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...

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.

Eating behavior during dexamethasone treatment in children with acute lymphoblastic leukemia.

PubMed

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

2017-12-01

Large prospective studies on dexamethasone-induced changes in eating behavior, energy, and nutrient intake are lacking in pediatric acute lymphoblastic leukemia (ALL). We prospectively studied eating behavior, energy, nutrient intake, and the effect on leptin and adiponectin levels during dexamethasone administration in children with ALL. Parents of patients with ALL (3-16 years) completed a dietary diary for their child during 4 days of dexamethasone (6 mg/m 2 ) administration. Energy intake and nutrient intake (energy percentage = E%) were assessed and compared with the recommended intake. The Dutch Eating Behavior Questionnaire for Children was completed before start and after 4 days of dexamethasone administration by patients of 7-12 years of age. Fasting leptin and adiponectin levels were also measured before start and after 4 days of dexamethasone administration. Energy intake per day(kcal) (N = 44) increased significantly during dexamethasone (median day 1: 1,103 (717-1,572) versus day 4: 1,482 (1,176-1,822), P < 0.01), including an increase in total protein, fat, saturated fat, carbohydrate, and sodium intake. Intake of saturated fat (median day 4: 12 E%) and salt (median day 4: 1.9 g/day) exceeded the healthy range for age and gender. With respect to eating behavior, dexamethasone significantly decreased restrained eating (P = 0.04). Leptin levels as well as adiponectin levels increased significantly during the dexamethasone course. Four days of dexamethasone treatment significantly increased energy intake, including excessive saturated fat and salt intake, and changed eating behavior in children with ALL. Nutritional and behavioral interventions during dexamethasone treatment are recommended to stimulate a healthy lifestyle. © 2017 Wiley Periodicals, Inc.

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...

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease

PubMed Central

Quinn, Charles T.; Stuart, Marie J.; Kesler, Karen; Ataga, Kenneth I.; Wang, Winfred C.; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ahsok; Hsu, Lewis L.; Krishnan, Suba; Kuypers, Frans A; Setty, B. N. Yamaja; Rhee, Seungshin; Key, Nigel S.; Buchanan, George R.

2011-01-01

Summary Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17.3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20.8 h compared to placebo (P=0.024). Rebound pain occurred in both groups (3 dexamethasone vs. 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. PMID:21848879

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

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

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

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-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.

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

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.

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.

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.

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

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

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.

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.

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.

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

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 level in experimental pneumococcal meningitis. Further dexamethasone-induced expressional changes reflect an increase of pro-apoptotic signals and a decrease of pro-neurogenic processes. The findings may help to identify potential mechanisms leading to apoptosis by dexamethasone in experimental pneumococcal meningitis. PMID:21412436

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 gastrocnemius muscle. Regulation of FOXO1, PGC-1{alpha} and p38 MAPK by testosterone may represent a novel mechanism by which this agent protects against dexamethasone-induced muscle atrophy.« less

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, but not systemic dexamethasone, could prevent axon degeneration and demyelination. There was no significant caspase-dependent apoptosis process in the mouse sciatic nerve among all study groups during our study period. Conclusions Perineural, not systemic, dexamethasone added to a clinical concentration of bupivacaine may not only prolong the duration of sensory and motor blockade of sciatic nerve, but also prevent the bupivacaine-induced reversible neurotoxicity and short-term “rebound hyperalgesia” after the resolution of nerve block. PMID:25856078

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease.

PubMed

Quinn, Charles T; Stuart, Marie J; Kesler, Karen; Ataga, Kenneth I; Wang, Winfred C; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ashok; Hsu, Lewis L; Krishnan, Suba; Kuypers, Frans A; Setty, Yamaja; Rhee, Seungshin; Key, Nigel S; Buchanan, George R

2011-10-01

Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17·3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20·8 h compared to placebo (P = 0·024). Rebound pain occurred in both groups (3 dexamethasone versus 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. © 2011 Blackwell Publishing Ltd.

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.

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

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

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.

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.

Effects of the synthetic corticosteroid dexamethasone on bovine herpesvirus 1 productive infection.

PubMed

Zhu, Liqian; Thompson, Jesse; Ma, Fangrui; Eudy, James; Jones, Clinton

2017-05-01

Sensory neurons are a primary site for life-long latency of bovine herpesvirus 1 (BoHV-1). The synthetic corticosteroid dexamethasone induces reactivation from latency and productive infection, in part because the BoHV-1 genome contains more than 100 glucocorticoid receptor (GR) responsive elements (GREs). Two GREs in the immediate early transcription unit 1 promoter are required for dexamethasone induction. Recent studies also demonstrated that the serum and glucocorticoid receptor protein kinase (SGK) family stimulated BoHV-1 replication. Consequently, we hypothesized that dexamethasone influences several aspects of productive infection. In this study, we demonstrated that dexamethasone increased expression of the immediate early protein bICP4, certain late transcripts, and UL23 (thymidine kinase) by four hours after infection. SGK1 expression and Akt phosphorylation were also stimulated during early stages of infection and dexamethasone treatment further increased this effect. These studies suggest that stress, as mimicked by dexamethasone treatment, has the potential to stimulate productive infection by multiple pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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.

Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model

PubMed Central

Liu, Chengcheng; Janke, Laura J.; Kawedia, Jitesh D.; Ramsey, Laura B.; Cai, Xiangjun; Mattano, Leonard A.; Boyd, Kelli L.; Funk, Amy J.; Relling, Mary V.

2016-01-01

Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids. PMID:26967741

Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model.

PubMed

Liu, Chengcheng; Janke, Laura J; Kawedia, Jitesh D; Ramsey, Laura B; Cai, Xiangjun; Mattano, Leonard A; Boyd, Kelli L; Funk, Amy J; Relling, Mary V

2016-01-01

Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006). Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007). As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001). This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027) and asparaginase (P = 0.036). We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids.

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-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature. CONCLUSIONS The authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients' prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

Perineural dexamethasone successfully prolongs adductor canal block when assessed by objective pinprick sensory testing: A prospective, randomized, dose-dependent, placebo-controlled equivalency trial.

PubMed

Turner, James D; Henshaw, Daryl S; Weller, Robert S; Jaffe, J Douglas; Edwards, Christopher J; Reynolds, J Wells; Russell, Gregory B; Dobson, Sean W

2018-05-08

To determine whether perineural dexamethasone prolongs peripheral nerve blockade (PNB) when measured objectively; and to determine if a 1 mg and 4 mg dose provide equivalent PNB prolongation compared to PNB without dexamethasone. Multiple studies have reported that perineural dexamethasone added to local anesthetics (LA) can prolong PNB. However, these studies have relied on subjective end-points to quantify PNB duration. The optimal dose remains unknown. We hypothesized that 1 mg of perineural dexamethasone would be equivalent in prolonging an adductor canal block (ACB) when compared to 4 mg of dexamethasone, and that both doses would be superior to an ACB performed without dexamethasone. This was a prospective, randomized, double-blind, placebo-controlled equivalency trial involving 85 patients undergoing a unicompartmental knee arthroplasty. All patients received an ACB with 20 ml of 0.25% bupivacaine with 1:400,000 epinephrine. Twelve patients had 0 mg of dexamethasone (placebo) added to the LA mixture; 36 patients had 1 mg of dexamethasone in the LA; and 37 patients had 4 mg of dexamethasone in the LA. The primary outcome was block duration determined by serial neurologic pinprick examinations. Secondary outcomes included time to first analgesic, serial pain scores, and cumulative opioid consumption. The 1 mg (31.8 ± 10.5 h) and 4 mg (37.9 ± 10 h) groups were not equivalent, TOST [Mean difference (95% CI); 6.1 (-10.5, -2.3)]. Also, the 4 mg group was superior to the 1 mg group (p-value = 0.035), and the placebo group (29.7 ± 6.8 h, p-value = 0.011). There were no differences in opioid consumption or time to analgesic request; however, some pain scores were significantly lower in the dexamethasone groups when compared to placebo. Dexamethasone 4 mg, but not 1 mg, prolonged the duration of an ACB when measured by serial neurologic pinprick exams. NCT02462148. Copyright © 2018 Elsevier Inc. All rights reserved.

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-mail: journals.permissions@oup.com

[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 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

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 Experimental Therapeutics.

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

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

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

PubMed Central

San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

2015-01-01

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

Mitogen‐inducible gene‐6 partly mediates the inhibitory effects of prenatal dexamethasone exposure on endochondral ossification in long bones of fetal rats

PubMed Central

Shang‐Guan, Yangfan; Ma, Jing; Hu, Hang; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin

2016-01-01

Abstract Background and Purpose Prenatal exposure to dexamethasone slows down fetal linear growth and bone mineralization but the regulatory mechanism remains unknown. Here we assessed how dexamethasone regulates bone development in the fetus. Experimental Approach Dexamethasone (1 mg·kg−1·day−1) was injected subcutaneously every morning in pregnant rats from gestational day (GD)9 to GD20. Fetal femurs and tibias were harvested at GD20 for histological and gene expression analysis. Femurs of 12‐week‐old female offspring were harvested for microCT (μCT) measurement. Primary chondrocytes were treated with dexamethasone (10, 50, 250 and 1000 nM). Key Results Prenatal dexamethasone exposure resulted in accumulation of hypertrophic chondrocytes and delayed formation of the primary ossification centre in fetal long bone. The retardation was accompanied by reduced maturation of hypertrophic chondrocytes, decreased osteoclast number and down‐regulated expression of osteocalcin and bone sialoprotein in long bone. In addition, the mitogen‐inducible gene‐6 (Mig6) and osteoprotegerin (OPG) expression were stimulated, and the receptor activator of NF‐κB ligand (RANKL) expression was repressed. Moreover, dexamethasone activated OPG and repressed RANKL expression in both primary chondrocytes and primary osteoblasts, and the knockdown of Mig6 abolished the effect of dexamethasone on OPG expression. Further, μCT measurement showed loss of bone mass in femur of 12‐week‐old offspring with prenatal dexamethasone exposure. Conclusions and Implications Prenatal dexamethasone exposure delays endochondral ossification by suppressing chondrocyte maturation and osteoclast differentiation, which may be partly mediated by Mig6 activation in bone. Bone development retardation in the fetus may be associated with reduced bone mass in later life. PMID:27128203

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.

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

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.

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.

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.

Dexamethasone Regulates Cochlear Expression of Deafness-associated Proteins Myelin Protein Zero and Heat Shock Protein 70, as Revealed by iTRAQ Proteomics.

PubMed

Maeda, Yukihide; Fukushima, Kunihiro; Kariya, Shin; Orita, Yorihisa; Nishizaki, Kazunori

2015-08-01

Using proteomics, we aimed to identify the proteins differentially regulated by dexamethasone in the mouse cochlea based on mass-spectrometry data. Glucocorticoid therapy is widely used for many forms of sensorineural hearing loss; however, the molecular mechanism of its action in the cochlea remains poorly understood. Dexamethasone or control saline was intratympanically applied to the cochleae of mice. Twelve hours after application, proteins differentially regulated by dexamethasone in the cochlea were analyzed by isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-mass spectrometry. Next, dexamethasone-dependent regulation of these proteins was verified in the cochleae of mice with noise-induced hearing loss (NIHL) and systemic administration of dexamethasone by western blotting. Immunolocalizations of these proteins were examined in cochleae with NIHL. A total of 247 proteins with a greater than 95% confidence interval of protein identification were found, and 11 differentially expressed proteins by dexamethasone were identified by the iTRAQ-mass spectrometry. One protein, myelin protein zero (Mpz), was upregulated (1.870 ± 0.201-fold change, p < 0.01) at 6 hours post-systemic dexamethasone and noise exposure in a mouse model of NIHL. Heat shock protein 70 (Hsp70) was downregulated (0.511 ± 0.274-fold change, p < 0.05) at 12 hours post-systemic dexamethasone. Immunohistochemistry confirmed Mpz localization to the efferent and afferent processes of the spiral neurons, whereas Hsp70 showed a more ubiquitous expression pattern in the cochlea. Both Mpz and Hsp70 have been reported to be closely associated with sensorineural hearing loss in humans. Dexamethasone significantly modulated the expression levels of these proteins in the cochleae of mice.

Dexamethasone promotes granulocyte mobilization by prolonging the half-life of granulocyte-colony-stimulating factor in healthy donors for granulocyte transfusions.

PubMed

Hiemstra, Ida H; van Hamme, John L; Janssen, Machiel H; van den Berg, Timo K; Kuijpers, Taco W

2017-03-01

Granulocyte transfusion (GTX) is a potential approach to correcting neutropenia and relieving the increased risk of infection in patients who are refractory to antibiotics. To mobilize enough granulocytes for transfusion, healthy donors are premedicated with granulocyte-colony-stimulating factor (G-CSF) and dexamethasone. Granulocytes have a short circulatory half-life. Consequently, patients need to receive GTX every other day to keep circulating granulocyte counts at an acceptable level. We investigated whether plasma from premedicated donors was capable of prolonging neutrophil survival and, if so, which factor could be held responsible. The effects of plasma from G-CSF/dexamethasone-treated donors on neutrophil survival were assessed by annexin-V, CD16. and CXCR4 staining and nuclear morphology. We isolated an albumin-bound protein using α-chymotrypsin and albumin-depletion and further characterized it using protein analysis. The effects of dexamethasone and G-CSF were assessed using mifepristone and G-CSF-neutralizing antibody. G-CSF plasma concentrations were determined by Western blot and Luminex analyses. G-CSF/dexamethasone plasma contained a survival-promoting factor for at least 2 days. This factor was recognized as an albumin-associated protein and was identified as G-CSF itself, which was surprising considering its reported half-life of only 4.5 hours. Compared with coadministration of dexamethasone, administration of G-CSF alone to the same GTX donors led to a faster decline in circulating G-CSF levels, whereas dexamethasone itself did not induce any G-CSF, demonstrating a role for dexamethasone in increasing G-CSF half-life. Dexamethasone increases granulocyte yield upon coadministration with G-CSF by extending G-CSF half-life. This observation might also be exploited in the coadministration of dexamethasone with other recombinant proteins to modulate their half-life. © 2016 AABB.

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

PubMed

Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

2017-01-01

Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

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.

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. ...

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.

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.

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.

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.

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 free drug level at 2-week was 107.23+/−10.54 ng/mL that is well above the therapeutic level but only around 20% level of dexamethasone released from OZURDEX ® (dexamethasone intravitreal implant) in a rabbit eye model. In conclusion, dexamethasone is able to covalently load to the pSiO2 particles and provide sustained drug release for at least 3 months in vitro. Intravitreal injection of these particles were well tolerated in rabbit eyes and free drug level in vitreous at 2-week was well above the therapeutic level. PMID:25446320

GLUCOCORTICOID TREATMENT—EFFECT ON ADRENAL MEDULLARY CATECHOLAMINE PRODUCTION

PubMed Central

Sharara-Chami, Rana I.; Joachim, Maria; Pacak, Karel; Majzoub, Joseph A.

2016-01-01

Glucocorticoid and epinephrine are important stress hormones secreted from the adrenal gland during critical illness. Adrenal glucocorticoid stimulates phenylethanolamine N-methyltransferase (PNMT) to convert norepinephrine to epinephrine in the adrenal medulla. Glucocorticoid is sometimes used in catecholamine-resistant septic shock in critically ill patients. By suppressing adrenal glucocorticoid production, glucocorticoid therapy might also reduce the secretion of epinephrine during stress. To investigate this, we used a mouse model subjected to glucocorticoid therapy under basal conditions (experiment 1) and during stress (experiment 2). In experiment 1, pellets containing 0% to 8% dexamethasone were implanted subcutaneously in mice for 4 weeks. In experiment 2, animals received 14 days of intraperitoneal injections of normal saline, low- or high-dose dexamethasone, followed by 2 h of restraint. We found that in experiment 1, adrenal corticosterone did not differ with dexamethasone treatment. Phenylethanolamine N-methyltransferase messenger RNA levels and adrenal catecholamines were highest in the 8% dexamethasone group. Compared with experiment 1, restrained control mice in experiment 2 had high adrenal corticosterone, which decreased with dexamethasone. Phenylethanolamine N-methyltransferase messenger RNA content doubled with restraint but decreased with dexamethasone treatment. As in experiment 1, adrenal catecholamine content increased significantly with dexamethasone treatment. We conclude that without stress, when adrenocorticotropic hormone is low, high doses of exogenous dexamethasone stimulate PNMT and catecholamine synthesis, likely independently of adrenal corticosterone concentration. After stress, adrenocorticotropic hormone levels are elevated, and exogenous dexamethasone suppresses endogenous corticosterone and PNMT production. Nonetheless, catecholamines increase, possibly due to direct neural stimulation, which may override the hormonal regulation of epinephrine synthesis during stress. PMID:19503019

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.

Identification of cysteine-644 as the covalent site of attachment of dexamethasone 21-mesylate to murine glucocorticoid receptors in WEHI-7 cells

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

Smith, L.I.; Bodwell, J.E.; Mendel, D.B.

1988-05-17

Dexamethasone 21-mesylate is a highly specific synthetic glucocorticoid derivative that binds covalently to glucocorticoid receptors via sulfhydryl groups. The authors have identified the amino acid that reacts with the dexamethasone 21-mesylate by using enzymatic digestion and microsequencing for radiolabel. Nonactivated glucocorticoid receptors obtained from labeling intact WEHI-7 mouse thymoma cells with (/sup 3/H)dexamethasone 21-mesylate were immunopurified and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Trypsin digestion followed by reversed-phase high-performance liquid chromatography (reversed-phase HPLC) produced a single (/sup 3/H)dexamethasone 21-mesylate labeled peptide. Automated Edman degradation of this peptide revealed that the (/sup 3/H)dexamethasone 21-mesylate was located at position 5 frommore » the amino terminus. Dual-isotope labeling studies with (/sup 3/H)dexamethasone 21-mesylate and (/sup 35/S)methionine demonstrated that this peptide contained methionine. Staphylococcus aureus V8 protease digestion of (/sup 3/H)dexamethasone 21-mesylate labeled steroid-binding subunits generated a different radiolabeled peptide containing label at position 7 from the amino terminus. On the basis of the published amino acid sequence of the murine glucocorticoid receptor, their data clearly identify cysteine-644 as the single residue in the steroid-binding domain that covalently binds dexamethasone 21-mesylate. They have confirmed this finding by demonstrating that a synthetic peptide representing the amino acid sequence 640-650 of the murine glucocorticoid receptor behaves in an identical manner on reversed-phase HPLC as the trypsin-generated peptide from intact cells.« less

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.

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.

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.

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.

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 endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. ISRCTN16345835 (date of registration 2010-08-24).

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.

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

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

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

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 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; studies 27). Postoperative pain intensity at 12 and 24 hours was significantly lower in the perineural dexamethasone group compared with control (MD -2.08, 95% CI -2.63 to -1.53; participants 257; studies 5) and (MD -1.63, 95% CI -2.34 to -0.93; participants 469; studies 9), respectively. There was no significant difference at 48 hours (MD -0.61, 95% CI -1.24 to 0.03; participants 296; studies 4). The quality of evidence is very low for postoperative pain intensity at 12 hours and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the perineural dexamethasone group compared with placebo (MD 19.25 mg, 95% CI 5.99 to 32.51; participants 380; studies 6). Intravenous dexamethasone versus placeboDuration of sensory block was significantly longer in the intravenous dexamethasone group compared with placebo (MD 6.21, 95% CI 3.53 to 8.88; participants 499; studies 8). Postoperative pain intensity at 12 and 24 hours was significantly lower in the intravenous dexamethasone group compared with placebo (MD -1.24, 95% CI -2.44 to -0.04; participants 162; studies 3) and (MD -1.26, 95% CI -2.23 to -0.29; participants 257; studies 5), respectively. There was no significant difference at 48 hours (MD -0.21, 95% CI -0.83 to 0.41; participants 172; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. Cumulative 24-hour postoperative opioid consumption was significantly lower in the intravenous dexamethasone group compared with placebo (MD -6.58 mg, 95% CI -10.56 to -2.60; participants 287; studies 5). Perinerual versus intravenous dexamethasoneDuration of sensory block was significantly longer in the perineural dexamethasone group compared with intravenous by three hours (MD 3.14 hours, 95% CI 1.68 to 4.59; participants 720; studies 9). We found that postoperative pain intensity at 12 hours and 24 hours was significantly lower in the perineural dexamethasone group compared with intravenous, however, the MD did not surpass our pre-determined minimally important difference of 1.2 on the Visual Analgue Scale/Numerical Rating Scale, therefore the results are not clinically significant (MD -1.01, 95% CI -1.51 to -0.50; participants 217; studies 3) and (MD -0.77, 95% CI -1.47 to -0.08; participants 309; studies 5), respectively. There was no significant difference in severity of postoperative pain at 48 hours (MD 0.13, 95% CI -0.35 to 0.61; participants 227; studies 3). The quality of evidence is moderate for duration of sensory block and postoperative pain intensity at 24 hours, and low for the remaining outcomes. There was no difference in cumulative postoperative 24-hour opioid consumption (MD -3.87 mg, 95% CI -9.93 to 2.19; participants 242; studies 4). Incidence of severe adverse eventsFive serious adverse events were reported. One block-related event (pneumothorax) occurred in one participant in a trial comparing perineural dexamethasone and placebo; however group allocation was not reported. Four non-block-related events occurred in two trials comparing perineural dexamethasone, intravenous dexamethasone and placebo. Two participants in the placebo group required hospitalization within one week of surgery; one for a fall and one for a bowel infection. One participant in the placebo group developed Complex Regional Pain Syndrome Type I and one in the intravenous dexamethasone group developed pneumonia. The quality of evidence is very low due to the sparse number of events. Low- to moderate-quality evidence suggests that when used as an adjuvant to peripheral nerve block in upper limb surgery, both perineural and intravenous dexamethasone may prolong duration of sensory block and are effective in reducing postoperative pain intensity and opioid consumption. There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not apply to participants at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe.There is not enough evidence to determine the effectiveness of dexamethasone as an adjuvant to peripheral nerve block in lower limb surgeries and there is no evidence in children. The results of our review may not be apply to participants who at risk of dexamethasone-related adverse events for whom clinical trials would probably be unsafe. The nine ongoing trials registered at ClinicalTrials.gov may change the results of this review.

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 define the benefits and risks of prophylactic dexamethasone in potential patients with a high risk for PONV. PMID:25330115

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 of the drug as when the same dose is administered intramuscularly with demonstration of similar clinical effects.

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.

Comparison of dexamethasone or intravenous fluids or combination of both on postoperative nausea, vomiting and pain in pediatric strabismus surgery.

PubMed

Sayed, Jehan Ahmed; F Riad, Mohamed Amir; M Ali, Mohamed Omar

2016-11-01

Strabismus surgery is perhaps a pediatric surgical procedure that has the strongest evidence of postoperative nausea and vomiting (PONV) risk. This randomized controlled blind study was designed to evaluate the efficacy of combined therapy of dexamethasone and intraoperative superhydration vs their monotherapy on the incidence and severity of PONV and on pain intensity after pediatric strabismus surgery. A total of 120 children aged 6 to 12 years undergoing strabismus surgery were randomized to equally 3 groups to receive 0.15 mg/kg dexamethasone (dexamethasone group) or intraoperative superhydration of lactated Ringer's solution in a dose of 30 mL/kg per fasting time (superhydration group), or a combination of dexamethasone and intraoperative fluid in the same strategy (combination therapy group). The incidence and severity of PONV and pain using visual analog scale score, and need for supplemental antiemetic and analgesic therapy and their consumptions were assessed and compared in the 3 studied groups for 24 hours postoperatively. The incidence of PONV and postoperative vomiting was significantly lower (P> .001) in the combination therapy group (5% and 5% respectively) compared with the dexamethasone group (35% and 30%) and superhydration group (32.5% and 35%). There was no significant difference among patients in the superhydration group and dexamethasone group in the cumulative incidences of PONV in the whole 24 hours postoperatively. Postoperative aggregated visual analog scale pain score and total acetaminophen consumption showed a significant reduction (P> .05) in the combination therapy group together with significant prolongation of time to the first analgesic request compared with both the superhydration group and the dexamethasone group. Combined therapy of 0.15 mg/kg dexamethasone 1 minute before induction and intraoperative fluid superhydration is an effective and safe way to reduce PONV and pain better than monotherapy of dexamethasone, or intraoperative superhydration separately for pediatric strabismus surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

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.

The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

PubMed

Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

2015-11-01

The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction—A Phase III Double Blind, Randomized Clinical Trial

PubMed Central

Pereira, Valeria Fontenelle Angelim; Pietrobon, Ricardo S.; Schmidt, Andre P.; Oses, Jean P.; Portela, Luis V.; Souza, Diogo O.; Vissoci, João Ricardo Nickenig; da Luz, Vinicius Fernando; Trintoni, Leticia Maria de Araujo de Souza; Nielsen, Karen C.; Carmona, Maria José Carvalho

2016-01-01

Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients. This study evaluated the effect of dexamethasone on POCD incidence after noncardiac and nonneurologic surgery. METHODS: One hundred and forty patients (ASA I-II; age 60–87 years) took part in a prospective phase III, double blind, randomized study involving the administration or not of 8 mg of IV dexamethasone before general anesthesia under bispectral index (BIS) between 35–45 or 46–55. Neuropsychological tests were applied preoperatively and on the 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. The generalized estimating equations (GEE) method was applied, followed by the posthoc Bonferroni test considering P<0.05 as significant. RESULTS: On the 3rd postoperative day, POCD was diagnosed in 25.2% and 15.3% of patients receiving dexamethasone, BIS 35–45, and BIS 46–55 groups, respectively. Meanwhile, POCD was present in 68.2% and 27.2% of patients without dexamethasone, BIS 35–45 and BIS 46–55 groups (p<0.0001). Neuropsychological tests showed that dexamethasone associated to BIS 46–55 decreased the incidence of POCD, especially memory and executive function. The administration of dexamethasone might have prevented the postoperative increase in S100β serum levels. CONCLUSION: Dexamethasone can reduce the incidence of POCD in elderly patients undergoing surgery, especially when associated with BIS 46–55. The effect of dexamethasone on S100β might be related with some degree of neuroprotection. Trial Registration: www.clinicaltrials.gov NCT01332812 PMID:27152422

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 Elsevier Inc. All rights reserved.

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.

Dexamethasone treatment induces the reprogramming of pancreatic acinar cells to hepatocytes and ductal cells.

PubMed

Al-Adsani, Amani; Burke, Zoë D; Eberhard, Daniel; Lawrence, Katherine L; Shen, Chia-Ning; Rustgi, Anil K; Sakaue, Hiroshi; Farrant, J Mark; Tosh, David

2010-10-27

The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype. These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ.

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.

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.

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 treatment decreases replication of viral hemorrhagic septicemia virus in Epithelioma papulosum cyprini cells.

PubMed

Kim, Min Sun; Lee, Su Jin; Choi, Seung Hyuk; Kang, Yue Jai; Kim, Ki Hong

2017-05-01

The expression of Mx1 in EPC cells after treatment with poly(I:C) or infection with viral hemorrhagic septicemia virus (VHSV) was significantly suppressed by treatment with dexamethasone. However, the titer of VHSV did not increase but instead decreased after dexamethasone treatment. This suggests that dexamethasone not only downregulates type I IFN but also affects certain factors that are necessary for VHSV replication. An important effect of HSP90 on replication of RNA viruses and downregulation of HSP90 by glucocorticoids have been reported. In this study, dexamethasone downregulated HSP90α expression in EPC cells that were stimulated with poly(I:C) or infected with VHSV. Furthermore, cells treated with an HSP90 inhibitor, geldanamycin, showed significantly decreased titers of VHSV, suggesting that HSP90 may be an important host component involved in VHSV replication, and HSP90 inhibition might be one of the causes for the observed reduction in viral titer caused by dexamethasone treatment.

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 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.

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

PubMed

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

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.

Effect of submucosal dexamethasone injection on postoperative pain, oedema, and trismus following mandibular third molar surgery: a prospective, randomized, double-blind clinical trial.

PubMed

Mojsa, I M; Pokrowiecki, R; Lipczynski, K; Czerwonka, D; Szczeklik, K; Zaleska, M

2017-04-01

The aim of this study was to investigate the effect of the submucosal injection of 1ml dexamethasone (4mg/ml) on pain, swelling, and trismus following the extraction of retained lower third molars. Ninety patients (mean age 23.5 years) were split randomly into three equal study groups (30 patients in each): the 'before' group received dexamethasone 15min before surgery and placebo 15min after surgery; the 'after' group received placebo 15min before surgery and dexamethasone 15min after surgery; the 'placebo' group received placebo 15min before surgery and placebo 15min after surgery. Postoperative pain was recorded by the patients using a visual analogue scale, numerical rating scale, and the McGill Pain Questionnaire at 1, 2, 4, 6, 8, 12, and 24h after surgery. The patients also recorded the total number of analgesic doses consumed during the 24h after the procedure. Swelling (determined using linear measurements of the face) and trismus (determined through measurement of maximum mouth opening) were assessed at 48h, 72h, and 7 days following surgery. Better control of pain, swelling, and trismus was demonstrated for dexamethasone in comparison to placebo. Postoperative dexamethasone provided better pain control than preoperative dexamethasone. There was no difference in total rescue analgesic intake between the preoperative and postoperative dexamethasone groups. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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.

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

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.

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

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.

Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor.

PubMed

Wells, Elizabeth; Kambhampati, Madhuri; Damsker, Jesse M; Gordish-Dressman, Heather; Yadavilli, Sridevi; Becher, Oren J; Gittens, Jamila; Stampar, Mojca; Packer, Roger J; Nazarian, Javad

2017-02-07

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug efficacy, post-treatment behavioral activity and side effects were assessed by treating two cohorts of brain tumor bearing mice with dexamethasone, vamorolone, or vehicle control. Our investigation showed that treatment with vamorolone resulted in a reduction of pro-inflammatory signals in tumor cells in vitro similar to treatment with dexamethasone. Treatment with vamorolone resulted in a better safety profile in comparison to dexamethasone treatment. Vamorolone- treated mice showed similar or better activity and survival when compared to dexamethasone-treated mice. Our data indicate vamorolone is a potential steroid-sparing alternative for treating patients with brain tumors.

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

Effects of Dexamethasone and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation - A Randomized Controlled Trial.

PubMed

Sami, Mehrdad; Mohri, Mehrdad; Seifi, Hesam A

2015-01-01

This study investigated the effects of dexamethasone and insulin, when administered at 3rd or 10th day of lactation on energy and protein metabolism in dairy cows. Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow. There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages. The results suggested that administration of glucocorticoids in early lactation resulted in short-term improvement of metabolism in postpartum dairy cows in biochemical terms.

