplasty: A retrospective study.

PubMed

Nurok, Michael; Cheng, Jennifer; Romeo, Giulio R; Vecino, Stephanie M; Fields, Kara G; YaDeau, Jacques T

2017-02-01

Perioperative dexamethasone is commonly used to prevent nausea. It can also increase blood glucose levels, and recent concern about its blood glucose-elevating effect in humans has been raised. This study aimed to demonstrate relationships between dexamethasone administration and elevated perioperative blood glucose in patients undergoing total joint arthroplasty. Retrospective study. Academic, orthopedic hospital. A total of 625 patients (18-99years) who underwent total hip or total knee arthroplasty with an ASA ≤3 were included in the study. Patients who received dexamethasone perioperatively were compared to those who did not receive dexamethasone. The primary outcome, which was any postoperative glucose >200mg/dl, was compared between groups using multiple logistic regression. Demographic information, intraoperative information, incidence of postoperative nausea and vomiting, white blood cell count, medication use, and length of stay were also collected. Perioperative dexamethasone (median [1st quartile, 3rd quartile] dose=4 [4, 8] mg) was administered to 76% of patients. Only 5.6% (95% CI: 3.8-7.5) of patients had postoperative glucose levels >200mg/dl. After covariate adjustment, there was no evidence of a difference in odds of experiencing postoperative glucose levels >200mg/dl (odds ratio [95% CI]: 0.76 [0.28-2.07]; P=0.594) and maximum glucose levels (P=0.518) between groups. Dexamethasone-treated patients had greater changes in white blood cell count between baseline and postoperative days 0-1. There was no evidence of a difference in wound healing and length of stay between groups. There was no evidence of an association between perioperative dexamethasone administration and the odds of having postoperative glucose levels >200mg/dl or higher maximum glucose levels. However, these findings may not be generalizable to patients having different baseline characteristics or procedures. Copyright © 2016 Elsevier Inc. All rights reserved.

Co-administration of walnut (Juglans regia) prevents systemic hypertension induced by long-term use of dexamethasone: a promising strategy for steroid consumers.

PubMed

Joukar, Siyavash; Ebrahimi, Sahar; Khazaei, Majid; Bashiri, Alireza; Shakibi, Mohammad Reza; Naderi, Vida; Shahouzehi, Beydolah; Alasvand, Masoud

2017-12-01

The long-term consumption of glucocorticoids (GCs) may induce serious adverse effects such as hypertension. There is sufficient evidence related to the benefit of walnuts on the cardiovascular system. This study assesses the effect of methanol extract of walnut [Juglans regia L. (Juglandaceae)] on dexamethasone-induced hypertension and the possible mechanisms in Wistar rats. Animals were randomized into control, kernel extract (100 and 200 mg/kg/d, orally), dexamethasone (0.03 mg/kg/d, subcutaneously), dexamethasone + kernel (100 and 200 mg/kg/d, separately), and dexamethasone + captopril (25 mg/kg/d, orally) groups. Animals were treated with water, kernel extract or captopril by gavage 4 d before and during 11 d of saline or dexamethasone treatment. On the 16th day, blood pressure (BP) was recorded and blood samples were collected to measure nitric oxide (NO). Animal hearts were frozen for measurement of malondialdehyde (MDA) and glutathione peroxidase (GPX). Dexamethasone increased the diastolic BP and MDA/GPX ratio in comparison with control group (128 ± 7 vs. 105 ± 3 mmHg, p < 0.05 and 0.2 ± 0.046 vs. 0.08 ± 0.02, p < 0.05). Combination of dexamethasone and walnut (200 mg/kg) prevented the dexamethasone-induced diastolic hypertension (109 ± 3 vs. 128 ± 7 mmHg; p < 0.05), increased the GPX level (14.8 ± 1.46 vs. 5.1 ± 0.64 unit/mg, p < 0.05), reduced the MDA/GPX ratio (0.16 ± 0.015 vs. 0.2 ± 0.046) and improved serum NO level. Similar to captopril, walnut extract normalized dexamethasone-induced hypertension. A part of this beneficial effect apparently involves maintaining balance of the redox system and NO production.

Which is your choice for prolonging the analgesic duration of single-shot interscalene brachial blocks for arthroscopic shoulder surgery? intravenous dexamethasone 5 mg vs. perineural dexamethasone 5 mg randomized, controlled, clinical trial.

PubMed

Chun, Eun Hee; Kim, Youn Jin; Woo, Jae Hee

2016-06-01

The aim of this study was to compare the effect of intravenous (I.V.) dexamethasone with that of perineural dexamethasone on the prolongation of analgesic duration of single-shot interscalene brachial plexus blocks (SISB) in patients undergoing arthroscopic shoulder surgery. We performed a prospective, randomized, double-blind, placebo-controlled study. Patients undergoing elective arthroscopic shoulder surgery with ultrasound-guided SISB were enrolled and randomized into 2 groups. A total volume of 12 mL of the study drug was prepared with a final concentration of 0.5% ropivacaine. In the I.V. group, patients received SISB using ropivacaine 5 mg mL with normal saline (control) with dexamethasone 5 mg I.V. injection. In the perineural group, patients received SISB using ropivacaine 5 mg mL with dexamethasone 5 mg, with normal saline 1 mL I.V. injection. The primary outcome was the time to the first analgesic request, defined as the time between the end of the operation and the first request of analgesics by the patient. The secondary outcomes included patient satisfaction scores, side effects, and neurological symptoms. Patients were randomly assigned to 1 of the 2 groups using a computer-generated randomization table. An anesthesiologist blinded to the group assignments prepared the solutions for injection. The patients and the investigator participating in the study were also blinded to the group assignments. One hundred patients were randomized. Data were analyzed for 99 patients. One case in the I.V. group was converted to open surgery and was therefore not included in the study. Perineural dexamethasone significantly prolonged analgesic duration (median, standard error: 1080 minutes, 117.5 minutes) compared with I.V. dexamethasone (810 minutes, 48.1 minutes) (P = 0.02). There were no significant differences in side effects, neurological symptoms, or changes in blood glucose values between the 2 groups. Our results show that perineural

21 CFR 522.542 - Dexamethasone suspension.

Code of Federal Regulations, 2014 CFR

2014-04-01

... dexamethasone-21-isonicotinate. (b) Sponsor. No. 000010 in § 510.600(c) of this chapter. (c) Conditions of use—(1) Amount. Administer by intramuscular injection as follows: Dogs: 0.25 to 1 mg; cats: 0.125 to 0.5... inflammatory conditions associated with the musculoskeletal system in dogs, cats, and horses. (3) Limitations...

Dose response effect of NutriTek on leukocyte functionality during a dexamethasone challenge in Holstein steer calves.

USDA-ARS?s Scientific Manuscript database

The objective of this study was to determine the dose response effects of supplementing NutriTek® on leukocyte functionality and ex vivo cytokine production during a dexamethasone (DEX) challenge. Holstein steers (125.1±8.16kg; N=32) were assigned to treatments including 0, 20, 40, or 60g/head/d of ...

Piper sarmentosum is comparable to glycyrrhizic acid in reducing visceral fat deposition in adrenalectomised rats given dexamethasone.

PubMed

Fairus, A; Ima Nirwana, S; Elvy Suhana, M R; Tan, M H; Santhana, R; Farihah, H S

2013-01-01

Visceral obesity may be due to the dysregulation of cortisol production or metabolism that lead to metabolic disease. In adipose tissue, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 regulates cortisol metabolism (11beta-HSD1). A previous study showed an increase in the visceral fat deposition in adrenalectomised rats given intramuscular dexamethasone. Glycyrrhizic acid (GCA) has been shown to reduce fat deposition because it is a known potent inhibitor of the 11beta-HSD1 enzyme. Piper sarmentosum (PS) is an edible medicinal plant commonly used in Asia as traditional medicine for treating diabetes, hypertension and joint pains. In this study, we determined the effects of PS extract on the disposition and morphology of perirenal adipocytes of adrenalectomised rats given intramuscular dexamethasone. A total of 21 male Spraque Dawley rats were adrenalectomised and given intramuscular dexamethasone, 120 μg/kg/day. These rats were further divided into three groups: adrenalectomised control (ADR+Dexa; n=7), GCA-treated (ADR+Dexa+GCA; dose=240 mg/kg/day; n=7) and PS-treated (ADR+Dexa+PS; dose=125 mg/kg/day; n=7) groups. The various treatments were given via gastric gavage following 2 weeks of adrenalectomy. Treatment with PS extract for 8 weeks showed decreased deposition of perirenal adipocytes which was similar to the GCA-treated group. However, PS-treated rats had thinner adipocyte membrane compared with that of the GCA-treated group. In conclusion, PS extract decreased perirenal fat deposition and reduced the diameter of the adipocyte membrane. However, the mechanisms of action needed further study.

A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients.

PubMed

Jeong, Yusook; Han, Hye Sook; Lee, Hyo Duk; Yang, Jiyoul; Jeong, Jiwon; Choi, Moon Ki; Kwon, Jihyun; Jeon, Hyun-Jung; Oh, Tae-Keun; Lee, Ki Hyeong; Kim, Seung Taik

2016-10-01

Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A 1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.

Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention

PubMed Central

Kelmendi-Doko, Arta; Rubin, J Peter; Klett, Katarina; Mahoney, Christopher; Wang, Sheri; Marra, Kacey G

2017-01-01

Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for 6 months. The hypothesis that the continued release of dexamethasone from polymeric microspheres would enhance both adipogenesis and angiogenesis more significantly when compared to the single-walled microsphere model, resulting in long-term adipose volume retention, was tested. Dexamethasone was encapsulated within single-walled poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and compared to dexamethasone encapsulated in a poly(lactic-co-glycolic acid) core surrounded by a shell of poly-l-lactide. The double-walled polymer microsphere system in the second model was developed to create a more sustainable drug delivery process. Dexamethasone-loaded poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and dexamethasone-loaded poly(lactic-co-glycolic acid)/poly-l-lactide double-walled microspheres (Dex DW MS) were prepared using single and double emulsion/solvent techniques. In vitro release kinetics were determined. Two doses of each type of microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with 0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate-only controls were examined. Samples were analyzed grossly and histologically after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere-containing samples demonstrated greater adipose tissue retention compared to the control group. Histological analysis, including hematoxylin and eosin and CD31 staining, indicated increased vascularization (p < 0.05) within the Dex MS-containing samples. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly

Dexamethasone-(C21-phosphoramide)-[anti-EGFR]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency against pulmonary adenocarcinoma (A549)

PubMed Central

Coyne, Cody P; Narayanan, Lakshmi

2016-01-01

Purpose Corticosteroids are effective in the management of a variety of disease states, such as several forms of neoplasia (leukemia and lymphoma), autoimmune conditions, and severe inflammatory responses. Molecular strategies that selectively “target” delivery of corticosteroids minimize or prevents large amounts of the pharmaceutical moiety from passively diffusing into normal healthy cell populations residing within tissues and organ systems. Materials and methods The covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR] was synthesized by reacting dexamethasone-21-monophosphate with a carbodiimide reagent to form a dexamethasone phosphate carbodiimide ester that was subsequently reacted with imidazole to create an amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate. Monoclonal anti-EGFR immunoglobulin was combined with the amine-reactive dexamethasone-(C21-phosphorylimidazolide) intermediate, resulting in the synthesis of the covalent immunopharmaceutical, dexamethasone-(C21-phosphoramide)-[anti-EGFR]. Following spectrophotometric analysis and validation of retained epidermal growth factor receptor type 1 (EGFR)-binding avidity by cell-ELISA, the selective anti-neoplasic cytotoxic potency of dexamethasone-(C21-phosphoramide)-[anti-EGFR] was established by MTT-based vitality stain methodology using adherent monolayer populations of human pulmonary adenocarcinoma (A549) known to overexpress the tropic membrane receptors EGFR and insulin-like growth factor receptor type 1. Results The dexamethasone:IgG molar-incorporation-index for dexamethasone-(C21-phosphoramide)-[anti-EGFR] was 6.95:1 following exhaustive serial microfiltration. Cytotoxicity analysis: covalent bonding of dexamethasone to monoclonal anti-EGFR immunoglobulin did not significantly modify the ex vivo antineoplastic cytotoxicity of dexamethasone against pulmonary adenocarcinoma at and between the standardized dexamethasone equivalent concentrations of 10�

Australasian randomised trial to evaluate the role of maternal intramuscular dexamethasone versus betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability (A*STEROID): study protocol.

