Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DEXAMETHASONE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources
PubMed2004

Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults.

BACKGROUND: Tuberculous meningitis kills or disables more than half of those affected with the disease. Previous studies have been too small to determine whether adjunctive treatment with corticosteroids can reduce the risk of disability or death among adults with tuberculous meningitis, and the effect of coinfection with the human immunodeficiency virus (HIV) is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial in Vietnam in patients over 14 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adjunctive treatment with dexamethasone reduced the risk of death or severe disability after nine months of follow-up. We conducted prespecified subgroup analyses and intention-to-treat analyses. RESULTS: A total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment with dexamethasone was associated with a reduced risk of death (relative risk, 0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not associated with a significant reduction in the proportion of severely disabled patients (34 of 187 patients [18.2 percent] among survivors in the dexamethasone group vs. 22 of 159 patients [13.8 percent] in the placebo group, P=0.27) or in the proportion of patients who had either died or were severely disabled after nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13; P=0.22). The treatment effect was consistent across subgroups that were defined by disease-severity grade (stratified relative risk of death, 0.68; 95 percent confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04; P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone group than in the placebo group (26 of 274 patients vs. 45 of 271 patients, P=0.02). CONCLUSIONS: Adjunctive treatment with dexamethasone improves survival in patients over 14 years of age with tuberculous meningitis but probably does not prevent severe disability.

AIDS-Related Opportunistic Infections↗
PubMed2000

A meta-analysis of dexamethasone use with tonsillectomy.

OBJECTIVE: To determine the quantitative impact of intravenous dexamethasone on recovery after tonsillectomy using established principles for meta-analysis. STUDY DESIGN/SETTING: Double-blind randomized-control trials in which subjects were treated identically except for the presence or absence of perioperative intravenous dexamethasone. Six articles met inclusion criteria. Two investigators extracted data regarding postoperative emesis and return to a soft/regular diet. RESULTS: Pooled analysis using a random effects model revealed a 27% decrease (P<0.00001) in postoperative emesis attributable to dexamethasone (95% CI, 12% to 42%). Dexamethasone increased the tolerance of a soft/regular diet at 24 hours by 22% (P< 0.001), but studies were heterogenous with low precision (95% CI, 1% to 44%). CONCLUSION: To prevent emesis in 1 child after tonsillectomy, approximately 4 children must receive perioperative dexamethasone. An additional benefit is earlier tolerance of a soft/regular diet, but low precision and heterogeneity among studies preclude definitive conclusions. SIGNIFICANCE: Perioperative dexamethasone administration had a positive impact on recovery from tonsillectomy.

Antiemetics↗
PubMed2001

Oral dexamethasone pulse treatment for vitiligo.

BACKGROUND: Oral corticosteroid pulse therapy has provided inconsistent results in the treatment of Indian patients with vitiligo. OBJECTIVE: We wanted to evaluate the efficacy, safety, and tolerability of oral dexamethasone pulse therapy in a cohort of Austrian patients with vitiligo. METHODS: Twenty-nine patients with vitiligo were included in the study. Of these, 25 had progressive and 4 had stable disease. The patients were given weekly pulses of 10 mg dexamethasone each on 2 consecutive days followed by 5 days off treatment for a maximum period of 24 weeks. Clinical response and side effects were evaluated in monthly intervals. Plasma cortisol and corticotropin levels were monitored before and up to 6 days after the dexamethasone pulse in the first and fourth week of treatment in 14 patients. RESULTS: After a mean treatment period of 18.2 +/- 5.2 weeks, the disease activity was arrested in 22 of 25 patients (88%) who had active vitiligo before the study. Marked repigmentation occurred in 2 patients (6.9%) and moderate or slight repigmentation in 3 patients (10.3%) each. No response was noted in 21 patients (72.4%). Side effects were recorded in 20 patients (69%) and included weight gain, insomnia, acne, agitation, menstrual disturbance, and hypertrichosis. Plasma cortisol and corticotropin values were markedly decreased 24 hours after the second dexamethasone dose, yet returned to baseline values within the off treatment period before the next dexamethasone pulse. CONCLUSION: Our data show that oral dexamethasone pulse treatment is effective in arresting progression of vitiligo yet fails to induce satisfactory repigmentation in the great majority of our patient cohort. Mild to moderate side effects are common with this treatment modality; however, sustained suppression of endogenous cortisol production does not occur with the pulse regimen.