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 of the CNS and help explain the in vivo findings of significantly reduced inflammatory mediators in the CSF and lack of inflammatory neurodegenerative lesions in the brain and spinal cord of Bb-infected animals that were treated with dexamethasone but not meloxicam. Signaling cascades altered by dexamethasone could serve as possible therapeutic targets for limiting CNS inflammation and tissue damage in LNB.

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 dexamethasone 5 mg is more effective than I.V. dexamethasone 5 mg with regard to analgesic duration of SISB for arthroscopic shoulder surgery.

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

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.

The effect of preoperative dexamethasone on pain 1 year after lumbar disc surgery: a follow-up study.

PubMed

Nielsen, Rikke Vibeke; Fomsgaard, Jonna; Mathiesen, Ole; Dahl, Jørgen Berg

2016-11-16

It has been hypothesized that dexamethasone can inhibit persistent postoperative pain, but data on humans is lacking and results from animal studies are conflicting. We explored the effect of 16 mg dexamethasone IV administered preoperatively on persistent pain 1 year after lumbar discectomy. This is a prospective 1-year follow-up on a single-centre, randomized, and blinded trial exploring the analgesic effect of 16 mg IV dexamethasone or placebo after lumbar discectomy. One year follow-up was a written questionnaire including back and leg pain (VAS 0-100 mm), Short Form 36 survey (SF-36), EuroQol 5D (EQ-5D), OSWESTRY Low Back Pain Questionnaire, duration of sick leave, working capability, contentment with surgical result. Response rate was 71% (55 patients) in the dexamethasone group, 58% (44 patients) in the placebo group. Leg pain (VAS) was significantly lower in the placebo group compared to the dexamethasone group: 17 (95% CI 10-26) vs 26 (95% CI 19-33) mm, respectively (mean difference 9 mm (95% CI -1 to 0), (P = 0.03). No difference regarding back pain. The placebo group reported significantly more improvement of leg pain and were significantly more satisfied with the surgical result. Patients in the dexamethasone group reported significantly higher pain levels in EQ-5D- and Oswestry questionnaires. No difference in the SF-36 survey or daily analgesic consumption. We found significantly higher pain levels in the dexamethasone group compared to placebo 1 year after lumbar disc surgery. Clinicaltrials.gov ( NCT01953978 ). Registered 26 Sep 2013.

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.

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

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.

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala

PubMed Central

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-01-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression. PMID:26174596

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

PubMed

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-02-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

Effect of ginkgo biloba and dexamethasone in the treatment of 3-methylindole-induced anosmia mouse model.

PubMed

Lee, Chul Hee; Mo, Ji-Hun; Shim, Seung Hee; Ahn, Jung-Min; Kim, Jeong-Whun

2008-01-01

Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.

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.

Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.

PubMed

Chang, Diane T W; Herceg, Michael C; Bilonick, Richard A; Camejo, Larissa; Schuman, Joel S; Noecker, Robert J

2009-01-01

To evaluate whether dexamethasone injected intracamerally at the conclusion of surgery can safely and effectively reduce postoperative inflammation and improve surgical outcomes in eyes with and without glaucoma. Retrospective chart review of 176 consecutive eyes from 146 patients receiving uncomplicated phacoemulsification (PE) (n = 118 total, 82 with glaucoma), glaucoma drainage device (GDD) (n = 35), combined PE/GDD (n = 11) and combined PE/endoscopic cyclophotocoagulation (n = 12). Ninety-one eyes from 76 patients were injected with 0.4 mg dexamethasone intracamerally at the conclusion of surgery. All eyes received standard postoperative prednisolone and ketorolac eyedrops. Outcomes were measured for four to eight weeks by subjective complaints, visual acuity (VA), slit-lamp biomicroscopy, intraocular pressure (IOP) and postoperative complications. Dexamethasone significantly reduced the odds of having an increased anterior chamber (AC) cell score after PE (p = 0.0013). Mean AC cell score +/- SD in nonglaucomatous eyes was 1.3 +/- 0.8 in control and 0.8 +/- 0.7 with dexamethasone; scores in glaucomatous eyes were 1.3 +/- 0.7 in control and 0.9 +/- 0.8 with dexamethasone. Treated nonglaucomatous eyes had significantly fewer subjective complaints after PE (22.2% vs 64.7% in control; p = 0.0083). Dexamethasone had no significant effects on VA, corneal changes, IOP one day and one month after surgery, or long-term complications. Intracameral dexamethasone given at the end of cataract surgery significantly reduces postoperative AC cells in eyes with and without glaucoma, and improves subjective reports of recovery in nonglaucomatous eyes. There were no statistically significant risks of IOP elevation or other complications in glaucomatous eyes.

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

Biodegradable hyaluronic acid hydrogels to control release of dexamethasone through aqueous Diels-Alder chemistry for adipose tissue engineering.

PubMed

Fan, Ming; Ma, Ye; Zhang, Ziwei; Mao, Jiahui; Tan, Huaping; Hu, Xiaohong

2015-11-01

A robust synthetic strategy of biopolymer-based hydrogels has been developed where hyaluronic acid derivatives reacted through aqueous Diels-Alder chemistry without the involvement of chemical catalysts, allowing for control and sustain release of dexamethasone. To conjugate the hydrogel, furan and maleimide functionalized hyaluronic acid were synthesized, respectively, as well as furan functionalized dexamethasone, for the covalent immobilization. Chemical structure, gelation time, morphologies, swelling kinetics, weight loss, compressive modulus and dexamethasone release of the hydrogel system in PBS at 37°C were studied. The results demonstrated that the aqueous Diels-Alder chemistry provides an extremely selective reaction and proceeds with high efficiency for hydrogel conjugation and covalent immobilization of dexamethasone. Cell culture results showed that the dexamethasone immobilized hydrogel was noncytotoxic and preserved proliferation of entrapped human adipose-derived stem cells. This synthetic approach uniquely allows for the direct fabrication of biologically functionalized gel scaffolds with ideal structures for adipose tissue engineering, which provides a competitive alternative to conventional conjugation techniques such as copper mediated click chemistry. Copyright © 2015. Published by Elsevier B.V.

The sequential appearance of sperm abnormalities after scrotal insulation or dexamethasone treatment in bulls.

PubMed Central

Barth, A D; Bowman, P A

1994-01-01

Scrotal insulation and dexamethasone treatment were used as a model to compare the effect of testicular heating and stress on spermatogenesis. Insulation was applied to the scrotum of eight bulls (insulated) for a period of four days, eight bulls were treated daily for seven days with 20 mg dexamethasone injected intramuscularly, and four bulls were untreated controls. Semen from four bulls in each group was collected and evaluated over a six-week period after treatment. Blood samples for testosterone analysis were taken hourly for eight hours at the beginning and the end of the six-week period from the control bulls and before and after treatment from the four insulated and four dexamethasone-treated bulls that were not used for semen collection. At the end of the last blood sampling period, the four bulls in each group were castrated for the collection of testicular tissue for the determination of testosterone concentrations. Basal, peak episodic, and mean serum testosterone concentrations among control bulls, pre and postinsulated bulls, and pretreatment samples of dexamethasone-treated bulls were not different (p > 0.05); however, bulls that had received dexamethasone treatments had significantly lower basal, peak episodic, and mean testosterone concentrations (p < 0.05). Tissue concentrations of testosterone in control, insulated, and dexamethasone-treated bulls were not significantly different but tended to be lower in dexamethasone-treated bulls (p > 0.13). The spermiograms of the control bulls varied insignificantly over the six-week sampling period; however, there was a marked increase in sperm defects in insulated and dexamethasone-treated bulls. The types of sperm defects and the temporal relationships of rises and declines of sperm defects were quite similar for both treatments. All bulls recovered to approximately pretreatment levels of sperm defects by six weeks after the initiation of treatment. Results indicate that two of the most common types of insults to spermatogenesis in bulls, heat and stress, result in similar spermiograms. PMID:8069831

Glucocorticoids suppress calcium mobilization and phospholipid hydrolysis in anti-Ig antibody-stimulated B cells.

PubMed

Dennis, G; June, C H; Mizuguchi, J; Ohara, J; Witherspoon, K; Finkelman, F D; McMillan, V; Mond, J J

1987-10-15

Glucocorticoids have been shown to play a major role in influencing the activation of B lymphocytes. In view of our recent observation that dexamethasone exerts a marked suppressive effect on an early event in B cell activation that is stimulated by anti-Ig antibody, we investigated its activity on other stimuli that induce intracellular events similar to those produced by anti-Ig antibody. Because the intracellular events that occur after B cell stimulation with phorbol myristate acetate and the calcium ionophore A23187 appear to mimic those that occur after B cell stimulation with anti-Ig antibody, we studied whether the cellular responses elicited by these activation stimuli are affected in a similar fashion by dexamethasone. Whereas anti-Ig antibody-stimulated entry of G0 B cells to the G1 and S phase of the cell cycle was markedly suppressed by dexamethasone, phorbol myristate acetate/A23187 stimulation of these events was resistant to dexamethasone. Our finding that anti-Ig-induced cross-linking of B cell surface Ig, as measured by surface Ig capping, was not inhibited by dexamethasone suggested that corticosteroids inhibit anti-Ig-induced B cell proliferation at a step distal to membrane Ig cross-linking and proximal to phosphatidylinositol bisphosphate hydrolysis. This hypothesis is supported by experiments presented in this manuscript which demonstrate that dexamethasone inhibits anti-Ig-stimulated phosphatidylinositol bisphosphate hydrolysis. We also found that dexamethasone markedly inhibited anti-Ig antibody-stimulated increases in intracellular ionized calcium concentrations. This dexamethasone-mediated suppression is time-dependent as it is not seen when B cells are cultured with dexamethasone for less than 6 hr. Our data suggest that the immunomodulatory activity of glucocorticoids is exerted by binding to its nuclear receptor, thereby preventing the generation of second messengers required for cell activation after agonist-receptor interaction.

The influence of a prophylactic dose of dexamethasone for postoperative nausea and vomiting on plasma interleukin concentrations after laparoscopic cholecystectomy: a randomised trial.

PubMed

Ionescu, Daniela C; Hadade, Adina I; Mocan, Teodora A; Margarit, Simona D

2014-04-01

Little is known about the effects of small doses of dexamethasone used for the prophylaxis of postoperative nausea and vomiting on the innate host response. We studied the influence of dexamethasone 4 mg on the perioperative plasma concentrations of interleukins after laparoscopic cholecystectomy. We hypothesised that there would be differences in pro-inflammatory interleukin concentrations in patients who received dexamethasone. A randomised controlled study. University hospital. Forty-six patients undergoing laparoscopic cholecystectomy under total intravenous anaesthesia were allocated randomly into one of two study groups; 42 patients completed the study. Patients in group 1 (dexamethasone, n = 22) received dexamethasone 4 mg and group 2 (n = 20) acted as controls. Plasma levels of tumour necrosis factor alpha and interleukins 1β, 6, 8, 10 and 13 were measured before anaesthesia, before surgery and 2 and 24 h after surgery. The frequency and number of episodes of postoperative nausea and vomiting were recorded. Areas under the curve of the percentage variation of interleukins 6 and 8 were significantly lower in the dexamethasone group. There were no significant differences between groups in the areas under the curve for tumour necrosis factor alpha and interleukins 1β, 10 and 13. The greatest variation in interleukin concentrations was 2 h postoperatively, when the concentration of interleukin 6 was greater in the control group, whereas the concentration of interleukin 10 was higher in the dexamethasone group. Twenty-four hours after surgery, only the concentration of interleukin 6 remained significantly increased in both groups (P = 0.001 and P = 0.002, respectively). There were no significant differences between groups in respect of postoperative nausea and vomiting. Prophylactic dexamethasone given before laparoscopic cholecystectomy produced a significant decrease in concentrations of interleukins 6 and 8. Further studies are needed to investigate the clinical implications of these findings.

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.

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.

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 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.

Dexamethasone Protects Neonatal Hypoxic-Ischemic Brain Injury via L-PGDS-Dependent PGD2-DP1-pERK Signaling Pathway

PubMed Central

Gonzalez-Rodriguez, Pablo J.; Li, Yong; Martinez, Fabian; Zhang, Lubo

2014-01-01

Background and Purpose Glucocorticoids pretreatment confers protection against neonatal hypoxic-ischemic (HI) brain injury. However, the molecular mechanism remains poorly elucidated. We tested the hypothesis that glucocorticoids protect against HI brain injury in neonatal rat by stimulation of lipocalin-type prostaglandin D synthase (L-PGDS)-induced prostaglandin D2 (PGD2)-DP1-pERK mediated signaling pathway. Methods Dexamethasone and inhibitors were administered via intracerebroventricular (i.c.v) injections into 10-day-old rat brains. Levels of L-PGD2, D prostanoid (DP1) receptor, pERK1/2 and PGD2 were determined by Western immunoblotting and ELISA, respectively. Brain injury was evaluated 48 hours after conduction of HI in 10-day-old rat pups. Results Dexamethasone pretreatment significantly upregulated L-PGDS expression and the biosynthesis of PGD2. Dexamethasone also selectively increased isoform pERK-44 level in the neonatal rat brains. Inhibitors of L-PGDS (SeCl4), DP1 (MK-0524) and MAPK (PD98059) abrogated dexamethasone-induced increases in pERK-44 level, respectively. Of importance, these inhibitors also blocked dexamethasone-mediated neuroprotective effects against HI brain injury in neonatal rat brains. Conclusion Interaction of glucocorticoids-GR signaling and L-PGDS-PGD2-DP1-pERK mediated pathway underlies the neuroprotective effects of dexamethasone pretreatment in neonatal HI brain injury. PMID:25474649

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.

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial.

PubMed

Tabari, Masumeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Moammad; Khazaeni, Kamran

2013-09-01

Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application.

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

Dose- and time-dependent activation of rat alveolar macrophages by glucocorticoids

PubMed Central

BROUG-HOLUB, E; KRAAL, G

1996-01-01

Effects of glucocorticoids on immune functions are generally thought to be suppressive and anti-inflammatory. However, most reports dealing with this issue describe effects of long-term treatment with high doses of glucocorticoids on immune functions. In the present study we have investigated both dose and timing effects of exposure of alveolar macrophages with dexamethasone on lipopolysaccharide (LPS)-induced IL-1β and nitric oxide secretion. For this purpose, alveolar macrophages were preincubated with various doses of dexamethasone during varying intervals, followed by stimulation of the cells with endotoxin, either in the absence or presence of dexamethasone. Subsequently, the effects of this treatment on IL-1β and nitric oxide secretion were measured. It was shown that both short-term incubation of alveolar macrophages with high doses of dexamethasone and long-term incubation with low doses of dexamethasone lead to enhanced nitric oxide and enhanced IL-1β secretion upon subsequent stimulation of the cells with LPS. In contrast, long-term incubation of alveolar macrophages with high-dose dexamethasone leads to decreased IL-1β and nitric oxide secretion upon subsequent stimulation. Thus, it is concluded that the effects of dexamethasone on rat alveolar macrophages are both time- and dose-dependent. It is therefore argued that effects of glucocorticoids on immune functions are not a priori suppressive, but that both dose and timing effects should be taken into account. PMID:8625529

The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony.

PubMed

Bennett, K A; Fedak, M A; Moss, S E W; Pomeroy, P P; Speakman, J R; Hall, A J

2013-03-15

Seals must manage their energy reserves carefully while they fast on land to ensure that they go to sea with sufficient fuel to sustain them until they find food. Glucocorticoids (GCs) have been implicated in the control of fuel metabolism and termination of fasting in pinnipeds. Here we tested the hypothesis that dexamethasone, an artificial GC, increases fat and protein catabolism, and induces departure from the breeding colony in wild, fasting grey seal pups. A single intramuscular dose of dexamethasone completely suppressed cortisol production for 24-72 h, demonstrating activation of GC receptors. In experiment 1, we compared the effects of a single dose of dexamethasone or saline administered 10 days after weaning on fasting mass and body composition changes, cortisol, blood urea nitrogen (BUN) and glucose levels, and timing of departure from the colony. In experiment 2, we investigated the effects of dexamethasone on short-term (5 days) changes in mass loss, body composition and BUN levels. In experiment 1, dexamethasone induced a short-lived increase in mass loss, but there was no difference in timing of departure between dexamethasone- and saline-treated pups (N=10). In experiment 2, dexamethasone increased protein and water loss and prevented a decrease in BUN levels (N=11). Our data suggest changes in cortisol contribute to regulation of protein catabolism in fasting seal pups, irrespective of the sex of the animal, but do not terminate fasting. By affecting the rate of protein depletion, lasting changes in cortisol levels could influence the amount of time seal pups have to find food, and thus may have important consequences for their survival.

The inhibitory effect of dexamethasone on platelet-derived growth factor-induced vascular smooth muscle cell migration through up-regulating PGC-1{alpha} expression

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

Xu, Wei; Department of cardiology, the Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin 150081; Guo, Ting

2011-05-01

Dexamethasone has been shown to inhibit vascular smooth muscle cell (VSMC) migration, which is required for preventing restenosis. However, the mechanism underlying effect of dexamethasone remains unknown. We have previously demonstrated that peroxisome proliferator-activated receptor gamma (PPAR{gamma}) coactivator-1 alpha (PGC-1{alpha}) can inhibit VSMC migration and proliferation. Here, we investigated the role of PGC-1{alpha} in dexamethasone-reduced VSMC migration and explored the possible mechanism. We first examined PGC-1{alpha} expression in cultured rat aortic VSMCs. The results revealed that incubation of VSMCs with dexamethasone could significantly elevate PGC-1{alpha} mRNA expression. In contrast, platelet-derived growth factor (PDGF) decreased PGC-1{alpha} expression while stimulating VSMC migration.more » Mechanistic study showed that suppression of PGC-1{alpha} by small interfering RNA strongly abrogated the inhibitory effect of dexamethasone on VSMC migration, whereas overexpression of PGC-1{alpha} had the opposite effect. Furthermore, an analysis of MAPK signal pathways showed that dexamethasone inhibited ERK and p38 MAPK phosphorylation in VSMCs. Overexpression of PGC-1{alpha} decreased both basal and PDGF-induced p38 MAPK phosphorylation, but it had no effect on ERK phosphorylation. Finally, inhibition of PPAR{gamma} activation by a PPAR{gamma} antagonist GW9662 abolished the suppressive effects of PGC-1{alpha} on p38 MAPK phosphorylation and VSMC migration. These effects of PGC-1{alpha} were enhanced by a PPAR{gamma} agonist troglitazone. Collectively, our data indicated for the first time that one of the anti-migrated mechanisms of dexamethasone is due to the induction of PGC-1{alpha} expression. PGC-1{alpha} suppresses PDGF-induced VSMC migration through PPAR{gamma} coactivation and, consequently, p38 MAPK inhibition.« less

Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions.

PubMed

Baptista, Igor L; Silva, Willian J; Artioli, Guilherme G; Guilherme, Joao Paulo L F; Leal, Marcelo L; Aoki, Marcelo S; Miyabara, Elen H; Moriscot, Anselmo S

2013-01-01

In the present study we have compared the effects of leucine supplementation and its metabolite β-hydroxy-β-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.

Leucine and HMB Differentially Modulate Proteasome System in Skeletal Muscle under Different Sarcopenic Conditions

PubMed Central

Baptista, Igor L.; Silva, Willian J.; Artioli, Guilherme G.; Guilherme, Joao Paulo L. F.; Leal, Marcelo L.; Aoki, Marcelo S.; Miyabara, Elen H.; Moriscot, Anselmo S.

2013-01-01

In the present study we have compared the effects of leucine supplementation and its metabolite β-hydroxy-β-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB. PMID:24124592

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Kim, Dong Yeon; Cho, Sooyoung

2015-09-01

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

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.

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.

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.

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.

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.

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

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

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.

Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions

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

Werb, Z.

1978-01-01

The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1 to 1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contast, secretion of lysozyme was not affectedmore » by glucocorticoids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1 to 10 nM) similar to those that half-saturated the specific glucocorticoid receptors. At high concentrations of dexamethasone (100 to 1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (>95%) than the secretion of elastase (60 to 80%).Progesterone alone had no effect on secretion, but blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1 to 100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone.« less

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

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study.

PubMed

Sethi, Rakesh; Naqash, Imtiaz A; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only.

Evaluation of hyperglycaemic response to intra-operative dexamethasone administration in patients undergoing elective intracranial surgery: A randomised, prospective study

PubMed Central

Sethi, Rakesh; Naqash, Imtiaz A.; Bajwa, Sukhminder Jit Singh; Dutta, Vikas; Ramzan, Altaf Umar; Zahoor, Syed Amir

2016-01-01

Background and Aim: The glucocorticoid dexamethasone in a bolus dose of 8-10 mg followed by quarterly dose of 4 mg is commonly used during intracranial surgery so as to reduce oedema and vascular permeability. However, the detrimental hyperglycaemic effects of dexamethasone may override its potentially beneficial effects. The present prospective, randomised study aimed at comparing the degree and magnitude of hyperglycaemia induced by prophylactic administration of dexamethasone in patients undergoing elective craniotomy. Materials and Methods: Sixty American Society of Anaesthesiologist (ASA) grade-I and II patients were randomly assigned to three groups of 20 patients each. Group-I received dexamethasone during surgery for the first time. Group-II received dexamethasone in addition to receiving it pre-operatively, whereas Group-III (control group) patients were administered normal saline as placebo. Baseline blood glucose (BG) was measured in all the three groups before induction of anaesthesia and thereafter after every hour for 4 h and then two-hourly. Besides intra- and intergroup comparison of BG, peak BG concentration was also recorded for each patient. Statistical analysis was carried out with analysis of variance (ANOVA) and Student's t-test and value of P < 0.05 was considered statistically significant. Results: Baseline BG reading were higher and statistically significant in Group-II as compared with Group-I and Group-III (P < 0.05). However, peak BG levels were significantly higher in Group-I than in Group-II and III (P < 0.05). Similarly, the magnitude of change in peak BG was significantly higher in Group-I as compared to Group-II and III (P < 0.05). Conclusion: Peri-operative administration of dexamethasone during neurosurgical procedures can cause significant increase in BG concentration especially in patients who receive dexamethasone intra-operatively only. PMID:27057213

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 (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) 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

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.

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

Results of intravenous steroid injection on reduction of postoperative edema in rhinoplasty.

PubMed

Alajmi, Monther Ali; Al-Abdulhadi, Khalid A; Al-Noumas, Hamoud Saud; Kavitha, Gopalan

2009-12-01

To determine the efficacy of intravenous dexamethasone in reducing postrhinoplasty edema. A prospective, randomized clinical trial with placebo control. Department of Otorhinolaryngology, Al-Sabah and Zain Hospital, Kuwait. Eighty-four patients (male = 28; female = 56) aged between 20 and 40 years, undergoing open rhinoplasty with hump removal and bilateral lateral osteotomies were enrolled in this study. Patients were randomized to receive two doses of 10 mg of dexamethasone intravenously or placebo, first dose during surgery and second dose 12 hours after surgery. Patients were evaluated postoperatively at 24 hours, days 2, 5, 7 and 10 for periorbital edema. 10 mg of dexamethasone given intravenously during rhinoplasty and a second dose 12 hours after surgery, reduced postoperative periorbital edema significantly. This study showed a statistically significant benefit of dexamethasone over placebo in reducing periorbital edema after rhinoplasty. No complications were attributed to the administration of dexamethasone.

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.

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.

Short-term application of dexamethasone on stem cells derived from human gingiva reduces the expression of RUNX2 and β-catenin.

PubMed

Kim, Bo-Bae; Kim, Minji; Park, Yun-Hee; Ko, Youngkyung; Park, Jun-Beom

2017-06-01

Objective Next-generation sequencing was performed to evaluate the effects of short-term application of dexamethasone on human gingiva-derived mesenchymal stem cells. Methods Human gingiva-derived stem cells were treated with a final concentration of 10 -7  M dexamethasone and the same concentration of vehicle control. This was followed by mRNA sequencing and data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and western blot analysis of RUNX2 and β-catenin. Results In total, 26,364 mRNAs were differentially expressed. Comparison of the results of dexamethasone versus control at 2 hours revealed that 7 mRNAs were upregulated and 25 mRNAs were downregulated. The application of dexamethasone reduced the expression of RUNX2 and β-catenin in human gingiva-derived mesenchymal stem cells. Conclusion The effects of dexamethasone on stem cells were evaluated with mRNA sequencing, and validation of the expression was performed with qualitative real-time polymerase chain reaction and western blot analysis. The results of this study can provide new insights into the role of mRNA sequencing in maxillofacial areas.

The role of dexamethasone in decreasing early recurrence of acute intussusception in children: A retrospective study.

PubMed

Efrati, Yigal; Klin, Baruch; Kozer, Eran; Abu-Kishk, Ibrahim

2017-07-01

Early recurrent intussusception (RI) is a concern after a successful pneumatic reduction. Steroids have been suggested as a treatment that decreases early RI. The purpose of this study was to examine the role of dexamethasone in decreasing early RI. A retrospective review of 174 pediatric patients that underwent successful pneumatic reduction was conducted. Two groups were identified: group 1 that received intravenous dexamethasone (0.5mg/kg/dose) on diagnosis or immediately after the reduction maneuver, and group 2 that were not given dexamethasone. There were 113 boys and 61 girls ranging in age from 2 to 36months. There were no statistical differences between the groups except for younger age in the dexamethasone group (P=0.03). There was no significant difference (p=0.08) in the rate of early RI between the non-steroid group (5.4%, 4/74) and the steroid group 14% (14/100). Mean admission length was 30h. The majority of RIs occurred in the first 8h of admission. We found that premedication of children with idiopathic intussusception with dexamethasone did not decrease early RI. Level III retrospective comparative study. Copyright © 2016 Elsevier Inc. All rights reserved.

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 and Insulin Alone or in Combination on Energy and Protein Metabolism Indicators and Milk Production in Dairy Cows in Early Lactation – A Randomized Controlled Trial

PubMed Central

Sami, Mehrdad; Mohri, Mehrdad; Seifi, Hesam A.

2015-01-01

Objectives This study investigated the effects of dexamethasone and insulin, when administered at 3rd or 10th day of lactation on energy and protein metabolism in dairy cows. Materials and Methods Two hundred Holstein cows were enrolled in a randomized controlled clinical trial. The cows were randomly assigned to receive 1 of 4 treatments at 3 or 10 days in milk: control group, 10-mL i.m. injection of sterile water, group insulin, s.c. injection of 100 units of insulin, group dexamethasone, i.m. injection of 20 mg of dexamethasone, group insulin plus dexamethasone, i.m. injection of 20 mg of dexamethasone and 100 units of insulin. The cows randomly assigned to receive the treatments on 3 or 10 days of lactation. Serum samples obtained at the time of enrollment, time of treatment and at 2, 4, 7 and 14 days after intervention. The sera were analyzed for β-hydroxybutyrate (BHBA), nonesterified fatty acids (NEFA), glucose, cholesterol, albumin, urea, and aspartate amino transferase (AST). Data were analyzed using a repeated measures mixed model that accounted for the effects of parity, body condition score, dystocia, retained placenta, metritis and the random effect of cow. Results There was no significant interaction of group of treatment and time of intervention (day 3 or 10 post-partum) on serum components. Cows that received insulin or dexamethasone alone or in combination, had lower BHBA 2 days after treatment compared with control cows, whereas concentrations of NEFA, were unaffected suggesting that glucocorticoids lipolytic effects do not appear to be important in healthy cows. AST activities significantly reduced in cows that received dexamethasone with or without insulin at 2 and 4 days after treatment. Albumin and urea concentrations 2 days after treatment were higher for cows that received dexamethasone only or dexamethasone plus insulin compared with control and Ins received cows. There were no treatment effects on test-day milk production, milk fat and protein percentages. Conclusions The results suggested that administration of glucocorticoids in early lactation resulted in short-term improvement of metabolism in postpartum dairy cows in biochemical terms. PMID:26422371

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 significant differences were found when comparing the effect of dexamethasone in men and women. In addition, dexamethasone had no statistically significant effect on the incidence of permanent cranial nerve injuries. Finally, no adverse effect related to the administration of dexamethasone was observed. Perioperative administration of dexamethasone is effective in minimizing the incidence of temporary cranial nerve injuries during CEA.

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

To evaluate the toxicokinetics and tolerability (local ocular and general toxicity) of the anti-inflammatory agent, dexamethasone phosphate (a prodrug of dexamethasone) delivered to the eye in rabbits by transscleral iontophoresis. Female rabbits (n=6/group) received dexamethasone phosphate (40 mg/mL ophthalmic solution, EGP-437) transsclerally to the right eye (OD) using the Eyegate(®) II ocular iontophoresis delivery system once biweekly for 24 consecutive weeks at current doses of 10, 14, and 20 mA-min and current levels up to, and including -4 mA for 3.5-5 min. The study included 2 control groups (n=6/group): (1) a noniontophoresis control [an ocular applicator-loaded citrate buffer (placebo) without current] and (2) an iontophoresis control (a citrate buffer plus cathode iontophoresis at 20 mA-min, -4 mA for 5 min). Recoverability was evaluated 4 weeks following the last dose in 2 animals per group. The left eye (OS) was untreated and served as an internal control for each animal. Ocular and general safety of dexamethasone phosphate and dexamethasone were assessed. Other evaluations included toxicokinetics, ophthalmic examinations, intraocular pressure (IOP) measurements, electroretinographs, clinical observations, body weight, hematology and serum chemistry, gross necropsy, organ weight, and microscopic histopathology. The biweekly transscleral iontophoresis with either the citrate buffer or dexamethasone phosphate at cathodic doses up to, and including 20 mA-min and currents up to, and including -4 mA for 24 weeks was well-tolerated. Transient signs of conjunctival hyperemia and chemosis, mild corneal opacity, and fluorescein staining of the cornea were noted and attributed to expected ocular reactions to the temporary placement of the ocular applicator and application of iontophoresis. There were no dexamethasone phosphate-, dexamethasone-, or iontophoresis-related effects on IOP, electroretinography, or histopathology. Reductions in body weight gain, 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.

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.

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.

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

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.

[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.