PubMed

Crowther, Caroline A; Harding, Jane E; Middleton, Philippa F; Andersen, Chad C; Ashwood, Pat; Robinson, Jeffrey S

2013-05-03

Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child.This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks' gestation increases the chance of their children surviving free of neurosensory disability at two years' corrected age, compared with betamethasone. Design randomised, multicentre, placebo controlled trial.Inclusion criteria women at risk of preterm birth at less than 34 weeks' gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent.Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack.Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart.Primary study outcome death or any neurosensory disability measured in children at two years' corrected age.Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2). This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly results in significantly fewer deaths and fewer

Acetazolamide or dexamethasone use versus placebo to prevent acute mountain sickness on Mount Rainier.

PubMed

Ellsworth, A J; Meyer, E F; Larson, E B

1991-03-01

Eighteen climbers actively ascended Mount Rainier (elevation 4,392 m) twice during a randomized, double-blind, concurrent, placebo-controlled, crossover trial comparing the use of acetazolamide, 250 mg, dexamethasone, 4 mg, and placebo every 8 hours as prophylaxis for acute mountain sickness. Each subject was randomly assigned to receive placebo during one ascent and one of the active medications during the other ascent. Assessment of acute mountain sickness was performed using the Environmental Symptoms Questionnaire and a clinical interview. At the summit or high point attained above base camp, the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms. Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone (0.26 +/- 0.16 and 0.20 +/- 0.19, respectively) were significantly lower than similar scores for both acetazolamide (0.80 +/- 0.80 and 1.20 +/- 1.05; P = 0.25) and placebo (1.11 +/- 1.02 and 1.45 +/- 1.27; P = .025). Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects. Compared with placebo, dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent. The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known, but it can be considered for persons without contraindications who are intolerant of acetazolamide, for whom acetazolamide is ineffective, or who must make forced, rapid ascent to high altitude for a short period of time with a guaranteed retreat route.

Acetazolamide or dexamethasone use versus placebo to prevent acute mountain sickness on Mount Rainier.

PubMed Central

Ellsworth, A. J.; Meyer, E. F.; Larson, E. B.

1991-01-01

Eighteen climbers actively ascended Mount Rainier (elevation 4,392 m) twice during a randomized, double-blind, concurrent, placebo-controlled, crossover trial comparing the use of acetazolamide, 250 mg, dexamethasone, 4 mg, and placebo every 8 hours as prophylaxis for acute mountain sickness. Each subject was randomly assigned to receive placebo during one ascent and one of the active medications during the other ascent. Assessment of acute mountain sickness was performed using the Environmental Symptoms Questionnaire and a clinical interview. At the summit or high point attained above base camp, the use of dexamethasone significantly reduced the incidence of acute mountain sickness and the severity of symptoms. Cerebral and respiratory symptom severity scores for subjects receiving dexamethasone (0.26 +/- 0.16 and 0.20 +/- 0.19, respectively) were significantly lower than similar scores for both acetazolamide (0.80 +/- 0.80 and 1.20 +/- 1.05; P = 0.25) and placebo (1.11 +/- 1.02 and 1.45 +/- 1.27; P = .025). Neither the use of dexamethasone nor that of acetazolamide measurably affected other physical or mental aspects. Compared with placebo, dexamethasone appears to be effective for prophylaxis of symptoms associated with acute mountain sickness accompanying rapid ascent. The precise role of dexamethasone for the prophylaxis of acute mountain sickness is not known, but it can be considered for persons without contraindications who are intolerant of acetazolamide, for whom acetazolamide is ineffective, or who must make forced, rapid ascent to high altitude for a short period of time with a guaranteed retreat route. PMID:2028586

Near-Fatal Gastrointestinal Hemorrhage in a Child with Medulloblastoma on High Dose Dexamethasone.

PubMed

Yecies, Derek; Tawfik, Daniel; Damman, Jennifer; Thorson, Chad; Hong, David S; Grant, Gerald A; Bensen, Rachel; Damian, Mihaela

2017-07-07

A four-year-old female was admitted to a university-based children's hospital with a newly-diagnosed posterior fossa tumor. She was started on famotidine and high-dose dexamethasone and underwent gross total resection of a medulloblastoma. She was continued on dexamethasone and famotidine. She exhibited postoperative posterior fossa syndrome and was started on enteral feeds via the nasoduodenal tube. She had small gastrointestinal bleeds on postoperative days eight, 11, and 18, and was found to have a well-circumscribed posterior duodenal ulcer. On postoperative day 19, she suffered a massive life-threatening gastrointestinal bleed requiring aggressive resuscitation with blood products. She required an emergent laparotomy due to ongoing blood loss and she was found to have posterior duodenal wall erosion into her gastroduodenal artery. She recovered and subsequently began delayed chemotherapy. This case demonstrates a rare and life-threatening complication of high-dose dexamethasone therapy in the setting of posterior fossa pathology despite stress ulcer prophylaxis. We present a historical perspective with the review of the association between duodenal and intracranial pathology and the usage of high-dose dexamethasone in such cases.

Variable effects of dexamethasone on protein synthesis in clonal rat osteosarcoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodge, B.O.; Kream, B.E.

1988-05-01

We examined the effects of dexamethasone on protein synthesis in clonal rat osteoblastic osteosarcoma (ROS) cell lines by measuring the incorporation of (/sup 3/H)proline into collagenase-digestible and noncollagen protein in the cell layer and medium of the cultures. In ROS 17/2 and subclone C12 of ROS 17/2.8, dexamethasone decreased collagen synthesis with no change in DNA content of the cultures. In ROS 17/2.8 and its subclone G2, dexamethasone stimulated collagen and noncollagen protein synthesis, with a concomitant decrease in the DNA content of the cells. These data indicate that ROS cell lines are phenotypically heterogeneous and suggest that in normalmore » bone there may be distinct subpopulations of osteoblasts with varying phenotypic traits with respect to the regulation of protein synthesis.« less

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm.

PubMed

Qin, Gordon; Lo, Jessica W; Marlow, Neil; Calvert, Sandy A; Greenough, Anne; Peacock, Janet L

2017-01-01

Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. The study included 412 infants born at 23-28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm

PubMed Central

Marlow, Neil; Calvert, Sandy A.; Greenough, Anne

2017-01-01

Importance Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Objective Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. Materials and methods The study included 412 infants born at 23–28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. Results After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Conclusions Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities. PMID:28723921

Preliminary study on the relationship between dexamethasone and pathogen susceptibility on crucian carp (Carassius auratus).

PubMed

Qi, Xiao-Zhou; Li, Dong-Liang; Tu, Xiao; Song, Chen-Guang; Ling, Fei; Wang, Gao-Xue

2016-12-01

Dexamethasone, a known immunosuppressant, can inhibit the immune response and increase the amount of pathogen in body, but the role of dexamethasone affecting susceptibility of crucian carp (Carassius auratus) to pathogen is unclear. The effects of dexamethasone on susceptibility of crucian carp to Aeromonas hydrophila were investigated in this study. The fish were divided into four groups randomly and injected intraperitoneally by dexamethasone for 0 day (group D), 3 days (group C), 6 days (group B), and 9 days (group A), respectively. The serum lysozyme activity was significantly declined in group A, B and C. Relative immune gene expression such as il-1β, cxcl-8, tnfα and crp in kidney were down-regulation compared to group D. After that crucian carp were infected with A. hydrophila, crucian carp treated by dexamethasone had higher mortality (group A 95%, group B 76%, group C 31%) when compared to group D (4% mortality); the amount of pathogen in was significantly increased (P < 0.05) in liver, kidney and spleen of fish in group A-C compared to group D. These results implicated that higher susceptibility caused by dexamethasone may be induced by the decrease of lysozyme activity and the down-regulation of some immune genes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self-Assembling Nanoparticles Containing Dexamethasone as a Novel Therapy in Allergic Airways Inflammation

PubMed Central

Kenyon, Nicholas J.; Bratt, Jennifer M.; Lee, Joyce; Luo, Juntao; Franzi, Lisa M.; Zeki, Amir A.; Lam, Kit S.

2013-01-01

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78±0.44×105 (n = 18) vs. 5.98±1.3×105 (n = 13), P<0.05) and eosinophils (1.09±0.28×105 (n = 18) vs. 2.94±0.6×105 (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43±1.2 (n = 11) vs. 8.56±2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1±3.6 (n = 8) vs. 28.8±8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma. PMID:24204939

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

PubMed

Tanaka, Nobumichi; Nishimura, Kazuo; Okajima, Eijiro; Ina, Kenji; Ogawa, Osamu; Nagata, Hirohiko; Akakura, Koichiro; Fujimoto, Kiyohide; Gotoh, Momokazu; Teramukai, Satoshi; Hirao, Yoshihiko

2017-03-01

Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dexamethasone treatment differentially alters viral shedding and the antibody and acute phase protein response after multivalent respiratory vaccination in beef steers

USDA-ARS?s Scientific Manuscript database

Our objective was to examine immunosuppression induced by dexamethasone (DEX) administration in cattle upon immunological responses to a multivalent respiratory vaccine containing replicating and non-replicating agents. Steers ( n = 32; 209 +/- 8 kg) seronegative to infectious bovine rhinotracheitis...

The Impact of Prophylactic Dexamethasone on Nausea and Vomiting after Thyroidectomy: A Systematic Review and Meta-Analysis

PubMed Central

Zou, Zhenhong; Jiang, Yuming; Xiao, Mingjia; Zhou, Ruiyao

2014-01-01

Background We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. Methods We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Results Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P<0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD –1.17, 95% CI –1.91 to –0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50–0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8–10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25–5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86–1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Conclusions Prophylactic dexamethasone 8–10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to

Genetic variation in the glucocorticoid receptor and psychopathology after dexamethasone administration in cardiac surgery patients.

PubMed

Kok, Lotte; Hillegers, Manon H; Veldhuijzen, Dieuwke S; Boks, Marco Pm; Dieleman, Jan M; van Dijk, Diederik; Joëls, Marian; Vinkers, Christiaan H

2018-08-01

The glucocorticoid receptor (GR) agonist dexamethasone is frequently used for its anti-inflammatory properties. We recently showed that a single high-dose of dexamethasone had long-lasting protective effects on the development of psychopathology after cardiac surgery and postoperative intensive care unit stay. In this study, we investigated whether common genetic variation in the hypothalamic-pituitary-adrenal (HPA)-axis would influence the susceptibility for PTSD and depression after dexamethasone administration. Participants (n = 996) of the Dexamethasone for Cardiac Surgery (DECS) randomized clinical trial were followed after receiving a single high intraoperative dose of dexamethasone (1 mg/kg), a GR agonist, or placebo. PTSD and depressive symptoms were assessed up to four years after cardiac surgery. We focused primarily on five common single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR). Secondarily, we comprehensively assessed common genetic variation in the FK506 binding protein (FKBP5) and the mineralocorticoid receptor (MR). The protective effects of dexamethasone on postoperative PTSD symptoms were dependent on the GR polymorphisms rs41423247 (p = .009), rs10052957 (p = .003), and rs6189 (p = .002), but not on rs6195 (p = .025) or rs6198, (p = .026) after Bonferroni correction. No genotype-dependent effects were found for postoperative depressive symptoms. Also, no associations of FKBP5 and MR polymorphisms were found on PTSD and depression outcomes. Protective effects of dexamethasone on PTSD symptoms after cardiac surgery and ICU stay seem to depend on common genetic variation in its target receptor, the GR. These effects indicate that pre-operative genetic screening could potentially help in stratifying patients for their vulnerability for developing PTSD symptoms after surgery. Copyright © 2018. Published by Elsevier Ltd.