Administration, Oral↗
PubMed1995

Lipocortin 1 mediates the inhibition by dexamethasone of the induction by endotoxin of nitric oxide synthase in the rat.

Administration of Escherichia coli lipopolysaccharide (LPS; 10 mg/kg i.v.) to male Wistar rats caused within 240 min (i) a sustained fall (approximately 30 mmHg) in mean arterial blood pressure, (ii) a reduction (> 75%) in the pressor responses to norepinephrine (1 microgram/kg i.v.), and (iii) an induction of nitric oxide synthase (iNOS) as measured in the lung. Dexamethasone (1 mg/kg i.p. at 2 h prior to LPS) attenuated the hypotension and the vascular hyporeactivity to norepinephrine and reduced (by approximately 77%) the expression of iNOS in the lung. These effects of dexamethasone were prevented by pretreatment of LPS-treated rats with a neutralizing antiserum to lipocortin 1 (anti-LC1; 60 mg/kg s.c. at 24 h prior to LPS) but not by a control nonimmune sheep serum. Stimulation of J774.2 macrophages with LPS (1 microgram/ml for 24 h) caused the expression of iNOS and cyclooxygenase 2 (COX-2) protein and significantly increased nitrite generation; this was prevented by dexamethasone (0.1 microM at 1 h prior to LPS), which also increased cell surface lipocortin 1. Pretreatment of J774.2 cells with anti-LC1 (1:60 dilution at 4 h prior to LPS) also abolished the inhibitory effect of dexamethasone on iNOS expression and nitrite accumulation but not that on COX-2 expression. A lipocortin 1 fragment (residues 1-188 of human lipocortin 1; 20 micrograms/ml at 1 h prior to LPS) also blocked iNOS in J774.2 macrophages activated by LPS (approximately 78% inhibition), and this too was prevented by anti-LC1. We conclude that the extracellular release of endogenous lipocortin 1 (i) mediates the inhibition by dexamethasone of the expression of iNOS, but not of COX-2, and (ii) contributes substantially to the beneficial actions of dexamethasone in rats with endotoxic shock.

Amino Acid Oxidoreductases↗
PubMed1997

Mechanisms of suppression of inducible nitric-oxide synthase (iNOS) expression in interferon (IFN)-gamma-stimulated RAW 264.7 cells by dexamethasone. Evidence for glucocorticoid-induced degradation of iNOS protein by calpain as a key step in post-transcriptional regulation.

The murine macrophage cell line RAW 264.7 expresses inducible nitric-oxide synthase (iNOS) activity upon stimulation with interferon (IFN)-gamma and/or bacterial lipopolysaccharide. We have studied the mechanisms by which the synthetic glucocorticoid dexamethasone suppresses IFN-gamma-stimulated iNOS expression in RAW 264.7 cells. Treatment of cells with dexamethasone reduces the formation of nitrite, one of the stable end products of NO production measured in culture supernatants with an IC50 of 9 nM. The reduction of iNOS activity is caused by decreased iNOS protein levels as assessed by immunoblotting using a specific anti-iNOS antibody. Dexamethasone treatment also reduces the formation of iNOS mRNA steady state levels to about 50% in IFN-gamma-stimulated cells. This is due to decreased iNOS gene transcription and iNOS mRNA stability. More importantly, dexamethasone reduces the amount of iNOS protein by two additional mechanisms: reduction of the translation of iNOS mRNA and increased degradation of the iNOS protein. Using a specific protease inhibitor for the cysteine protease calpain I, N-acetyl-Leu-Leu-norleucinal (calpain inhibitor I), the enhanced proteolysis of the iNOS protein can efficiently be blocked, whereas other protease inhibitors such as tosyl-L-lysine chloromethyl ketone have no effect. Dexamethasone does not significantly alter calpain gene expression. Northern blot analyses reveal that calpain mRNA steady state levels are virtually not affected upon incubation of the cells with IFN-gamma and dexamethasone. Immunoprecipitation using a polyclonal anti-calpain antibody reveals that calpain protein levels are also not affected by the glucocorticoid. This is the first evidence that the iNOS protein is a molecular target for the cysteine protease calpain.