Comparison of Effectiveness of Betamethasone gel Applied to the Tracheal Tube and IV Dexamethasone on Postoperative Sore Throat: A Randomized Controlled Trial

PubMed Central

Tabari, Masoomeh; Soltani, Ghasem; Zirak, Nahid; Alipour, Mohammad; Khazaeni, Kamran

2013-01-01

Introduction: Postoperative sore throat is a common complaint in patients with endotracheal intubation and has potentially dangerous complications. This randomized controlled trial study investigated the incidence of postoperative sore throat after general anesthesia when betamethasone gel is applied to a tracheal tube compared with when IV dexamethasone is prescribed. Materials and Methods: Two hundred and twenty five American Society of Anesthesiologist (ASA)-class I and II patients undergoing elective abdominal surgery with tracheal intubation were randomly divided into three groups: betamethasone gel, intravenous (IV) dexamethasone, and control groups. In the post-anesthesia care unit, a blinded anesthesiologist interviewed all patients regarding postoperative sore throat at 1,6, and 24 hours after surgery. Results: The incidence of sore throat was significantly lower in the betamethasone gel group compared with the IV dexamethasone and control groups, 1, 6, and 24 hours after surgery. In the first day after surgery 10.7% of the betamethasone group had sore throat whereas 26.7% of the IV dexamethasone group and 30.7% of the control group had sore throat. Bucking before extubation was observed in 14(18.4%), 8(10.4%), and 9(12.2%) patients, in the IV dexamethasone, betamethasone gel, and control group, respectively. Conclusion: We concluded that wide spread application of betamethasone gel over tracheal tubes effectively mitigates postoperative sore throat, compared with IV dexamethasone application. PMID:24303443

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.

Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.

PubMed

Gomes, Rachel L R; Viana, Rodrigo Galvão; Melo, Luiz Alberto S; Cruz, Alessandro Carvalho; Suenaga, Eunice Mayumi; Kenyon, Kenneth R; Campos, Mauro

2017-03-01

To compare aqueous humor concentrations of topically applied moxifloxacin 0.5% ophthalmic solution alone or in combination with dexamethasone 0.1% and to correlate these concentrations with the minimum inhibitory concentrations (MICs) for common endophthalmitis-causing organisms. Sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% alone or moxifloxacin 0.5% combined with dexamethasone. For both groups, 1 drop of the test solution was instilled 4 times daily 1 day preoperatively and 1 drop 1 h preoperatively. An aqueous humor sample obtained immediately before paracentesis was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin concentration. The mean concentrations of moxifloxacin were 986.6 ng/mL in the moxifloxacin with dexamethasone group and 741.3 ng/mL in the moxifloxacin group (P = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (P = 0.06). Aqueous humor moxifloxacin concentrations were higher when topically administrated in combination with dexamethasone compared to the moxifloxacin alone. However, this difference was not statistically significant. Nevertheless, the MICs of the most common pathogens associated with endophthalmitis were exceeded in both study groups.

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 effective for reducing postoperative pain. Especially, an epidural dexamethasone dose of 10 mg was more effective than a lower dose in patients undergoing gastrectomy which was associated with moderate to severe postoperative pain.

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 results in higher MDI scores. Such increases in allergic diseases may be related to increased IL-5 and IL-10 levels.

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.

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 patients who received panobinostat, bortezomib, and dexamethasone versus 19·5 months (14·1-32·5) in 74 who received placebo (HR 1·01, 95% CI 0·68-1·50). The overall survival benefit with panobinostat over placebo with bortezomib and dexamethasone was modest. However, optimisation of the regimen could potentially prolong treatment duration and improve patients' outcomes, although further trials will be required to confirm this. Novartis Pharmaceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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.

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

Fetal endocrine therapy for congenital adrenal hyperplasia should not be done.

PubMed

Miller, Walter L

2015-06-01

Prenatal treatment of congenital adrenal hyperplasia by administering dexamethasone to a woman presumed to be carrying an at-risk fetus remains a controversial experimental treatment. Review of data from animal experimentation and human trials indicates that dexamethasone cannot be considered safe for the fetus. In animals, prenatal dexamethasone decreases birth weight, affects renal, pancreatic beta cell and brain development, increases anxiety and predisposes to adult hypertension and hyperglycemia. In human studies, prenatal dexamethasone is associated with orofacial clefts, decreased birth weight, poorer verbal working memory, and poorer self-perception of scholastic and social competence. Numerous medical societies have cautioned that prenatal treatment of adrenal hyperplasia with dexamethasone is not appropriate for routine clinical practice and should only be done in Institutional Review Board approved, prospective clinical research settings with written informed consent. The data indicate that this treatment is inconsistent with the classic medical ethical maxim to 'first do no harm'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria.

PubMed

Yahi, Dauda; Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly ( p < 0.05) decreased progesterone concentrations and caused abortion in Yankasa sheep but had no significant ( p > 0.05) effect on estrogen, while progesterone receptors (PR) were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep.

Influence of Dexamethasone on Some Reproductive Hormones and Uterine Progesterone Receptor Localization in Pregnant Yankasa Sheep in Semiarid Zones of Nigeria

PubMed Central

Ojo, Nicholas Adetayo; Mshelia, Gideon Dauda

2017-01-01

Dexamethasone is widely used in both veterinary and human medical practices. However, it seems to cause some deleterious effects on pregnancy probably by causing changes in the reproductive hormone levels and their corresponding receptor concentrations. This study investigated the effects of dexamethasone on these parameters. Twenty healthy adult Yankasa sheep comprising 18 ewes and 2 rams were used for this study. Pregnancies were achieved by natural mating after estrus synchronization. Dexamethasone was administered at 0.25 mg/kg body weight on days 1, 3, and 5 during first trimester; days 51, 53, and 55 during second trimester; and days 101, 103, and 105 during the third trimester. Blood samples were collected biweekly for hormonal assay. Uterine biopsies were harvested through caesarean section for immunohistochemical analysis. Results showed that dexamethasone significantly (p < 0.05) decreased progesterone concentrations and caused abortion in Yankasa sheep but had no significant (p > 0.05) effect on estrogen, while progesterone receptors (PR) were upregulated. The abortion could probably be due to decreased progesterone concentrations as a consequence of the adverse effects on placenta. The PR upregulation may be a compensatory mechanism to increase progesterone sensitivity. It was concluded that dexamethasone should not be used in advanced pregnancy in Yankasa sheep. PMID:29181440

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

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

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.

Effects of insulin, dexamethasone and cytokines on {alpha}{sub 1}-acid glycoprotein gene expression in primary cultures of normal rat hepatocytes

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

Barraud, B.; Balavoine, S.; Feldmann, G.

1996-04-01

While the effects of insulin, dexamethasone and cytokines on {alpha}{sub 1}-acid glycoprotein gene expression have been investigated in various hepatoma cell lines, the individual and combined effects of these components on the expression of this gene have been rarely studied in cultured normal rat hepatocytes. In this cell model, we have shown that mRNA levels of {alpha}{sub 1}-acid glycoprotein were not decreased at least during the first 24 h of culture under basal conditions. During these short-term cultures, the expression of {alpha}{sub 1}-acid glycoprotein in normal hepatocytes showed a high degree of responsiveness to dexamethasone alone (20-fold increase) and tomore » dexamethasone associated with various cytokines (interleukin-1{beta}, interleukin-6 and tumor necrosis factor {alpha}) with a 40 to 100-fold increase depending on the cytokine. Insulin alone did not modify {alpha}{sub 1}-acid glycoprotein mRNA; however, this hormone exerted a positive effect (about 50% increase) in the presence of dexamethasone or dexamethasone with cytokines. These results indicate that the regulation of {alpha}{sub 1}-acid glycoprotein in cultured normal rat hepatocytes presents major differences when compared to reported observations in rat hepatoma cell lines. 49 refs., 2 figs., 2 tabs.« less

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

PubMed Central

Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

2014-01-01

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

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.

Ginseng ameliorates chronic histopathologic changes in a murine model of asthma.

PubMed

Babayigit, Arzu; Olmez, Duygu; Karaman, Ozkan; Bagriyanik, H Alper; Yilmaz, Osman; Kivcak, Bijen; Erbil, Guven; Uzuner, Nevin

2008-01-01

Currently, asthma therapies are effective in reducing inflammation but airway remodeling is poorly responsive to these agents. New therapeutic options that have fewer side effects and reverse chronic changes in the lungs are essential. This study aimed to determine the efficacy of oral administration of ginseng on lung histopathology in a murine model of chronic asthma. BALB/c mice were divided into four groups: control, placebo, ginseng, and dexamethasone. All mice except those in the control group were sensitized and challenged with ovalbumin. Then, mice in the ginseng group were given 2 gr/kg per day of ginseng and mice in the dexamethasone group received 1 mg/kg per day of dexamethasone via orogastic gavage once daily for 1 week. Lung histopathology was evaluated by using light and electron microscopy in all groups. All of the chronic changes of airways in the ginseng group were significantly ameliorated when compared with the placebo group. When compared with the dexamethasone group, the ginseng group had significantly lower numbers of mast cell count. Thicknesses of basement membrane, epithelium, and subepithelial smooth muscle were not statistically different between the ginseng and dexamethasone groups. Goblet cell numbers were much more reduced in the dexamethasone group. Ginseng is effective in resolving the established chronic histopathological changes of the lungs in the murine model of asthma.

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.

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.

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

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.

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

A randomized clinical trial to compare the efficacy of submucosal aprotinin injection and intravenous dexamethasone in reducing pain and swelling after third molar surgery: a prospective study.

PubMed

Arakeri, Gururaj; Rai, Kirthi Kumar; Shivakumar, H R; Jayade, Bhushan

2013-03-01

The purpose of this study was to compare two different groups of drugs, aprotinin and dexamethasone for its efficacy in reducing post operative swelling and pain after third molar surgery. Fifty consecutive patients requiring surgical removal of single mandibular third molar (class II position B) under local anesthesia were randomly divided into two groups, each group consisting of 25 patients. One group was administered 8 mg dexamethasone through intravenous route pre-operatively. The other group received 1 ml of Aprotinin through submucosal route in operating area after the onset of local anesthesia. Swelling was assessed by measuring facial contours at baseline and at 1st, 3rd and 7th post-operative days. Pain was measured on the 1st, 3rd and 7th post-operative days using visual analog scale. Based on statistical analysis (paired t test and Wilcoxon's signed ranking test), the results showed statistically significant difference in post operative swelling and pain on 3rd postoperative day in dexamethasone group as compared to aprotinin group. The results of present study showed a similar reduction in the severity of pain and swelling at the aprotinin and dexamethasone sites on 1st and 7th postoperative day. It was also noticed that the aprotinin promoted a greater reduction of swelling and pain on 3rd postoperative day. It appeared that, benefits of aprotinin against the risks of dexamethasone and its efficacy in controlling pain and swelling after third molar surgery makes aprotinin to be a valuable alternative to dexamethasone.

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

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 Dexamethasone on Characteristics of Supraclavicular Nerve Block with Bupivacaine and Ropivacaine: A Prospective, Double-blind, Randomized Control Trial.

PubMed

Bindal, Deeksha; Narang, Neeraj; Mahindra, Rekha; Gupta, Himanshu; Kubre, Jyotsna; Saxena, Anudeep

2018-01-01

Dexamethasone as an adjuvant to bupivacaine and ropivacaine for supraclavicular brachial plexus (SCBP) block prolongs motor and sensory blockade. However, comparison of effect of dexamethasone (8 mg) when added to these two local anesthetics has not been well studied. This study was conducted to compare analgesic efficacy of dexamethasone as adjuvant to bupivacaine and ropivacaine in SCBP block. Nerve stimulator-guided SCBP block was given to 120 patients, randomly assigned to one of four groups: ( n = 30 in each group) Group B, BD, R, and RD received 30 ml (0.5%) bupivacaine + 2 ml saline, 30 ml (0.5%) bupivacaine + dexamethasone 8 mg, 30 ml (0.5%) ropivacaine + 2 ml saline, and 30 ml (0.5%) ropivacaine + dexamethasone 8 mg, respectively. Time for request of the first rescue analgesic, 24-h analgesic consumption, and different block characteristics were assessed. Student's t -test, Chi-square test, ANOVA were used for statistical analysis. Dexamethasone significantly prolonged time for request of the first rescue analgesic of both ropivacaine (1211.83 ± 32.86 vs. 283.17 ± 7.71 min){ p R, RD < 0.001} and bupivacaine (1205.17 ± 34.32 vs. 364.67 ± 16.50 min) {p B, BD < 0.001}. 24-h requirement for rescue analgesics was more in Groups B and R when compared to Groups BD and RD. The increase in duration of analgesia was more when Groups R and RD (928.66 min) were compared than Groups B and BD (840.5 min). Similar results were seen with onset times and duration of sensory and motor block. The addition of dexamethasone to bupivacaine and ropivacaine in SCBP block prolonged time for first rescue analgesia and reduced the requirement of rescue analgesics with faster onset and prolonged duration of sensory and motor block, with the effect being stronger with ropivacaine.

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 anti-inflammatory agents, such as dexamethasone, may be effective in normalizing the rewarding effects of cocaine following CCI-TBI.

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.

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.

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.

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

Observational study on the palatability and tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK.

PubMed

Aljebab, Fahad; Alanazi, Mofadhi; Choonara, Imti; Conroy, Sharon

2018-01-01

Short-course oral corticosteroids are routinely used to treat acute asthma and croup. We evaluated their tolerability and palatability in Saudi Arabian (SA) and UK children. Prospective observational/interview study (3 months in each country). Palatability was evaluated using a 5-point facial Hedonicscale and tolerability by direct questioning of patient/parents. In SA, of 122 patients (2-10 years) recruited, 52 received prednisolone base tablets, 37 prednisolone sodium phosphate syrup and 33 received dexamethasone elixir. In the UK, of 133 patients (2-16 years), 38 received prednisolone base tablets (mainly crushed and dispersed), 42 prednisolone sodium phosphate soluble tablets and 53 received dexamethasone sodium phosphate oral solution.In both countries, dexamethasone had the highest palatability scores (SA mean: 1.97; UK mean: 3) and prednisolone base tablets had the lowest (SA mean: 1.12; UK mean: 1.39). Palatability scores improved for all formulations of prednisolone with each subsequent daily dose.In SA, prednisolone base tablets were associated with more nausea (24vs7 patients) and vomiting (5vs0 patients) than sodium phosphate syrup (p=0.008 and p=0.073, respectively). In the UK, vomiting occurred more frequently with prednisolone base (8 patients) than sodium phosphate soluble tablets (2 patients) (p=0.041).In both centres, dexamethasone was associated with less side effects. Vomiting (1vs0 patients), nausea (7vs3 patients) and abdominal pain (10vs8 patients) occurred more with dexamethasone sodium phosphate solution than dexamethasone elixir. Dexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated least palatable and were least well tolerated. Palatability scores improved with each dose taken. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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 (p<0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.

PubMed

Chen, Shi; Li, Ran; Lu, Lin; Duan, Lian; Zhang, Xuebin; Tong, Anli; Pan, Hui; Zhu, Huijuan; Lu, Zhaolin

2018-01-01

To evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Retrospective study. The patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016. Serum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST). After LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity. The ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.

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.

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 Wiley & Sons Ltd.

[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.

Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

PubMed

Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

2009-01-01

Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to <50 nM (1.8 microg/dL) after dexamethasone administration was chosen as the cut-off point for normal suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

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 ...

Regulation of bone sialoprotein mRNA by steroid hormones

PubMed Central

1989-01-01

In this report we demonstrate an increase in the steady-state level of bone sialoprotein (BSP) mRNA in rat calvaria and a rat osteosarcoma cell line (ROS 17/2.8) after treatment with the synthetic glucocorticoid, dexamethasone. In contrast, 1.25-dihydroxyvitamin D3 reduced the amount of BSP mRNA in calvaria and inhibited the dexamethasone induction in ROS 17/2.8 cells. The increase in BSP mRNA is most likely due to an increase in the transcriptional rate. The stability of mRNA was unchanged after dexamethasone treatment with a half-life of approximately 5 h. Nuclear transcription experiments with nuclei isolated from ROS 17/2.8 cells showed an increased BSP mRNA synthesis in cells treated with dexamethasone. PMID:2592421

Regulation of synthesis and activity of NAD(+)-dependent 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) by dexamethasone and phorbol ester in human erythroleukemia (HEL) cells

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

Xun, C.Q.; Ensor, C.M.; Tai, H.H.

1991-06-28

Dexamethasone stimulated 15-PGDH activity in HEL cells in a time and concentration dependent manner. Increase in 15-PGDH activity by dexamethasone was found to be accompanied by an increase in enzyme synthesis as revealed by Western blot and (35S)methionine labeling studies. In addition to dexamethasone, other anti-inflammatory steroids also increased 15-PGDH activity in the order of their glucocorticoid activity. Among sex steroids only progesterone increased significantly 15-PGDH activity. 12-0-Tetradecanoylphorbol-13-acetate (TPA) also induced the synthesis of 15-PGDH but inhibited the enzyme activity. It appears that TPA caused a time dependent inactivation of 15-PGDH by a protein kinase C mediated mechanism.

Optimal Dose of Perineural Dexamethasone to Prolong Analgesia After Brachial Plexus Blockade: A Systematic Review and Meta-analysis.

PubMed

Kirkham, Kyle Robert; Jacot-Guillarmod, Alain; Albrecht, Eric

2018-01-01

Perineural dexamethasone has gained popularity in regional anesthesia to prolong analgesia duration. However, uncertainty remains regarding the optimal perineural dose. Clarification of this characteristic is of significant importance as the administration of dexamethasone may lead to dose-dependent complications. The objective of this meta-analysis was to define the optimal perineural dexamethasone dose to prolong analgesia after brachial plexus blockade for adult patients undergoing upper limb surgery. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines and searched databases including MEDLINE, PubMed, and EMBASE until January 2017, without language restriction. Only trials comparing perineural dexamethasone and local anesthetics with local anesthetics alone for brachial plexus blocks were included in the present meta-analysis. The Cochrane Collaboration's Risk of Bias Tool was used to assess the methodological quality of each trial and meta-analyses were performed following a random effects model. The primary outcome was duration of analgesia for each type of local anesthetic (short-/intermediate-acting and long-acting local anesthetics). A meta-regression followed by a subgroup analysis were performed to assess the impact of different perineural dexamethasone doses on duration of analgesia; for the latter analysis, trials were grouped in low (1-4 mg) and moderate (5-10 mg) dexamethasone doses. Secondary outcomes included the rate of neurologic complication and resting pain scores and morphine consumption within the first 24 hours. Thirty-three controlled trials, including 2138 patients, were identified. The meta-regression revealed a ceiling effect with a perineural dexamethasone dose of 4 mg when combined with short-/intermediate-acting (8 trials; 366 participants) or long-acting local anesthetics (23 trials; 1869 participants). This finding was confirmed by subgroup analyses comparing low and moderate dexamethasone doses. With short-/intermediate-acting local anesthetics, the mean difference (95% confidence interval) of analgesia duration with low and moderate doses was 277 (234-322) minutes and 229 (161-297) minutes, respectively. With long-acting local anesthetics, the mean differences with low and moderate doses were 505 (342-669) minutes and 509 (443-575) minutes. Perineural dexamethasone did not increase the rate of neurologic complications (risk ratio [95% confidence interval], 1.40 [0.54-3.63]). The Grades of Recommendation, Assessment, Development, and Evaluation quality of evidence for the primary and secondary outcomes were very low, due mainly to limitations, inconsistency, indirectness, and publication bias. There is currently very low quality evidence that 4 mg of perineural dexamethasone represents a ceiling dose that prolongs analgesia duration by a mean period of 6 and 8 hours when combined with short-/intermediate- or long-acting local anesthetics, respectively. Additional data are needed to explore the threshold for this effect, particularly with doses below 4 mg. The risk of neurologic complications is probably not increased (very low evidence).

The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial.

PubMed

Kok, Lotte; Hillegers, Manon H; Veldhuijzen, Dieuwke S; Cornelisse, Sandra; Nierich, Arno P; van der Maaten, Joost M; Rosseel, Peter M; Hofland, Jan; Sep, Milou S; Dieleman, Jan M; Vinkers, Christiaan H; Peelen, Linda M; Joëls, Marian; van Dijk, Diederik

2016-03-01

Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission. Follow-up study of a randomized clinical trial. Five Dutch heart centers. Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.

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 affects adipose tissue retention by maintaining healthy tissue formation and vascularization. Dex DW MS provide an improved model to former Dex SW MS, resulting in notably longer release time and, consequently, larger volumes of adipose retained in vivo. The use of microspheres, specifically double-walled, as vehicles for controlled drug delivery of adipogenic factors therefore present a clinically relevant model of adipose retention that has the potential to greatly improve soft tissue repair. PMID:29051810

Dexamethasone does not diminish sugammadex reversal of neuromuscular block - clinical study in surgical patients undergoing general anesthesia.

PubMed

Rezonja, Katja; Mars, Tomaz; Jerin, Ales; Kozelj, Gordana; Pozar-Lukanovic, Neva; Sostaric, Maja

2016-10-21

Sugammadex reverses neuromuscular block (NMB) through binding aminosteroid neuromuscular blocking agents. Although sugammadex appears to be highly selective, it can interact with other drugs, like corticosteroids. A prospective single-blinded randomized clinical trial was designed to explore the significance of interactions between dexamethasone and sugammadex. Sixty-five patients who were anesthetized for elective abdominal or urological surgery were included. NMB was assessed using train-of-four stimulation (TOF), with rocuronium used to maintain the desired NMB depth. NMB reversal at the end of anaesthesia was achieved using sugammadex. According to their received antiemetics, the patients were randomized to either the granisetron or dexamethasone group. Blood samples were taken before and after NMB reversal, for plasma dexamethasone and rocuronium determination. Primary endpoint was time from sugammadex administration to NMB reversal. Secondary endpoints included the ratios of the dexamethasone and rocuronium concentrations after NMB reversal versus before sugammadex administration. There were no differences for time to NMB reversal between the control (mean 121 ± 61 s) and the dexamethasone group (mean 125 ± 57 s; P = 0.760). Time to NMB reversal to a TOF ratio ≥0.9 was significantly longer in patients with lower TOF prior to sugammadex administration (Beta = -0.268; P = 0.038). The ratio between the rocuronium concentrations after NMB reversal versus before sugammadex administration was significantly affected by sugammadex dose (Beta = -0.375; P = 0.004), as was rocuronium dose per hour of operation (Beta = -0.366; p = 0.007), while it was not affected by NMB depth before administration of sugammadex (Beta = -0.089; p = 0.483) and dexamethasone (Beta = -0.186; p = 0.131). There was significant drop in plasma dexamethasone after sugammadex administration and NMB reversal (p < 0.001). Administration of dexamethasone to anesthetized patients did not delay NMB reversal by sugammadex. The trial was retrospectively registered with The Australian New Zealand Clinical Trials Registry (ANZCTR) on February 28th 2012 (enrollment of the first patient on February 2nd 2012) and was given a trial ID number ACTRN12612000245897 and universal trial number U1111-1128-5104.

Paracrine and autocrine signals promoting full chondrogenic differentiation of a mesoblastic cell line.

PubMed

Locker, Morgane; Kellermann, Odile; Boucquey, Marie; Khun, Huot; Huerre, Michel; Poliard, Anne

2004-01-01

The pluripotent mesoblastic C1 cell line was used under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to drive chondrogenesis. Sequential addition of two systemic hormones, dexamethasone and triiodothyronine, permits full chondrogenic differentiation. The cell intrinsic activation of the BMP signaling pathway and Sox9 expression occurring on mesoblastic condensation is insufficient for recruitment of the progenitors. Dexamethasone-dependent Sox9 upregulation is essential for chondrogenesis. Differentiation of lineage stem cells relies on cell autonomous regulations modulated by external signals. We used the pluripotent mesoblastic C1 cell line under serum-free culture conditions to investigate how paracrine and autocrine signals cooperate to induce differentiation of a precursor clone along the chondrogenic lineage. C1 cells, cultured as aggregates, were induced toward chondrogenesis by addition of 10(-7) M dexamethasone in serum-free medium. After 30 days, dexamethasone was replaced by 10 nM triiodothyronine to promote final hypertrophic conversion. Mature and hypertrophic phenotypes were characterized by immunocytochemistry using specific antibodies against types II and X collagens, respectively. Type II collagen, bone morphogenetic proteins (BMPs), BMP receptors, Smads, and Sox9 expression were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blot, and/or Western blot analysis. Once C1 cells have formed nodules, sequential addition of two systemic hormones is sufficient to promote full chondrogenic differentiation. In response to dexamethasone, nearly 100% of the C1 precursors engage in chondrogenesis and convert within 30 days into mature chondrocytes, which triggers a typical cartilage matrix. On day 25, a switch in type II procollagen mRNA splicing acted as a limiting step in the acquisition of the mature chondrocyte phenotype. On day 30, substitution of dexamethasone with triiodothyronine triggers the final differentiation into hypertrophic chondrocytes within a further 15 days. The chondrogenic process is supported by intrinsic expression of Sox9 and BMP family genes. Similarly to the in vivo situation, activation of Sox9 expression and the BMP signaling pathway occurred on mesoblastic condensation. After induction, BMP-activated Smad nuclear translocation persisted throughout the process until the onset of hypertrophy. After dexamethasone addition, Sox9 expression was upregulated. Dexamethasone withdrawal reversed the increase in Sox9 expression and stopped differentiation. Thus, Sox9 seems to be a downstream mediator of dexamethasone action.

The Effect of Ketamine and Dexamethasone in Combination with Lidocaine on the Onset and Duration of Axillary Block in Hand and Forearm Soft Tissue Surgery.

PubMed

Zaman, Behrooz; Hojjati Ashrafi, Siavash; Seyed Siamdoust, Seyedalireza; Hassani, Valiollah; Mohamad Taheri, Siavash; Noorizad, Samad

2017-10-01

Using peripheral nerve block compared to general anesthesia has gained more popularity due to reduced postoperative pain, less need for post-surgery analgesic drugs, reduced incidence of nausea, shortness of PACU time, and increased patient satisfaction. The aim of this study was to compare the effect of ketamine and dexamethasone as additives to lidocaine on duration and onset of axillary block action. In this clinical trial, all patients who referred to Hazrat-e-Fatemeh hospital for forearm and hand soft tissue surgery with informed consent were randomly divided into three groups in order to examine the onset and duration of axillary block: lidocaine + ketamine, lidocaine + dexamethasone in axillary block, and lidocaine alone (control). Then, the onset and duration of sensory and motor blocks were measured and recorded every three minutes and after the surgery. Quantitative and qualitative variables were analyzed using ANOVA or Kruskal-Wallis test and Chi-square or Fisher exact test in SPSS v.22. Duration of sensory and motor block axillary was significantly higher in lidocaine + dexamethasone group than in lidocaine + ketamine group (P < 0.05); it was also significantly higher in lidocaine + ketamine group compared to lidocaine group (P < 0.05). However, there was no significant difference in the onset of sensory and motor block axillary between the three groups (P > 0.05). According to the results of our study, we can conclude that adding dexamethasone or ketamine to lidocaine could improve duration of sensory and motor axillary block in patients undergoing forearm and hand soft tissue surgery. However, dexamethasone had the highest effect on duration of block axillary. We proved that dexamethasone or ketamine added to lidocaine had no effect on the onset of block axillary.

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

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

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.

Dexamethasone inhibits high glucose-, TNF-alpha-, and IL-1beta-induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes.

PubMed

Nehmé, Alissar; Edelman, Jeffrey

2008-05-01

To characterize the effects of dexamethasone in human retinal pericytes (HRMPs), monocytes (THP-1), and retinal endothelial cells (HRECs) treated with high glucose, TNF-alpha, or IL-1beta. HRMP and HREC phenotypes were verified by growth factor stimulation of intracellular calcium-ion mobilization. Glucocorticoid receptor phosphorylation was assessed with an anti-phospho-Ser(211) glucocorticoid receptor antibody. Secretion of 89 inflammatory and angiogenic proteins were compared in cells incubated with (1) normal (5 mM) or high (25 mM) D-glucose and (2) control medium, TNF-alpha (10 ng/mL), or IL-1beta (10 ng/mL), with or without dexamethasone (1 nM to 1 microM). The proteins were compared by using multianalyte profile testing. HRMPs and HRECs expressed functional PDGFB-R and VEGFR-2, respectively. Dexamethasone induction of glucocorticoid receptor phosphorylation was dose-dependent in all cell types. High glucose increased secretion of inflammatory mediators in HRMPs, but not in HRECs. Dexamethasone dose dependently inhibited secretion of these mediators in HRMPs. For all cells, TNF-alpha and IL-1beta induced a fivefold or more increase in inflammatory and angiogenic mediators; HRMPs secreted the greatest number and level of mediators. Dexamethasone dose dependently inhibited the secretion of multiple proteins from HRMPs and THP-1 cells, but not from HRECs (IC(50) 2 nM to 1 microM). High glucose, TNF-alpha, and IL-1beta induced an inflammatory phenotype in HRMPs, characterized by hypersecretion of inflammatory and angiogenic mediators. Dexamethasone at various potencies blocked hypersecretion of several proteins. Pericytes may be a key therapeutic target in retinal inflammatory diseases, including diabetic retinopathy. Inhibition of pathologic mediators may depend on delivering high levels ( approximately 1 microM) of glucocorticoid to the retina.

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.

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.

Effects of dexamethasone and insulin on the synthesis of triacylglycerols and phosphatidylcholine and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by monolayer cultures of rat hepatocytes.

PubMed Central

Mangiapane, E H; Brindley, D N

1986-01-01

Rat hepatocytes in monolayer culture were preincubated for 19 h with 1 microM-dexamethasone, and the incubation was continued for a further 23 h with [14C]oleate, [3H]glycerol and 1 microM-dexamethasone. Dexamethasone increased the secretion of triacylglycerol into the medium in particles that had the properties of very-low-density lipoproteins. The increased secretion was matched by a decrease in the triacylglycerol and phosphatidylcholine that remained in the hepatocytes. Preincubating the hepatocytes for the total 42 h period with 36 nM-insulin decreased the amount of triacylglycerol in the medium and in the cells after the final incubation for 23 h with radioactive substrates. However, insulin had no significant effect on the triacylglycerol content of the cell and medium when it was present only in the final 23 h incubation. Insulin antagonized the effects of dexamethasone in stimulating the secretion of triacylglycerol from the hepatocytes, especially when it was present throughout the total 42 h period. The labelling of lysophosphatidylcholine in the medium when hepatocytes were incubated with [14C]oleate and [3H]glycerol was greater than that of phosphatidylcholine. The appearance of this lipid in the medium, unlike that of triacylglycerol and phosphatidylcholine, was not stimulated by dexamethasone, or inhibited by colchicine. However, the presence of lysophosphatidylcholine in the medium was decreased when the hepatocytes were incubated with both dexamethasone and insulin. These findings are discussed in relation to the control of the synthesis of glycerolipids and the secretion of very-low-density lipoproteins and lysophosphatidylcholine by the liver, particularly in relation to the interactions of glucocorticoids and insulin. PMID:3513755

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

Differential regulation of glyceroneogenesis by glucocorticoids in epididymal and retroperitoneal white adipose tissue from rats.