Influence of long-term, high-dose dexamethasone administration on proliferation and apoptosis in porcine hepatocytes.

PubMed

Mikiewicz, Mateusz; Otrocka-Domagała, Iwona; Paździor-Czapula, Katarzyna; Rotkiewicz, Tadeusz

2017-06-01

The aim of this study was to examine the influence of long-term, high-dose dexamethasone administration on the liver, with particular emphasis on hepatocyte proliferation and apoptosis, using a swine model. The study included 48 large, female Polish breed pigs aged 3months (weighing ca. 30kg) divided into groups I (control; n=24) and II (dexamethasone; n=24) that receiving intra-muscular injections of monosodium phosphate dexamethasone for 29days. The pigs were euthanized on days subsequent to the experiment. Immediately after the euthanasia, the pig livers were sampled, fixed, and processed routinely for histopathology, histochemistry, and immunohistochemistry (for proliferating cell nuclear antigen, Bcl-2, and caspase-3). Apoptosis was visualized by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL). Dexamethasone administration gradually caused hepatocyte glycogen degeneration and finally lipid degeneration, accompanied by sinusoid and central vein dilatation and nuclear chromatin condensation. The proliferating cell nuclear antigen index, mean number of argyrophilic nucleolar organizer regions and proliferation index of argyrophilic nucleolar organizer regions were lower, while Bcl-2 expression was higher in group II compared with group I. The results from this study suggest that safe high-dose dexamethasone administration time is difficult to establish. Long-term, high-dose dexamethasone administration can cause pronounced morphological changes in hepatocytes by diminishing their transcriptional and proliferation activity but also protects them from apoptosis by potentially affecting Bcl-2 expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qin, Weiping, E-mail: weiping.qin@mssm.edu; Department of Medicine, Mount Sinai School of Medicine, NY; Pan, Jiangping

Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis,more » REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the

Cholecystokinin-producing (I) cells of intestinal mucosa in dexamethasone-treated rats.

PubMed

Glišić, Radmila; Koko, Vesna; Cvijić, Gordana; Milošević, Maja Čakić; Obradović, Jasmina

2011-11-10

The aim of this study was to investigate the morphological, immunohistochemical and ultrastructural changes of cholecystokinin-producing (I) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2mg/kg dexamethasone, rats developed diabetes similar to human diabetes mellitus type 2. The mean diameter of the duodenum was significantly decreased due to significant reduction of volume fraction and profile area of lamina propria. There was a decrease in volume fraction and number of cholecystokinin (CCK)-producing cells per mm(2) of mucosa, as well as their numerical density, but without statistical significance. Also, dexamethasone induced appearance of hyperactive duodenal I-cells with small number of granules and dilated endoplasmic reticulum. In conclusion, the present study showed that morphological changes in duodenum cholecystokinin-producing (I) cells occurred in diabetic rats, in a manner which, suggests compensatory effort of CCK cells in diabetic condition. Copyright © 2011 Elsevier B.V. All rights reserved.

Functional capacities of blood neurtrophils are influenced by both acute and chronic dexamethasone stress models in beef steers

USDA-ARS?s Scientific Manuscript database

This study investigated the effects of acute and chronic stress models on the functional capacity of blood neutrophils in beef steers. Steers (N=32; 209 +/- 8 kg) were blocked by BW and assigned to 1 of 3 treatments: 1) Control (CON), no dexamethasone (DEX); 2) Chronic stress (CHR), 0.5 mg/kg BW DEX...

Phase II trial of high-dose, intermittent calcitriol (1,25 dihydroxyvitamin D3) and dexamethasone in androgen-independent prostate cancer.

PubMed

Trump, Donald L; Potter, Douglas M; Muindi, Josephia; Brufsky, Adam; Johnson, Candace S

2006-05-15

Data suggest that vitamin D plays a role in the treatment and prevention of prostate cancer. The combination of high-dose, intermittent calcitriol (1,25 dihydroxyvitamin D3) plus dexamethasone was studied based on evidence that dexamethasone potentiates the antitumor effects of calcitriol and ameliorates hypercalcemia. Oral calcitriol was administered weekly, Monday, Tuesday, and Wednesday (MTW), at a dose of 8 microg, for 1 month, at a dose of 10 microg every MTW for 1 month, and at a dose of 12 microg every MTW thereafter. Dexamethasone at a dose of 4 mg was administered each Sunday, and MTW weekly. Calcium and creatinine were determined weekly and radiographs of the urinary tract were performed every 3 months. All patients were considered evaluable for toxicity. Forty-three men with androgen-independent prostate cancer were entered; 37 received at least 1 month of calcitriol given at a dose of 12 microg every day x 3 per week. The majority of patients had bone metastases and rising prostate-specific antigen (PSA) levels. All had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eight patients (19%) experienced partial responses by PSA criterion (PSA decline of > or =50%, persisting for > or = 28 days). Subjective clinical improvement occurred in some patients. Toxicity was minimal: urinary tract stones in 2 patients; and a readily reversible, CTC (v.3.0) Grade <2 creatinine increase in 4 patients. Throughout the study only 4 patients ever had a serum calcium level >11.0 mg/dL and no patient had a calcium level >12.0 mg/dL. The response rate reported in the current study (19%) was not found to be clearly higher than expected with dexamethasone alone. High-dose intermittent calcitriol plus dexamethasone appears to be safe, feasible, and has antitumor activity. Copyright 2006 American Cancer Society

Improved pulmonary function in the nitrofen model of congenital diaphragmatic hernia following prenatal maternal dexamethasone and/or sildenafil.

PubMed

Burgos, Carmen Mesas; Pearson, Erik G; Davey, Marcus; Riley, John; Jia, Huimin; Laje, Pablo; Flake, Alan W; Peranteau, William H

2016-10-01

Pulmonary hypoplasia and hypertension is a leading cause of morbidity and mortality in congenital diaphragmatic hernia (CDH). The etiologic insult occurs early in gestation highlighting the potential of prenatal interventions. We evaluated prenatal pharmacologic therapies in the nitrofen CDH model. Olive oil or nitrofen were administered alone or with dexamethasone (DM), sildenafil, or DM+sildenafil to pregnant rats. Newborn pups were assessed for lung function, structure and pulmonary artery (PA) flow and resistance. Prenatal DM treatment of CDH pups increased alveolar volume density (Vva), decreased interalveloar septal thickness, increased tidal volumes and improved ventilation without improving oxygenation or PA resistance. Sildenafil decreased PA resistance and improved oxygenation without improving ventilation or resulting in significant histologic changes. DM+sildenafil decreased PA resistance, improved oxygenation and ventilation while increasing Vva and decreasing interalveolar septal and pulmonary arteriole medial wall thickness. Lung and body weights were decreased in pups treated with DM and/or sildenafil. Prenatal DM or sildenafil treatment increased pulmonary compliance and decreased pulmonary vascular resistance respectively, and was associated with improved neonatal gas exchange but had a detrimental effect on lung and fetal growth. This study highlights the potential of individual and combined prenatal pharmacologic therapies for CDH management.

Effect of Dexamethasone Intraligamentary Injection on Post-Endodontic Pain in Patients with Symptomatic Irreversible Pulpitis: A Randomized Controlled Clinical Trial

PubMed Central

Mehrvarzfar, Payman; Esnashari, Ehsan; Salmanzadeh, Reyhaneh; Fazlyab, Mahta; Fazlyab, Mahyar

2016-01-01

Introduction: The aim of this randomized-controlled clinical trial was to assess the effect of intraligamentary (PDL) injection of dexamethasone on onset and severity of post-treatment pain in patients with symptomatic irreversible pulpitis. Methods and Materials: A total number of 60 volunteers were included according to the inclusion criteria and were assigned to three groups (n=20). After administration of local anesthesia and before treatment, group 1 (control) PDL injection was done with syringe containing empty cartridge, while in groups 2 and 3 the PDL injection was done with 0.2 mL of 2% lidocaine or dexamethasone (8 mg/2 mL), respectively. Immediately after endodontic treatment patients were requested to mark their level of pain on a visual analogue scale (VAS) during the next 48 h (on 6, 12, 24 and 48-h intervals). They were also asked to mention whether analgesics were taken and its dosage. Considering the 0-170 markings on the VAS ruler, the level of pain was scored as follows: score 0 (mild pain; 0-56), score 1 (moderate pain; 57-113) and score 3 (severe pain; 114-170). The data were analyzed using the Kruskal-Wallis and the Chi-square tests and the level of significance was set at 0.05. Results: After 6 and 12 h, group 1 and group 3 had the highest and lowest pain values, respectively (P<0.01 and P<0.001 for 6 and 12 h, respectively). However, after 24 and 48 h the difference in the pain was not significant between groups 1 and 2 (P<0.6) but group 3 had lower pain levels (P<0.01 and P<0.8 for 24 and 48 h, respectively). Conclusion: Pretreatment PDL injection of dexamethasone can significantly reduce the post-treatment endodontic pain in patients with symptomatic irreversible pulpitis. PMID:27790253

Pre-operative use of dexamethasone does not reduce incidence or intensity of bleaching-induced tooth sensitivity. A triple-blind, parallel-design, randomized clinical trial.

PubMed

da Costa Poubel, Luiz Augusto; de Gouvea, Cresus Vinicius Deppes; Calazans, Fernanda Signorelli; Dip, Etyene Castro; Alves, Wesley Veltri; Marins, Stella Soares; Barcelos, Roberta; Barceleiro, Marcos Oliveira

2018-04-25

This study evaluated the effect of the administration of pre-operative dexamethasone on tooth sensitivity stemming from in-office bleaching. A triple-blind, parallel-design, randomized clinical trial was conducted on 70 volunteers who received dexamethasone or placebo capsules. The drugs were administered in a protocol of three daily 8-mg doses of the drug, starting 48 h before the in-office bleaching treatment. Two bleaching sessions with 37.5% hydrogen peroxide gel were performed with a 1-week interval. Tooth sensitivity (TS) was recorded on visual analog scales (VAS) and numeric rating scales (NRS) in different periods up to 48 h after bleaching. The color evaluations were also performed. The absolute risk of TS and its intensity were evaluated by using Fisher's exact test. Comparisons of the TS intensity (NRS and VAS data) were performed by using the Mann-Whitney U test and a two-way repeated measures ANOVA and Tukey's test, respectively. In both groups, a high risk of TS (Dexa 80% x Placebo 94%) was detected. No significant difference was observed in terms of TS intensity. A whitening of approximately 3 shade guide units of the VITA Classical was detected in both groups, which were statistically similar. It was concluded that the administration pre-operatively of dexamethasone, in the proposed protocol, does not reduce the incidence or intensity of bleaching-induced tooth sensitivity. The use of dexamethasone drug before in-office bleaching treatment does not reduce incidence or intensity of tooth sensitivity. NCT02956070.

Cochlear Transcriptome Following Acoustic Trauma and Dexamethasone Administration Identified by a Combination of RNA-seq and DNA Microarray.