Animals↗
PubMed1997

Dexamethasone induces posttranslational degradation of GLUT2 and inhibition of insulin secretion in isolated pancreatic beta cells. Comparison with the effects of fatty acids.

GLUT2 expression is strongly decreased in glucose-unresponsive pancreatic beta cells of diabetic rodents. This decreased expression is due to circulating factors distinct from insulin or glucose. Here we evaluated the effect of palmitic acid and the synthetic glucocorticoid dexamethasone on GLUT2 expression by in vitro cultured rat pancreatic islets. Palmitic acid induced a 40% decrease in GLUT2 mRNA levels with, however, no consistent effect on protein expression. Dexamethasone, in contrast, had no effect on GLUT2 mRNA, but decreased GLUT2 protein by about 65%. The effect of dexamethasone was more pronounced at high glucose concentrations and was inhibited by the glucocorticoid antagonist RU-486. Biosynthetic labeling experiments revealed that GLUT2 translation rate was only minimally affected by dexamethasone, but that its half-life was decreased by 50%, indicating that glucocorticoids activated a posttranslational degradation mechanism. This degradation mechanism was not affecting all membrane proteins, since the alpha subunit of the Na+/K+-ATPase was unaffected. Glucose-induced insulin secretion was strongly decreased by treatment with palmitic acid and/or dexamethasone. The insulin content was decreased ( approximately 55 percent) in the presence of palmitic acid, but increased ( approximately 180%) in the presence of dexamethasone. We conclude that a combination of elevated fatty acids and glucocorticoids can induce two common features observed in diabetic beta cells, decreased GLUT2 expression, and loss of glucose-induced insulin secretion.

Animals↗
PubMed2006

Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1.

The mammalian target of rapamycin (mTOR), a critical modulator of cell growth, acts to integrate signals from hormones, nutrients, and growth-promoting stimuli to downstream effector mechanisms involved in the regulation of protein synthesis. Dexamethasone, a synthetic glucocorticoid that represses protein synthesis, acts to inhibit mTOR signaling as assessed by reduced phosphorylation of the downstream targets S6K1 and 4E-BP1. Dexamethasone has also been shown in one study to up-regulate the expression of REDD1 (also referred to RTP801, a novel stress-induced gene linked to repression of mTOR signaling) in lymphoid, but not nonlymphoid, cells. In contrast to the findings of that study, here we demonstrate that REDD1, but not REDD2, mRNA expression is dramatically induced following acute dexamethasone treatment both in rat skeletal muscle in vivo and in L6 myoblasts in culture. In L6 myoblasts, the effect of the drug on mTOR signaling is efficiently blunted in the presence of REDD1 RNA interference oligonucleotides. Moreover, the dexamethasone-induced assembly of the mTOR regulatory complex Tuberin. Hamartin is disrupted in L6 myoblasts following small interfering RNA-mediated repression of REDD1 expression. Finally, overexpression of Rheb, a downstream target of Tuberin function and a positive upstream effector of mTOR, reverses the effect of dexamethasone on phosphorylation of mTOR substrates. Overall, the data support the conclusion that REDD1 functions upstream of Tuberin and Rheb to down-regulate mTOR signaling in response to dexamethasone.