PubMed

Ferreira, Graziella Nascimento; Rossi-Valentim, Rafael; Buzelle, Samyra Lopes; Paula-Gomes, Sílvia; Zanon, Neusa Maria; Garófalo, Maria Antonieta Rissato; Frasson, Danúbia; Navegantes, Luiz Carlos Carvalho; Chaves, Valéria Ernestânia; Kettelhut, Isis do Carmo

2017-08-01

Investigate the glycerol-3-phosphate generation pathways in epididymal (EPI) and retroperitoneal (RETRO) adipose tissues from dexamethasone-treated rats. Rats were treated with dexamethasone for 7 days. Glycerol-3-phosphate generation pathways via glycolysis, glyceroneogenesis and direct phosphorylation of glycerol were evaluated, respectively, by 2-deoxyglucose uptake, phosphoenolpyruvate carboxykinase (PEPCK-C) activity and pyruvate incorporation into triacylglycerol (TAG)-glycerol, and glycerokinase activity and glycerol incorporation into TAG-glycerol. Dexamethasone treatment markedly decreased the body weight, but increased the weight and lipid content of EPI and RETRO and plasma insulin, glucose, non-esterified fatty acid and TAG levels. EPI and RETRO from dexamethasone-treated rats showed increased rates of de novo fatty acid synthesis (80 and 100%) and basal lipolysis (20%). In EPI, dexamethasone decreased the 2-deoxyglucose uptake (50%), as well as glyceroneogenesis, evidenced by a decrease of PEPCK-C activity (39%) and TAG-glycerol synthesis from pyruvate (66%), but increased the glycerokinase activity (50%) and TAG-glycerol synthesis from glycerol (72%) in this tissue. In spite of a similar reduction in 2-deoxyglucose uptake in RETRO, dexamethasone treatment increased glyceroneogenesis, evidenced by PEPCK activity (96%), and TAG-glycerol synthesis from pyruvate (110%), accompanied by a decrease in glycerokinase activity (50%) and TAG-glycerol synthesis from glycerol (50%). Dexamethasone effects on RETRO were accompanied by a decrease in p-Akt content and by lower insulin effects on the rates of glycerol release in the presence of isoproterenol and on the rates of glucose uptake in isolated adipocytes. Our data demonstrated differential regulation of glyceroneogenesis and direct phosphorylation of glycerol by glucocorticoids in EPI and RETRO from rats.

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

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.

Analgesic effect of a single-dose of perineural dexamethasone on ultrasound-guided femoral nerve block after total knee replacement.

PubMed

Morales-Muñoz, C; Sánchez-Ramos, J L; Díaz-Lara, M D; González-González, J; Gallego-Alonso, I; Hernández-Del-Castillo, M S

2017-01-01

Total knee replacement is usually a very painful procedure. A single-dose of femoral nerve block has been shown to provide similar analgesia to an epidural, with fewer side effects, but limited in time. To compare the analgesia provided by dexamethasone used at perineural level in the femoral nerve block after total knee replacement with the one used at intravenous level, and with that of a control group. A prospective, randomised, double-blind controlled trial was conducted on 81 patients randomly assigned to one of three groups: 1)IV dexamethasone (8mg); 2)perineural dexamethasone (8mg), and 3)placebo. All patients received 20ml of ropivacaine 0.5% for femoral nerve block. The primary outcome was the duration of the sensory-analgesic block of the femoral nerve block. The secondary outcomes included pain intensity measurements, patient satisfaction, and incidence of complications. Randomisation was effective. Analgesia duration was significantly higher (P<.0001) in the perineural dexamethasone group (mean 1152.2min, 95% confidence interval [95% CI]: 756.9-1547.6) in comparison with the control group (mean 186min, 95%CI: 81.2-292) and dexamethasone IV group (mean 159.4min, 95%CI: 109.8-209). Postoperative pain, complications and side effects were also lower in this group. Dexamethasone prolongs sensory block of single dose of femoral nerve block using ropivacaine. It also provides better analgesia and patient satisfaction, with fewer side effects. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

Comparison of Effect of Oral Premedication with Ibuprofen or Dexamethasone on Anesthetic Efficacy of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.

PubMed

Bidar, Maryam; Mortazavi, Soheil; Forghani, Maryam; Akhlaghi, Saeed

2017-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of preoperative oral administration of ibuprofen or dexamethasone on the success rate of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. Seventy-eight patients with irreversible pulpitis were randomly divided into 3 groups (26 per group) and given one of the following at 1 hr prior to performing local anesthesia: a placebo; 400 mg ibuprofen; or 4 mg dexamethasone. Each patient recorded their pain level on a visual analog scale before taking the medication or placebo, at 15 min after completion of IANB, and during treatment if pain occurred. The success of the anesthesia was defined as no or mild pain at any stage during the endodontic procedure. The success rate of the IANB was 38.5, 73.1, and 80.8% with the placebo, ibuprofen, and dexamethasone, respectively. Both ibuprofen and dexamethasone were significantly more effective than the placebo. No significant difference was observed, however, between the two experimental medications in terms of effectiveness. The results of the present study suggest that premedication with ibuprofen or dexamethasone increases the success rate of an IANB in patients with symptomatic irreversible pulpitis in the mandibular molars.

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

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

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.

Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone

PubMed Central

Graversen, Jonas H; Svendsen, Pia; Dagnæs-Hansen, Frederik; Dal, Jakob; Anton, Gabriele; Etzerodt, Anders; Petersen, Mikkel D; Christensen, Peter A; Møller, Holger J; Moestrup, Søren K

2012-01-01

Synthetic glucocorticoids are potent anti-inflammatory drugs but serious side effects such as bone mobilization, muscle mass loss, immunosuppression, and metabolic alterations make glucocorticoid therapy a difficult balance. The therapeutic anti-inflammatory effect of glucocorticoids relies largely on the suppressed release of tumor-necrosis factor-α and other cytokines by macrophages at the sites of inflammation. We have now developed a new biodegradable anti-CD163 antibody-drug conjugate that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages. The conjugate, that in average contains four dexamethasone molecules per antibody, exhibits retained high functional affinity for CD163. In vitro studies in rat macrophages and in vivo studies of Lewis rats showed a strong anti-inflammatory effect of the conjugate measured as reduced lipopolysaccharide-induced secretion of tumor-necrosis factor-α. The in vivo potency of conjugated dexamethasone was about 50-fold that of nonconjugated dexamethasone. In contrast to a strong systemic effect of nonconjugated dexamethasone, the equipotent dose of the conjugate had no such effect, measured as thymus lymphocytes apoptosis, body weight loss, and suppression of endogenous cortisol levels. In conclusion, the study shows antibody-drug conjugates as a future approach in anti-inflammatory macrophage-directed therapy. Furthermore, the data demonstrate CD163 as an excellent macrophage target for anti-inflammatory drug delivery. PMID:22643864

Multilayer poly(3,4-ethylenedioxythiophene)-dexamethasone and poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate-carbon nanotubes coatings on glassy carbon microelectrode arrays for controlled drug release.

PubMed

Castagnola, Elisa; Carli, Stefano; Vomero, Maria; Scarpellini, Alice; Prato, Mirko; Goshi, Noah; Fadiga, Luciano; Kassegne, Sam; Ricci, Davide

2017-07-13

The authors present an electrochemically controlled, drug releasing neural interface composed of a glassy carbon (GC) microelectrode array combined with a multilayer poly(3,4-ethylenedioxythiophene) (PEDOT) coating. The system integrates the high stability of the GC electrode substrate, ideal for electrical stimulation and electrochemical detection of neurotransmitters, with the on-demand drug-releasing capabilities of PEDOT-dexamethasone compound, through a mechanically stable interlayer of PEDOT-polystyrene sulfonate (PSS)-carbon nanotubes (CNT). The authors demonstrate that such interlayer improves both the mechanical and electrochemical properties of the neural interface, when compared with a single PEDOT-dexamethasone coating. Moreover, the multilayer coating is able to withstand 10 × 10 6 biphasic pulses and delamination test with negligible change to the impedance spectra. Cross-section scanning electron microscopy images support that the PEDOT-PSS-CNT interlayer significantly improves the adhesion between the GC substrate and PEDOT-dexamethasone coating, showing no discontinuities between the three well-interconnected layers. Furthermore, the multilayer coating has superior electrochemical properties, in terms of impedance and charge transfer capabilities as compared to a single layer of either PEDOT coating or the GC substrate alone. The authors verified the drug releasing capabilities of the PEDOT-dexamethasone layer when integrated into the multilayer interface through repeated stimulation protocols in vitro, and found a pharmacologically relevant release of dexamethasone.

Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line.

PubMed Central

Mukaida, N; Gussella, G L; Kasahara, T; Ko, Y; Zachariae, C O; Kawai, T; Matsushima, K

1992-01-01

In order to analyse the effects of glucocorticoids on interleukin-8 (IL-8) production more precisely, we examined the effects of dexamethasone on IL-8 production at the molecular level in a human fibrosarcoma cell line, 8387, which IL-1 induces to express IL-8 messenger RNA (mRNA) and to secrete IL-8. Over a wide dose range, dexamethasone inhibited IL-8 production induced by IL-1 alpha stimulation. Northern blotting analysis showed that dexamethasone also inhibited the IL-8 mRNA accumulation in a similar dose-related manner. Nuclear run-off assay revealed that dexamethasone decreased the transcription of the IL-8 gene and the degree of inhibition of transcription correlated well with the inhibition of IL-8 production, suggesting that the action of glucocorticoids is mainly at the transcriptional level. Furthermore, transfection with chloramphenicol acetyl transferase (CAT) expression vectors inserted with the 5'-deleted IL-8 gene demonstrated that the 5'-flanking region which contains the glucocorticoid response element (GRE) was mainly involved in the dexamethasone-induced repression of the IL-8 gene. These data suggest that the inhibition of the IL-8 gene transcription by glucocorticoids occurs through the interaction of the glucocorticoid receptor complex with GRE in the 5'-flanking region of the IL-8 gene. Images Figure 1 Figure 2 Figure 3 PMID:1592440

Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

PubMed

Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

2016-03-01

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

Facile preparation of magnetic molecularly imprinted polymers for the selective extraction and determination of dexamethasone in skincare cosmetics using HPLC.

PubMed

Du, Wei; Zhang, Bilin; Guo, Pengqi; Chen, Guoning; Chang, Chun; Fu, Qiang

2018-03-15

Dexamethasone-imprinted polymers were fabricated by reversible addition-fragmentation chain transfer polymerization on the surface of magnetic nanoparticles under mild polymerization conditions, which exhibited a narrow polydispersity and high selectivity for dexamethasone extraction. The dexamethasone-imprinted polymers were characterized by scanning electron microscopy, transmission electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive spectrometry, and vibrating sample magnetometry. The adsorption performance was evaluated by static adsorption, kinetic adsorption and selectivity tests. The results confirmed the successful construction of an imprinted polymer layer on the surface of the magnetic nanoparticles, which benefits the characteristics of high adsorption capacity, fast mass transfer, specific molecular recognition, and simple magnetic separation. Combined with high-performance liquid chromatography, molecularly imprinted polymers as magnetic extraction sorbents were used for the rapid and selective extraction and determination of dexamethasone in skincare cosmetic samples, with the accuracies of the spiked samples ranging from 93.8 to 97.6%. The relative standard deviations were less than 2.7%. The limit of detection and limit of quantification were 0.05 and 0.20 μg/mL, respectively. The developed method was simple, fast and highly selective and could be a promising method for dexamethasone monitoring in cosmetic products. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

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.

Budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme upon high-altitude exposure.

PubMed

Li, Hui-Jie; Zheng, Cheng-Rong; Chen, Guo-Zhu; Qin, Jun; Zhang, Ji-Hang; Yu, Jie; Zhang, En-Hao; Huang, Lan

2016-01-01

Inhaled budesonide is a novel approach to prevent acute mountain sickness (AMS). However, its mechanism is not completely understood. We aimed to investigate the effects of budesonide and dexamethasone on renin-angiotensin-aldosterone system in AMS prevention. Data were obtained from a randomised controlled trial including 138 participants. The participants were randomly assigned to receive budesonide, dexamethasone or placebo as prophylaxis before they travelled to 3450 m altitude from 400 m by car. Their plasma concentrations of renin, angiotensin-converting enzyme (ACE) and aldosterone were measured at both altitudes. All parameters were comparable among the three groups at 400 m. After high-altitude exposure of 3450, renin in all groups increased significantly; the ACE, aldosterone concentrations, as well as the aldosterone/renin ratio, rose markedly in the dexamethasone and placebo groups but not in the budesonide group. Moreover, the aldosterone/renin ratio correlated closely with ACE concentration. Upon acute high-altitude exposure, budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme. © The Author(s) 2016.

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

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.

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.

Budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme upon high-altitude exposure

PubMed Central

Li, Hui-Jie; Zheng, Cheng-Rong; Chen, Guo-Zhu; Qin, Jun; Zhang, Ji-Hang; Yu, Jie; Zhang, En-Hao; Huang, Lan

2016-01-01

Introduction: Inhaled budesonide is a novel approach to prevent acute mountain sickness (AMS). However, its mechanism is not completely understood. We aimed to investigate the effects of budesonide and dexamethasone on renin–angiotensin–aldosterone system in AMS prevention. Materials and methods: Data were obtained from a randomised controlled trial including 138 participants. The participants were randomly assigned to receive budesonide, dexamethasone or placebo as prophylaxis before they travelled to 3450 m altitude from 400 m by car. Their plasma concentrations of renin, angiotensin-converting enzyme (ACE) and aldosterone were measured at both altitudes. Results: All parameters were comparable among the three groups at 400 m. After high-altitude exposure of 3450, renin in all groups increased significantly; the ACE, aldosterone concentrations, as well as the aldosterone/renin ratio, rose markedly in the dexamethasone and placebo groups but not in the budesonide group. Moreover, the aldosterone/renin ratio correlated closely with ACE concentration. Conclusions: Upon acute high-altitude exposure, budesonide, but not dexamethasone, blunted the response of aldosterone to renin elevation by suppressing angiotensin converting enzyme. PMID:27317302

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 ...

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.

Ciclesonide Oral Inhalation

MedlinePlus

... you were taking an oral steroid such as dexamethasone, methylprednisolone (Medrol), or prednisone (Rayos), your doctor may ... the following: ketoconazole (Nizoral); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); and medications for ...

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

[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) receptor.

Glucocorticoid Repression of Inflammatory Gene Expression Shows Differential Responsiveness by Transactivation- and Transrepression-Dependent Mechanisms

PubMed Central

King, Elizabeth M.; Chivers, Joanna E.; Rider, Christopher F.; Minnich, Anne; Giembycz, Mark A.; Newton, Robert

2013-01-01

Binding of glucocorticoid to the glucocorticoid receptor (GR/NR3C1) may repress inflammatory gene transcription via direct, protein synthesis-independent processes (transrepression), or by activating transcription (transactivation) of multiple anti-inflammatory/repressive factors. Using human pulmonary A549 cells, we showed that 34 out of 39 IL-1β-inducible mRNAs were repressed to varying degrees by the synthetic glucocorticoid, dexamethasone. Whilst these repressive effects were GR-dependent, they did not correlate with either the magnitude of IL-1β-inducibility or the NF-κB-dependence of the inflammatory genes. This suggests that induction by IL-1β and repression by dexamethasone are independent events. Roles for transactivation were investigated using the protein synthesis inhibitor, cycloheximide. However, cycloheximide reduced the IL-1β-dependent expression of 13 mRNAs, which, along with the 5 not showing repression by dexamethasone, were not analysed further. Of the remaining 21 inflammatory mRNAs, cycloheximide significantly attenuated the dexamethasone-dependent repression of 11 mRNAs that also showed a marked time-dependence to their repression. Such effects are consistent with repression occurring via the de novo synthesis of a new product, or products, which subsequently cause repression (i.e., repression via a transactivation mechanism). Conversely, 10 mRNAs showed completely cycloheximide-independent, and time-independent, repression by dexamethasone. This is consistent with direct GR transrepression. Importantly, the inflammatory mRNAs showing attenuated repression by dexamethasone in the presence of cycloheximide also showed a significantly greater extent of repression and a higher potency to dexamethasone compared to those mRNAs showing cycloheximide-independent repression. This suggests that the repression of inflammatory mRNAs by GR transactivation-dependent mechanisms accounts for the greatest levels of repression and the most potent repression by dexamethasone. In conclusion, our data indicate roles for both transrepression and transactivation in the glucocorticoid-dependent repression of inflammatory gene expression. However, transactivation appears to account for the more potent and efficacious mechanism of repression by glucocorticoids on these IL-1β-induced genes. PMID:23349769

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 + 2 levels. Conclusions Dexamethasone inhibits endotoxin-induced coagulopathy in lungs. This trial is the first to provide insights into the effects of glucocorticoids on pulmonary coagulation in response to endotoxin. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

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 disabled children then it should be used consistently in women at risk of preterm birth and would be of great importance to women at risk of preterm birth, their children, health services and communities. ACTRN12608000631303.

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 effective system to evaluate and optimize therapeutics. ► Show that doxycycline and dexamethasone reduce NM-caused ocular injuries ► Demonstrate that silibinin effectively reverses NM-caused ocular injury endpoints ► Suggest optimization of identified agents against ocular injuries by vesicants.« less

Pomalidomide for Multiple Myeloma

Cancer.gov

A summary of results from a phase III trial that compared the combination of pomalidomide (Pomalyst®) and low-dose dexamethasone versus high-dose dexamethasone alone in patients with multiple myeloma that has progressed despite other treatments.

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

Periapical Microsurgery: The Effects of Locally Injected Dexamethasone on Pain, Swelling, Bruising, and Wound Healing.

PubMed

Kan, Elena; Coelho, Marcelo Santos; Reside, Jonathan; Card, Steven J; Tawil, Peter Z

2016-11-01

The purpose of this prospective, double-blind, randomized clinical trial was to evaluate the postoperative healing of endodontic periapical microsurgery after local administration of dexamethasone. Sixty patients were divided into 2 groups. The dexamethasone group received a single local submucosal injection of 4 mg dexamethasone, and the placebo group received a submucosal injection of saline solution at the conclusion of standardized periapical microsurgery. Acetaminophen and hydrocodone/acetaminophen were prescribed for pain relief. A Likert-like 6-point scale was used for self-evaluation of pain, bruising, swelling, and wound healing at 24, 48, 72, 96 hours and at 1 week. The number of tablets taken was registered. Data were analyzed using the chi-square and Fisher exact tests at a significance level of P < .05. No improvements in pain, bruising, and wound healing were registered at any time interval. No difference was found in the number of tablets taken for pain relief. Subjects who received the dexamethasone injection reported less swelling 24 hours after periapical microsurgery (P < .05) but showed no significant benefit for the longer follow-up periods. This study shows that a 4-mg dose of dexamethasone administered through a local submucosal injection after periapical microsurgery has minimal impact on pain, bruising, and apparent wound healing at any time over a 7-day interval, and the impact on swelling seems limited. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Placental hormones, nutrition, and fetal development.

PubMed

Mulay, S; Browne, C A; Varma, D R; Solomon, S

1980-02-01

Fetal growth retardation due to maternal malnutrition is widespread especially in the Third World. Little is known about the mechanisms that regulate the growth of the fetus and placenta during protein malnutrition. It is known that the placental size and levels of circulating placental hormones such as human chorionic gonadotrophins (hCG), human placental lactogen (hPL), and estrogens are affected by the nutritional status of the mother. There is suggestive evidence that during malnutrition, hPL may increase lipolysis and exert a glucose sparing effect in the mother, thereby promoting glucose availability to the fetus. We have studied the influence of dietary protein deficiency on the binding of dexamethasone to the specific cytosol receptors in adult and fetal tissues. A low protein diet in adult male rats is associated with a decrease in dexamethasone binding to liver cytosol receptors. On the other hand, protein deprivation in pregnant female rats leads to an increase in dexamethasone binding to liver cytosol receptors of both the mother and fetus. However, the influences of maternal protein deprivation on dexamethasone receptors in the fetal liver and lungs are not similar. At 21 days gestation the binding of dexamethasone to fetal lung receptors of protein-deficient mothers is lower than that in the controls. These differences at a critical time in the fetal lung development indicate that a fall in receptors for dexamethasone may lead to impaired phospholipid synthesis in fetuses of protein-deficient mothers and point to the importance of nutritional factors in the biochemistry of fetal development.

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.

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.

Effects of Dexamethasone in the Treatment of Recurrent Chronic Subdural Hematoma.

PubMed

Zhang, Yu; Chen, Shiping; Xiao, Yangchun; Tang, Wenhua

2017-09-01

Recurrent chronic subdural hematoma (CSDH) is not rare. Some studies have demonstrated the role of dexamethasone in the medical management of chronic subdural hematoma. However, no systematic study in the treatment of recurrent CSDH has been published. The aim of our study is to evaluate the efficacy and safety of dexamethasone in patients with recurrent CSDH. We retrospectively reviewed medical records of consecutive patients from July 2010 to September 2014. A total of 27 patients with symptomatic recurrent CSDH were included in the analysis. Follow-up for each patient consisted of computed tomography or magnetic resonance imaging every 28 days from admission to the resolution of hematoma. Data were collected on hematoma volume, complications, and outcome. Among the 27 patients, 3 patients with recurrent CSDH were only treated by burr hole surgery. Of the other 24 patients who primarily underwent dexamethasone treatment, 17 (70.8%) patients were treated successfully with medical treatment, whereas 7 patients required reoperation. Complications were noted in 3 (12.5%) patients (1 hyperglycemia, 1 urinary tract infection, and 1 pneumonia). There was 1 mortality (4.2%) for massive brain infarction. Twenty-one of the 24 patients (87.5%) recovered to their previous functional levels. There was no statistical significance in Fisher text between surgery and dexamethasone regarding success, complication, and functional recovery rate. Patients with recurrent CSDH can be treated successfully and safely with the nonsurgical medical treatment of dexamethasone. By use of this method, reoperation may be avoided. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235

PubMed Central

Hall, Connor P.; Reynolds, C. Patrick; Kang, Min H.

2015-01-01

Purpose The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in ALL. Experimental Design The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The underlying mechanism of BEZ235 and dexamethasone was evaluated using immunoblotting, TaqMan RT-PCR, siRNA, immunohistochemistry and immunoprecipitation. Results Inhibition of the PI3K/AKT/mTOR pathway with the dual PI3K/mTOR inhibitor BEZ235 enhanced dexamethasone-induced anti-leukemic activity in in vitro (continuous cell lines and primary ALL cultures) and systemic in vivo models of T-ALL (including a patient-derived xenograft). Through inhibition of AKT1, BEZ235 was able to alleviate AKT1-mediated suppression of dexamethasone-induced apoptotic pathways leading to increased expression of the pro-apoptotic BCL-2 protein BIM. Downregulation of MCL-1 by BEZ235 further contributed to the modulation of dexamethasone resistance by increasing the amount of BIM available to induce apoptosis, especially in PTEN-null T-ALL where inhibition of AKT only partially overcame AKT-induced BIM suppression. Conclusion Our data support the further investigation of agents targeting the PI3K/mTOR pathway to modulate glucocorticoid resistance in T-ALL. PMID:26080839

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.

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

Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.

PubMed Central

Piedimonte, G; McDonald, D M; Nadel, J A

1991-01-01

Glucocorticoids inhibit plasma extravasation induced in the rat tracheal mucosa by substance P and other tachykinins released from sensory nerves. This study was performed to determine whether this antiinflammatory effect of glucocorticoids is mediated by the tachykinin-degrading enzymes neutral endopeptidase (NEP) and kininase II (angiotensin converting enzyme, ACE). In addition, we studied the effect of dexamethasone on a nonpeptide inflammatory mediator, platelet-activating factor (PAF), which is not degraded by NEP or ACE. Adult male pathogen-free F344 rats were treated for 2 d with dexamethasone (0.5 mg/kg per d i.p.), or with the vehicle used to dissolve the steroid. The magnitude of plasma extravasation produced by an intravenous injection of substance P (5 micrograms/kg) or PAF (10 micrograms/kg) was then assessed by using Monastral blue pigment as an intravascular tracer. The role of NEP and ACE activities in the changes produced by dexamethasone was investigated by examining the effect of the selective inhibitors of these enzymes, phosphoramidon and captopril. Dexamethasone reduced the substance P-induced extravasation by 57% but did not affect the PAF-induced extravasation. The suppressive effect of dexamethasone on substance P-induced extravasation was completely reversed by simultaneously inhibiting NEP and ACE activities, but the inhibition of these enzymes had no effect on PAF-induced extravasation, regardless of whether the rats were pretreated with dexamethasone or not. These results suggest that NEP and ACE mediate a selective inhibitory effect of glucocorticoids on neurogenic plasma extravasation. PMID:1711545

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.

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.

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.

Regulation of ODC activity in the thymus and liver of rats by adrenal hormones.

PubMed

Zahner, S L; Prahlad, K V; Mitchell, J L

1986-01-01

The activity of L-ornithine decarboxylase (EC 4.1.1.17, ODC) has become a useful indicator of hormone responsiveness. Various regimens of dexamethasone, aldosterone and epinephrine, alone or in combination, were administered to adrenalectomized rats either in acute or chronic doses. In addition, adrenalectomized rats, which were chronically treated with aldosterone and epinephrine, were given a single injection of 50 micrograms dexamethasone and sacrificed at various time intervals after hormone treatment. Hepatic and thymic ODC activity was measured. The expected dexamethasone effect, an increase in hepatic and a decrease in thymic ODC, was observed. This study also revealed that aldosterone induced similar responses in these tissues. Epinephrine had the opposite effect since chronic administration of dexamethasone or aldosterone with epinephrine resulted in control levels of ODC. Furthermore, when aldosterone and epinephrine were chronically administered to adrenalectomized rats, to study the acute effects of dexamethasone on rat thymus and liver, the time course of the response in each tissue was found to be distinct. The influence of the adrenal gland on rat thymus and liver is not restricted only to glucocorticoids, but may also involve other hormones which it secretes.

The effect of RU 486 and related compounds on cultured macrophage differentiation and function.

PubMed

Roberts, C P; Murphy, A A; Santanam, N; Parthasarathy, S

1996-08-01

Our purpose was to examine RU 486 and related compounds on macrophage scavenger receptors and cellular adhesion. THP-1 cells were activated with phorbol myristate acetate and treated with dexamethasone, levonorgestrel, and RU 486 alone or in combination. Scavenger receptor activity was determined by counting adhered cells. In addition, fluorescently labeled acetyl low density lipoprotein uptake was determined. Both dexamethasone and RU 486 significantly decreased activated macrophages (81% and 26% of control). Levonorgestrel stimulated adherent cells in activated monocytes (130% of control). RU 486 and dexamethasone were antagonistic when combined (p < 0.001). In contrast, dexamethasone could not overcome the stimulatory effect of levonorgestrel (p < 0.001). Fluorescent studies yielded similar results. RU 486 is a known antiglucocorticoid with novel antioxidant properties. Levonorgestrel has antiglucocorticoid but no antioxidant activity. Glucocorticoids decrease scavenger receptors and antioxidants regulate inflammatory cytokines. RU 486 antagonized the inhibitory effect of dexamethasone on scavenger receptors, whereas levonorgestrel was stimulatory. It is therapeutically important to up-regulate scavenger receptor activity by antiglucocorticoids in the peritoneal cavity of women with endometriosis. However, because these mechanisms also induce inflammatory cytokines, a balance of antioxidants and antiglucocorticoids may prove beneficial.

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

Synergistic Cytotoxicity of Lenalidomide and Dexamethasone in Mantle Cell Lymphoma via Cereblon-dependent Targeting of the IL-6/STAT3/PI3K Axis.

PubMed

Ma, Jiexian; Wu, Kefei; Bai, Weiya; Cui, Xiaoxian; Chen, Yan; Xie, Youhua; Xie, Yanhui

2017-06-01

At our center, relapsed mantle cell lymphoma (MCL) can be treated with maintenance therapy composed of consecutive low-dose lenalidomide and short-term, high-dose dexamethasone (LD regimen), which achieves good responses (longer overall survival and progression-free survival) and low toxicity. Cereblon is probably targeted by both lenalidomide and dexamethasone, which leads to synergistic cytotoxicity in MCL by inhibiting the interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3), phosphatidylinositol 3-kinase (PI3K)/AKT and AKT2/Forkhead box O3 (FOXO3A)/BCL2-like 11 (BIM) pathways. The two drugs synergistically inhibit the same pathways, but through different sites. Cereblon was found expressed in most of the MCL tissues (91.3% positivity). Moreover, cereblon expression is positively correlated with LD regimen sensitivity: long-term lenalidomide exposure downregulates cereblon and induces multi-drug resistance against lenalidomide, dexamethasone, cytarabine, cisplatin, and methotrexate in vitro. Removal of lenalidomide resensitizes lenalidomide-resistant MCL cells to lenalidomide and dexamethasone. Our work suggests that rotating the LD regimen with other regimens would improve MCL maintenance therapy. Copyright © 2017. Published by Elsevier B.V.