PubMed

Maeda, Yukihide; Omichi, Ryotaro; Sugaya, Akiko; Kariya, Shin; Nishizaki, Kazunori

2017-08-01

To elucidate molecular mechanisms of noise-induced hearing loss (NIHL) and glucocorticoid therapy in the cochlea. Glucocorticoids are used to treat many forms of acute sensorineural hearing loss, but their molecular action in the cochlea remains poorly understood. Dexamethasone was administered intraperitoneally immediately following acoustic overstimulation at 120 dB SPL for 2 hours to mice. The whole cochlear transcriptome was analyzed 12 and 24 hours following noise trauma and dexamethasone administration by both next-generation sequencing (RNA-seq) and DNA microarray. Differentially expressed genes (DEGs) with more than 2-fold changes after noise trauma and dexamethasone administration were identified. The functions of these DEGs were analyzed by David Bioinformatics Resources and a literature search. Twelve hours after acoustic overstimulation, immune-related gene pathways such as "chemokine signaling activity," "cytokine-cytokine receptor interaction," and "cell adhesion molecules (CAMs) in the immune system" were significantly changed compared with the baseline level without noise. These DEGs were involved in immune and defense responses in the cochlea. Dexamethasone was administered to this NIHL model, and it modulated gene pathways of "cytokine-cytokine receptor interaction" and "cell adhesion molecules (CAMs) in the immune system" at 12 hours, compared with saline-injected control. Dexamethasone-dependent DEGs were also involved in immune and defense responses. A literature search showed that 10 other genes associated with hearing functions were regulated by dexamethasone both at 12 and 24 hours post-administration. Dexamethasone modulates the immune reaction in the traumatized cochlea following acoustic overstimulation. Dexamethasone may also regulate cochlear functions other than immunity.

Dexamethasone diffusion across contact lenses is inhibited by Staphylococcus epidermidis biofilms in vitro.

PubMed

Brothers, Kimberly M; Nau, Amy C; Romanowski, Eric G; Shanks, Robert M Q

2014-10-01

This study was designed to measure the impact of bacterial biofilms on diffusion of an ocular therapeutic through silicone hydrogel bandage lenses in vitro. An assay was designed to study the passage of a commonly used steroid, dexamethasone, through silicone hydrogel soft contact lenses. Diffused dexamethasone was measured using a spectrophotometer over a period of 18 hours and quantified using a standard curve. This assay was performed with control and Staphylococcus epidermidis biofilm-coated contact lenses comprised of lotrafilcon A and methafilcon. Biofilms were formed in brain heart infusion broth supplemented with D-glucose. The presented data validate a simple in vitro model that can be used to measure the penetration of a topical therapeutic through silicone hydrogel soft contact lenses. Using this model, we measured a reduction in dexamethasone diffusion up to 88% through S. epidermidis biofilm-coated silicone hydrogel lenses compared with control lenses. The results of this in vitro study demonstrate that bacterial biofilms impede dexamethasone diffusion through silicone hydrogel contact lenses and warrant future studies regarding the clinical benefit of using ocular therapeutics in the setting of bandage contact lens use for corneal epithelial defects.

Dexamethasone diffusion across contact lenses is inhibited by Staphylococcus epidermidis biofilms in vitro

PubMed Central

Brothers, Kimberly M.; Nau, Amy C.; Romanowski, Eric G.; Shanks, Robert M. Q.

2014-01-01

Purpose This study was designed to measure the impact of bacterial biofilms on diffusion of an ocular therapeutic through silicone hydrogel bandage lenses in vitro. Methods An assay was designed to study the passage of a commonly used steroid dexamethasone through the silicone hydrogel soft contact lenses. Diffused dexamethasone was measured using a spectrophotometer over a period of 18 hours and quantified using a standard curve. This assay was performed with control and Staphylococcus epidermidis biofilm-coated contact lenses composed of lotrafilcon A and methafilcon. Biofilms were formed in brain heart infusion broth supplemented with D-glucose. Results The presented data validate a simple in vitro model that can be used to measure penetration of a topical therapeutic through silicone hydrogel soft contact lenses. Using this model we measured a reduction of dexamethasone diffusion by up to 88% through S. epidermidis biofilm-coated silicon hydrogel lenses compared to control lenses. Conclusions The results of this in vitro study demonstrate that bacterial biofilms impede dexamethasone diffusion through silicon hydrogel contact lenses, and warrant future studies regarding the clinical benefit of using ocular therapeutics in the setting of bandage contact lens use for corneal epithelial defects. PMID:25090165

Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis

PubMed Central

Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

2017-01-01

Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopy surgery. No significant differences in adverse reactions (dizziness and headache) were found in association with dexamethasone. Conclusion Granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopic surgery, with no difference in adverse reactions between the two groups. Granisetron alone or granisetron plus dexamethasone can be used to prevent PONV in patients undergoing laparoscopic surgery. PMID:28436248

Granisetron plus dexamethasone for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery: A meta-analysis.

PubMed

Zhu, Min; Zhou, Chengmao; Huang, Bing; Ruan, Lin; Liang, Rui

2017-06-01

Objective This study was designed to compare the effectiveness of granisetron plus dexamethasone for preventing postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic surgery. Methods We searched the literature in the Cochrane Library, PubMed, EMBASE, and CNKI. Results In total, 11 randomized controlled trials were enrolled in this analysis. The meta-analysis showed that granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopy surgery. No significant differences in adverse reactions (dizziness and headache) were found in association with dexamethasone. Conclusion Granisetron in combination with dexamethasone was significantly more effective than granisetron alone in preventing PONV in patients undergoing laparoscopic surgery, with no difference in adverse reactions between the two groups. Granisetron alone or granisetron plus dexamethasone can be used to prevent PONV in patients undergoing laparoscopic surgery.

Technique Development Results for the Study of a Novel Dexamethasone Impregnated Bandage Contact Lens in a Rabbit Model After Photorefractive Keratectomy

DTIC Science & Technology

2017-10-22

PRK Inflammation in a Rabbit Model Timothy A. Soekenl, Michael Merkley!, Wesley Brundridgel, Gary Legaultl, Matthew Caldwelll, Joseph Ciolino2...7 .0 Dexamethasone Impregnated Contact Lenses in the Treatment of Post- PRK Inflammation · in a Rabbit Model Timothy A. Soeken 1, Michael Merkley1

Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking?

PubMed

Gudina, Esayas Kebede; Tesfaye, Markos; Adane, Aynishet; Lemma, Kinfe; Shibiru, Tamiru; Wieser, Andreas; Pfister, Hans-Walter; Klein, Matthias

2016-08-26

Bacterial meningitis is associated with significant morbidity and mortality despite advances in medical care. The main objective of this study was to assess the association of adjunctive dexamethasone treatment with discharge outcome of patients treated as bacterial meningitis in low income setting. A retrospective study was conducted at four teaching hospitals across Ethiopia. Patients of age 14 years and older treated as cases of bacterial meningitis between January 1, 2011 and April 30, 2015 were included in this study. Information regarding sociodemographic data, clinical presentations, laboratory data, treatments given and status at hospital discharge were retrieved from patients' medical records using a structured questionnaire. Predefined outcome variables at discharge were analysed using descriptive statistics. Multivariable logistic regression was used to identify factors independently associated with poor outcome. A total of 425 patients treated with the presumptive clinical diagnosis of bacterial meningitis were included in this study (lumbar puncture done in 56 %; only 19 % had CSF findings compatible with bacterial meningitis, and only 3 % had proven etiology). The overall in hospital mortality rate was 20.2 %. Impaired consciousness, aspiration pneumonia, and cranial nerve palsy at admission were independently associated with increased mortality. Adjuvant dexamethasone, which was used in 50.4 % of patients, was associated with increased in-hospital mortality (AOR = 3.38; 95 % CI 1.87-6.12, p < 0.001) and low Glasgow outcome scale (GOS) at discharge (AOR = 4.46 (95 % CI 1.98-10.08). This association between dexamethasone and unfavorable outcome was found to be more pronounced in suspected but unproven cases and in those without CSF alterations compatible with bacterial meningitis. Most patients treated for suspected bacterial meningitis did not receive proper diagnostic workup. Adjuvant dexamethasone use in clinically suspected but

Hyponatremia due to Secondary Adrenal Insufficiency Successfully Treated by Dexamethasone with Sodium Chloride.

PubMed

Kazama, Itsuro; Tamada, Tsutomu; Nakajima, Toshiyuki

2015-08-28

Patients who were surgically treated for Cushing's syndrome postoperatively surrender to "primary" adrenal insufficiency. However, the preoperative over-secretion of cortisol or the postoperative administration of excessive glucocorticoids can cause "secondary" adrenal insufficiency, in which the prevalence of hyponatremia is usually lower than that of primary adrenal insufficiency. A 60-year-old woman with a past medical history of Cushing's syndrome developed hyponatremia with symptoms of acute glucocorticoid deficiency, such as prolonged general fatigue and anorexia, after upper respiratory tract infection. A decrease in the serum cortisol level and the lack of increase in the ACTH level, despite the increased demand for cortisol, enabled a diagnosis of "secondary" adrenal insufficiency. Although the initial fluid replacement therapy was not effective, co-administration of dexamethasone and sodium chloride quickly resolved her symptoms and ameliorated the refractory hyponatremia. In this case, the hypothalamic-pituitary axis of the patient was thought to have become suppressed long after the surgical treatment for Cushing's syndrome. This case suggested a mechanism of refractory hyponatremia caused by secondary adrenal insufficiency, for which the administration of dexamethasone and sodium chloride exerted additional therapeutic efficacy.

Dexamethasone for Prevention of Postoperative Shivering: A Randomized Double-Blind Comparison with Pethidine

PubMed Central

Entezariasl, Masood; Isazadehfar, Khatereh

2013-01-01

Background: Postoperative shivering is very common and followed by many problems such as increasing oxygen consumption, blood pressure, intracranial and intraocular pressure, and postoperative pain. Therefore, prevention of shivering is important, especially in elderly and ischemic heart disease patients. The goal of this study was to compare the effect of pethidine (meperidine), dexamethasone, and placebo on prevention of shivering. Methods: This double-blind clinical trial study was carried out on 120 patients who were candidates for surgery under general anesthesia. The patients were randomly divided into three groups. Induction and maintenance of anesthesia for all patients were similar. Temperature of patients was measured every 5 min interval. After induction, saline 0.9%, dexamethasone and pethidine were injected to groups a, b, and c, respectively. In recovery, patients were controlled for visible shivering. All data were statistically analyzed by analysis of variance (ANOVA) and Chi-square tests. Results: There were no significant differences among three mentioned groups regarding gender, age, duration of surgery and anesthesia, extubation time, duration of recovery, and basic clinical characteristics. Nineteen cases (47.5%) of placebo group had postoperative shivering, whereas in dexamethasone group only four cases (10%) had shivering and the difference between the two groups was significant. Also in pethidine group, 15 cases (37.5%) had shivering and the difference with placebo group was significant (P value = 0.001). Conclusion: The present study showed that pethidine and dexamethasone are effective drugs for prevention of postoperative shivering in elective surgery and the effect of dexamethasone in preventing the postoperative shivering is better than pethidine. PMID:24049601

Dexamethasone acetate encapsulation into Trojan particles.

PubMed

Gómez-Gaete, Carolina; Fattal, Elias; Silva, Lídia; Besnard, Madeleine; Tsapis, Nicolas

2008-05-22

We have combined the therapeutic potential of nanoparticles systems with the ease of manipulation of microparticles by developing a hybrid vector named Trojan particles. We aim to use this new delivery vehicle for intravitreal administration of dexamethasone. Initialy, dexamethasone acetate (DXA) encapsulation into biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles was optimized. Then, Trojan particles were formulated by spray drying 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC), hyaluronic acid (HA) and different concentrations of nanoparticle suspensions. The effect of nanoparticles concentration on Trojan particle physical characteristics was investigated as well as the effect of the spray drying process on nanoparticles size. Finally, DXA in vitro release from nanoparticles and Trojan particles was evaluated under sink condition. SEM and confocal microscopy show that most of Trojan particles are spherical, hollow and possess an irregular surface due to the presence of nanoparticles. Neither Trojan particle tap density nor size distribution are significantly modified as a function of nanoparticles concentration. The mean nanoparticles size increase significantly after spray drying. Finally, the in vitro release of DXA shows that the excipient matrix provides protection to encapsulated nanoparticles by slowing drug release.