Animals↗
PubMed2002

Differential induction of midazolam metabolism in the small intestine and liver by oral and intravenous dexamethasone pretreatment in rat.

1. Midazolam is metabolized in the rat by CYP3A enzymes to 4-OH-midazolam (4-OH-MDZ) and 1'-OH-midazolam (1'-OH-MDZ). The induction of midazolam metabolism was studied in male Wistar rats treated with dexamethasone (50 mg kg(-1) day(-1)) during 4 days via the oral or intravenous routes. Microsomes were prepared from the liver and the proximal small intestine and in vitro metabolism of midazolam was determined. In addition, CYP3A1- and CYP3A2-like protein levels were measured by gel electrophoresis and immunoblotting. 2. The V(max)'s (mean SEM) for 4-OH-MDZ and 1'-OH-MDZ formation were much lower in intestinal (0.078 +/- 0.002 and 0.074 +/- 0.002 microM min(-1) mg(-1) protein, respectively) compared with hepatic microsomes prepared from the uninduced rat (0.870 +/- 0.007 and 0.310 +/- 0.020 microM min(-1) mg(-1) protein, respectively). Induction by oral or intravenous dexamethasone pretreatment led to significant increases in V(max) for 4-OH-MDZ and 1'-OH-MDZ by both intestinal and hepatic microsomes. Oral dexamethasone pretreatment via the oral route resulted in a more pronounced increase in V(max) compared with intravenous administration of the inducer. 3. CYP3A1 and CYP3A2 protein levels in liver microsomes were significantly increased following oral (3.7- and 3.2-fold, respectively) or intravenous (2.6- and 2.1-fold, respectively) pretreatment with dexamethasone. On the contrary, only oral dexamethasone pretreatment resulted in a significant change in intestinal CYP3A2-like protein (7.3-fold). A slight difference in the migration distance of the immunoreactive band for CYP3A2 was also observed for intestinal microsomes. 4. These results suggest that intestinal CYP3A enzymes in the rat differ from hepatic CYP3A1 and CYP3A2. They also demonstrate that systemic dexamethasone administration can induce intestinal microsome activity.

Administration, Oral↗
PubMed2000

Dexamethasone treatment and fluid balance in preterm infants at risk for chronic lung disease.

UNLABELLED: The influence of dexamethasone on diuresis in preterm infants has not been well studied. We examined 15 preterm infants at risk for chronic lung disease with gestational ages ranging from 26 to 29 wk (median 27.6 wk) and birthweights ranging from 700 to 1485 g (median 965 g). Urine output, blood glucose, serum urea, serum creatinine, serum sodium and serum potassium, as well as systolic, diastolic and mean arterial pressure were measured on the day before, and on 4 consecutive days after starting treatment with dexamethasone (0.25 mg kg-1 i.v., twice daily). We found an increase of diuresis of 30 ml kg -1 d-1, 48-96 h after starting dexamethasone treatment. This coincided with a gradual but significant increase of serum urea levels and arterial pressure. During the study period, fluid and protein intake remained constant. Blood glucose and serum creatinine levels did not change. Our findings suggest that the increased urine output following dexamethasone treatment might be caused by two factors: (1) pressure diuresis induced by the increase of arterial pressure and (2) an increase of the osmolar load to the kidney due to an increase of serum urea. CONCLUSIONS: This study demonstrates that a significant increase of diuresis occurs in preterm infants, 48-96 h after starting dexamethasone. A careful monitoring of fluid balance during the first days of dexamethasone treatment is recommended.

Anti-Inflammatory Agents↗
PubMed2003

Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-kappaB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line.