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

Quercetin induces cell apoptosis of myeloma and displays a synergistic effect with dexamethasone in vitro and in vivo xenograft models

PubMed Central

Zhang, Enfan; Zi, Fuming; Chen, Jing; Chen, Qingxiao; Lin, Xuanru; Yang, Li; Li, Yi; Wu, Wenjun; Yang, Yang; He, Jingsong; Cai, Zhen

2016-01-01

Quercetin, a kind of dietary flavonoid, has shown its anticancer activity in many kinds of cancers including hematological malignancies (acute myelogenous leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, and MM) in vitro and in vivo. However, its effects on MM need further investigation. In this study, MM cell lines were treated with quercetin alone or in combination with dexamethasone. In order to observe the effects in vivo, a xenograft model of human myeloma was established. Quercetin inhibited proliferation of MM cells (RPMI8226, ARP-1, and MM.1R) by inducing cell cycle arrest in the G2/M phase and apoptosis. Western blot showed that quercetin downregulated c-myc expression and upregulated p21 expression. Quercetin also activated caspase-3, caspase-9, and poly(ADP-ribose)polymerase 1. Caspase inhibitors partially blocked apoptosis induced by quercetin. Furthermore, quercetin combined with dexamethasone significantly increased MM cell apoptosis. In vivo xenograft models, quercetin obviously inhibited tumor growth. Caspase-3 was activated to a greater extent when quercetin was combined with dexamethasone. In conclusion, quercetin alone or in combination with dexamethasone may be an effective therapy for MM. PMID:27329589

An Effect of Dexamethasone on Adenosine 3′,5′ -Monophosphate Content and Adenosine 3′,5′ -Monophosphate Phosphodiesterase Activity of Cultured Hepatoma Cells

PubMed Central

Manganiello, Vincent; Vaughan, Martha

1972-01-01

The effect of dexamethasone on adenosine 3′,5′-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated. Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cAMP (2-5 μm and 50 μm). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or more with 1 μm dexamethasone. Acid phosphatase activity in the same cells was not decreased. α-Methyl testosterone, 1 μm, was without effect on phosphodiesterase activity. Incubation for 10 min with epinephrine plus theophylline increased the cAMP content of the HTC cells 3- to 6-fold. In cells incubated for 72 hr with dexamethasone, the basal concentration of cAMP was slightly increased and the increment produced by epinephrine plus theophylline was markedly increased. We believe that in many cells the so-called permissive effects of steroid hormones on cAMP mediated processes may be due to an effect of these hormones on cAMP phosphodiesterase activity similar to that observed in HTC cells incubated with dexamethasone. PMID:4341439

Antenatal dexamethasone before asphyxia promotes cystic neural injury in preterm fetal sheep by inducing hyperglycemia.

PubMed

Lear, Christopher A; Davidson, Joanne O; Mackay, Georgia R; Drury, Paul P; Galinsky, Robert; Quaedackers, Josine S; Gunn, Alistair J; Bennet, Laura

2018-04-01

Antenatal glucocorticoid therapy significantly improves the short-term systemic outcomes of prematurely born infants, but there is limited information available on their impact on neurodevelopmental outcomes in at-risk preterm babies exposed to perinatal asphyxia. Preterm fetal sheep (0.7 of gestation) were exposed to a maternal injection of 12 mg dexamethasone or saline followed 4 h later by asphyxia induced by 25 min of complete umbilical cord occlusion. In a subsequent study, fetuses received titrated glucose infusions followed 4 h later by asphyxia to examine the hypothesis that hyperglycemia mediated the effects of dexamethasone. Post-mortems were performed 7 days after asphyxia for cerebral histology. Maternal dexamethasone before asphyxia was associated with severe, cystic brain injury compared to diffuse injury after saline injection, with increased numbers of seizures, worse recovery of brain activity, and increased arterial glucose levels before, during, and after asphyxia. Glucose infusions before asphyxia replicated these adverse outcomes, with a strong correlation between greater increases in glucose before asphyxia and greater neural injury. These findings strongly suggest that dexamethasone exposure and hyperglycemia can transform diffuse injury into cystic brain injury after asphyxia in preterm fetal sheep.

Effect of dexamethasone on gliosis, ischemia, and dopamine extraction during microdialysis sampling in brain tissue.

PubMed

Jaquins-Gerstl, Andrea; Shu, Zhan; Zhang, Jing; Liu, Yansheng; Weber, Stephen G; Michael, Adrian C

2011-10-15

Microdialysis sampling of the brain is an analytical technique with numerous applications in neuroscience and the neurointensive care of brain-injured human patients. Even so, implanting microdialysis probes into brain tissue causes a penetration injury that triggers gliosis (the activation and proliferation of glial cells) and ischemia (the interruption of blood flow). Thus, the probe samples injured tissue. Mitigating the effects of the penetration injury might refine the technique. The synthetic glucocorticoid dexamethasone is a potent anti-inflammatory and immunosuppressant substance. We performed microdialysis in the rat brain for 5 days, with and without dexamethasone in the perfusion fluid (10 μM for the first 24 h and 2 μM thereafter). On the first and fourth day of the perfusion, we performed dopamine no-net-flux measurements. On the fifth day, we sectioned and stained the brain tissue and examined it by fluorescence microscopy. Although dexamethasone profoundly inhibited gliosis and ischemia around the probe tracks it had only modest effects on dopamine no-net-flux results. These findings show that dexamethasone is highly effective at suppressing gliosis and ischemia but is limited in its neuroprotective activity. © 2011 American Chemical Society

Pathophysiology of Peptide Toxins of Microcystis aeruginosa and Amanita phalloides

DTIC Science & Technology

1986-06-30

minimal for dexamethasone . Thp chronic toxicity of repeated sublethal doses of toxin-LR has received limited study, but a definite lesion has been... 1 /12 1 /12 Dexamethasone 0.02 mg/gbw 5/5 4/5 5/5 4/5 Dexamethasone 0.20 mg/gbw 10/10 15/15 12/12 9/10 *Fractional mortality. 52 Table 15: Effect of...n For U’i. [IJ*•i •l .......................... 1 1 t !7 ... ... ’, D •-. .. .. a -+ .< # TABLE OF CONTENTS Page STATEMENT OF PROBLEM UNDER STUDY BACK

Maintenance of Glucose Homeostasis through Acetylation of the Metabolic Transcriptional Coactivator PGC1-alpha

DTIC Science & Technology

2009-02-01

media or incubated with Forskolin and dexamethasone for 4 hours. Finally, cells were incubated with insulin for 2h. 0.0 0.5 1.0 1.5 0.0 1.0 2.0 3.0 4.0...depletion decreases its own endogenous mRNA levels. We mimicked the fed/fasting response by using insulin (fed) and forskolin and dexamethasone (that...expression of GK or LPK (Fig. 3). As a control we show that under forskolin /dexamethasone treatment expression of both genes as strongly decreased as

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 development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood. PMID:27390302

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.

Postinduction Dexamethasone and Individualized Dosing of Escherichia Coli L-Asparaginase Each Improve Outcome of Children and Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a Randomized Study—Dana-Farber Cancer Institute ALL Consortium Protocol 00-01

PubMed Central

Vrooman, Lynda M.; Stevenson, Kristen E.; Supko, Jeffrey G.; O'Brien, Jane; Dahlberg, Suzanne E.; Asselin, Barbara L.; Athale, Uma H.; Clavell, Luis A.; Kelly, Kara M.; Kutok, Jeffery L.; Laverdière, Caroline; Lipshultz, Steven E.; Michon, Bruno; Schorin, Marshall; Relling, Mary V.; Cohen, Harvey J.; Neuberg, Donna S.; Sallan, Stephen E.; Silverman, Lewis B.

2013-01-01

Purpose We assessed the toxicity and efficacy of dexamethasone and a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL). Patients and Methods Patients achieving complete remission (CR) on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 were eligible for random assignment to 1) dexamethasone or prednisone, administered as 5-day pulses, every 3 weeks, and 2) weekly EC-Asnase, administered as a 25,000 IU/m2 fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m2, adjusted every 3 weeks based on nadir serum asparaginase activity (NSAA) determinations. Results Between 2000 and 2004, 492 evaluable patients (ages 1 to 18 years) enrolled; 473 patients (96%) achieved CR. Four hundred eight patients (86%) participated in the corticosteroid randomization and 384 patients (81%) in the EC-Asnase randomization. With 4.9 years of median follow-up, dexamethasone was associated with superior 5-year event-free survival (EFS; 90% v 81% for prednisone; P = .01) but higher rates of infection (P = .03) and, in older children, higher cumulative incidence of osteonecrosis (P = .02) and fracture (P = .06). ID EC-Asnase had superior 5-year EFS (90% v 82% for FD; P = .04), but did not reduce the frequency of asparaginase-related toxicity. Multivariable analysis identified both dexamethasone and ID EC-Asnase as independent predictors of favorable EFS. Conclusion There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method. Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL. PMID:23358966

The ocular endothelin system: a novel target for the treatment of endotoxin-induced uveitis with bosentan.

PubMed

Keles, Sadullah; Halici, Zekai; Atmaca, Hasan Tarik; Yayla, Muhammed; Yildirim, Kenan; Ekinci, Metin; Akpinar, Erol; Altuner, Durdu; Cakici, Ozgur; Bayraktutan, Zafer

2014-05-15

We compared the anti-inflammatory effects of bosentan and dexamethasone in endotoxin-induced uveitis (EIU). Endotoxin-induced uveitis was induced by subcutaneous injection of lipopolysaccharide (LPS, 200 μg) in Wistar rats. Rats were divided randomly into 10 groups (n = 6). Bosentan at doses of 50 and 100 mg/kg were administered orally 1 hour before and 12 hours after LPS injection, and dexamethasone was administered by intraperitoneally 30 minutes before and 30 minutes after LPS injection at a dose of 1 mg/kg. Data were collected at two time points for each control and treatment; animals were killed at either 3 or 24 hours after LPS injection. Histopathologic evaluation and aqueous humour measurements of TNF-α level were performed, and endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS), and endothelin receptor A and B (EDNRA and B) expression were analyzed. The group treated with 100 mg/kg bosentan at 24 hours displayed significantly milder uveitis and fewer inflammatory cells compared to LPS-injected animals, and there were similar findings in the dexamethasone-treated group at 24 hours. The TNF-α levels in the dexamethasone treatment group were lower than those in the LPS-induced uveitis control group (P < 0.05); however, there was no difference between the dexamethasone and bosentan treatment groups at 3 and 24 hours after LPS administration. Bosentan treatment at doses of 50 and 100 mg/kg significantly decreased iNOS expression compared to LPS-injected animals (P < 0.001). The ET-1 expression was suppressed significantly by bosentan and dexamethasone at 3 and 24 hours after LPS administration (P < 0.001). The EDNRA expression in the bosentan treatment groups was statistically significantly lower than that in the LPS-induced uveitis control group at 3 and 24 hours after LPS administration (P < 0.05). Bosentan reduces intraocular inflammation and has similar effects as dexamethasone in a rat model of EIU. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

PubMed

Fahlenkamp, Astrid V; Stoppe, Christian; Cremer, Jan; Biener, Ingeborg A; Peters, Dirk; Leuchter, Ricarda; Eisert, Albrecht; Apfel, Christian C; Rossaint, Rolf; Coburn, Mark

2016-01-01

Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis. 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up. Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups. In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea. EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial

PubMed Central

Fahlenkamp, Astrid V.; Stoppe, Christian; Cremer, Jan; Biener, Ingeborg A.; Peters, Dirk; Leuchter, Ricarda; Eisert, Albrecht; Apfel, Christian C.; Rossaint, Rolf; Coburn, Mark

2016-01-01

Objective Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis. Methods 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up. Results Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02–5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups. Conclusion In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea. Trial Registration EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663 PMID:27111335

Palonosetron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting during gemcitabine/cisplatin in urothelial cancer patients.

PubMed

Kitamura, Hiroshi; Takahashi, Atsushi; Hotta, Hiroshi; Kato, Ryuichi; Kunishima, Yasuharu; Takei, Fumiyasu; Horita, Hiroki; Masumori, Naoya

2015-10-01

To evaluate the appearance of chemotherapy-induced nausea and vomiting, and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-hydroxytryptamine 3-receptor antagonists and dexamethasone during gemcitabine and cisplatin chemotherapy in patients with advanced urothelial cancer. We carried out a multi-institutional study including 122 patients who received gemcitabine and cisplatin for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled chemotherapy-induced nausea and vomiting events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake. First-generation 5-hydroxytryptamine 3-receptor antagonists (ondansetron or granisetron) plus dexamethasone were used for 75 patients (cohort 1), and palonosetron with dexamethasone plus aprepitant for 47 patients (cohort 2). Patients in cohort 2 had significantly higher complete response (defined as no emetic episodes and no rescue medication use) rates than those in cohort 1 during the overall phase in the first cycle (85.7% vs 65.3%, P = 0.012), and all cycles (78.7% vs 50.7%, P = 0.0019) of gemcitabine and cisplatin. Patients in cohort 2 were more likely to achieve more favorable chemotherapy-induced nausea and vomiting control; that is, a lower grade of nausea, vomiting or anorexia, lower incidence of rescue therapy required, and shorter time to become chemotherapy-induced nausea- and vomiting-free than patients in cohort 1. The present results show that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in urothelial cancer patients treated with gemcitabine and cisplatin than first-generation 5-hydroxytryptamine 3-receptor antagonists plus dexamethasone. © 2015 The Japanese Urological Association.

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

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 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

[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.

The establishment of insulin resistance model in FL83B and L6 cell

NASA Astrophysics Data System (ADS)

Liu, Lanlan; Han, Jizhong; Li, Haoran; Liu, Mengmeng; Zeng, Bin

2017-10-01

The insulin resistance models of mouse liver epithelial and rat myoblasts cells were induced by three kinds of inducers: dexamethasone, high insulin and high glucose. The purpose is to select the optimal insulin resistance model, to provide a simple and reliable TR cell model for the study of the pathogenesis of TR and the improvement of TR drugs and functional foods. The MTT method is used for toxicity screening of three compounds, selecting security and suitable concentration. We performed a Glucose oxidase peroxidase (GOD-POD) method involving FL83B and L6 cell with dexamethasone, high insulin and high glucose-induced insulin resistance. Results suggested that FL83B cells with dexamethasone-induced (0.25uM) were established insulin resistance and L6 cells with high-glucose (30mM) and dexamethasone-induced (0.25uM) were established insulin resistance.

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.

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.

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.

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, lipocortin-12–26 (30 and 100 μg ml−1) inhibited/abolished PGE2 release by J774 cells stimulated with LPS (3 μg ml−1). These data suggest that, in inflammatory hyperalgesia, inhibition of the induction of cyclo-oxygenase 2 (COX-2), rather than phospholipase A2, by dexamethasone and lipocortin-12–26 accounts for the anti-hyperalgesic effects of these agents. The above data support the notion that induction of lipocortin by dexamethasone plays a major role in the inhibition by dexamethasone of inflammatory hyperalgesia evoked by carrageenin, bradykinin and the cytokines TNFα, IL-1β and IL-6, and provides additional evidence that the biological activity of lipocortin resides within the peptide lipocortin-12–26. Further, the data suggest that inhibition of lipocortin-12–26 of eicosanoid production by COX-2 also contributes to the anti-hyperalgesic effect of lipocortin-1. PMID:9222544

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.

The effects of hydroalcoholic extract of Allium elburzense Wendelbo bulb on dexamethasone-induced dyslipidemia, hyperglycemia, and oxidative stress in rats

PubMed Central

Safaeian, Leila; Zolfaghari, Behzad; Karimi, Sajad; Talebi, Ardeshir; Ghazvini, Mohammadreza Aghaye

2018-01-01

Recent evidences have suggested the beneficial cardiovascular effects of some plants belonging to the genus Allium. The present study is an attempt to investigate the effects of hydroalcoholic extract of Allium elburzense bulb on dexamethasone-induced dyslipidemia in rats. Total phenolic content of A. elburzense bulb hydroalcoholic extract was determined using Folin-Ciocalteu method. Thirty-six male Wistar albino rats in 6 groups were studied. Group 1 (dyslipidemic control) received dexamethasone (10 mg/kg/day, s.c.) for 7 days, groups 2-4 (treated) received dexamethasone and simultaneously treated orally with 100, 200, or 400 mg/kg of A. elburzense extract, group 5 (normal control) received a single daily injection of normal saline (1 mL/kg, s.c.) and the vehicle orally, and group 6 (reference) received dexamethasone and atorvastatin (40 mg/kg) orally. At the end of experiment, blood glucose, lipid profile, and malondialdehyde (MDA) levels were assessed in serum samples. Livers were processed for histopathological examination. Total phenolic content of A. elburzense extract was estimated to be 33.52 ± 1.3% mg gallic acid equivalent/g of the dried plant extract. The plant extract significantly reduced serum blood glucose, triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and MDA levels and increased the high density lipoprotein-cholesterol level and also improved liver steatosis compared to the dyslipidemic control group. These results suggest the hydroalcoholic extract of A. elburzense bulb has anti-dyslipidemic, anti-hyperglycemic, and antioxidant effects on rats receiving high doses of dexamethasone. PMID:29387108

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

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

PubMed

Shin, Yong Un; Hong, Eun Hee; Lim, Han Woong; Kang, Min Ho; Seong, Mincheol; Cho, Heeyoon

2017-10-03

To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.

PubMed

Stewart, E A; Saker, S; Amoaku, W M

2016-10-01

Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone combined with ketamine gargle for evaluation of post-operative sore throat and hoarseness: A randomized, placebo-controlled, double blind clinical trial

PubMed Central

Safavi, Mohammadreza; Honarmand, Azim; Fariborzifar, Arghavan; Attari, Mohammadali

2014-01-01

Background: Sore throat and hoarseness are the most frequent subjective complaints after tracheal intubation for general anesthesia. We conducted a prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intravenous (IV) dexamethasone plus ketamine gargle for reducing the incidence and severity of post-operative sore throat (POST) and hoarseness. Materials and Methods: 140 patients (aged 16-65 year) scheduled for elective surgery were enrolled. Patients were randomly allocated into four groups of 35 subjects each: Group K, gargled 40 mg ketamine in 30 ml saline; Group D, were infused 0.2 mg/kg IV dexamethasone; Group KD, gargled 40 mg ketamine in 30 ml saline plus 0.2 mg/kg IV dexamethasone; Group P (placebo) that received saline (gargle and IV). POST was graded at 0, 2, 4, 8, 16 and 24 h after operation on a four-point scale (0-3). Results: The incidence and severity of POST were significantly lower in Group KD, compared with the other groups at all times after tracheal extubation for up to 24 h (P < 0.05). Also the incidence and severity of hoarseness were significantly lower in each Groups of KD and K and D compared with group placebo (P < 0.05). Conclusion: The prophylactic use of 0.2 mg/kg of IV dexamethasone plus ketamine gargle significantly reduced the incidence and severity of POST compared with using each of these drugs alone or using placebo. PMID:25371869

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 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

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.

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.

Dysregulated diurnal cortisol pattern is associated with glucocorticoid resistance in women with major depressive disorder

PubMed Central

Jarcho, Michael R.; Slavich, George M.; Tylova-Stein, Hana; Wolkowitz, Owen M.; Burke, Heather M.

2013-01-01

Dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis is believed to play a role in the pathophysiology of depression. To investigate mechanisms that may underlie this effect, we examined several indices of HPA axis function – specifically, diurnal cortisol slope, cortisol awakening response, and suppression of cortisol release following dexamethasone administration – in 26 pre-menopausal depressed women and 23 never depressed women who were matched for age and body mass index. Salivary cortisol samples were collected at waking, 30 min after waking, and at bedtime over three consecutive days. On the third day, immediately after the bedtime sample, participants ingested a 0.5 mg dexamethasone tablet; they then collected cortisol samples at waking and 30 min after waking the following morning. As predicted, depressed women exhibited flatter diurnal cortisol rhythms and more impaired suppression of cortisol following dexamethasone administration than non-depressed women over the three sampling days. In addition, flatter diurnal cortisol slopes were associated with reduced cortisol response to dexamethasone treatment, both for all women and for depressed women when considered separately. Finally, greater self-reported depression severity was associated with flatter diurnal cortisol slopes and with less dexamethasone-related cortisol suppression for depressed women. Depression in women thus appears to be characterized by altered HPA axis functioning, as indexed by flatter diurnal cortisol slopes and an associated impaired sensitivity of cortisol to dexamethasone. Given that altered HPA axis functioning has been implicated in several somatic conditions, the present findings may be relevant for understanding the pathophysiology of both depression and depression-related physical disease. PMID:23410758

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

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

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.

Use of the Dexamethasone Suppression Test with Mentally Retarded Persons: Review and Recommendations.

ERIC Educational Resources Information Center

Wolkowitz, Owen M.

1990-01-01

Studies on the use of the Dexamethasone Suppression Test to detect depression are described, with special emphasis on use of the test with children, demented elderly persons, and mentally retarded persons. (Author/JDD)

Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

PubMed Central

Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

2013-01-01

Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac dysfunction at adulthood. Combined neonatal treatment with antioxidant vitamins is an effective intervention. PMID:23940378

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

77 FR 32010 - New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-31

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 516, 520, 522, and 558 [Docket No. FDA-2012-N-0002] New Animal Drugs; Altrenogest; Dexamethasone; Florfenicol AGENCY: Food and Drug Administration, HHS. [[Page 32011

Interaction between glucocorticoids and glucagon in the hormonal modification of calcium retention by isolated rat liver mitochondria.

PubMed

Hughes, B P; Barritt, G J

1979-05-15

1. The administration of dexamethasone to intact fed rats by intraperitoneal injection for 3h was associated with a 6-fold increase in the time for which mitochondria subsequently isolated from the liver retain a given load of exogenous Ca2+. This effect was blocked by the co-administration of cycloheximide with dexamethasone, and partially blocked by the co-administration of puromycin. Daily administration of dexamethasone for periods of 4--7 days resulted in liver mitochondria that exhibited a decreased ability to retain exogenous Ca2+. 2. When glucagon was administered to fed adrenalectomized rats, the increase in mitochondrial Ca2+-retention time that results from the action of this hormone was reduced by 50% when compared with its effect on intact animals. The administration of dexamethasone to adrenalectomized rats partially restored the full effect of glucagon. 3. Dexamethasone did not enhance the effect of glucagon on mitochondrial Ca2+-retention time when administered to intact fed rats. 4. It is concluded that these data support the hypothesis that the hormone-induced modification of liver mitochondria, which results in an increase in the time for which exogenous Ca2+ is retained, involves a step in which new protein is synthesized.

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

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.

Compatibility and stability of tramadol and dexamethasone in solution and its use in terminally ill patients.

PubMed

Negro, S; Salama, A; Sánchez, Y; Azuara, M L; Barcia, E

2007-10-01

Delivery of drug admixtures by continuous subcutaneous infusion is common practice in palliative medicine, but analytical confirmation of their compatibility and stability is not always available. To study the compatibility and stability of tramadol hydrochloride and dexamethasone sodium phosphate combined in solution and to report on its use in terminally ill patients. Twelve different solutions containing tramadol hydrochloride (8.33-33.33 mg/mL) and dexamethasone sodium phosphate (0.33-3.33 mg/mL) were prepared in saline and stored in polypropylene syringes for 5 days (25 degrees C). Analysis was performed on days 1, 3 and 5 days with simultaneous determination by HPLC. pH was measured at 0 and 5 days. Clinical performance was assessed retrospectively in six terminal-ill oncology patients. Maximum losses of 7% and 6% were observed for tramadol and dexamethasone. Pain was completely controlled in four patients. Local tolerance resulted in haematoma in three patients, which resolved by switching to a butterfly insertion site. Tramadol hydrochloride (100-400 mg/day) and dexamethasone sodium phosphate (4-40 mg/day) are stable for at least 5 days when combined in saline and stored at 25 degrees C. These results are only valid for the type of syringes and the specific commercial preparations tested.

Histone Deacetylase 6 (HDAC6) Is an Essential Modifier of Glucocorticoid-Induced Hepatic Gluconeogenesis

PubMed Central

Winkler, Robin; Benz, Verena; Clemenz, Markus; Bloch, Mandy; Foryst-Ludwig, Anna; Wardat, Sami; Witte, Nicole; Trappiel, Manuela; Namsolleck, Pawel; Mai, Knut; Spranger, Joachim; Matthias, Gabriele; Roloff, Tim; Truee, Oliver; Kappert, Kai; Schupp, Michael; Matthias, Patrick; Kintscher, Ulrich

2012-01-01

In the current study, we investigated the importance of histone deacetylase (HDAC)6 for glucocorticoid receptor–mediated effects on glucose metabolism and its potential as a therapeutic target for the prevention of glucocorticoid-induced diabetes. Dexamethasone-induced hepatic glucose output and glucocorticoid receptor translocation were analyzed in wild-type (wt) and HDAC6-deficient (HDAC6KO) mice. The effect of the specific HDAC6 inhibitor tubacin was analyzed in vitro. wt and HDAC6KO mice were subjected to 3 weeks’ dexamethasone treatment before analysis of glucose and insulin tolerance. HDAC6KO mice showed impaired dexamethasone-induced hepatic glucocorticoid receptor translocation. Accordingly, dexamethasone-induced expression of a large number of hepatic genes was significantly attenuated in mice lacking HDAC6 and by tubacin in vitro. Glucose output of primary hepatocytes from HDAC6KO mice was diminished. A significant improvement of dexamethasone-induced whole-body glucose intolerance as well as insulin resistance in HDAC6KO mice compared with wt littermates was observed. This study demonstrates that HDAC6 is an essential regulator of hepatic glucocorticoid-stimulated gluconeogenesis and impairment of whole-body glucose metabolism through modification of glucocorticoid receptor nuclear translocation. Selective pharmacological inhibition of HDAC6 may provide a future therapeutic option against the prodiabetogenic actions of glucocorticoids. PMID:22210316

Post-operative pain control after tonsillectomy: dexametasone vs tramadol.

PubMed

Topal, Kubra; Aktan, Bulent; Sakat, Muhammed Sedat; Kilic, Korhan; Gozeler, Mustafa Sitki

2017-06-01

Tramadol was found to be more effective than dexamethasone in post-operative pain control, with long-lasting relief of pain. This study aimed to compare the effects of pre-operative local injections of tramadol and dexamethasone on post-operative pain, nausea and vomiting in patients who underwent tonsillectomy. Sixty patients between 3-13 years of age who were planned for tonsillectomy were included in the study. Patients were divided into three groups. Group 1 was the control group. Patients in Group 2 received 0.3 mg/kg Dexamethasone and Group 3 received 0.1 mg/kg Tramadol injection to the peritonsillary space just before the operation. Patients were evaluated for nausea, vomiting, and pain. When the control and the dexamethasone groups were compared; there were statistically significant differences in pain scores at post-operative 15 and 30 min, whereas there was no statistically significant difference in pain scores at other hours. When the control and tramadol groups were compared, there was a statistically significant difference in pain scores at all intervals. When tramadol and dexamethasone groups were compared, there was no statistically significant difference in pain scores at post-operative 15 and 30 min, 1 and 2 h, whereas there was a statistically significant difference in pain scores at post-operative 6 and 24 h.

Effects of awakening and the use of topical dexamethasone and levofloxacin on the cytokine levels in tears following corneal transplantation.

PubMed

Fodor, Mariann; Petrovski, Goran; Pásztor, Dorottya; Gogolák, Péter; Rajnavölgyi, Éva; Berta, András

2014-01-01

To study the short-term effect of eye opening and use of topical dexamethasone phosphate 0.1% and levofloxacin 0.5% on the cytokine levels in human tears. Prospective experimental design was used for tear collection from eyes of 10 healthy controls and 20 patients four days after penetrating keratoplasty (PKP) at awakening and after instilling dexamethasone or levofloxacin. The concentrations of different cytokines were measured by cytometric bead array. At eye opening, IL-6 levels were higher in the PKP group as compared to the controls. Thirty minutes later, the released levels of IL-10, IL-13, IL-17, IFNγ, and CCL5 increased in controls, while CXCL8 decreased in both control and PKP groups. The release of the cytokines remained stable after 30 mins except for IFNγ, which showed a decrease in the controls following levofloxacin instillation. No short-term effects of the topically used dexamethasone and levofloxacin could be detected on the cytokine levels in controls and after PKP. Evidence of changes in the levels and time course of tear cytokines after awakening or eye opening could be established and the short-term confounding effects of dexamethasone and levofloxacin on the levels of released cytokines in human tears could be excluded.

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.

Glucocorticoid levels after exposure to predator odor and chronic psychosocial stress with dexamethasone application in rats.

PubMed

Starcevic, Ana; Petricevic, Sasa; Radojicic, Zoran; Djulejic, Vuk; Ilankovic, Andrej; Starcevic, Branislav; Filipovic, Branislav

2016-05-01

This study was conducted to explore the effects of specific psychosocial paradigm on predator animal posttraumatic stress model and to test the hypothesis that psychosocially stressed rats would exibit abnormal levels of cortisol and a larger suppression of cortisol levels after the application of dexamethasone. Animals were divided in two groups: experimental and control groups. The experimental group was exposed to two types of stressors: acute immobilization stress, and combined predator stress and daily social stress with application of dexamethasone. Blood sampling was performed at three different times. We found statistically significant results after analyzing the differences between cortisol levels in different times of blood sampling in the group of animals exposed to stress with dexamethasone application. Statistical significance was found when we compared the experimental group with the control group in terms of elevated cortisol levels during blood sampling after stress paradigm exposition. Many significant disruptions in the functioning of the hypothalamic-pituitary-adrenal axis were observed, such as decrease in basal cortisol levels and enhanced dexamethasone-induced inhibition of cortisol levels. These findings are important because their impact can translate to human individuals with posttraumatic stress disorder, which is the most important role of every animal model in research. Copyright © 2016. Published by Elsevier Taiwan.

Lenalidomide in multiple myeloma: an evidence-based review of its role in therapy

PubMed Central

Richardson, Paul; Mitsiades, Constantine; Laubach, Jacob; Schlossman, Robert; Ghobrial, Irene; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth

2010-01-01

Introduction: Multiple myeloma (MM) is a relatively common and incurable hematological malignancy. Currently, there is no single standard therapy, with choice of treatment dependent on individual patient factors. Lenalidomide is an immunomodulatory drug with potent antitumor, antiangiogenic, immunomodulatory, and proapoptotic activity in MM. Aims: To evaluate the evidence for the use of lenalidomide in its current indication in relapsed or refractory MM, and additionally its investigational use for the treatment of newly diagnosed MM. Evidence review: In patients with relapsed and refractory MM, adding lenalidomide to high-dose dexamethasone significantly improves response rates and time-to-progression, relative to high-dose dexamethasone alone. This translates into a significant extension of overall survival (with a median extension of 9.1 months in a pivotal phase III study). Outcome is independent of patient age, number of previous therapies, type of previous therapy (including thalidomide or autologous stem cell transplantation), renal impairment, and β2-microglobulin level. Evidence suggests that combining lenalidomide with low-dose dexamethasone improves outcomes in patients with newly diagnosed disease and is superior to lenalidomide combined with high-dose dexamethasone. Myelosuppression is the predominant toxicity observed, although some studies have shown high incidences of venous thromboembolism in the absence of prophylactic antithrombotic anticoagulation therapy. There is currently only limited evidence regarding the health economics of lenalidomide. Role in therapy: The encouraging results obtained with lenalidomide alone and in combination with dexamethasone in patients with relapsed or refractory MM have led to its adoption as a recommended therapy in patients who have received at least one prior treatment. Emerging evidence supports the ongoing investigation of lenalidomide in combination with low-dose dexamethasone, and in other combinations including bortezomib, for use both in relapsed, refractory, and newly diagnosed MM. PMID:20694078

Pre-emptive effect of dexamethasone injection and consumption on post-operative swelling, pain, and trismus after third molar surgery. A prospective, double blind and randomized study.