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis.

PubMed

Moreau, Philippe; Dimopoulos, Meletios A; Richardson, Paul G; Siegel, David S; Cavo, Michele; Corradini, Paolo; Weisel, Katja; Delforge, Michel; O'Gorman, Peter; Song, Kevin; Chen, Christine; Bahlis, Nizar; Oriol, Albert; Hansson, Markus; Kaiser, Martin; Anttila, Pekka; Raymakers, Reinier; Joao, Cristina; Cook, Gordon; Sternas, Lars; Biyukov, Tsvetan; Slaughter, Ana; Hong, Kevin; Herring, Jennifer; Yu, Xin; Zaki, Mohamed; San-Miguel, Jesus

2017-09-01

Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs are important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy. Patients received 28-day cycles of pomalidomide 4 mg/day on days 1-21 and low-dose dexamethasone 40 mg (20 mg if aged > 75 years) weekly until disease progression or unacceptable toxicity. Thromboprophylaxis was required. The most common grade 3/4 AEs were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%), which occurred within the first few cycles of treatment. Grade 3/4 infections occurred in 33.7% patients, of whom 13.9% had pneumonia, and 40.3% had neutropenia. Pomalidomide dose reductions or interruptions were reported in 24.2% and 66.0% of patients, respectively. AEs were managed by dose modifications and/or supportive care. Pomalidomide plus low-dose dexamethasone showed an acceptable safety profile, and AEs were well managed according to study protocols and established guidelines. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dexamethasone-induced catatonia in a patient with multiple myeloma.

PubMed

Vanstechelman, Sylvie; Vantilborgh, Anna; Lemmens, Gilbert

2016-12-01

Catatonia is a complex neuropsychiatric syndrome, caused by different underlying metabolic, neurologic, psychiatric and toxic conditions. Although catatonia is often associated with psychiatric disorders such as schizophrenia or depression, in about 20 to 39% of the patients a somatic illness is found. Unfortunately, this diagnosis is often missed although catatonia is characterized by a specific symptom complex. We report a case of acute catatonia with psychotic features in a patient with multiple myeloma (MM), caused by systemic use of dexamethasone. Physicians should be aware of possible psychiatric side effects when prescribing high doses of dexamethasone. Further, MM patients on corticosteroids should be closely monitored for mild psychological and/or psychiatric symptoms since they may be predictive for the onset of catatonia.

Expression of TNF-α system members in bovine ovarian follicles and the effects of TNF-α or dexamethasone on preantral follicle survival, development and ultrastructure in vitro.

PubMed

Silva, A W B; Ribeiro, R P; Menezes, V G; Barberino, R S; Passos, J R S; Dau, A M P; Costa, J J N; Melo, L R F; Bezerra, F T G; Donato, M A M; Peixoto, C A; Matos, M H T; Gonçalves, P B D; van den Hurk, R; Silva, J R V

2017-07-01

This study was conducted to detect the protein expression of TNF-α system members (TNF-α/TNFR1/TNFR2) in bovine ovarian follicles and to evaluate the effects of TNF-α or dexamethasone on the survival and growth of primordial follicles in vitro, as well as on gene expression in cultured ovarian tissue. It was hypothesized that TNF-α induces follicular atresia in ovarian tissues cultured in vitro, and that dexamethasone suppresses the production of endogenous TNF-α, which can improve follicle viability in vitro. Ovarian fragments were cultured for 6days in α-MEM + supplemented with TNF-α (0, 1, 10, 100 or 200ng/ml) or dexamethasone (0, 1, 10, 100 or 200ng/ml). After culture, the expression of mRNAs for BCL-2, BAX, P53, TNF-α, and CASP3 and CASP6 were evaluated. Immunohistochemical results showed that the TNF-α system members, were detected in bovine preantral and antral follicles. After 6days, the TNF-α (10ng/ml) treatment reduced the percentage of normal preantral follicles and increased the number of TUNEL-positive cells in cultured tissue. Dexamethasone (10ng/ml) during 6days of culture did maintain the percentage of normal follicles and the ultrastructure of follicles, while the presence of TNF-α or dexamethasone did not influence primordial follicle activation. However, TNF-α or dexamethasone had no effect on the levels of mRNA for P53, BCL-2, BAX and CASP6, in cultured tissues, but the presence of dexamethasone reduced the levels of CASP3 compared to ovarian slices cultured in control medium (α-MEM + ). In conclusion, proteins of the TNF-α system are expressed at different bovine follicle stages. The addition of TNF-α in culture reduces follicle survival and increases the number of apoptotic cells in ovarian tissue, while the presence of dexamethasone maintains follicle ultrastructure in cultured tissue. Copyright © 2017. Published by Elsevier B.V.

Antenatal Dexamethasone after Asphyxia Increases Neural Injury in Preterm Fetal Sheep

PubMed Central

Koome, Miriam E.; Davidson, Joanne O.; Drury, Paul P.; Mathai, Sam; Booth, Lindsea C.; Gunn, Alistair Jan; Bennet, Laura

2013-01-01

Background and Purpose Maternal glucocorticoid treatment for threatened premature delivery dramatically improves neonatal survival and short-term morbidity; however, its effects on neurodevelopmental outcome are variable. We investigated the effect of maternal glucocorticoid exposure after acute asphyxia on injury in the preterm brain. Methods Chronically instrumented singleton fetal sheep at 0.7 of gestation received asphyxia induced by complete umbilical cord occlusion for 25 minutes. 15 minutes after release of occlusion, ewes received a 3 ml i.m. injection of either dexamethasone (12 mg, n = 10) or saline (n = 10). Sheep were killed after 7 days recovery; survival of neurons in the hippocampus and basal ganglia, and oligodendrocytes in periventricular white matter were assessed using an unbiased stereological approach. Results Maternal dexamethasone after asphyxia was associated with more severe loss of neurons in the hippocampus (CA3 regions, 290±76 vs 484±98 neurons/mm2, mean±SEM, P<0.05) and basal ganglia (putamen, 538±112 vs 814±34 neurons/mm2, P<0.05) compared to asphyxia-saline, and with greater loss of both total (913±77 vs 1201±75/mm2, P<0.05) and immature/mature myelinating oligodendrocytes in periventricular white matter (66±8 vs 114±12/mm2, P<0.05, vs sham controls 165±10/mm2, P<0.001). This was associated with transient hyperglycemia (peak 3.5±0.2 vs. 1.4±0.2 mmol/L at 6 h, P<0.05) and reduced suppression of EEG power in the first 24 h after occlusion (maximum −1.5±1.2 dB vs. −5.0±1.4 dB in saline controls, P<0.01), but later onset and fewer overt seizures. Conclusions In preterm fetal sheep, exposure to maternal dexamethasone during recovery from asphyxia exacerbated brain damage. PMID:24204840

Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat

PubMed Central

Wigati, Dyan; Anwar, Khoerul; Sudarsono; Nugroho, Agung Endro

2016-01-01

The effect of ethanolic extract of Morinda citrifolia leaves and fruit on blood pressure in dexamethasone-induced hypertension rat was evaluated. Total phenolic content of Morinda citrifolia leaves ethanolic extract (MCLEE) and Morinda citrifolia leaves ethanolic extract (MCFEE) was 1.789 ± 0.116 and 1.677 ± 0.051 mg of gallic acid equivalents per gram sample, respectively. Rutin level in MCLEE was 0.92 ± 0.19%, and scopoletin level in MCFEE was 0.46 ± 0.05%. MCLEE, MCFEE, and its extract combination significantly decreased the blood pressure of hypertensive rats. The combination group showed highest hypotensive activity by lowering systolic blood pressure by 16.71 ± 3.95%, diastolic blood pressure by 21.49 ± 7.90%, and mean arterial blood pressure by 19.58% ± 6.35. All extract treatments have not been able to repair or inhibit renal damage caused by dexamethasone induction. PMID:27313228

Effects of sustained release dexamethasone hydrogels in hearing preservation cochlear implantation.

PubMed

Honeder, Clemens; Zhu, Chengjing; Schöpper, Hanna; Gausterer, Julia Clara; Walter, Manuel; Landegger, Lukas David; Saidov, Nodir; Riss, Dominik; Plasenzotti, Roberto; Gabor, Franz; Arnoldner, Christoph

2016-11-01

It has been shown that glucocorticoids reduce the hearing threshold shifts associated with cochlear implantation. Previous studies evaluated the administration of glucocorticoids immediately before surgery or the repeated pre- or perioperative systemic application of glucocorticoids. The aim of this study was to evaluate the effects of a sustained release dexamethasone hydrogel in hearing preservation cochlear implantation. To address this issue, a guinea pig model of cochlear implantation was used. 30 normal hearing pigmented guinea pigs were randomized into a group receiving a single dose of a dexamethasone/poloxamer407 hydrogel one day prior to surgery, a second group receiving the hydrogel seven days prior to surgery and a control group. A silicone cochlear implant electrode designed for the use in guinea pigs was inserted to a depth of 5 mm through a cochleostomy. Compound action potentials of the auditory nerve (frequency range 0.5-32 kHz) were measured preoperatively, directly postoperatively and on postoperative days 3, 7, 14, 21 and 28. Following the last audiometry, temporal bones were harvested and histologically evaluated. Dexamethasone hydrogel application one day prior to surgery resulted in significantly reduced hearing threshold shifts at low, middle and high frequencies measured at postoperative day 28 (p < 0.05). Application of the hydrogel seven days prior to surgery did not show such an effect. Dexamethasone application one day prior to surgery resulted in increased outer hair cell counts in the cochlear apex and in reduced spiral ganglion cell counts in the basal and middle turn of the cochlea, a finding that was associated with a higher rate of electrode translocation in this group. In this study, we were able to demonstrate functional benefits of a single preoperative intratympanic application of a sustained release dexamethasone hydrogel in a guinea pig model of cochlear implantation. Copyright © 2016 The Authors. Published by Elsevier

High performance liquid chromatography determination of dexamethasone in plasma to evaluate its systemic absorption following intra-space pterygomandibular injection of twin-mix (mixture of 2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone): randomized control trial.

PubMed

Bhargava, Darpan; Deshpande, Ashwini; Thomas, Shaji; Sharma, Yogesh; Khare, Piush; Sahu, Sanjeev Kumar; Dubey, Suyash; Pandey, Ankit; Sreekumar, K

2016-09-01

To determine systemic absorption of dexamethasone by detection of plasma concentration using high performance liquid chromatography following its administration along with local anesthetic agent as a mixture via pterygomandibular space. A prospective randomized double-blind clinical study was undertaken to analyze the plasma concentration of dexamethasone after intra-space pterygomandibular injection along with local anesthesia. The study was performed as per split mouth model where the mandibular quadrant allocation was done on a random basis considering each of the 30 patients is included in the two study interventions (SS and CS). For the study site (SS) procedures, dexamethasone was administered as a mixture (2 % lignocaine with 1:200,000 epinephrine and 4 mg dexamethasone) intra-space. In the control site (CS) procedures, a regular standard inferior alveolar nerve block was administered, and dexamethasone was given as intramuscular injection. The plasma dexamethasone determination was done in venous blood 30- and 60-min post injection using high performance liquid chromatography (HPLC). The clinical parameters like pain; swelling; and mouth opening on the first, third, and seventh post-operative day were analyzed and compared. No significant difference was found in the clinical parameters assessed; comparative evaluation showed less swelling in the SS interventions. The plasma concentration of dexamethasone for the CS interventions was 226 ± 47 ng/ml at 30-min and 316 ± 81.6 ng/ml at 60-min post injection, and for SS, it was 221 ± 81.6 ng/ml at 30-min and 340 ± 105 ng/ml at 60-min post injection. On inter-site (CS and SS) comparison, no statistically significant difference was ascertained in dexamethasone plasma concentration at 30-min post injection (P = 0.77) and at 60-min post injection. (P = 0.32). Intra-space (pterygomandibular space) administration of dexamethasone can achieve statistically similar plasma concentration

Is the Use of Dexamethasone Effective in Controlling Pain Associated with Symptomatic Irreversible Pulpitis? A Systematic Review.