AIMS: Nitric oxide (NO) has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in a mouse fetal skin dendritic cell line. METHODS: NO production was assessed by the method of Griess. Expression of the inducible isoform of nitric oxide synthase (iNOS) protein was evaluated by western blot analysis and immunofluorescence microscopy. Western blot analysis was also performed to evaluate cytosolic IkappaB-alpha (IkappaB-alpha) protein levels. The electrophoretic mobility shift assay was used to evaluate the activation or inhibition of nuclear factor kappa B (NF-kappaB). RESULTS: GM-CSF induced iNOS expression and NO production, and activated the transcription factor NF-kappaB. Dexamethasone inhibited, in a dose-dependent manner, NO production induced by GM-CSF. Addition of dexamethasone to the culture, 30 min before GM-CSF stimulation, significantly inhibited the cellular expression of iNOS. Dexamethasone also inhibited GM-CSF-induced NF-kappaB activation by preventing a significant decrease on the IkappaB-alpha protein levels, thus blocking NF-kappaB migration to the nucleus. CONCLUSIONS: The corticosteroid dexamethasone inhibits GM-CSF-induced NF-kappaB activation, iNOS protein expression and NO production. These results suggest that dexamethasone is a potent inhibitor of intracellular events that are involved on NO synthesis, in skin dendritic cells.

Animals↗
PubMed2004

Effect of dexamethasone treatment on oxidative energy metabolism in rat liver mitochondria during postnatal developmental periods.

Dexamethasone--a potent synthetic glucocorticoid--has multiple therapeutic applications and is used in all age groups, as well as for antenatal and perinatal treatments. However, side-effects of dexamethasone treatment, including those on development, are becoming increasingly apparent. Since developmental processes are energy-dependent, we examined the effects of chronic dexamethasone treatment on oxidative energy metabolism in liver mitochondria from rats belonging to different developmental age groups. Dexamethasone treatment adversely affected the state 3 respiration rates in 2- and 3-week groups and in the adults with glutamate as the substrates, whereas for pyruvate + malate, the adverse effects were seen for the 3 week and the adult groups. Oxidation of succinate was severely impaired in all the age groups. For ascorbate + TMPD as the substrate, elevated respiration was noted for the 5-week group and the impaired oxidation was observed in adults. Dexamethasone treatment also resulted in site-specific uncoupling with the effect being seen predominantly in the 3- and 5-week and adult animals. The activity of dehydrogenases decreased in a manner comparable to the respiration rates. The mitochondrial cytochromes decreased in an age-dependent manner. The ATPase activity also decreased significantly. The results thus emphasize the adverse effects of dexamethasone treatment on mitochondrial energy metabolism especially in critical age groups.

Age Factors↗
PubMed1988

Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: effect of dexamethasone.

RCJ 3.1, a clonally derived cell population isolated from 21-d fetal rat calvaria, expresses the osteoblast-associated characteristics of polygonal morphology, a cAMP response to parathyroid hormone, synthesis of predominantly type I collagen, and the presence of 1,25-dihydroxyvitamin D3-regulated alkaline phosphatase activity. When cultured in the presence of ascorbic acid, sodium beta-glycerophosphate, and the synthetic glucocorticoid dexamethasone, this clone differentiated in a time-dependent manner into four morphologically distinct phenotypes of known mesenchymal origin. Multinucleated muscle cells were observed as early as 9-10 d in culture, lipid-containing adipocytes formed after 12 d, chondrocyte nodules were observed after 16 d, and mineralized bone nodules formed after 21 d in culture. The differentiated cell types were characterized morphologically, histochemically, and immunohistochemically. The formation of adipocytes and chondrocytes was dependent upon the addition of dexamethasone; the muscle and bone phenotypes were also expressed at low frequency in the absence of dexamethasone. The sex steroid hormones progesterone and 17 beta-estradiol had no effect on differentiation in this system, suggesting that the effects of dexamethasone represent effects specific for glucocorticosteroids. Increasing concentrations of dexamethasone (10(-9)-10(-6) M) increased the numbers of myotubes, adipocytes, and chondrocytes; however, when present continuously for 35 d, the lower concentrations appeared to better maintain the muscle and adipocyte phenotypes. Bone nodules were not quantitated because the frequency of bone nodule formation was too low. Single cells obtained by plating RCJ 3.1 cells at limiting dilutions in the presence of dexamethasone, were shown to give rise to subclones that could differentiate into either single or multiple phenotypes. Thus, the data suggest that this clonal cell line contains subpopulations of mesenchymal progenitor cells which can, under the influence of glucocorticoid hormones, differentiate in vitro into four distinct cell types. It is, therefore, a unique cell line which will be of great use in the study of the regulation of mesenchymal stem cell differentiation.