PubMed

Chaudhary, Pradeep D; Rastogi, Sanjay; Gupta, Prashant; Niranjanaprasad Indra, B; Thomas, Roy; Choudhury, Rupshikha

2015-01-01

To evaluate the preventative effect of intravenous 4 mg of dexamethasone and 8 mg oral dexamethasone on post-operative pain, swelling and trismus after the surgical extraction of mandibular third molars. A randomized clinical trial comprised of 200 patients (control group I intravenous and experimental group II orally) with impacted lower third molars, average age 20.8 years with no local or systemic problems, with bilateral impacted lower third molars, were operated under local anesthesia. Group I was given 4 mg IV and group II was given 8 mg orally of dexamethasone 1 h before procedure. The choice of which side to operate first and the amount of concentration of medication to use was made randomly and double-blindly. Post-operative pain was evaluated using a visual analog scale (VAS) and the degree of swelling was evaluated through facial reference points' variation. The presence of trismus was analyzed through measurement of the interincisal distance (IID). These assessments were obtained before the operation and 24 h, 48 h and 7th POD. No significant difference was found in facial swelling and trismus between IV 4 mg injection and oral 8 mg consumption after lower third molar surgery (student t test P > 0.05). The visual analogue scale scores for pain assessment showed no significant difference between IV injection and oral route of dexamethasone (student t test P > 0.05). Patients can be administered 8 mg oral dexamethasone is as effective as 4 mg intra venous route without much difference in final outcome at any given point of time.

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.).

Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles.

PubMed Central

de Wit, R.; van den Berg, H.; Burghouts, J.; Nortier, J.; Slee, P.; Rodenburg, C.; Keizer, J.; Fonteyn, M.; Verweij, J.; Wils, J.

1998-01-01

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase. PMID:9652766

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.

Effects of Combination of Thiazolidinediones with Melatonin in Dexamethasone-induced Insulin Resistance in Mice

PubMed Central

Ghaisas, M. M.; Ahire, Y. S.; Dandawate, P. R.; Gandhi, S. P.; Mule, M.

2011-01-01

In type 2 Diabetes, oxidative stress plays an important role in development and aggregation of insulin resistance. In the present study, long term administration of the dexamethasone led to the development of insulin resistance in mice. The effect of thiazolidinediones pioglitazone and rosiglitazone, with melatonin on dexamethasone-induced insulin resistance was evaluated in mice. Insulin resistant mice were treated with combination of pioglitazone (10 mg/kg/day, p.o.) or rosiglitazone (5 mg/kg/day, p.o.) with melatonin 10 mg/kg/day p.o. from day 7 to day 22. In the biochemical parameters, the serum glucose, triglyceride levels were significantly lowered (P<0.05) in the combination groups as compared to dexamethasone treated group as well as with individual groups of pioglitazone, rosiglitazone, and melatonin. There was also, significant increased (P<0.05) in the body weight gain in combination treated groups as compared to dexamethasone as well as individual groups. The combination groups proved to be effective in normalizing the levels of superoxide dismutase, catalase, glutathione reductase and lipid peroxidation in liver homogenates may be due to antioxidant effects of melatonin and decreased hyperglycemia induced insulin resistance by thiazolidinediones. The glucose uptake in the isolated hemidiaphragm of mice was significantly increased in combination treated groups (PM and RM) than dexamethasone alone treated mice as well as individual (pioglitazone, rosiglitazone, melatonin) treated groups probably via increased in expression of GLUT-4 by melatonin and thiazolidinediones as well as increased in insulin sensitivity by thiazolidinediones. Hence, it can be concluded that combination of pioglitazone and rosiglitazone, thiazolidinediones, with melatonin may reduces the insulin resistance via decreased in oxidative stress and control on hyperglycemia. PMID:23112392

Effects of carprofen and dexamethasone on canine chondrocytes in a three-dimensional culture model of osteoarthritis.

PubMed

Dvorak, Laura D; Cook, James L; Kreeger, John M; Kuroki, Keiichi; Tomlinson, James L

2002-10-01

To determine effects of carprofen and dexamethasone on chondrocytes in a culture model of osteoarthritis (OA). Chondrocytes isolated from articular cartilage of the humeral head of 5 adult dogs. Chondrocytes were harvested, cultured and subcultured in monolayer, and then cultured in a 3-dimensional (3-D) medium. Cells from each dog were distributed into 6 groups with differing content of liquid medium for each 3-D construct (agarose [AG], AG plus interleukin [IL]-1beta, AG plus carprofen [4 microg/mL], AG plus dexamethasone [1 mg/mL], AG plus IL-1beta [20 ng/mL] plus carprofen [4 microg/mL], and AG plus IL-1beta (20 ng/mL) plus dexamethasone (1 mg/mL). On days 3, 6, 12, and 20 of culture, samples from all groups were collected. Liquid media were assayed for glycosaminoglycan, prostaglandin (PG)E2, matrix metalloprotease (MMP)-3, and MMP-13 concentrations. All 3-D constructs were evaluated for viability, cell morphology, proteoglycan staining, and collagen type-II concentration. Total glycosaminoglycan content in each 3-D construct was quantitated by spectrophotometric assay. Addition of IL-1beta caused a significant loss of cell viability and matrix production. Addition of carprofen or dexamethasone caused significant decreases in PGE2 in the liquid media, and each was minimally effective in protecting chondrocytes against negative effects of IL-1beta. Human recombinant IL-1beta resulted in loss of cell viability, alterations in extracellular matrix components, and production of PG and MMP Carprofen and dexamethasone had little effect on cell and matrix variables but did decrease PGE2 concentrations and primarily affected the inflammatory pathway of osteoarthritis.

A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

PubMed

Sanchez-Ledesma, M J; López-Olaondo, L; Pueyo, F J; Carrascosa, F; Ortega, A

2002-12-01

In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.

Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells.

PubMed

Prabhala, Pavan; Bunge, Kristin; Ge, Qi; Ammit, Alaina J

2016-10-01

Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroids. MKP-1 is known to deactivate p38 MAPK phosphorylation and can control the expression and activity of the mRNA destabilizing protein-tristetraprolin (TTP). But whether corticosteroid-induced MKP-1 acts via p38 MAPK-mediated modulation of TTP function in a pivotal airway cell type, airway smooth muscle (ASM), was unknown. While pretreatment of ASM cells with the corticosteroid dexamethasone (preventative protocol) is known to reduce ASM synthetic function in vitro, the impact of adding dexamethasone after stimulation (therapeutic protocol) had not been explored. Whether dexamethasone modulates TTP in a p38 MAPK-dependent manner in this cell type was also unknown. We address this herein and utilize an in vitro model of asthmatic inflammation where ASM cells were stimulated with the pro-asthmatic cytokine tumor necrosis factor (TNF) and the impact of adding dexamethasone 1 h after stimulation assessed. IL-6 mRNA expression and protein secretion was significantly repressed by dexamethasone acting in a temporally distinct manner to increase MKP-1, deactivate p38 MAPK, and modulate TTP phosphorylation status. In this way, dexamethasone-induced MKP-1 acts via p38 MAPK to switch on the mRNA destabilizing function of TTP to repress pro-inflammatory cytokine secretion from ASM cells. J. Cell. Physiol. 231: 2153-2158, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial‡.

PubMed

Kurz, A; Fleischmann, E; Sessler, D I; Buggy, D J; Apfel, C; Akça, O

2015-09-01

Tissue oxygenation is a strong predictor of surgical site infection. Improving tissue oxygenation should thus reduce wound infection risk. Supplemental inspired oxygen can improve tissue oxygenation, but whether it reduces infection risk remains controversial. Low-dose dexamethasone is often given to reduce the risk of postoperative nausea and vomiting, but steroid-induced immunosuppression can increase infection risk. We therefore tested the hypotheses that supplemental perioperative oxygen reduces infection risk and that dexamethasone increases it. Using a factorial design, patients having colorectal resections expected to last ≥2 h were randomly assigned to 30% (n=270) or 80% (n=285) inspired oxygen during and for 1 h after surgery, and to 4 mg intraoperative dexamethasone (n=283) or placebo (n=272). Physicians blinded to group assignments evaluated wounds postoperatively, using US Centers for Disease Control criteria. Subject and surgical characteristics were similar among study groups. Surgical site infection incidence was similar among groups: 30% oxygen 15.6%, 80% oxygen 15.8% (P=1.00); dexamethasone 15.9%, placebo 15.4%, (P=0.91). Supplemental oxygen did not reduce surgical site infection risk. The preponderance of clinical evidence suggests that administration of 80% supplemental inspired oxygen does not reduce infection risk. We did not observe an increased risk of surgical site infection with the use of a single low dose of dexamethasone, indicating that it can be used for nausea and vomiting prophylaxis without promoting wound infections. ClinicalTrials.gov number: NCT00273377. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Stability of extemporaneously compounded dexamethasone in glass and plastic bottles and plastic syringes.

PubMed

Ensom, Mary H H; Décarie, Diane

2014-07-01

Dexamethasone is widely used to treat rheumatic and endocrine disorders and chemotherapy-induced nausea and vomiting. A palatable, alcohol-free liquid formulation, with a suitable concentration to allow reasonable administration volume, is available only via extemporaneous compounding. To evaluate the stability of dexamethasone suspensions in commercially available vehicles (Oral Mix and Oral Mix SF) in various types of containers after storage at 25°C and 4°C for up to 91 days. Dexamethasone suspensions (1 mg/mL) were prepared in Oral Mix and Oral Mix SF and then transferred to amber glass and plastic prescription bottles and plastic oral syringes. Suspensions in all 3 types of containers were stored at 25°C; suspensions in glass and plastic bottles were also stored at 4°C. Samples were collected weekly from each container up to 28 days and then every 2 weeks up to 91 days. The samples were analyzed by a validated, stability-indicating high-performance liquid chromatography - ultraviolet detection method. A suspension was considered stable if it maintained at least 90% of its initial dexamethasone concentration. Changes in colour, taste, odour, precipitation (and ease of resuspension), and pH were used to assess physical compatibility. All suspensions maintained at least 96% of the original concentration for up to 91 days with storage at 25°C or at 4°C. No notable changes in colour, taste, odour, precipitation, or pH were observed over the 91-day period. Dexamethasone suspensions (1 mg/mL) in Oral Mix and Oral Mix SF, stored in amber glass or plastic bottles or plastic syringes at 25°C or in amber glass or plastic bottles at 4°C can be expected to remain stable for up to 91 days.

Effect of adding dexamethasone to bupivacaine on transversus abdominis plane block for abdominal hysterectomy: A prospective randomized controlled trial

PubMed Central

Ammar, Amany S.; Mahmoud, Khaled M.

2012-01-01

Purpose: Different adjuvants have been used to improve the quality and increase the duration of local anesthetics during various nerve block techniques. The current study was aimed to evaluate the effect of adding dexamethasone to bupivacaine on the quality and duration of transversus abdominis plane (TAP) block. Methods: Sixty adult patients undergoing elective open abdominal hysterectomy were randomly allocated to receive TAP block using 20 mL of bupivacaine hydrochloride 0.25% + 2 mL saline 0.9% (control group, n=30) or 20 mL of bupivacaine hydrochloride 0.25% + 2 mL dexamethasone “8 mg” (dexamethasone group, n=30). The primary outcome was postoperative pain, as evaluated by visual analog scale (VAS) for pain scoring at 1, 2, 4, 12, 24 and 48 h postoperatively, whereas the secondary outcomes were time to first analgesia (TFA), morphine consumption and the occurrence of nausea, vomiting or somnolence. Results: The pain VAS score was significantly lower at the postoperative 2 h (4.9 vs. 28.1, P=0.01), 4 h (12.2 vs. 31.1, P=0.01) and 12 h (15.7 vs. 25.4, P=0.02). Furthermore, TFA was significantly longer in the dexamethasone group (459.8 vs. 325.4 min, P=0.002), with lesser morphine requirements in the postoperative 48 h (4.9 vs. 21.2 mg, P=0.003) and lower incidence of nausea and vomiting (6 vs. 14, P=0.03). No complications attributed to the block were recorded. Conclusion: Addition of dexamethasone to bupivacaine in TAP block prolonged the duration of the block and decreased the incidence of nausea and vomiting. PMID:23162395

Participation of the hypothalamus-hypophysis axis in the sympathetic activation of human obesity.

PubMed

Grassi, G; Seravalle, G; Dell'Oro, R; Turri, C; Pasqualinotto, L; Colombo, M; Mancia, G

2001-12-01

Previous studies have shown that hypothalamic and hypophyseal factors are involved in the acute sympathoexcitation induced by a variety of laboratory stimuli. Whether a chronic condition of sympathetic activation, such as that characterizing human obesity, is also dependent on these factors has never been investigated. In 40 normotensive obese subjects ([mean+/-SEM] age, 39.1+/-0.8 years) we measured blood pressure (Finapres), heart rate (ECG), and postganglionic muscle sympathetic nerve activity (MSNA) (microneurography). In 20 subjects measurements were repeated, according to a double-blind randomized sequence, after a midnight oral dose of dexamethasone (1 mg) (n=10) or placebo (n=10), while in the remaining subjects they were performed again after 1 week of a daily evening oral administration of 1 mg of dexamethasone (n=10) or placebo (n=10). The same protocol was performed in 16 age-matched lean normotensives. In both groups acute dexamethasone administration markedly reduced plasma cortisol (radioimmunoassay), without affecting hemodynamic and neural variables. In contrast to the acute administration, in obese subjects prolonged dexamethasone administration, although not affecting blood pressure and heart rate, significantly reduced both plasma cortisol (from 16.0+/-1.3 to 0.7+/-0.1 microg/dL; P<0.01) and MSNA (from 59.5+/-2.8 to 39.6+/-2.9 bursts per 100 heartbeats; P<0.02; -33.1+/-4.1%). This was not the case in lean subjects, in which the dexamethasone-induced reduction in plasma cortisol was associated with a slight and nonsignificant MSNA decrease. In both lean and obese subjects, placebo administration caused no change in any variable. Thus, prolonged dexamethasone administration exerts in obese subjects marked sympathoinhibitory effects that are not detectable in lean individuals. This suggests that hypothalamic and hypophyseal factors substantially contribute to the sympathoexcitation of obesity.

Inhibition of SUR1 Decreases the Vascular Permeability of Cerebral Metastases1

PubMed Central

Thompson, Eric M; Pishko, Gregory L; Muldoon, Leslie L; Neuwelt, Edward A

2013-01-01

Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 reduces cerebral edema due to metastases, the most common brain tumor, and explored the putative association of SUR1 and the endothelial tight junction protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 mg, intravenous). Blood-tumor barrier (BTB) permeability (Ktrans) was evaluated before and after treatment using dynamic contrast-enhanced magnetic resonance imaging. SUR1 and ZO-1 expression was evaluated using immunofluorescence and Western blots. In both models, SUR1 expression was significantly increased (P < .05) in tumors. In animals with SCLC, control mean Ktrans (percent change ± standard error) was 101.8 ± 36.6%, and both glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) decreased BTB permeability. In animals with melanoma, compared to controls (117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < .05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective as dexamethasone at halting increased BTB permeability caused by SCLC and melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema. PMID:23633925

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists.

PubMed

Bošnjak, Snežana M; Gralla, Richard J; Schwartzberg, Lee

2017-05-01

Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.

The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in in vitro and in vivo models of multiple myeloma by blockade of Ikaros and MYC signaling

PubMed Central

Díaz, Tania; Rodríguez, Vanina; Lozano, Ester; Mena, Mari-Pau; Calderón, Marcos; Rosiñol, Laura; Martínez, Antonio; Tovar, Natalia; Pérez-Galán, Patricia; Bladé, Joan; Roué, Gaël; de Larrea, Carlos Fernández

2017-01-01

Most patients with multiple myeloma treated with current therapies, including immunomodulatory drugs, eventually develop relapsed/refractory disease. Clinical activity of lenalidomide relies on degradation of Ikaros and the consequent reduction in IRF4 expression, both required for myeloma cell survival and involved in the regulation of MYC transcription. Thus, we sought to determine the combinational effect of an MYC-interfering therapy with lenalidomide/dexamethasone. We analyzed the potential therapeutic effect of the combination of the BET bromodomain inhibitor CPI203 with the lenalidomide/dexamethasone regimen in myeloma cell lines. CPI203 exerted a dose-dependent cell growth inhibition in cell lines, indeed in lenalidomide/dexamethasone-resistant cells (median response at 0.5 μM: 65.4%), characterized by G1 cell cycle blockade and a concomitant inhibition of MYC and Ikaros signaling. These effects were potentiated by the addition of lenalidomide/dexamethasone. Results were validated in primary plasma cells from patients with multiple myeloma co-cultured with the mesenchymal stromal cell line stromaNKtert. Consistently, the drug combination evoked a 50% reduction in cell proliferation and correlated with basal Ikaros mRNA expression levels (P=0.04). Finally, in a SCID mouse xenotransplant model of myeloma, addition of CPI203 to lenalidomide/dexamethasone decreased tumor burden, evidenced by a lower glucose uptake and increase in the growth arrest marker GADD45B, with simultaneous downregulation of key transcription factors such as MYC, Ikaros and IRF4. Taken together, our data show that the combination of a BET bromodomain inhibitor with a lenalidomide-based regimen may represent a therapeutic approach to improve the response in relapsed/refractory patients with multiple myeloma, even in cases with suboptimal prior response to immunomodulatory drugs. PMID:28751557

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

Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

PubMed

Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H

2017-10-03

Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts

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

Ohnaka, Keizo; Tanabe, Mizuho; Kawate, Hisaya

2005-04-01

To explore the mechanism of glucocorticoid-induced osteoporosis, we investigated the effect of glucocorticoid on canonical Wnt signaling that emerged as a novel key pathway for promoting bone formation. Wnt3a increased the T-cell factor (Tcf)/lymphoid enhancer factor (Lef)-dependent transcriptional activity in primary cultured human osteoblasts. Dexamethasone suppressed this transcriptional activity in a dose-dependent manner, while 1,25-dihydroxyvitamin D3 increased this transcriptional activity. LiCl, an inhibitor of glycogen synthase kinase-3{beta}, also enhanced the Tcf/Lef-dependent transcriptional activity, which was, however, not inhibited by dexamethasone. The addition of anti-dickkopf-1 antibody partially restored the transcriptional activity suppressed by dexamethasone. Dexamethasone decreased the cytosolic amount of {beta}-cateninmore » accumulated by Wnt3a and also inhibited the nuclear translocation of {beta}-catenin induced by Wnt3a. These data suggest that glucocorticoid suppresses the canonical Wnt signal in cultured human osteoblasts, partially through the enhancement of the dickkopf-1 production.« less

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

PubMed

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

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

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty.

PubMed

Zafar, Andleeb; Aslanides, Ioannis M; Selimis, Vasileios; Tsoulnaras, Konstantinos I; Tabibian, David; Kymionis, George D

2018-01-01

We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

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.

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.

Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents.

PubMed

Navari, Rudolph M

2003-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Although the 5-HT3 receptor antagonists, dexamethasone, and metoclopramide have been used to prevent delayed CINV, only dexamethasone appears to have much efficacy with acceptable toxicity. Recent studies have introduced two new agents, palonosetron and aprepitant, for the prevention of both acute and delayed CINV. Palonosetron is a new 5-HT3 receptor antagonist with a longer half life and a higher binding affinity than older 5-HT3 receptor antagonists. It improves the complete response rate (no emesis, no need for rescue) of acute and delayed CINV in patients receiving moderately emetogenic chemotherapy compared to the older 5-HT3 receptor antagonists. The other agent, aprepitant, is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when compared to placebo and when used in combination with dexamethasone compared to dexamethasone alone. Acute and delayed nausea may also be improved by aprepitant when used in combination with a 5-HT3 and dexamethasone prechemotherapy or with daily dosing for 3-5 days following chemotherapy. Based on these studies, new guidelines for the prevention of CINV are proposed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Efficacy of 0.5% Hyperbaric Bupivacaine with Dexamethasone versus 0.5% Hyperbaric Bupivacaine alone in Spinal Anaesthesia for Patient Undergoing Lower Abdominal Urological and Lower Limb Orthopedic Surgeries.

PubMed

Haque, M M; Aleem, M A; Haque, F H; Siddique, A B; Afrose, R

2018-04-01

Spinal anaesthesia with local anaesthetics has limited duration. Different additives have been used to prolong spinal anaesthesia. The aim of this study was to determine the efficacy of adding dexamethasone to bupivacaine in spinal anaesthesia specially whether it would prolong the duration of sensory block/ surgical analgesia and post-operative analgesia/pain free period or not. This randomized, prospective, double-blind, clinical study was conducted in the Department of Anaesthesia, Analgesia and Critical Care of Combined Military Hospital, Chittagong from October 2016 to August 2017. Seventy two (72) adult patients scheduled for lower abdominal urological and lower limb orthopedic surgery under spinal anaesthesia were included. They were divided in two groups; each group comprised 36 patients to receive 20mg 0.5% hyperbaric bupivacaine (Bupivacaine group) or 15mg 0.5% hyperbaric bupivacaine plus 5mg dexamethasone (Bupivacaine-Dexamethasone/case group) intrathecally. The patients were evaluated for quality, quantity and duration of sensory block/surgical analgesia, post-operative analgesia/pain free period, blood pressure, heart rate, nausea, and vomiting or other complications. There were no significant differences in demographic data, sensory level and onset time of the sensory block between two groups. Duration of sensory block/Surgical analgesia in the bupivacaine group was 92.32±8.34 minutes and in the bupivacaine- dexamethasone/case group was 122.11±10.59 minutes which was statistically highly significant (p<0.001). The duration of post-operative analgesia/pain free period was 208.78±41.57 minutes in the bupivacaine group; whereas it was 412.82±71.51 minutes in the bupivacaine-dexamethasone/case group which was also statistically highly significant (p<0.001). The frequency of complications was not different between two groups. This study has shown that the addition of dexamethasone to bupivacaine in spinal anaesthesia significantly improved the duration of sensory block/surgical analgesia as well as post-operative analgesia/pain free period without any complications.

Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

PubMed

Fischer, C P; Bode, B P; Takahashi, K; Tanabe, K K; Souba, W W

1996-05-01

The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL-6 receptor expression on the cell surface. It is likely that this upregulation of IL-6 receptors "primes" human liver cells for subsequent stimulation by cytokines. The resulting increase in hepatic amino acid transport provides the liver with substrate to support key metabolic pathways during catabolic states.

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 groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Steroid depressed wound healing and Tridax procumbens.

PubMed

Diwan, P V; Tilloo, L D; Kulkarni, D R

1983-01-01

Dexamethasone 0.33 mg/kg (I.M.) on first day and half this dose thereafter daily, depressed wound contraction, epithelization, tensile strength and process of granulation of wounds in experimental animals. Juice from the leaves of Tridex procumbens (T.P. 1 ml, I.P., daily) resembled dexamethasone in effects on wound contraction and granulation; but it significantly (P less than 0.001) counteracted the effects of dexamethasone on tensile strength and epithelization. TP caused increase in adrenal weight and decrease in thymus weight. These observations suggest that TP exerts a direct pro-healing effect along with an indirect anti-healing influences probably mediated through release of adrenal steroids.

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.

[Elevated expression of endothelin 2 in lung tissues of asthmatic rats after exposed to cigarette smoke and its mechanism].

PubMed

Han, Fangfang; Zhu, Shuyang; Chen, Bi; Li, Jingjing

2017-08-01

Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH) 3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg.d), intragastric administration of ET receptor inhibitor bosentan 100 mg/(kg.d) and combined use, respectively named dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, 6 rats in every group. What's more, other 6 rats were only subjected to intraperitoneal injection of 1 mL normal saline as normal controls; in addition to the injection of saline, cigarette smoke control group (n=6) was set up by the exposure to smoking gas for four weeks with 10 cigarettes per day. Bronchoalveolar lavage fluid (BALF) was collected from the upper lobe of the left lung for cell counting and classification. Pathological changes of the right upper lung lobe tissues were observed by HE staining. In other lung tissues, the expression of JNK1/2 was detected by Western blotting; ET-2 was tested by Western blotting and immunohistochemistry; thiobarbituric acid reactive substances (TBARS) assay and trace enzyme standard method were used to measure malondialdehyde (MDA) and glutathione (GSH), respectively. Results Compared with normal control group, the number of airway inflammation cells increased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH increased in the lung tissues of cigarette smoke control group, asthma model group and cigarette smoke-exposed asthma group. Compared with cigarette smoke-exposed asthma group, the number of airway inflammation cells decreased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH decreased in the lung tissues of the dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group. Airway inflammation was attenuated and the staining intensity of ET-2 in the lung tissue was reduced in the dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, which were more obvious in the dexamethasone-bosentan treated group. Conclusion Cigarette smoke exposure obviously aggravates airway inflammation in asthmatic rats, and bosentan can effectively alleviate the airway inflammation. The mechanism of the inflammation may be related to ET-2 and JNK1/2 signaling pathway.

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan.

PubMed

Suzuki, Kenshi; Ri, Masaki; Chou, Takaaki; Sugiura, Isamu; Takezako, Naoki; Sunami, Kazutaka; Ishida, Tadao; Izumi, Tohru; Ozaki, Shuji; Shumiya, Yoshihisa; Ota, Kenji; Iida, Shinsuke

2017-03-01

This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m 2 , followed by 27 mg/m 2 . Lenalidomide and dexamethasone were administered at 25 mg (days 1-21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty-six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High-risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Combined intraoperative paracetamol and preoperative dexamethasone reduces postoperative sore throat: a prospective randomized study.

PubMed

Lee, Jiwon; Park, Hee-Pyoung; Jeong, Mu-Hui; Kim, Hyun-Chang

2017-12-01

Postoperative sore throat (POST) after general anesthesia with endotracheal intubation is a common and undesirable complication. In this study, we evaluated the combined effects of paracetamol and dexamethasone on the prevention of POST in patients after general anesthesia. A total of 226 patients scheduled for urologic surgery under general anesthesia were randomly assigned to one of two groups. In the DexaPara group (n = 113), dexamethasone (10 mg) and paracetamol (1000 mg) was infused. In the Dexa group (n = 113), dexamethasone (10 mg) alone was given. POST, hoarseness, and dysphagia were monitored. The postoperative wound pain score and perioperative opioid requirements were compared. In addition, complications related to opioids were compared between the groups. The overall incidence of POST was lower in the DexaPara group than in the Dexa group [42 (37%) vs. 72 (64%), p < 0.001]. The incidence of POST while resting at postoperative 1 and 6 h was lower in the DexaPara group than in the Dexa group (p = 0.008 and p = 0.004, respectively). The incidence of postoperative nausea, vomiting, drowsiness, shivering, and headache was comparable between the groups. Paracetamol and dexamethasone infusion reduced the incidence of POST without serious complications in patients for urologic surgery under general anesthesia.

Combination of haloperidol, dexamethasone, and ondansetron reduces nausea and pain intensity and morphine consumption after laparoscopic sleeve gastrectomy.

PubMed

Benevides, Márcio Luiz; Oliveira, Sérgio de Souza; Aguilar-Nascimento, José Eduardo

2013-01-01

Postoperative nausea and vomiting (PONV) occur frequently after laparoscopic bariatric surgery. The combination of haloperidol, dexamethasone, and ondansetron may reduce these undesirable events. The aim of this study was to evaluate the intensity of nausea and pain, the number of vomiting episodes, and morphine consumption in postoperative (PO) obese patients undergoing laparoscopic sleeve gastrectomy (LSG). A clinical, randomized, controlled, double-blind study conducted with 90 patients with body mass index ≥ 35 kg.cm-2. Patients were divided into three groups of 30 individuals to receive ondansetron 8 mg (Group O); ondansetron 8 mg and dexamethasone 8 mg (Group OD); and ondansetron 8 mg, dexamethasone 8 mg, and haloperidol 2 mg (Group HDO). We evaluated the intensity of nausea and pain using the verbal numeric scale, cumulative number of vomiting episodes, and morphine consumption in the period of 0-2, 2-12, 12-24, and 24-36 hours postoperatively. Nausea intensity was lower in Group HDO compared to Group O (p = 0.001), pain intensity was lower in Group HDO compared to Group O (p = 0.046), and morphine consumption was lower in Group HDO compared to Group O (p = 0.037). There was no difference between groups regarding the number of vomiting episodes (p = 0.052). The combination of haloperidol, ondansetron, and dexamethasone reduced nausea and pain intensity and morphine consumption in postoperative obese patients undergoing LSG.

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

PubMed

Gueneau, Pauline; Chretien, Marie-Lorraine; Cransac-Miet, Amelie; Aho, Ludwig Serge; Lafon, Ingrid; Favennec, Camille; Guy, Julien; Caillot, Denis; Boulin, Mathieu

2018-05-01

To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10 -3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Bcl2-independent chromatin cleavage is a very early event during induction of apoptosis in mouse thymocytes after treatment with either dexamethasone or ionizing radiation.

PubMed

Hahn, Peter J; Lai, Zhi-Wei; Nevaldine, Barbara; Schiff, Ninel; Fiore, Nancy C; Silverstone, Allen E

2003-11-01

We have quantified the emergence of early chromatin breaks during the signal transduction phase of apoptosis in mouse thymocytes after treatment with either ionizing radiation or dexamethasone. Dexamethasone at 1 microM can induce significant levels of DNA breaks (equivalent to the amount induced directly by 7.5 Gy ionizing radiation) within 0.5 h of treatment. The execution phase of apoptosis was not observed until 4-6 h after the same treatment. The presence of the Bcl2 transgene under the control of the p56lck promoter almost completely inhibited apoptosis up to 24 h after treatment, but it had virtually no effect on the early chromatin cleavage occurring in the first 6 h. Ionizing radiation induced chromatin cleavage both directly by damaging DNA and indirectly with kinetics similar to the induction of chromatin cleavage by dexamethasone. The presence of the Bcl2 transgene had no effect on the direct or indirect radiation-induced cleavage in the first 6 h, but after the first 6 h, the Bcl2 gene inhibited further radiation-induced chromatin cleavage. These results suggest that endonucleases are activated within minutes of treatment with either dexamethasone or ionizing radiation as part of the very early signal transduction phase of apoptosis, and prior to the irreversible commitment to cell death.

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

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

CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

PubMed Central

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

2012-01-01

Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

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.

Corticosteroids augment BRAF inhibitor vemurafenib induced lymphopenia and risk of infection.