PubMed

Nogueira, Brenna M L; Silva, Ludmylla G; Mesquita, Carla R M; Menezes, Sílvio A F; Menezes, Tatiany O A; Faria, Antônio G M; Porpino, Mariana T M

2018-05-01

Endodontic pain is a symptom of pulpal and/or periapical inflammation. One strategy for pain reduction is using medications, such as dexamethasone. A definitive protocol for preventing and controlling pain caused by irreversible pulpitis during endodontic treatment has not yet been established. This is a systematic review to answer the following question: is the use of dexamethasone effective in controlling pain associated with symptomatic irreversible pulpitis? This study was registered in the PROSPERO database (CRD42017058704), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement recommendations were followed. MEDLINE, Scopus, ScienceDirect, Web of Science, Latin American Caribbean Health Sciences Literature, Cochrane Library, and Google Scholar databases were used in our research. No restrictions were applied to dates or language of publication. All records identified electronically were organized and evaluated by 2 independent authors, and, in case of doubt, a third author made the decision. The Cochrane Collaboration tool was used. The data were analyzed with RevMan 5 software (The Cochrane Collaboration, Copenhagen, Denmark), and data from eligible studies were dichotomous (with and without pain). A total of 4825 studies were identified. After screening, 523 studies were selected, and, after careful evaluation, only 5 articles remained. All meta-analyses revealed a global effect (P < .05, P < .05, and P < .05), which means that 4 mg dexamethasone helps relieve pain, sometimes for up to 8, 12, and 24 hours. The pain felt by patients diagnosed with symptomatic irreversible pulpitis may be alleviated by administering 4 mg dexamethasone either by mouth or through intraligamentary and mainly supraperiosteal injections into the root canal for up to 24 hours. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs.

PubMed

Schiffner, René; Rodríguez-González, Guadalupe L; Rakers, Florian; Nistor, Marius; Nathanielsz, Peter W; Daneva, Teodora; Schwab, Matthias; Lehmann, Thomas; Schmidt, Martin

2017-10-27

Prenatal glucocorticoid administration alters the activity of the fetal hypothalamic-pituitary-adrenocortical axis (HPAA), and correspondingly the adenocorticotropic hormone (ACTH) and cortisol levels after birth. The dosages required for these effects are critically discussed. Activation of the HPAA is related to metabolic syndrome and diabetes mellitus. Hypoglycemia is the classic side effect of antidiabetic treatment. We hypothesized that a low dosage of dexamethasone in late pregnancy alters the HPAA response to hypoglycemia in pigs. 12 pregnant sows were randomly assigned to two groups which received either a low-dose intramuscular injection (99th and 100th day of gestation) of dexamethasone (0.06 μg/kg body weight) or vehicle. Three months after birth, 18 dexamethasone-treated anaesthetized offspring and 12 control offspring underwent a 75 min hypoglycemic clamp (blood glucose below 4 mmol/L) procedure. Heart rate (HR), blood pressure, ACTH and cortisol levels and body weight (at birth and after three months) were recorded. Dexamethasone-treated animals exhibited significantly elevated ACTH (139.9 ± 12.7 pg/mL) and cortisol (483.1 ± 30.3 nmol/L) levels during hypoglycemia as compared to the control group (41.7 ± 6.5 pg/mL and 257.9 ± 26.7 nmol/L, respectively), as well as an elevated HR (205.5 ± 5.7 bpm) and blood pressure (systolic: 128.6 ± 1.5, diastolic: 85.7 ± 0.7 mmHg) response as compared to the control group (153.2 ± 4.5 bpm; systolic: 118.6 ± 1.6, diastolic: 79.5 ± 1.4 mmHg, respectively; p < 0.001). Low-dose prenatal administration of dexamethasone not only exerts effects on the HPAA (ACTH and cortisol concentration) and vital parameters (HR and diastolic blood pressure) under baseline conditions, but also on ACTH, HR and systolic blood pressure during hypoglycemia.

Magnetic hyaluronic acid nanospheres via aqueous Diels-Alder chemistry to deliver dexamethasone for adipose tissue engineering.

PubMed

Jia, Yang; Fan, Ming; Chen, Huinan; Miao, Yuting; Xing, Lian; Jiang, Bohong; Cheng, Qifan; Liu, Dongwei; Bao, Weikang; Qian, Bin; Wang, Jionglu; Xing, Xiaodong; Tan, Huaping; Ling, Zhonghua; Chen, Yong

2015-11-15

Biopolymer-based nanospheres have great potential in the field of drug delivery and tissue regenerative medicine. In this work, we present a flexible way to conjugate a magnetic hyaluronic acid (HA) nanosphere system that are capable of vectoring delivery of adipogenic factor, e.g. dexamethasone, for adipose tissue engineering. Conjugation of nanospheres was established by aqueous Diels-Alder chemistry between furan and maleimide of HA derivatives. Simultaneously, a furan functionalized dexamethasone peptide, GQPGK, was synthesized and covalently immobilized into the nanospheres. The magnetic HA nanospheres were fabricated by encapsulating super-paramagnetic iron oxide nanoparticles, which exhibited quick magnetic sensitivity. The aqueous Diels-Alder chemistry made nanospheres high binding efficiency of dexamethasone, and the vectoring delivery of dexamethasone could be easily controlled by a external magnetic field. The potential application of the magnetic HA nanospheres on vectoring delivery of adipogenic factor was confirmed by co-culture of human adipose-derived stem cells (ASCs). In vitro cytotoxicity tests demonstrated that incorporation of dexamethasone into magnetic HA nanospheres showed high efficiency to promote ASCs viabilities, in particular under a magnetic field, which suggested a promising future for adipose regeneration applications. Copyright © 2015 Elsevier Inc. All rights reserved.

[Effects of dexamethasone on the expression of muscarinic receptor mRNA in asthmatic guinea pig airway smooth muscle and eosinophil infiltration in bronchoalveolar lavage fluid].

PubMed

Shi, Liang; Luo, Ya-ling; Lai, Wen-yan; Luo, Liang

2005-08-01

To investigate the effect of dexamethasone on the expression of muscarinic receptor (MR) mRNA in smooth muscle and infiltration of eosinophils (Eos) in the airway of asthmatic guinea pigs. Thirty healthy guinea pigs were randomized into 3 equal groups, the control group, asthmatic group and dexamethasone therapy group. Asthma was induced in the latter 2 groups with the asthma-inducing agents and received treatments as indicated. Bronchial alveolar lavage fluid(BALF) were collected subsequently from the guinea pigs for examining the total cell number and cell classification, and histopathologic examination of the lung tissue was performed. Semi-quantitative analysis with reverse transcriptional- polymerase chain reaction (RT-PCR) was performed for M(2) and M(3) receptor mRNA in airway smooth muscle. Compared with the control and the asthmatic group, the number of Eos in the BALF of dexamethasone therapy group was significantly lower (P<0.01). In spite of the presence of hyperemia and edema in the lung tissues of the dexamethasone therapy group, Eos infiltration was less severe than that in the asthmatic group. As found by RT-PCR, the quantity of M(2) receptor mRNA in the airway smooth muscle of the dexamethasone therapy group was significantly higher than those in both the control and asthmatic groups (P<0.01), and the quantity of M(3) receptor mRNA in the airway smooth muscle of dexamethasone therapy group was significantly higher than that in the asthmatic group, but did not significantly differ from that in the control group. The quantities of M(2) and M(3) receptor mRNAs in the control group were both significantly higher than that in asthmatic group (P<0.01). The expression of M(2) receptor is increased in antigen- challenged guinea pigs, and that of M(3) receptor decreased. Dexamethasone can treat asthma by inhibiting inflammatory action involving Eos infiltration, regulating the expressions of M(2) and M(3) receptors and restoring the function of M(2

Effects of perioperatively administered dexamethasone on surgical wound healing in patients undergoing surgery for zygomatic fracture: a prospective study.

PubMed

Snäll, Johanna; Kormi, Eeva; Koivusalo, Anna-Maria; Lindqvist, Christian; Suominen, Anna Liisa; Törnwall, Jyrki; Thorén, Hanna

2014-06-01

The aims of the study were to clarify the occurrence of disturbance in surgical wound healing (DSWH) after surgery of zygomatic complex (ZC) fractures and to determine whether perioperatively applied dexamethasone increases the risk for DSWH. Of 64 patients who were included in a single-blind prospective trial, 33 perioperatively received a total dose of 10 mg or 30 mg of dexamethasone. The remaining 31 patients served as controls. DSWH occurred in 9 patients (14.1%). Occurrence of DSWH was 24.4% in patients who received dexamethasone and 3.2% in controls. The association between DSWH and dexamethasone was significant (P = .016). Intraoral approach also was associated with DSWH significantly (P = .042). No association emerged between DSWH and age, gender, time span from accident to surgery, or duration of surgery. DSWH occurred significantly more frequently in patients who received perioperative dexamethasone. Because of increased risk of DSWH, perioperative dexamethasone cannot be recommended in open reduction and fixation of ZC fractures. Copyright © 2014 Elsevier Inc. All rights reserved.

Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy

PubMed Central

de Wit, R; de Boer, A C; vd Linden, G H M; Stoter, G; Sparreboom, A; Verweij, J

2001-01-01

In view of the similarity in chemical structure of the available 5HT3-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT3-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT3-receptor antagonists, and that patients who have acute protection failure on one 5HT3-receptor antagonist should be offered cross-over to another 5HT3-receptor antagonist. © 2001 Cancer Research Campaign  http://www.bjcancer.com PMID:11710819

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study.

PubMed

Han, Hye Sook; Park, Ji Chan; Park, Suk Young; Lee, Kyu Taek; Bae, Sang Byung; Kim, Han Jo; Kim, Samyoung; Yun, Hwan Jung; Bae, Woo Kyun; Shim, Hyun-Jeong; Hwang, Jun-Eul; Cho, Sang-Hee; Park, Moo-Rim; Shim, Hyeok; Kwon, Jihyun; Choi, Moon Ki; Kim, Seung Taik; Lee, Ki Hyeong

2015-12-01

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate. ©AlphaMed Press.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

PubMed

Doyle, Lex W; Cheong, Jeanie L; Ehrenkranz, Richard A; Halliday, Henry L

2017-10-24

Bronchopulmonary dysplasia remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to prevent or treat bronchopulmonary dysplasia because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of systemic postnatal corticosteroids commenced within the first seven days of life for preterm infants at risk of developing bronchopulmonary dysplasia. For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. For this review, we selected RCTs examining systemic postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants. Most studies evaluated the use of dexamethasone, but we also included studies that assessed hydrocortisone, even when used primarily for management of hypotension. We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes that included mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. We included 32 RCTs enrolling a total of 4395 participants. The overall risk of bias of included studies was probably low, as all were RCTs, and most trials used rigorous methods. Investigators reported significant benefits for the following outcomes overall: lower rates of failure to extubate, decreased

Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone.