Adipose Tissue↗
PubMed2001

Dexamethasone inhibits CD4 T cell deletion mediated by macrophages from human immunodeficiency virus-infected persons.

Prednisolone slows the loss of CD4 T cells in individuals with human immunodeficiency virus (HIV) disease and inhibits antigen-induced apoptosis of recently HIV-infected CD4 cells in vitro. This study investigated whether dexamethasone inhibits the ability of macrophages to delete CD4 T cells via anti-CD4 antibody or immune-complexed HIV envelope protein gp120. Peripheral blood mononuclear cells from HIV-negative persons were incubated with CD4-reactive ch412 monoclonal antibody or with gp120/IgG immune complexes and resident macrophages, with and without dexamethasone. Dexamethasone inhibited CD4 cell deletion in a dose-dependent manner. The deletion of normal CD4 cells by macrophages from HIV-infected patients also was inhibited by dexamethasone. Furthermore, up-regulation of CD95 expression on T cells exposed to anti-CD4 and gp120/IgG, which predisposes T cells to CD95-mediated apoptosis, is inhibited by dexamethasone in a dose-dependent fashion. Dexamethasone inhibits the macrophage-mediated deletion of CD4 lymphocytes in HIV-infected persons.

Adult↗
PubMed1997

Enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

The purpose of this study was to determine glucocorticoid modulation of ocular pressure to epinephrine applied topically to rabbit eyes that were pretreated with dexamethasone. Rabbit eyes were pretreated with five applications of topical 0.07% dexamethasone (0.1% dexamethasone phosphate) or saline drops, administered at ten minute intervals. The eyes were then treated with epinephrine bitartrate drops at concentrations of free base epinephrine of 1.1%, 0.27%, 0.05%, 0.027%, 0.005% or 0.0005%. An additional group of rabbits received dexamethasone pretreatment only. Intraocular pressure (IOP) was measured for the next four hours. Enhanced lowering of intraocular pressure was observed with dexamethasone pretreatment. Rabbits receiving the smaller dose of epinephrine with dexamethasone had the largest decrease in IOP at 135 minutes after instillation of the epinephrine drops (0.005% epinephrine, mean difference +/- standard error of mean = 5.4 +/- 1.1 mmHg). Similarly, the duration of significant decrease of the IOP was prolonged in the groups receiving the lower concentrations of epinephrine (0.005% epinephrine, 255 minutes after administration of epinephrine). The synergism between glucocorticoids and adrenergic agonists in lowering IOP may be potentially useful in the therapy of ocular hypertension and glaucoma.

Administration, Topical↗
PubMed1992

Effects of dexamethasone, calcium and 1,25-dihydroxycholecalciferol on calcitonin and calcitonin gene-related peptide mRNA levels from the CA-77 C cell line.