PubMed

Sondermann, Wiebke; Griewank, Klaus G; Schilling, Bastian; Livingstone, Elisabeth; Leyh, Julia C; Rompoti, Natalia; Cosgarea, Ioana; Schimming, Tobias; Schadendorf, Dirk; Zimmer, Lisa; Hillen, Uwe

2015-01-01

We have previously demonstrated an impact of the BRAF inhibitor vemurafenib on patient lymphocyte counts. In the current study, the extent to which concomitant use of corticosteroids in BRAF inhibitor treated patients affects lymphocyte counts and predisposes to infection was investigated. A cohort of 102 patients receiving either the selective BRAF inhibitor vemurafenib or dabrafenib was analyzed. The amount of patients receiving either medication with or without systemic corticosteroids (dexamethasone) was determined and lymphocyte counts before and under therapy assessed. Additionally, the number and severity of infections occurring in these groups was analyzed. Vemurafenib treatment led to a considerable decrease in lymphocyte cell counts, with 62.3% of patients having lymphopenia. Dabrafenib treated patients only rarely demonstrated lymphopenia (12.5%). Dexamethasone co-administration further diminished lymphocyte counts. Lymphopenias were observed in 84.6% of patients receiving vemurafenib and dexamethasone. In our cohort, infections were noted in 9 patients, 4 of these were severe and 2 eventually fatal. All 9 cases with infections demonstrated lymphopenia, 8 of these had received dexamethasone and 7 of these a therapy with vemurafenib. Our findings demonstrate a significant lymphopenia in patients treated with the BRAF inhibitor vemurafenib, which is further augmented by dexamethasone and predisposes to infection. If validated in other studies, risk of infection should be considered when applying corticosteroids in combination with BRAF inhibitors, in particular vemurafenib.

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

21 CFR 520.540 - Dexamethasone oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540...

The Dexamethasone Suppression Test as an Indication of Depression in Patients with Mental Retardation.

ERIC Educational Resources Information Center

Mattes, Jeffrey A.; Amsell, Loren

1993-01-01

Administration of the Dexamethasone Suppression Test (DST) for three groups of institutionalized patients with severe/profound mental retardation found that the 12 depressed patients more frequently (though not significantly) had positive DSTs and significantly higher cortisol levels compared with nondepressed patients with and without other…

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...

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...

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...

Manipulation of Human Primary Endothelial Cell and Osteoblast Coculture Ratios to Augment Vasculogenesis and Mineralization

DTIC Science & Technology

2014-06-01

lization occurs in OB monocultures in osteogenic media containing A glycerophosphate and dexamethasone. In this study, the media used do not contain...dexamethasone or A glycerophosphate and, therefore, did not promote mineralization in OB monocultures after 21 days of culture. Because of this

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 pré-LPIVM (grupo dexametasona); administração de salina pré-LPIVM (grupo controle); e somente ventilação (grupo sham). A LPIVM foi realizada por ventilação com volume corrente alto. Os animais dos grupos dexametasona e controle foram sacrificados em 0, 4, 24 e 168 h após LPIVM. Analisamos gasometria arterial, edema pulmonar, contagens de células (totais e diferenciais) no lavado broncoalveolar e histologia de tecido pulmonar. Em 0, 4 e 24 h após LPIVM, os escores de lesão pulmonar aguda (LPA) foram maiores no grupo controle que no grupo sham (p < 0,05). A administração de dexametasona antes da LPIVM reduziu a gravidade da lesão pulmonar. Em 4 e 24 h após a indução, o escore de LPA no grupo dexametasona não foi significativamente diferente daquele observado no grupo sham e foi menor que o observado no grupo controle (p < 0,05). As contagens de neutrófilos no lavado broncoalveolar estavam aumentadas nos grupos controle e dexametasona, com pico em 4 h após LPIVM (p < 0,05). Entretanto, as contagens de neutrófilos foram menores no grupo dexametasona que no grupo controle em 4 e 24 h após LPIVM (p < 0,05). O pré-tratamento com dexametasona também impediu o comprometimento da oxigenação após a indução visto no grupo controle. A administração de dexametasona antes de LPIVM atenua os efeitos da lesão em ratos Wistar. Os mecanismos moleculares dessa lesão e o possível papel clínico dos corticosteroides na LPIVM ainda precisam ser elucidados.

Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro

NASA Technical Reports Server (NTRS)

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

1987-01-01

The regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture is studied. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle.

21 CFR 520.540c - Dexamethasone chewable tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

21 CFR 520.540c - Dexamethasone chewable tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

21 CFR 520.540c - Dexamethasone chewable tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Dexamethasone chewable tablets. 520.540c Section 520.540c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.540c...

76 FR 7219 - Determination That DECASPRAY (Dexamethasone) Topical Aerosol, 0.04%, and AEROSEB-DEX...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-09

... Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... (dexamethasone) Topical Aerosol, 0.01%, were not withdrawn from sale for reasons of safety or effectiveness. This... safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of...

Improved Cryptosporidium parvum oocysts propagation using dexamethasone suppressed CF-1 mice

EPA Science Inventory

This study evaluates Cryptosporidium parvum oocyst production in dexamethasone suppressed CF-1 and C57BL/6 mice. Both models can yield 1 x 10⁹ total oocysts over a 20 day production period; however, only 20 CF-1 mice are required to reliably achieve this goal compared...

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

PubMed

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

[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.

Modulation of interleukin-1 secretion by immunosuppressive drugs, alone and in combination.

PubMed

Reisman, L; Lin, W G; Martinelli, G P

1995-03-01

This study evaluates the ability of the immunosuppressive drugs dexamethasone, cyclosporine, FK506 and rapamycin, alone and in combination to suppress interleukin-1 beta (IL-1 beta) secretion in vitro by THP-1 cells when stimulated by lipopolysaccharide. All four drugs, when added to cell culture medium at therapeutic concentrations, significantly decrease secretion of the monokine to well below control levels. However, only dexamethasone completely suppresses IL-1 beta secretion in a dose-dependent fashion. Cyclosporine, FK506 and rapamycin only partially suppress secretion of IL-1 beta at concentrations within their therapeutic ranges and increasing concentrations of the drugs do not result in further suppression of secretion. Likewise, the combination of any two of these three drugs does not provide any additional suppressive effect. Dexamethasone, however, when added in increasing concentrations in combination with any of the other drugs, results in further suppression of IL-1 secretion in a dose-dependent fashion. These data suggest that cyclosporine, FK506 and rapamycin all share a common effect on the production of IL-1 beta, different from that of dexamethasone.

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

Involvement of miR17 pathway in glucocorticoid-induced cell death in pediatric acute lymphoblastic leukemia.

PubMed

Harada, Masako; Pokrovskaja-Tamm, Katja; Söderhäll, Stefan; Heyman, Mats; Grander, Dan; Corcoran, Martin

2012-10-01

Analysis of the microRNA transcriptome following dexa- methasone treatment of the acute lymphocytic leukemia (ALL) cell line RS4;11 showed a global down-regulation of microRNA levels. MIR17HG was rapidly down-regulated following treatment, with chromatin immunoprecipitation (ChIP) analysis demonstrating the promoter to be a direct target of glucocorticoid (GC)-transcriptional repression and revealing the miR17-92 cluster as a prime target for dexamethasone-induced repression. The loss of miR17 family expression and concomitant increases in the miR17 target Bim occurred in an additional ALL cell line SUP-B15 but not in the dexamethasone-resistant REH. Alteration of miR17 levels through up-regulation or inhibition resulted in an decrease and increase, respectively, in Bim protein levels and dexamethasone-induced cell death. Primary ex vivo ALL cells that underwent apoptosis induced by dexamethasone also down-regulated miR17 levels. Thus, down-regulation of miR17 plays an important role in glucocorticoid-induced cell death suggesting that targeting miR17 may improve the current ALL combination therapy.

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.

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.

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty

PubMed Central

Zafar, Andleeb; Aslanides, Ioannis M.; Selimis, Vasileios; Tsoulnaras, Konstantinos I.; Tabibian, David; Kymionis, George D.

2018-01-01

Purpose We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. Methods The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. Results Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. Conclusion A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye. PMID:29643797

Noninvasive Prenatal Diagnosis of Congenital Adrenal Hyperplasia.

PubMed

Khattab, Ahmed; Yuen, Tony; Sun, Li; Yau, Mabel; Barhan, Ariella; Zaidi, Mone; Lo, Y M Dennis; New, Maria I

2016-01-01

A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures. This therapeutic dilemma calls for early prenatal diagnosis so that dexamethasone treatment can be directed to affected female fetuses only. We describe the utilization of cell-free fetal DNA in mothers carrying at-risk fetuses as early as 6 gestational weeks by targeted massively parallel sequencing of the genomic region including and flanking the CYP21A2 gene. Our highly personalized and innovative approach should permit the diagnosis of CAH before genital development begins, therefore restricting the purposeful administration of dexamethasone to mothers carrying affected females. © 2016 S. Karger AG, Basel.

Sevoflurane with or without antiemetic prophylaxis of dexamethasone in spontaneously breathing patients undergoing outpatient anorectal surgery.

PubMed

Wu, Jyh-I; Lu, Shao-Fong; Chia, Yuan-Yi; Yang, Lin-Cheng; Fong, Wen-Po; Tan, Ping-Heng

2009-11-01

To evaluate the prophylactic use of dexamethasone with sevoflurane in outpatient anorectal surgery. Randomized, controlled study. Operating room and Postanesthesia Care Unit of a general hospital. 60 adult, ASA physical status I and II outpatients undergoing anorectal surgery. Patients were randomized to receive either dexamethasone 5 mg intravenously (IV; Group D; n = 30) or an equal volume of saline (Group S; n = 30) before anesthesia induction. Anesthesia was induced with propofol 2.5 mg.kg(-1), fentanyl two microg.kg(-1), and 2% lidocaine one mg.kg(-1) followed by placement of a Laryngeal Mask Airway. Frequency of postoperative nausea and vomiting (PONV), visual analog scale (VAS) pain scores, and patient satisfaction were recorded. Frequency of PONV and VAS pain scores were significantly lower in Group D than Group S (P < 0.05). The time required for "home readiness" was significantly shorter in Group D than Group S (P < 0.05). The prophylactic administration of 5 mg dexamethasone IV can reduce the frequency of PONV, lower VAS pain scores, facilitate recovery to home readiness, and improve satisfaction in outpatients undergoing anorectal surgery.

Evaluation of Pentravan®, Pentravan® Plus, Phytobase®, Lipovan® and Pluronic Lecithin Organogel for the transdermal administration of antiemetic drugs to treat chemotherapy-induced nausea and vomiting at the hospital.

PubMed

Bourdon, F; Lecoeur, M; Leconte, L; Ultré, V; Kouach, M; Odou, P; Vaccher, C; Foulon, C

2016-12-30

The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase ® , Lipovan ® , Pentravan ® , Pentravan ® Plus and Pluronic Lecithin Organogel (PLO)), for the compounding of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) and their administration in combination to treat chemotherapy-induced nausea and vomiting (CINV) at the hospital. Drugs were individually formulated in these vehicles and in mixture in Pentravan ® Plus using different penetration enhancers. Quality control of the forms has demonstrated that formulation process was mastered and convenient for the hospital (time required: 20min). Diffusion experiments through synthetic membranes and pig ear epidermis performed using Franz-type diffusion cells, have shown that the release and permeation process were greater for ondansetron than for dexamethasone and aprepitant, with a release step not limiting. As permeation of aprepitant was too low, it was discarded of the study. When ondansetron and dexamethasone were compounded in combination in Pentravan ® Plus, the most efficient vehicle, a permeation decrease was observed. Finally, the use of tween 20 instead of EtOH as chemical enhancer has led to 2-fold factor increase in the flux of dexamethasone, resulting in fluxes convenient for transdermal administration of ondansetron to a child, but insufficient for an adult and for dexamethasone. Copyright © 2016 Elsevier B.V. All rights reserved.

Permissive effect of dexamethasone on the increase of proenkephalin mRNA induced by depolarization of chromaffin cells

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

Naranjo, J.R.; Mocchetti, I.; Schwartz, J.P.

1986-03-01

In cultured bovine chromaffin cells, changes in the dynamic state of enkephalin stores elicited experimentally were studied by measuring cellular proenkephalin mRNA, as well as enkephalin precursors and authentic enkephalin content of cells and culture media. In parallel, tyrosine hydroxylase mRNA and catecholamine cell content were also determined. Low concentrations (0.5-100 pM) of dexamethasone increased the cell contents of proenkephalin mRNA and enkephalin-containing peptides. High concentrations of the hormone(1 ..mu..M) were required to increase the cell contents of tyrosine hydroxylase mRNA and catecholamines. Depolarization of the cells with 10 ..mu..M veratridine resulted in a depletion of enkephalin and catecholamine storesmore » after 24 hr. The enkephalin, but not the catecholamine, content was restored by 48 hr. An increase in proenkephalin mRNA content might account for the recovery; this increase was curtailed by tetrodotoxin and enhanced by 10 pM dexamethasone. Tyrosine hydroxylase mRNA content was not significantly modified by depolarization, even in the presence of 1 ..mu..M dexamethasone. Aldosterone, progesterone, testosterone, or estradiol (1 ..mu..M) failed to change proenkephalin mRNA. Hence, dexamethasone appears to exert a specific permissive action on the stimulation of the proenkephalin gene elicited by depolarization. Though the catecholamines and enkephalins are localized in the same chromaffin granules and are coreleased by depolarization, the genes coding for the processes that are rate limiting in the production of these neuromodulators can be differentially regulated.« less

Dexamethasone as a ropivacaine adjuvant for ultrasound-guided interscalene brachial plexus block: A randomized, double-blinded clinical trial.

PubMed

Sakae, Thiago Mamôru; Marchioro, Patricia; Schuelter-Trevisol, Fabiana; Trevisol, Daisson José

2017-05-01

The purpose of this study was to evaluate the effect of intravenous or perineural dexamethasone added to ropivacaine on the duration of ultrasound-guided interscalene brachial plexus blocks (BPB). Randomized clinical trial. Sixty ASA physical status I-II patients with elective shoulder arthroscopic surgeries under interscalene brachial plexus blocks were randomly allocated to receive 20ml of 0.75% ropivacaine with 1ml of isotonic saline (C group, n=20), 20ml of 0.75% ropivacaine with 1ml (4mg) of perineural dexamethasone (Dpn group, n=20), or 20ml of 0.75% ropivacaine with 1ml of isotonic saline and intravenous 4mg dexamethasone (IV) (Div group, n=20). A nerve stimulation technique with ultrasound was used in all patients. The onset time and duration of sensory blocks were assessed. Secondary outcomes were pain scores (VAS) and postoperative vomiting and nausea (PONV). The duration of the motor and sensory block was extended in group Dpn compared with group Div and group C (P<0.05). In addition, within 24h, group Dpn presented lower levels of VAS and lower incidence of PONV as compared with the other groups. Moreover, there was a significant reduction on onset time between group Dpn and the other groups. Perineural 4mg dexamethasone was more effective than intravenous in extending the duration of ropivacaine in ultrasound-guided interscalene BPB. Moreover, Dpn has significant effects on onset time, PONV, and VAS. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

Adjuvant Agents in Regional Anesthesia in the Ambulatory Setting.

PubMed

Koyyalamudi, Veerandra; Sen, Sudipta; Patil, Shilpadevi; Creel, Justin B; Cornett, Elyse M; Fox, Charles J; Kaye, Alan D

2017-01-01

A majority of surgical practice has involved ambulatory centers with the number of outpatient operations in the USA doubling to 26.8 million per year. Local anesthesia delivery provides numerous benefits, including increased satisfaction, earlier discharge, and reduction in unplanned hospital admission. Further, with the epidemic of opioid mediated overdoses, local anesthesia can be a key tool in providing an opportunity to reduce the need for other analgesics postoperatively. Adjuvants such as epinephrine and clonidine enhance local anesthetic clinical utility. Further, dexmedetomidine prolongs regional blockade duration effects. There has also been a significant interest recently in the use of dexamethasone. Studies have demonstrated a significant prolongation in motor and sensory block with perineural dexamethasone. Findings are conflicting as to whether intravenous dexamethasone has similar beneficial effects. However, considering the possible neurotoxicity effects, which perineural dexamethasone may present, it would be prudent not to consider intravenously administered dexamethasone to prolong regional block duration. Many studies have also demonstrated neurotoxicity from intrathecally administered midazolam. Therefore, midazolam as an adjuvant is not recommended. Magnesium prolongs regional block duration but related to paucity of studies as of yet, cannot be recommended. Tramadol yields inconsistent results and ketamine is associated with psychotomimetic adverse effects. Buprenorphine consistently increases regional block duration and reduce opioid requirements by a significant amount. Future studies are warranted to define best practice strategies for these adjuvant agents. The present review focuses on the many roles of local anesthetics in current ambulatory practice.

Development and validation of a highly sensitive LC-MS/MS method for the determination of dexamethasone in nude mice plasma and its application to a pharmacokinetic study.

PubMed

Yuan, Yin; Zhou, Xuan; Li, Jian; Ye, Suofu; Ji, Xiwei; Li, Liang; Zhou, Tianyan; Lu, Wei

2015-04-01

In the current study, a simple, sensitive and rapid analytical method for the determination of dexamethasone was developed and applied to a pharmacokinetic study in nude mice. Using testosterone as an internal standard, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach after one-step precipitation with acetonitrile was validated and used to determine the concentrations of dexamethasone in nude mice plasma. The method utilized a simple isocratic reverse phase separation over a Dionex C18 column with a mobile phase composed of acetonitrile-water (40:60, v/v). The analyte was detected by a triple quadrupole tandem mass spectrometer via electrospray and multiple reaction monitoring was employed to select both dexamethasone at m/z 393.0/147.1 and testosterone at m/z 289.5/97.3 in the positive ion mode. The calibration curves were linear (r >0.99) ranging from 2.5 to 500 ng/mL with a lower limit of quantitation of 2.5 ng/mL. The relative standard deviation ranged from 1.69 to 9.22% while the relative error ranged from -1.92 to -8.46%. This method was successfully applied to a preclinical pharmacokinetic study of dexamethasone and its pharmacokinetics was characterized by a two-compartment model with first-order absorption in female nude mice. Copyright © 2014 John Wiley & Sons, Ltd.

Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats.

PubMed

Hozayen, Walaa G; El-Desouky, Mohamed A; Soliman, Hanan A; Ahmed, Rasha R; Khaliefa, Amal K

2016-06-02

Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin.

Bacterial Meningitis in Patients using Immunosuppressive Medication: a Population-based Prospective Nationwide Study.

PubMed

van Veen, Kiril E B; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

2017-06-01

We studied occurrence, presentation, disease course, effect of adjunctive dexamethasone, and prognosis of bacterial meningitis in patients using immunosuppressive medication. Patients were selected from our nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 1, 2006 through October 31, 2014. Eighty-seven of 1447 episodes (6 %) of bacterial meningitis occurred in patients using immunosuppressive medication, and consisted of corticosteroids in 82 %. Patients with bacterial meningitis using immunosuppressive medication were less likely to present with headache (P = 0.02) or neck stiffness (P = 0.005), as compared those not on immunosuppressive medication. In 46 % of episodes CSF leukocyte count was below 1000/mm 3 . CSF cultures revealed S. pneumoniae in 41 % and L. monocytogenes in 40 % of episodes. Outcome was unfavorable in 39 of 87 episodes (45 %) and death occurred in 22 of 87 episodes (25 %). Adjunctive dexamethasone was administered in 52 of 87 (60 %) episodes, and mortality tended to be lower in those on adjunctive dexamethasone therapy as compared to those without dexamethasone therapy (10 of 52 [19 %] vs 12 of 35 [34 %], P = 0.14). We conclude that bacterial meningitis in patients using immunosuppressive medication is likely to present with atypical clinical and laboratory features, and is often caused by atypical bacteria, mainly L. monocytogenes. Adjunctive dexamethasone is widely prescribed in these patients and was not associated with harm in this study.

Effect of venous dexamethasone, oral caffeine and acetaminophen on relative frequency and intensity of postdural puncture headache after spinal anesthesia.

PubMed

Masoudifar, Mehrdad; Aghadavoudi, Omid; Adib, Sajjad

2016-01-01

Postdural puncture headache (PDPH) is a relatively common complication after regional anesthesia, especially in younger people, bothersome to patients and needs prophylaxis to prevent this complication. This study was conducted aiming to determine the preventive effect of dexamethasone plus caffeine and acetaminophen on relative frequency and intensity of PDPH after spinal anesthesia. In a clinical trial study, 90 candidates for the lower extremities orthopedic elective operation were divided into two groups of 45 individuals each. Intervention group received the compound of 500 mg acetaminophen +65 mg oral caffeine +8 mg venous dexamethasone an hour before spinal blocking, and the control group received placebo tablets + a dexamethasone equivalent volume of venous normal saline. The level of postoperative headache at the time of entrance to recovery and discharge, 6, 12, 24, 48, and 72 h postoperatively were measured based on Visual Analog Scale criterion in the two groups and then compared with each other. During the study, 24 patients in the control group and 17 patients in the intervention group were afflicted with headache; however, with no significant difference (P = 0.14). Total frequency of headache incidence was 35 times in the control group and 27 times in the intervention group (P = 0.32). Though the taking of acetaminophen + caffeine + dexamethasone is associated with a decrease in headache intensity and duration and decrease in PDPH incidence, compared with placebo, however, no essentially and statistically significant effect was produced.

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 neuropsychological adverse effects and sleep-related difficulties in pediatric patients with ALL. © 2016 by American Society of Clinical Oncology.

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma

PubMed Central

Arkenau, Hendrik-Tobias; Gimsing, Peter; Krejcik, Jakub; Lemech, Charlotte; Minnema, Monique C.; Lassen, Ulrik; Laubach, Jacob P.; Palumbo, Antonio; Lisby, Steen; Basse, Linda; Wang, Jianping; Sasser, A. Kate; Guckert, Mary E.; de Boer, Carla; Khokhar, Nushmia Z.; Yeh, Howard; Clemens, Pamela L.; Ahmadi, Tahamtan; Lokhorst, Henk M.; Richardson, Paul G.

2016-01-01

Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, has activity as monotherapy in multiple myeloma (MM). This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractory and relapsed/refractory MM. Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on days 1-21 of each cycle) and dexamethasone (40 mg/week). Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus lenalidomide/dexamethasone. Safety, efficacy, pharmacokinetics, immunogenicity, and accelerated daratumumab infusions were studied. In part 1 (13 patients), no dose-limiting toxicities were observed, and 16 mg/kg was selected as the R2PD. In part 2 (32 patients), median time since diagnosis was 3.2 years, with a median of 2 prior therapies (range, 1-3 prior therapies), including proteasome inhibitors (91%), alkylating agents (91%), autologous stem cell transplantation (78%), thalidomide (44%), and lenalidomide (34%); 22% of patients were refractory to the last line of therapy. Grade 3 to 4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. In part 2, infusion-related reactions (IRRs) occurred in 18 patients (56%); most were grade ≤2 (grade 3, 6.3%). IRRs predominantly occurred during first infusions and were more common during accelerated infusions. In part 2 (median follow-up of 15.6 months), overall response rate was 81%, with 8 stringent complete responses (25%), 3 complete responses (9%), and 9 very good partial responses (28%). Eighteen-month progression-free and overall survival rates were 72% (95% confidence interval, 51.7-85.0) and 90% (95% confidence interval, 73.1-96.8), respectively. Daratumumab plus lenalidomide/dexamethasone resulted in rapid, deep, durable responses. The combination was well tolerated and consistent with the safety profiles observed with lenalidomide/dexamethasone or daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01615029. PMID:27531679

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.

Differential regulation of cyclo-oxygenase-2 and 5-lipoxygenase-activating protein (FLAP) expression by glucocorticoids in monocytic cells.

PubMed

Goppelt-Struebe, M; Schaefer, D; Habenicht, A J

1997-10-01

1. The objective of the present study was to determine the effects of dexamethasone on key constituents of prostaglandin and leukotriene biosynthesis, cyclo-oxygenase-2 (COX-2) and 5-lipoxygenase activating protein (FLAP). The human monocytic cell line THP-1 was used as a model system. mRNA and protein levels of COX-2 and FLAP were determined by Northern and Western blot analyses, respectively. 2. Low levels of COX-2 and FLAP mRNA were expressed in undifferentiated THP-1 cells, but were induced upon differentiation of the cells along the monocytic pathway by treatment with phorbol ester (TPA, 5 nM). Maximal expression was observed after two days. 3. Coincubation of the undifferentiated cells with dexamethasone (10(-9) - 10(-6) M) and phorbol ester prevented induction of COX-2 mRNA, but did not affect the induction of FLAP mRNA. 4. Dexamethasone downregulated COX-2 mRNA and protein in differentiated, monocyte-like THP-1 cells. In contrast, FLAP mRNA and protein were upregulated by dexamethasone in differentiated THP-1 cells. After 24 h, FLAP mRNA levels were increased more than 2 fold. Dexamethasone did not change 5-lipoxygenase mRNA expression. 5. Release of prostaglandin E2 (PGE2) and peptidoleukotrienes was determined in cell culture supernatants of differentiated THP-1 cells by ELISA. Calcium ionophore-dependent PGE2 synthesis was associated with COX-2 expression, whereas COX-1 and COX-2 seemed to participate in arachidonic acid-dependent PGE2 synthesis. Very low levels of peptidoleukotrienes were released from differentiated THP-1 cells upon incubation with ionophore. Treatment with dexamethasone did not significantly affect leukotriene release. 6. These data provide evidence that prostaglandin synthesis is consistently downregulated by glucocorticoids. However, the glucocorticoid-mediated induction of FLAP may provide a mechanism to maintain leukotriene biosynthesis through more efficient transfer of arachidonic acid to the 5-lipoxygenase reaction, in spite of inhibitory effects on other enzymes of the biosynthetic pathway.

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 are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.

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.

The expression profiling and ontology analysis of non-coding RNAs in dexamethasone induced steatosis in hepatoma cell.

PubMed

Liu, Fengqiong; Gong, Ruijie; Lv, Xiaofei; Li, Huangyuan

2018-04-15

Increasing amounts of evidence have indicated that non-coding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remain largely unknown. The aim of this study is to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of drug induced steatosis. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in dexamethasone treated HepG2 cell as well as control cell. Differential expression, pathway and gene network analyses were developed to identify possible functional RNA molecules in dexamethasone induced steatosis. Compared with control HepG2 cell, 652 lncRNAs (528 up-regulated and 124 down-regulated), 655 mRNAs (527 upregulated and 128 down-regulated) and 114 miRNAs (55 miRNAs up-regulated and 59 down-regulated) were differentially expressed in dexamethasone treated HepG2 cell. Pathway analysis showed that the fatty acid biosynthesis, insulin resistance, PPAR signaling pathway, regulation of lipolysis in adipocytes, carbohydrate digestion and absorption, steroid hormone biosynthesis signaling pathways had a close relationship with dexamethasone induced steatosis. 10 highly dysregulated mRNAs and 20 miRNAs, which are closely related to lipid metabolism, were identified and validated by PCR, which followed by ceRNA analysis. CeRNA network analysis identified 5 lipid metabolism related genes, including CYP7A1, CYP11A1, PDK4, ABHD5, ACSL1. It also identified 12 miRNAs (miR-23a-3p, miR-519d-3p, miR-4328, miR-15b-5p etc.) and 177 lncRNAs (ENST00000508884, ENST00000608794, ENST00000568457 etc.). Our results provide a foundation and an expansive view of the roles and mechanisms of ncRNAs in dexamethasone induced steatosis. Copyright © 2018 Elsevier B.V. All rights reserved.

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 B.V. All rights reserved.

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

PubMed Central

Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

2017-01-01

Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes. PMID:27998979

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 strategies are evaluated for clinical application.

Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database.

PubMed

Hosoya, Ryuichiro; Uesawa, Yoshihiro; Ishii-Nozawa, Reiko; Kagaya, Hajime

2017-01-01

Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present study to be helpful for the prevention and treatment of hiccups.

Neurotoxicity induced by dexamethasone in the human neuroblastoma SH-SY5Y cell line can be prevented by folic acid.

PubMed

Budni, J; Romero, A; Molz, S; Martín-de-Saavedra, M D; Egea, J; Del Barrio, L; Tasca, C I; Rodrigues, A L S; López, M G

2011-09-08

Folic acid (folate) is a vitamin of the B-complex group that is essential for cell replication. Folate is a major determinant of one-carbon metabolism, in which S-adenosylmethionine donates methyl groups that are crucial for neurological function. Many roles for folic acid have been reported, including neuroprotective and antidepressant properties. On the other hand, increased concentrations of corticoids have proven neurotoxic effects and hypersecretion of glucocorticoids has been linked to different mood disorders. The purpose of this study was to investigate the potential protective effect of folic acid on dexamethasone-induced cellular death in SH-SY5Y neuroblastoma cell line and the possible intracellular signaling pathway involved in such effect. Exposure to 1 mM dexamethasone for 48 h caused a significant reduction of cell viability measured as 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction. Exposure of SH-SY5Y cells for 72 h to increasing concentrations of folate (1-300 μM) was not cytotoxic. However, pretreatment with folate (10-300 μM) reduced dexamethasone-induced toxicity in a significant manner. To explore the putative intracellular signaling pathways implicated in the protective effect of folate we used different protein kinase inhibitors. The protective effect of folic acid on dexamethasone-induced neurotoxicity was reversed by the phosphatidylinositol-3 kinase/Akt (PI3K/Akt, LY294002), Ca²⁺/Calmodulin-dependent protein kinase II (CaMKII, KN-93), and protein kinase A (PKA, H-89) inhibitors, but not the mitogen-activated protein/extracellular signal-regulated kinase (MEK1/2, PD98059) and protein kinase C (PKC, chelerythrine) inhibitors. In conclusion, the results of this study show that folic acid can protect against dexamethasone-induced neurotoxicity and its protective mechanism is related to a signaling pathway that involves PI3K/Akt, CaMKII, and PKA. Copyright © 2011. Published by Elsevier Ltd.