PubMed

Yang, Li; Yang, Jin Bo; Chen, Jia; Yu, Guang Yao; Zhou, Pei; Lei, Lei; Wang, Zhen Zhen; Cy Chang, Catherine; Yang, Xin Ying; Chang, Ta Yuan; Li, Bo Liang

2004-08-01

In macrophages, the accumulation of cholesteryl esters synthesized by the activated acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) results in the foam cell formation, a hallmark of early atherosclerotic lesions. In this study, with the treatment of a glucocorticoid hormone dexamethasone (Dex), lipid staining results clearly showed the large accumulation of lipid droplets containing cholesteryl esters in THP-1-derived macrophages exposed to lower concentration of the oxidized low-density lipoprotein (ox-LDL). More notably, when treated together with specific anti-ACAT inhibitors, the abundant cholesteryl ester accumulation was markedly diminished in THP-1-derived macrophages, confirming that ACAT is the key enzyme responsible for intracellular cholesteryl ester synthesis. RT-PCR and Western blot results indicated that Dex caused up-regulation of human ACAT1 expression at both the mRNA and protein levels in THP-1 and THP-1-derived macrophages. The luciferase activity assay demonstrated that Dex could enhance the activity of human ACAT1 gene P1 promoter, a major factor leading to the ACAT1 activation, in a cell-specific manner. Further experimental evidences showed that a glucocorticoid response element (GRE) located within human ACAT1 gene P1 promoter to response to the elevation of human ACAT1 gene expression by Dex could be functionally bound with glucocorticoid receptor (GR) proteins. These data supported the hypothesis that the clinical treatment with Dex, which increased the incidence of atherosclerosis, may in part due to enhancing the ACAT1 expression to promote the accumulation of cholesteryl esters during the macrophage-derived foam cell formation, an early stage of atherosclerosis.

Comparison between self-formulation and compounded-formulation dexamethasone mouth rinse for oral lichen planus: a pilot, randomized, cross-over trial.

PubMed

Hambly, Jessica L; Haywood, Alison; Hattingh, Laetitia; Nair, Raj G

2017-08-01

There is a lack of appropriate, commercially-available topical corticosteroid formulations for use in oral lichen planus (OLP) and oral lichenoid reaction. Current therapy includes crushing a dexamethasone tablet and mixing it with water for use as a mouth rinse. This formulation is unpleasant esthetically and to use in the mouth, as it is a bitter and gritty suspension, resulting in poor compliance. Thus, the present study was designed to formulate and pilot an effective, esthetically-pleasing formulation. A single-blinded, cross-over trial was designed with two treatment arms. Patients were monitored for 7 weeks. Quantitative and qualitative data was assessed using VAS, numeric pain scales, the Treatment Satisfaction Questionnaire for Medication-9, and thematic analysis to determine primary patient-reported outcomes, including satisfaction, compliance, quality of life, and symptom relief. Nine patients completed the pilot trial. Data analysis revealed the new compounded formulation to be superior to existing therapy due to its convenience, positive contribution to compliance, patient-perceived faster onset of action, and improved symptom relief. Topical dexamethasone is useful in the treatment of OLP. When carefully formulated into a compounded mouth rinse, it improves patient outcomes. © 2016 John Wiley & Sons Australia, Ltd.

Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

PubMed Central

Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

2012-01-01

Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

Effect of early handling of turkey poults on later responses to a dexamethasone-Escherichia coli challenge. 1. Production values and physiological response.

PubMed

Huff, G R; Huff, W E; Balog, J M; Rath, N C

2001-09-01

The stress responses of mice and rats has been shown to be permanently altered by brief, gentle handling during the first 10 d of life, resulting in increased BW and resistance to stress-induced immunosuppression. The purpose of this study was to determine whether early handling of turkey poults could permanently affect production values and physiology of adult turkeys. Turkey poults were handled 0, 1 (1x), or 2 (2x) times daily for the first 10 d after hatch. Handling consisted of gently catching each poult and holding it for 10 s. On Day 11 after hatch, half of the birds from each handling treatment were treated with three injections of 2 mg dexamethasone (DEX)/kg BW on alternating days. On the day of the third DEX injection, duplicate pens of birds were also inoculated in the airsac with 0 or 50 cfu of Escherichia coli. The same birds were treated with a second series of DEX injections at 5 wk of age. Two weeks later, all birds were weighed, and 3 wk later four birds per pen were bled and 10 birds per pen were necropsied; relative organ weights were then determined. Surviving birds were treated with a third series of DEX injections at 10 wk of age; 2 wk later, all surviving turkeys were bled, weighed, and necropsied. Feed consumption was determined weekly. There were no differences due to handling treatment on the body weights or on the relative organ weights of birds that died after the first DEX treatment. Birds treated with a second DEX injection at 5 wk of age and handled 1x daily had decreased BW. Those handled 1x or 2x daily had higher feed conversion ratios. Surviving birds that were given a third DEX treatment had higher BW and no difference in feed conversion when handled 1x or 2x daily. Relative liver, heart, and spleen weights were affected by handling of DEX-E. coli-treated birds, as were serum chemistry values for calcium, iron, glucose, total protein, blood urea nitogen, uric acid, aspartate aminotransferase, alanine aminotransferase, lactate

Does Growth Impairment Underlie the Adverse Effects of Dexamethasone on Development of Noradrenergic Systems?

PubMed

Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J

2018-06-20

Glucocorticoids are given in preterm labor to prevent respiratory distress but these agents evoke neurobehavioral deficits in association with reduced brain region volumes. To determine whether the neurodevelopmental effects are distinct from growth impairment, we gave developing rats dexamethasone at doses below or within the therapeutic range (0.05, 0.2 or 0.8 mg/kg) at different stages: gestational days (GD) 17-19, postnatal days (PN) 1-3 or PN7-9. In adolescence and adulthood, we assessed the impact on noradrenergic systems in multiple brain regions, comparing the effects to those on somatic growth or on brain region growth. Somatic growth was reduced with exposure in all three stages, with greater sensitivity for the postnatal regimens; brain region growth was impaired to a lesser extent. Norepinephrine content and concentration were reduced depending on the treatment regimen, with a rank order of deficits of PN7-9 > PN1-3 > GD17-19. However, brain growth impairment did not parallel reduced norepinephrine content in magnitude, dose threshold, sex or regional selectivity, or temporal pattern, and even when corrected for reduced brain region weights (norepinephrine per g tissue), the dexamethasone-exposed animals showed subnormal values. Regression analysis showed that somatic growth impairment accounted for an insubstantial amount of the reduction in norepinephrine content, and brain growth impairment accounted for only 12%, whereas specific effects on norepinephrine accounted for most of the effect. The adverse effects of dexamethasone on noradrenergic system development are not simply related to impaired somatic or brain region growth, but rather include specific targeting of neurodifferentiation. Copyright © 2018. Published by Elsevier B.V.

Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells.

PubMed

Riddick, C A; Ring, W L; Baker, J R; Hodulik, C R; Bigby, T D

1997-05-15

The aim of this study was to assess the effect of dexamethasone on 5-lipoxygenase pathway expression in human peripheral blood monocytes and the acute monocytic leukemia cell line, THP-1. Cells were conditioned over a period of days with dexamethasone, at concentrations relevant in vivo, to study the effect of the glucocorticoid on calcium-ionophore-stimulated 5-lipoxygenase product and arachidonic acid release. The effect of dexamethasone on levels of immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and its activating protein (5-LAP) was also assessed. Dexamethasone increased the stimulated release of 5-lipoxygenase products from both monocytes and THP-1 cells in a dose-dependent fashion. The increase in product generation was not due to changes in the availability of arachidonic acid. However, immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and 5-LAP were increased by conditioning with dexamethasone. There was no apparent effect of the glucocorticoid on LTA4-hydrolase-immunoreactive protein levels or specific activity. We conclude that dexamethasone increases 5-lipoxygenase pathway expression in both monocytes and in THP-1 cells. This effect is due, at least in part, to increases in immunoreactive protein and steady-state messenger RNA encoding for 5-lipoxygenase and 5-LAP. These results suggest a role for glucocorticoids in the regulation of 5-lipoxygenase pathway expression in mononuclear phagocytes.

Corticosteroid Treatment for Metastatic Spinal Cord Compression: A Review.

PubMed

Skeoch, Gordon D; Tobin, Matthew K; Khan, Sajeel; Linninger, Andreas A; Mehta, Ankit I

2017-05-01

Narrative review. Metastatic spinal cord compression (MSCC) is a very frequent complication among cancer patients. Presenting commonly as nocturnal back pain, MSCC typically progresses to lower extremity paresis, loss of ambulatory capabilities, and paraplegia. In addition to standard treatment modalities, corticosteroid administration has been utilized in preclinical and clinical settings as adjunctive therapy to reduce local spinal cord edema and improve clinical symptoms. This article serves as a review of existing literature regarding corticosteroid management of MSCC and seeks to provide potential avenues of research on the topic. A literature search was performed using PubMed in order to consolidate existing information regarding dexamethasone treatment of MSCC. Of all search results, 7 articles are reviewed, establishing the current understanding of metastatic spine disease and dexamethasone treatment in both animal models and in clinical trials. Treatment with high-dose corticosteroids is associated with an increased rate of potentially serious systemic side effects. For this reason, definitive guidelines for the use of dexamethasone in the management of MSCC are unavailable. It is still unclear what role dexamethasone plays in the treatment of MSCC. It is evident that new, more localizable therapies may provide more acceptable treatment strategies using corticosteroids. Looking forward, the potential for more targeted, localized application of the steroid through the use of nanotechnology would decrease the incidence of adverse effects while maintaining the drug's efficacy.

Dexamethasone potently enhances phorbol ester-induced IL-1beta gene expression and nuclear factor NF-kappaB activation.

PubMed

Wang, Y; Zhang, J J; Dai, W; Lei, K Y; Pike, J W

1997-07-15

The synthetic glucocorticoid dexamethasone, an immunosuppressive and anti-inflammatory agent, was investigated for its effect on PMA-mediated expression of the inflammatory cytokine IL-1beta in the human monocytic leukemic cell line THP-1. PMA alone induced the production of low levels of IL-1beta in THP-1 cells, whereas dexamethasone alone had no effect. However, dexamethasone potently enhanced PMA-mediated IL-1beta production. Using a selective and potent inhibitor of protein kinase C, we found that synergistic interaction between PMA and dexamethasone requires protein kinase C activation. PMA has been known to activate nuclear factor NF-kappaB in THP-1 cells. Using an oligonucleotide probe corresponding to an NF-kappaB DNA-binding motif of the IL-1beta gene promoter in gel electrophoresis mobility shift assays, we demonstrated that PMA-induced NF-kappaB activation was greatly potentiated by dexamethasone. Our results indicate that glucocorticoids can be positive regulators of inflammatory cytokine gene expression during monocytic cell differentiation.

DEXAMETHASONE IMPLANT FOR DIABETIC MACULAR EDEMA IN NAIVE COMPARED WITH REFRACTORY EYES: The International Retina Group Real-Life 24-Month Multicenter Study. The IRGREL-DEX Study.