We used the CA-77 cell, a murine C-cell line derived from a medullary thyroid carcinoma, to study the effects of glucocorticoids, calcium, and vitamin D metabolites on calcitonin (CT) gene expression. Total RNA was isolated, and CT and CT gene-related peptide (CGRP) mRNAs were measured by Northern hybridizations using specific probes. A control mRNA probe (cyclophilin) was used to quantitate the specificity of the changes in CT and CGRP mRNAs. The CA-77 C cell line cultured in basal conditions with a medium deprived of fetal calf serum, but was supplemented by insulin, expressed mainly the CGRP mRNA. Dexamethasone was found to increase both CT and CGRP mRNAs in a time- and dose-dependent way without changing the alternative splicing. A slight but significant increase in the steady-state CT mRNA level was found 3 days after addition of 10(-10) M dexamethasone; the same dose slightly decreased the CGRP mRNA level; concentrations of dexamethasone > or = 10(-9) M elevated both mRNAs. A twelve-fold increase for CT mRNA, and an eightfold increase in CGRP mRNA occurred 3 days after administration of 10(-6) M dexamethasone. Kinetic data revealed inductions of both mRNAs 24 hours after exposure to 10(-7) M dexamethasone, and highest CT and CGRP mRNAs levels were observed after 72 hours of treatment. Calcium from 1-4 mM in short-term (1 hour and 4 hour) or long-term stimulations (1 day and 4 days), with or without dexamethasone cotreatment was ineffective. CT and CGRP mRNAs levels were both half-reduced 48 hours after addition of 10(-7) M 1,25-dihydroxycholecalciferol; this effect was transient, as it disappeared 2 days later.

Animals↗
PubMed1994

Dexamethasone enhances active cation transport in cultured aortic smooth muscle cells.

Previous studies have indicated that ouabain-sensitive cation transport is increased in arteries obtained from rats with glucocorticoid-induced hypertension. However, it remained unclear whether this effect reflected direct glucocorticoid activation or rather depended on the elevated arterial pressure per se. In the present study, we examined the effect of dexamethasone on cultured rat aortic smooth muscle cells. Dexamethasone (10(-9) mol/L) increased ouabain-sensitive 86Rb uptake by about 50% (control: 16.5 +/- 1.6 pmol/mg protein/10 min; dexamethasone 10(-9) mol/L: 24.4 +/- 1.3 pmol/mg protein/10 min). The effect was not apparent until 18 h of incubation and was partly inhibited by the mineralocorticoid antagonist spironolactone. Dexamethasone also increased membrane potential in these cells by an average of 9.5 mV (control: -43.3 +/- 4 mV; dexamethasone: -52.8 +/- 4 mV), presumably reflecting increased intracellular K+ activity as a result of dexamethasone's effect on the Na,K pump. These results suggest a direct effect of glucocorticoids on arterial Na,K pump. The physiopathological significance of this effect remains to be determined.

Aldosterone↗
PubMed2006

Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment.

BACKGROUND: We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days. PATIENTS AND METHODS: Patients scheduled to receive cisplatin > or =70 mg/m(2) were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2-3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1-4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1-5 post-cisplatin). RESULTS: Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2-5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P < or = 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P < or = 0.001). Rates of no rescue therapy were similar between groups. CONCLUSIONS: Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC00090207.

Adult↗
PubMed1998

Prophylactic antiemetic therapy with a combination of granisetron and dexamethasone in patients undergoing middle ear surgery.

We have compared the efficacy of granisetron in combination with dexamethasone with each drug alone in the prevention of postoperative nausea and vomiting (PONV) after middle ear surgery. In a randomized, double-blind study, 120 patients (85 females) received granisetron 3 mg, dexamethasone 8 mg or granisetron 3 mg with dexamethasone 8 mg i.v. (n = 40 in each group), immediately before induction of anaesthesia. A standardized general anaesthetic technique was used. A complete response, defined as no PONV and no need for another rescue antiemetic during the first 3 h after anaesthesia, was recorded in 83%, 50% and 98% of patients who had received granisetron, dexamethasone and granisetron-dexamethasone, respectively. The corresponding incidences during the next 21 h after anaesthesia were 80%, 55% and 98% (P < 0.05; overall Fisher's exact probability test). In summary, prophylactic use of combined granisetron and dexamethasone was more effective than each antiemetic alone for the prevention of PONV after middle ear surgery.

Adult↗