Stability of Extemporaneously Compounded Dexamethasone in Glass and Plastic Bottles and Plastic Syringes

PubMed Central

Ensom, Mary H H; Décarie, Diane

2014-01-01

Background Dexamethasone is widely used to treat rheumatic and endocrine disorders and chemotherapy-induced nausea and vomiting. A palatable, alcohol-free liquid formulation, with a suitable concentration to allow reasonable administration volume, is available only via extemporaneous compounding. Objective: To evaluate the stability of dexamethasone suspensions in commercially available vehicles (Oral Mix and Oral Mix SF) in various types of containers after storage at 25°C and 4°C for up to 91 days. Methods: Dexamethasone suspensions (1 mg/mL) were prepared in Oral Mix and Oral Mix SF and then transferred to amber glass and plastic prescription bottles and plastic oral syringes. Suspensions in all 3 types of containers were stored at 25°C; suspensions in glass and plastic bottles were also stored at 4°C. Samples were collected weekly from each container up to 28 days and then every 2 weeks up to 91 days. The samples were analyzed by a validated, stability-indicating high-performance liquid chromatography − ultraviolet detection method. A suspension was considered stable if it maintained at least 90% of its initial dexamethasone concentration. Changes in colour, taste, odour, precipitation (and ease of resuspension), and pH were used to assess physical compatibility. Results: All suspensions maintained at least 96% of the original concentration for up to 91 days with storage at 25°C or at 4°C. No notable changes in colour, taste, odour, precipitation, or pH were observed over the 91-day period. Conclusion: Dexamethasone suspensions (1 mg/mL) in Oral Mix and Oral Mix SF, stored in amber glass or plastic bottles or plastic syringes at 25°C or in amber glass or plastic bottles at 4°C can be expected to remain stable for up to 91 days. PMID:25214658

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.

TLC-Densitometric and RP-HPLC Methods for Simultaneous Determination of Dexamethasone and Chlorpheniramine Maleate in the Presence of Methylparaben and Propylparaben.

PubMed

Farid, Nehal F; Naguib, Ibrahim A; Moatamed, Radwa S; El Ghobashy, Mohamed R

2017-01-01

Validated simple, sensitive, and highly selective methods are applied for the quantitative determination of dexamethasone and chlorpheniramine maleate in the presence of their reported preservatives (methylparaben and propylparaben), whether in pure forms or in pharmaceutical formulation. TLC is the first method, in which dexamethasone, chlorpheniramine maleate, methylparaben, and propylparaben are separated on silica gel TLC F254 plates using hexane-acetone-ammonia (5.5 + 4.5 + 0.5, v/v/v) as the developing phase. Separated bands are scanned at 254 nm over a concentration range of 0.1-1.7 and 0.4-2.8 μg/band, with mean ± SD recoveries of 99.12 ± 0.964 and 100.14 ± 0.962%, for dexamethasone and chlorpheniramine maleate, respectively. Reversed-phase HPLC is the second method, in which a mixture of dexamethasone and chlorpheniramine maleate, methylparaben, and propylparaben is separated on a reversed-phase silica C18 (5 μm particle size, 250 mm, 4.6 mm id) column using 0.1 M ammonium acetate buffer-acetonitrile (60 + 40, v/v, pH 3) as the mobile phase. The drugs were detected at 220 nm over a concentration range of 5-50 μg/mL, 2-90 μg/mL, 4-100 μg/mL, and 7-50 μg/mL, with mean ± SD recoveries of 100.85 ± 0.905, 99.67 ± 1.281, 100.20 ± 0.906, and 99.81 ± 0.954%, for dexamethasone, chlorpheniramine maleate, methylparaben paraben, and propylparaben, respectively. The advantages of the suggested methods over previously reported methods are the ability to detect lower concentrations of the main drugs and to show better resolution of interfering preservatives; hence, these methods could be more reliable for routine QC analyses.

Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment.

PubMed

Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

2015-03-01

The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells. © 2014 British Society for Immunology.

Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment

PubMed Central

Molins, B; Mesquida, M; Lee, R W J; Llorenç, V; Pelegrín, L; Adán, A

2015-01-01

The aim of this study was to quantify the proportion of regulatory T cells (Treg) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)+ Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4+ T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3+ Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3+ Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3+ Treg cells. PMID:25354724

Grain dust induces IL-8 production from bronchial epithelial cells: the effect of dexamethasone on IL-8 production.

PubMed

Park, H S; Suh, J H; Kim, H Y; Kwon, O J; Choi, D C

1999-04-01

Recent publications have suggested an active participation of neutrophils to induce bronchoconstriction after inhalation of grain dust (GD). To further understand the role of neutrophils in the pathogenesis of GD-induced asthma, this investigation was designed to determine whether human bronchial epithelial cells could produce IL-8 production and to observe the effect of dexamethasone on IL-8 production. We cultured Beas-2B, a bronchial epithelial cell line. To observe GD-induced responses, four concentrations (1 to 200 microg/mL) of GD were incubated for 24 hours and compared with those without incubation of GD. To evaluate the effect of pro-inflammatory cytokines on IL-8 production, epithelial cells were incubated with peripheral blood mononuclear cell (PBMC) culture supernatant, which was derived from the culture of PBMC from a GD-induced asthmatic subject under the exposure to 10 microg/mL of GD, and compared with those cultured without addition of PBMC supernatant. The level of released IL-8 in the supernatant was measured by enzyme-linked immunosorbent assay. To evaluate the effect of dexamethasone on IL-8 production, four concentrations (5 to 5000 ng/mL) of dexamethasone were pre-incubated for 24 hours and the same experiments were repeated. There was significant production of IL-8 from bronchial epithelial cells with additions of GD in a dose-dependent manner (P < .05), which was significantly augmented with additions of PBMC supernatant (P < .05) at each concentration. Compared with the untreated sample, pretreatment of dexamethasone could induced a remarkable inhibitions (15% to 55%) of IL-8 production from bronchial epithelial cells in a dose-dependent manner. These results suggest that IL-8 production from bronchial epithelial cells may contribute to neutrophil recruitment occurring in GD-induced airway inflammation. The downregulation of IL-8 production by dexamethasone from bronchial epithelial cells may contribute to the efficacy of this compound in reducing cellular infiltration and ultimately to its anti-inflammatory property.

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

Glucocorticoids Recruit Tgfbr3 and Smad1 to Shift Transforming Growth Factor-β Signaling from the Tgfbr1/Smad2/3 Axis to the Acvrl1/Smad1 Axis in Lung Fibroblasts*

PubMed Central

Schwartze, Julian T.; Becker, Simone; Sakkas, Elpidoforos; Wujak, Łukasz A.; Niess, Gero; Usemann, Jakob; Reichenberger, Frank; Herold, Susanne; Vadász, István; Mayer, Konstantin; Seeger, Werner; Morty, Rory E.

2014-01-01

Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-β is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-β signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-β signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone drove expression of the accessory type III TGF-β receptor Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a “switch” that blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling. Dexamethasone acted synergistically with TGF-β to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts. Administration of dexamethasone to live mice recapitulated these observations and revealed a lung-specific impact of dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These data point to an interesting and hitherto unknown impact of glucocorticoids on TGF-β signaling in lung fibroblasts and other constituent cell types of the lung that may be relevant to lung physiology, as well as lung pathophysiology, in terms of drug/disease interactions. PMID:24347165

Moderate evidence to recommend submucosal injection of dexamethasone in reducing post-operative oedema and pain after third molar extraction.

PubMed

Freda, Nicolas M; Keenan, Analia Veitz

2016-06-01

Data sourcesThe electronic databases searched included: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (Central) and Web of Science until June 2015. There was no restriction to language and the reference lists from relevant studies were searched for further articles.Study selectionRandomised and prospective controlled trials that compared the effect of submucosal injection of dexamethasone with that of placebo after impacted third molar surgery in humans. Studies involving volunteers with decompensated metabolic disease were excluded.Data extraction and synthesisStudy selection, data extraction and quality assessment (risk of bias) were assessed by two reviewers. All disagreements were resolved through discussion. A meta-analysis was performed for all continuous variables (oedema, pain and trismus) when at least two of the studies analysed the same data type.ResultsEight studies involving a total of 476 patients of which six were included in the meta-analysis. All of the surgical procedures were performed on the lower molars, submucosal injections of dexamethasone were used in concentrations of 4 mg, 8 mg, or 10 mg, and saline was used as a control. Antibiotic medications were administered prophylactically before surgery or by continuous use after the procedure. Seven of the eight studies identified the impactions according to the Pell and Gregory Classification. Oedema was measured using facial contours of pre-established reference points. The meta-analysis presented a mean difference (MD) of -2.20 (95% CI -2.70 to -1.70), with a statistically significant difference favouring dexamethasone (P< 0.00001). Trismus (assessed using inter-incisal distance upon maximum opening) had a MD of -2.92 (95% CI -7.13 to 1.29) and showed no statistically significant difference between groups. Pain was assessed using both visual analogue scales and number of analgesic taken; however, only studies including a VAS were used for meta-analysis. Pain presented with a MD of -1.79 (95% CI -3.28 to -0.30) and showed a statistically significant difference favouring dexamethasone.ConclusionsThe review found moderate quality evidence that submucosal injections of dexamethasone reduced post-operative oedema and pain compared to a placebo following impacted third molar surgery. There was no significant difference, in regards to trismus, between placebo and dexamethasone.

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 cerebral palsy and visual impairment, and changes in intelligence quotient similar to those in the control group (RR = 1.26, 95%CI: 0.89-1.79; RR = 1.37, 95%CI: 0.73-2.59; RR = 0.53, 95%CI: 0.32-0.89; RR = 1.66, 95%CI: -4.7 to 8.01; P > 0.05). However, the incidence of hearing loss was significantly increased compared with that in the control group (RR = 0.53, 95%CI: 0.32-0.89; P = 0.02). Dexamethasone may affect the intelligence of preterm infants in the early stages after birth, but may lead to hearing impairment at later stages after birth. More reliable conclusions should be made through large-size, multi-center, well-designed randomized controlled trials.

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

REGULATION OF POSTNATAL B-ADRENERGIC RECEPTOR/ADENYLATE CYCLASE DEVELOPMENT BY PRENATAL AGONIST STIMULATION AND STEROIDS: ALTERATIONS IN RAT KIDNEY AND LUNG AFTER EXPOSURE TO TERBUTALINE OR DEXAMETHASONE

EPA Science Inventory

Glucocorticoids and adrenergic stimulation are both thought to control the development of adrenergic receptors/responses. n the current study, rats were exposed to dexamethasone or terbutaline during late gestation and the development of B-binding capabilities and adenylate cycla...

Fabrication of graphene oxide-modified chitosan for controlled release of dexamethasone phosphate

NASA Astrophysics Data System (ADS)

Sun, Huanghui; Zhang, Lingfan; Xia, Wei; Chen, Linxiao; Xu, Zhizhen; Zhang, Wenqing

2016-07-01

Functionalized graphene oxide with its unique physical and chemical properties is widely applied in biomaterials, especially in drug carrier materials. In the past few years, a number of different drugs have been loaded on functionalized graphene oxide via π-π stacking and hydrophobic interactions. The present report described a new approach, dexamethasone phosphate successfully loaded onto graphene oxide-chitosan nanocomposites as drug carrier materials by covalent bonding of phosphate ester linkage. Compared with the graphene oxide-chitosan nanocomposites that dexamethasone phosphate was loaded on via simple physical attachment, covalently linked composites as drug carrier materials were more biocompatible which effectively reduced the burst release of drug, and controlled the release of drug in different pH conditions.

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.

Sequential cyclophosphamide-bortezomib-dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light-chain cardiac amyloidosis.

PubMed

Le Bras, Fabien; Molinier-Frenkel, Valerie; Guellich, Aziz; Dupuis, Jehan; Belhadj, Karim; Guendouz, Soulef; Ayad, Karima; Colombat, Magali; Benhaiem, Nicole; Tissot, Claire Marie; Hulin, Anne; Jaccard, Arnaud; Damy, Thibaud

2017-05-01

Chemotherapy combining cyclophosphamide, bortezomib and dexamethasone is widely used in light-chain amyloidosis. The benefit is limited in patients with cardiac amyloidosis mainly because of adverse cardiac events. Retrospective analysis of our cohort showed that 39 patients died with 42% during the first month. A new escalation-sequential regimen was set to improve the outcomes. Nine newly-diagnosed patients were prospectively treated with close monitoring of serum N-terminal pro-brain natriuretic peptide, troponin-T and free light chains. The results show that corticoids may destabilise the heart through fluid retention. Thus, a sequential protocol may be a promising approach to treat these patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

ABCA1, ABCG1 and SR-BI: hormonal regulation in primary rat hepatocytes and human cell lines

PubMed Central

Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond

2007-01-01

Background Scavenger receptor type B class I (SR-BI), ABC transporter A1 (ABCA1) -and G1 (ABCG1) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA1, and ABCG1 by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. Results By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA1 and ABCG1 mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in primary rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-1 macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Conclusion Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the primary cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR. PMID:17241464

ABCA1, ABCG1 and SR-BI: hormonal regulation in primary rat hepatocytes and human cell lines.

PubMed

Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond

2007-01-22

Scavenger receptor type B class I (SR-BI), ABC transporter A1 (ABCA1) -and G1 (ABCG1) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA1, and ABCG1 by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA1 and ABCG1 mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in primary rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-1 macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the primary cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR.

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.

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.

Decreased H3K9ac level of StAR mediated testicular dysplasia induced by prenatal dexamethasone exposure in male offspring rats.

PubMed

Liu, Min; Chen, Biao; Pei, Linguo; Zhang, Qi; Zou, Yunfei; Xiao, Hao; Zhou, Jin; Chen, Liaobin; Wang, Hui

2018-06-11

Prenatal dexamethasone exposure (PDE) could induce testicular developmental toxicity in adults. The present study aims to confirm its intrauterine origination, and to explore its potential intrauterine programming mechanism. The pregnant rats were respectively injected subcutaneously with 0.2 and 0.8 mg/kg⋅d dexamethasone during gestational days (GD) 9 to 20. The testes and serum of offspring rats were collected on GD20 and postnatal week (PW) 12. In vivo, PDE significantly induced the abnormal testicular morphology in offspring from GD20 to PW12. Moreover, the serum and intratesticular testosterone levels and the expression of testicular steroidogenic acute regulatory protein (StAR) were reduced by PDE. The expression levels of glucocorticoid receptor (GR) and histone deacetylase 7 (HDAC7) were increased in fetal testes. Furthermore, the histone 3 lysine 9 acetylation (H3K9ac) level in the StAR promoter was decreased by PDE from GD20 to PW12. In vitro, mouse Leydig tumour cell line (MLTC-1) cells were treated with dexamethasone (20, 100 and 500 nM), and the testosterone production and StAR expression were reduced. Moreover, dexamethasone increased the expression of HDAC7 by activating GR, which decreased the H3K9ac level in the StAR promoter. Taken together, PDE caused testicular dysplasia before and after birth in male offspring rats, and its mechanism was related to the low-expressional programming of StAR mediated by decreasing H3K9ac level. Copyright © 2018. Published by Elsevier B.V.

[Experimental study on avascular necrosis of femoral head in chickens induced by different glucocorticoides].

PubMed

Xiao, Chun-Sheng; Lin, Na; Lin, Shi-Fu; Wan, Rong; Chen, Wei-Heng

2010-03-01

To study the effects of Methylprednisolone and Dexamethasone on the avascular necrosis of femoral head in chickens. Thirty-six chickens were randomly divided into 6 groups (n = 6): control group (group A), Methylprednisolone low dose group (group B), Methylprednisolone large dose group (group C), small dose Dexamethasone and horse serum group (group D), middle dose Dexamethasone and horse serum group (group E), and Dexamethasone large dose group (group F). On the 6th and 12th weeks, blood samples were obtained to determine the level of total cholesterol triglyeride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL). On the 12th week, femoral heads were taken off. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin staining. On the 6th week, compared with group A, the level of CHO increased significantly in group C and group F (P < 0.05), and TG increased in group B, C and group E, while HDL decreased in group B, C and group E. On the 12th week, the level of TG and CHO increased in group B, C, E and group F, and HDL decreased in group C, D and group E (P < 0.05). LDL was not detected in most chickens. The ratio of empty lacuna was higher in group C and group E compared with those of the control group (P < 0.05). Methylprednisolone is easier to induce osteonecrosis of femoral head than Dexamethasone. The condition of metabolic disorder in blood may be the basic pathomechanism of steroid-induced necrosis of femoral head.

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.

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.

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.

Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men.

PubMed Central

Fried, S K; Russell, C D; Grauso, N L; Brolin, R E

1993-01-01

There are marked variations in the activity of lipoprotein lipase (LPL) among adipose depots, particularly in women. Consistent with data on LPL activity, the level of expression of LPL mRNA was lower in omental (OM) than subcutaneous (SQ) adipose tissue of women. To investigate the cellular basis of these differences, OM and SQ adipose tissues obtained at surgery from obese men and women were placed in organ culture for 7 d with varying concentrations of insulin and dexamethasone. Insulin increased levels of LPL mRNA and LPL activity in abdominal SQ but not OM adipose tissue. Dexamethasone also increased LPL mRNA and LPL activity, and these effects were more marked in the OM adipose tissue, particularly in men. When insulin and dexamethasone were added together, synergistic increases in LPL activity were seen in both depots, and this was in part explained at the level of LPL mRNA. The SQ depot was more sensitive to the effects of submaximal doses of dexamethasone in the presence of insulin. The maximum activity of LPL induced by insulin or insulin plus dexamethasone was higher in the SQ than in the OM depot of women, and this was associated with higher levels of LPL mRNA. Rates of LPL synthesis paralleled LPL mRNA levels. These data show that insulin and glucocorticoids influence human adipose tissue LPL activity at the level of LPL gene expression, as well as posttranslationally, and that responsiveness to these hormonal effects is dependent on adipose depot and gender. Images PMID:8227334

Comparative analgesic efficacy of different doses of dexamethasone during infraumbilical surgery: A Randomized controlled trial

PubMed Central

Jain, Ragi; Dua, C. K.

2015-01-01

Background: Postoperative pain is a common complaint and despite the availability of various drugs, is still not managed well. Analgesic effects of glucocorticoids are still to be substantially established. Hence, we designed randomized, double-blind, placebo-controlled trial to compare the effect of two different doses of dexamethasone on postoperative pain in patients undergoing infra-umbilical surgeries under spinal anesthesia. Methods: Ninety American Society of Anesthesiologists Grade I and II patients were randomized to receive injection dexamethasone 8 mg (Group DI), dexamethasone 16 mg (Group DII) or placebo (Group C) prior to performance of intrathecal block. Outcome studied was postoperative pain on the rest and motion and nausea and vomiting. Result: There was no difference in Visual Analog Scale (VAS) scores during rest in all the three groups. However, VAS scores on motion showed a significant decrease in Group DII at 24 and 36 h when compared to Group C (95% confidence interval [CI] of mean at 24 h for Group C = 5.6093–7.1049 and Group DII = 4.8709–5.9567, P = 0.04; 95% CI of mean at 36 h for Group C = 4.5868–5.8418 and Group DII = 3.5388–4.7378, P = 0.01). There was no significant difference in the incidence of postoperative nausea and vomiting or additional analgesic requirements. Conclusion: Dexamethasone 16 mg reduces postoperative pain on motion at 24 and 36 h. It has no effect on postoperative pain at rest or on nausea and vomiting. PMID:25886418

Prenatal glucocorticoid exposure in rats: programming effects on stress reactivity and cognition in adult offspring.

PubMed

Zeng, Yan; Brydges, Nichola M; Wood, Emma R; Drake, Amanda J; Hall, Jeremy

2015-01-01

Human epidemiological studies have provided compelling evidence that prenatal exposure to stress is associated with significantly increased risks of developing psychiatric disorders in adulthood. Exposure to excessive maternal glucocorticoids may underlie this fetal programming effect. In the current study, we assessed how prenatal dexamethasone administration during the last week of gestation affects stress reactivity and cognition in adult offspring. Stress reactivity was assessed by evaluating anxiety-like behavior on an elevated plus maze and in an open field. In addition, to characterize the long-term cognitive outcomes of prenatal exposure to glucocorticoids, animals were assessed on two cognitive tasks, a spatial reference memory task with reversal learning and a delayed matching to position (DMTP) task. Our results suggest that prenatal exposure to dexamethasone had no observable effect on anxiety-like behavior, but affected cognition in the adult offspring. Prenatally dexamethasone-exposed animals showed a transient deficit in the spatial reference memory task and a trend to faster acquisition during the reversal-learning phase. Furthermore, prenatally dexamethasone-treated animals also showed faster learning of new platform positions in the DMTP task. These results suggest that fetal overexposure to glucocorticoids programs a phenotype characterized by cognitive flexibility and adaptability to frequent changes in environmental circumstances. This can be viewed as an attempt to increase the fitness of survival in a potentially hazardous postnatal environment, as predicted by intrauterine adversity. Collectively, our data suggest that prenatal exposure to dexamethasone in rats could be used as an animal model for studying some cognitive components of related psychiatric disorders.

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.

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.

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.

How do I provide leukapheresis products? Blood center experience and evidence for process improvement.

PubMed

Ginzburg, Yelena; Kessler, Debra; Narici, Manlio; Caltabiano, Melinda; Rebosa, Mark; Strauss, Donna; Shaz, Beth

2013-10-01

The past few decades have seen a resurgence of interest in leukapheresis products to improve the survival of infected patients with neutropenia. These products have a short shelf life and require donor stimulation with dexamethasone before collection. Additionally, a system with good communications and logistical support is essential. A recent survey of blood centers in North America revealed that the majority of centers collecting leukapheresis products use steroid-stimulated donors. The survey results suggested that an analysis of the process and potential process improvement would be of interest to the transfusion medicine community. Data from 2008 to 2011 regarding donor selection, donor dexamethasone stimulation, leukapheresis collection, and correlations between potentially pertinent variables for process improvement were analyzed. Results from an analysis of cost are also included. We evaluate 432 leukapheresis donations and demonstrate correlations between 1) pre- and poststimulation white blood cell (WBC) count (p<0.0001), 2) interval (donor stimulation to collection) and poststimulation WBC count (p<0.0001), and 3) poststimulation WBC count and leukapheresis product granulocyte yield (p<0.0001). Significant improvement in granulocyte quality and yield can be accomplished in dexamethasone-stimulated donors, by selecting eligible donors with relatively high normal prestimulation WBC counts and/or previously good responses to dexamethasone, increasing the duration between dexamethasone stimulation and granulocyte collection, and maintaining optimal hematocrit (5%-10%) in granulocyte collections. Because the majority of surveyed blood centers collecting stimulated granulocytes use steroids alone, modifications presented here may prove useful. Further assessment of correlation between granulocyte yield and clinical outcome will await results of additional studies. © 2012 American Association of Blood Banks.

Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats.

PubMed

Liu, Yanzhi; Cui, Yang; Chen, Yan; Gao, Xiang; Su, Yanjie; Cui, Liao

2015-01-01

To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats. Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses. The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats. This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.

Neural changes in periapical lesions after systemic steroids in the ferret.

PubMed

Holland, G R

1993-06-01

This study was intended to clarify the relationship between the neural changes which occur around the apex of the ferret canine after pulpectomy and the inflammatory process induced by the procedure. In 12 young adult ferrets, under general anesthesia, the pulps in the mandibular canine teeth were removed and replaced with gutta percha and Grossman's sealer. Six of the animals were treated with dexamethasone to reduce the inflammatory response. Three months later, the animals, again under general anesthesia, were perfused with a fixative mixture. Three unoperated animals that had not been treated with dexamethasone were also perfused. The mandibular canine teeth and their supporting tissues were removed, processed, and serially sectioned. Three-dimensional reconstructions of the periapical lesions in each animal were assembled and their volumes measured. The density of innervation in the periapical region was estimated. The mean lesion volume in the pulpectomized animals not treated with dexamethasone was 3.54 (+/- 2.27) mm3 and in the dexamethasone-treated animals 1.33 (+/- 1.31) mm3. The differences were statistically significant when tested by the Mann-Whitney U test (p < 0.01). Bacteria were not seen within any of the lesions. The innervation density beneath the canines in the pulpectomized animals not treated with dexamethasone was 164 units per mm2 (+/- 80) and in the steroid-treated animals 151 +/- 68 units per mm2. In the control, untreated animals, the innervation density was 22 +/- 10 units per mm2. The difference between the steroid-treated pulpectomized animals and the untreated pulpectomized animals was not statistically significant (p > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

PubMed

Greenberg, Chelsea B; Boria, Pedro A; Borgatti-Jeffreys, Antonella; Raskin, Rose E; Lucroy, Michael D

2007-01-01

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

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 ...

Effects of vitamin D and yeast extract supplementation on turkey mortality and clostridial dermatitis incidence in a dexamethasone immunosuppresssion model

USDA-ARS?s Scientific Manuscript database

Clostridial dermatitis is a production disease of commercial turkeys that is chararacterized by sudden mortality in market-aged male birds and lesions that include fluid and air bubbles under the skin of the thigh, breast, and tail area. We have developed a model for CD using dexamethasone (Dex) inj...

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...

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

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

[Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

PubMed

Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

2016-03-22

To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

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.

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.

Determination of induction period and crystal growth mechanism of dexamethasone sodium phosphate in methanol-acetone system

NASA Astrophysics Data System (ADS)

Hao, Hongxun; Wang, Jingkang; Wang, Yongli

2005-02-01

The induction period of dexamethasone sodium phosphate at different supersaturation was experimentally determined in a methanol-acetone system. The laser monitoring observation technique was used to determine the appearance of the first nucleus in solution. The effect of solution composition on induction period was discussed. Based on classical homogeneous nucleation theory, the solid-liquid interfacial tension and surface entropy factor were calculated from the induction period data. The experimentally determined values of interfacial tension are in agreement with the theoretical values predicted by the Mersmann equation. It was found that the nucleus of dexamethasone sodium phosphate grows continuously in pure methanol and turns from continuous growth to birth and spread growth with increasing acetone content in a methanol-acetone mixture.

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model.

PubMed

Bloudek, Lisa; Roy, Anuja; Kish, Jonathan K; Siegel, David S; Jagannath, Sundar; Globe, Denise; Orloski, Laurie; Kuriakose, Emil T

2016-08-01

Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost < $0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment. Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speaker's bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

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 infants treated with dexamethasone 7 days after birth demonstrated an incidence of cerebral palsy and visual impairment, and changes in intelligence quotient similar to those in the control group (RR = 1.26, 95%CI: 0.89–1.79; RR = 1.37, 95%CI: 0.73–2.59; RR = 0.53, 95%CI: 0.32–0.89; RR = 1.66, 95%CI: −4.7 to 8.01; P > 0.05). However, the incidence of hearing loss was significantly increased compared with that in the control group (RR = 0.53, 95%CI: 0.32–0.89; P = 0.02). CONCLUSION: Dexamethasone may affect the intelligence of preterm infants in the early stages after birth, but may lead to hearing impairment at later stages after birth. More reliable conclusions should be made through large-size, multi-center, well-designed randomized controlled trials. PMID:25206867

Dexamethasone facilitates erythropoiesis in murine embryonic stem cells differentiating into hematopoietic cells in vitro

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

Srivastava, Anand S.; Kaushal, Sharmeela; Mishra, Rangnath

2006-07-28

Differentiating embryonic stem (ES) cells are increasingly emerging as an important source of hematopoietic progenitors with a potential to be useful for both basic and clinical research applications. It has been suggested that dexamethasone facilitates differentiation of ES cells towards erythrocytes but the mechanism responsible for sequential expression of genes regulating this process are not well-understood. Therefore, we in vitro induced differentiation of murine ES cells towards erythropoiesis and studied the sequential expression of a set of genes during the process. We hypothesized that dexamethasone-activates its cognate nuclear receptors inducing up-regulation of erythropoietic genes such as GATA-1, Flk-1, Epo-R, andmore » direct ES cells towards erythropoietic differentiation. ES cells were cultured in primary hematopoietic differentiation media containing methyl-cellulose, IMDM, IL-3, IL-6, and SCF to promote embryoid body (EB) formation. Total RNA of day 3, 5, and 9-old EBs was isolated for gene expression studies using RT-PCR. Cells from day 9 EBs were subjected to secondary differentiation using three different cytokines and growth factors combinations: (1) SCF, EPO, dexamethasone, and IGF; (2) SCF, IL-3, IL-6, and TPO; and (3) SCF IL-3, IL-6, TPO, and EPO. Total RNA from day 12 of secondary differentiated ES cells was isolated to study the gene expression pattern during this process. Our results demonstrate an up-regulation of GATA-1, Flk-1, HoxB-4, Epo-R, and globin genes ({alpha}-globin, {beta}H-1 globin, {beta}-major globin, {epsilon} -globin, and {zeta}-globin) in the 9-day-old EBs, whereas, RNA from 5-day-old EBs showed expression of HoxB-4, {epsilon}-globin, {gamma}-globin, {beta}H1-globin, and Flk-1. Three-day-old EBs showed only HoxB-4 and Flk-1 gene expression and lacked expression of all globin genes. These findings indicate that erythropoiesis-specific genes are activated later in the course of differentiation. Gene expression studies on the ES cells of secondary EB origin cultured in media containing dexamethasone showed a down-regulation of GATA-3 and an up-regulation of GATA-1, Flk-1, and Epo-R in comparison to the two other cytokines and growth factor combinations containing media. The secondary differentiation also showed an enhanced production of erythrocytic precursors in dexamethasone containing media in comparison to that in the control media. Our results indicate that dexamethasone can prove to be an effective agent which can be employed to enhance differentiation towards erythrocytic progenitors from ES cells.« less

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 lower in the OVX-DEXA group compared with the other groups. Biglycan, runt-related transcription factor 2, osteoprotegerin, and lipoprotein receptor-related protein-5 were down-regulated in the DEXA, OVX, and OVX-DEXA groups compared with the BL and SHAM groups, whereas cathepsin K and sclerostin were up-regulated in the OVX-DEXA group compared with the DEXA and OVX groups. Ovariectomy combined with dexamethasone induced more serious osteoporosis in the rat lumbar spine than either ovariectomy or dexamethasone alone. The combined effect may be due to a combination of suppressed bone formation and increased bone resorption related to an estradiol deficit.

Dose response effect of NutriTek on leukocyte functionality and ex vivo cytokine production 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 ± 8.16 kg; N = 32) were assigned to treatments including 0, 20, 40, or 60 g/head/...

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...

Comparative efficacy of dexamethasone or corticotropin releasing hormone and vasopressin administration as a model to induce chronic physiological stress in beef cattle

USDA-ARS?s Scientific Manuscript database

The objective of this study was to delineate a model for chronic stress by evaluating physiological and hematological alterations in cattle administered: 1) 0.5 mg/kg body weight dexamethasone (DEX) once daily at 10am for 3 days consecutively, or 2) 0.3 micrograms/kg body weight corticotropin releas...

Role of the adrenocortical reaction to physical load in increase in the working capacity of the body

NASA Technical Reports Server (NTRS)

Viru, A. A.

1977-01-01

The maximal duration of swimming by rats with a load of 3% of their body weight increased after 5 weeks of training. This time did not increase in animals receiving dexamethasone in the process of training. The blood corticosterone level of these rats with the maximal load increased less than that of animals trained without administration of dexamethasone.

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