PubMed

Iglicki, Matias; Busch, Catharina; Zur, Dinah; Okada, Mali; Mariussi, Miriana; Chhablani, Jay Kumar; Cebeci, Zafer; Fraser-Bell, Samantha; Chaikitmongkol, Voraporn; Couturier, Aude; Giancipoli, Ermete; Lupidi, Marco; Rodríguez-Valdés, Patricio J; Rehak, Matus; Fung, Adrian Tien-Chin; Goldstein, Michaella; Loewenstein, Anat

2018-04-24

To investigate efficacy and safety of repeated dexamethasone (DEX) implants over 24 months, in diabetic macular edema (DME) eyes that were treatment naive compared with eyes refractory to anti-vascular endothelial growth factor treatment, in a real-life environment. This multicenter international retrospective study assessed best-corrected visual acuity and central subfield thickness (CST) of naive and refractory eyes to anti-vascular endothelial growth factor injections treated with dexamethasone implants. Safety data (intraocular pressure rise and cataract surgery) were recorded. A total of 130 eyes from 125 patients were included. Baseline best-corrected visual acuity and CST were similar for naive (n = 71) and refractory eyes (n = 59). Both groups improved significantly in vision after 24 months (P < 0.001). However, naive eyes gained statistically significantly more vision than refractory eyes (+11.3 ± 10.0 vs. 7.3 ± 2.7 letters, P = 0.01) and were more likely to gain ≥10 letters (OR 3.31, 95% CI 1.19-9.24, P = 0.02). At 6, 12, and 24 months, CST was significantly decreased compared with baseline in both naive and refractory eyes; however, CST was higher in refractory eyes than in naive eyes (CST 279 ± 61 vs. 313 ± 125 μm, P = 0.10). Over a follow-up of 24 months, vision improved in diabetic macular edema eyes after treatment with dexamethasone implants, both in eyes that were treatment naive and eyes refractory to anti-vascular endothelial growth factor treatment; however, improvement was greater in naive eyes.

Effects of dexamethasone on angiotensin II-induced changes of monolayer permeability and F-actin distribution in glomerular endothelial cells.

PubMed

Fang, Junyan; Wang, Miao; Zhang, Wei; Wang, Yingdeng

2013-11-01

The aim of this study was to investigate the changes in monolayer permeability and F-actin distribution caused by angiotensin II (Ang II)-induced injury in glomerular endothelial cells (GENCs) and the effects of dexamethasone on these changes. GENCs isolated and cultured from Wistar rats were used to examine the changes in monolayer permeability and F-actin distribution induced by Ang II. GENC permeability was evaluated by measuring the diffusion of biotin-conjugated bovine serum albumin (biotin-BSA) across a cell monolayer. The expression levels and distribution of F-actin were assessed by flow cytometry. The biotin-BSA concentrations were measured by capture enzyme-linked immunosorbent assay. Ang II at a concentration of 10 mg/l increased the permeability of the GENC monolayer at 6 h and 12 h (P<0.05 and P<0.01, respectively) and caused F-actin depolymerisation at 6 h and 12 h (P<0.01). The two effects attributed to Ang II were significantly inhibited by dexamethasone treatment (P<0.01). The increased permeability of the GENC monolayer induced by Ang II was significantly correlated with the depolymerisation of F-actin. Dexamethasone abrogated the Ang II-mediated damage to GENCs indicating that it may play an important role in protecting GENCs from injury.

Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hreiche, Raymond; Megarbane, Bruno; Pirnay, Stephane

In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, usingmore » whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.« less

Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells

PubMed Central

Son, Yonghae; Kim, Bo-Young; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

2016-01-01

Oxysterol like 27-hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx) affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells. PMID:27340507

Dexamethasone Suppresses Oxysterol-Induced Differentiation of Monocytic Cells.

PubMed

Son, Yonghae; Kim, Bo-Young; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

2016-01-01

Oxysterol like 27-hydroxycholesterol (27OHChol) has been reported to induce differentiation of monocytic cells into a mature dendritic cell phenotype. We examined whether dexamethasone (Dx) affects 27OHChol-induced differentiation using THP-1 cells. Treatment of monocytic cells with Dx resulted in almost complete inhibition of transcription and surface expression of CD80, CD83, and CD88 induced by 27OHChol. Elevated surface levels of MHC class I and II molecules induced by 27OHChol were reduced to basal levels by treatment with Dx. A decreased endocytosis ability caused by 27OHChol was recovered by Dx. We also examined effects of Dx on expression of CD molecules involved in atherosclerosis. Increased levels of surface protein and transcription of CD105, CD137, and CD166 by treatment with 27OHChol were significantly inhibited by cotreatment with Dx. These results indicate that Dx inhibits 27OHChol-induced differentiation of monocytic cells into a mature dendritic cell phenotype and expression of CD molecules whose levels are associated with atherosclerosis. In addition, we examined phosphorylation of AKT induced by 27OHChol and effect of Dx, where cotreatment with Dx inhibited the phosphorylation of AKT. The current study reports that Dx regulates oxysterol-mediated dendritic cell differentiation of monocytic cells.

Macroscopic and microscopic effects of GaAIAs diode laser and dexamethasone therapies on oral mucositis induced by fluorouracil in rats.

PubMed

Lara, Renata Nemetala; da Guerra, Eliete Neves Silva; de Melo, Nilce Santos

2007-01-01

To present an animal model for mucositis induced by fluorouracil in rats, and test two therapeutic options, the GaAIAs laser and topical dexamethasone, analysing them with regard to the quality and quantity of tissue alterations and comparing them with the phases of mucositis. Forty-five Wistar rats (250 g) were treated with fluorouracil (60 mg/kg) and, in order to mimic the clinical effect of chronic irritation, the palatal mucosa was irritated by superficial scratching with an 18-gauge needle. When all of the rats presented oral ulcers of mucositis, they were randomly allocated to one of three groups: group I was treated with laser (GaAIAs), group II was treated with topical dexamethasone, and group III was not treated. Excisional biopsies of the palatal mucosa were then performed, and the rats were killed. Tissue sections were stained with haematoxylin and eosin for morphological analyses, and with toluidine blue for mast-cell counts. Group I specimens showed higher prevalence of ulcers, bacterial biofilm, necrosis and vascularisation, while group II specimens showed higher prevalance of granulation tissue formation. There were no significant statistical differences in the numbers of mast cells and epithelial thickness between groups. For the present model of mucositis, rats with palatal mucositis treated with laser (GaAIAs) showed characteristics compatible with the ulcerative phase of oral mucositis, and rats treated with topical dexamethasone showed characteristics compatible with the healing phase of mucositis. Topical dexamethasone was more efficient in the treatment of rats' oral mucositis than the laser.

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

PubMed Central

Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

2015-01-01

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

Hypotensive Activity of Ethanolic Extracts of Morinda citrifolia L. Leaves and Fruit in Dexamethasone-Induced Hypertensive Rat.

PubMed

Wigati, Dyan; Anwar, Khoerul; Sudarsono; Nugroho, Agung Endro

2017-01-01

The effect of ethanolic extract of Morinda citrifolia leaves and fruit on blood pressure in dexamethasone-induced hypertension rat was evaluated. Total phenolic content of Morinda citrifolia leaves ethanolic extract (MCLEE) and Morinda citrifolia leaves ethanolic extract (MCFEE) was 1.789 ± 0.116 and 1.677 ± 0.051 mg of gallic acid equivalents per gram sample, respectively. Rutin level in MCLEE was 0.92 ± 0.19%, and scopoletin level in MCFEE was 0.46 ± 0.05%. MCLEE, MCFEE, and its extract combination significantly decreased the blood pressure of hypertensive rats. The combination group showed highest hypotensive activity by lowering systolic blood pressure by 16.71 ± 3.95%, diastolic blood pressure by 21.49 ± 7.90%, and mean arterial blood pressure by 19.58% ± 6.35. All extract treatments have not been able to repair or inhibit renal damage caused by dexamethasone induction. © The Author(s) 2016.

Induction of cell expansion of goldfish melanocytoma cells (GMM-1) by epinephrine and dexamethasone requires external calcium.

PubMed

Shih, Y L; Lo, S J

1993-05-01

Treatment of GMM-1 (a goldfish melanocytoma cell line) cells with epinephrine induced a rapid cell expansion (flattening of cells, extension and broadening of cellular processes) similar to the effect of dexamethasone reported previously (Shih et al., 1990). Studies on the possible involvement of secondary messengers in cell expansion indicated that (i) both 8-bromo-CAMP and forskolin caused cell shrinking (the opposite of cell expansion); (ii) TPA also caused cell shrinking; (iii) phospholipid derivatives, such as 1,2-dioctanoyl-sn-glycerol, lysophosphatidic acid, and arachidonic acid caused cell expansion; and (iv) EGTA (calcium chelator) and nifedipine (calcium channel blocker) inhibited the effect of epinephrine. Together with the previous findings, these observations indicate that epinephrine and dexamethasone may share a common pathway in triggering an external calcium influx to cause cell expansion. The results of the effects of epinephrine agonists and antagonists, together with those of other workers, also show that there are multiple isoforms of adrenoceptor in the goldfish.

Cochlear blood flow during occlusion and reperfusion of the anterior inferior cerebellar artery--effect of topical application of dexamethasone to the round window.

PubMed

Otake, Hironao; Yamamoto, Hiroshi; Teranishi, Masaaki; Sone, Michihiko; Nakashima, Tsutomu

2009-02-01

Topical application of dexamethasone may support autoregulation of cochlear blood flow (CBF), although it had no direct effect on CBF. Although intratympanic steroid therapy for patients with inner ear disorders is common, the mechanism by which steroids exert their effect is unclear. We investigated the response of CBF to topical application of dexamethasone onto the round window. Two concentrations of dexamethasone (3.3 mg/ml and 33 mg/ml dexamethasone in 0.5 microl saline) were applied to the round windows of rats, and CBF responses were measured using a laser Doppler flowmeter. The effects on CBF of a 2 h occlusion of the anterior inferior cerebellar artery (AICA) and subsequent release of the clamp with or without previous dexamethasone application were investigated. No significant change in CBF was observed after topical application of dexamethasone, and it did not affect the decrease in CBF caused by AICA occlusion. However, recovery of CBF after release of the AICA clamp was better in animals treated with dexamethasone than in those that did not receive dexamethasone.

A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

PubMed

Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

2017-09-23

Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P < 0.0001), female gender (P = 0.022), increased age (P = 0.048), and increased local anesthetic dose (P = 0.01). In a multivariable model, block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e

A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage.

PubMed

Mohney, Nathaniel; Williamson, Craig A; Rothman, Edward; Ball, Ron; Sheehan, Kyle M; Pandey, Aditya S; Fletcher, Jeffrey J; Jacobs, Teresa L; Thompson, B Gregory; Rajajee, Venkatakrishna

2018-01-01

An inflammatory response occurs after aneurysmal subarachnoid hemorrhage (aSAH) and predicts poor outcomes. Glucocorticoids suppress inflammation and promote fluid retention. Dexamethasone is often administered after aSAH for postoperative cerebral edema and refractory headache. Our objective was to examine the impact of dexamethasone use on functional outcomes and delayed cerebral ischemia (DCI) after aSAH. Patients with aSAH admitted between 2010 and 2015 were included; the data source was a single-center subarachnoid hemorrhage registry. The intervention of interest was a dexamethasone taper used <7 days from ictus. The primary outcome was poor discharge functional outcome, with a modified Rankin Scale score >3. Other outcomes included DCI and infection. A propensity score for use of dexamethasone was calculated using a logistic regression model that included potential predictors of dexamethasone use and outcome. The impact of dexamethasone on outcomes of interest was calculated and the propensity score was controlled for. A total of 440 patients with subarachnoid hemorrhage were admitted during the study period and 309 met eligibility criteria. Dexamethasone was administered in 101 patients (33%). A total of 127 patients (41%) had a discharge modified Rankin Scale score >3, 105 (34%) developed DCI, and 94 (30%) developed an infection. After propensity score analysis, dexamethasone use was associated with a significant reduction in poor functional outcomes (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.19-0.66) but showed no significant association with DCI (OR, 0.93; 95% CI, 0.53-1.64) or infection (OR, 0.60; 95% CI, 0.34-1.06). Dexamethasone use after aSAH was associated with a reduction in poor functional outcomes at discharge but not DCI, controlling for predictors of dexamethasone use. Copyright © 2017 Elsevier Inc. All rights reserved.