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 559 records · Page 31Linked to original sources
PubMed1997

Protection by dexamethasone of the functional desensitization to beta 2-adrenoceptor-mediated responses in human lung mast cells.

1. The beta-adrenoceptor agonist, isoprenaline, inhibited the IgE-mediated release of histamine from human lung mast cells (HLMC) in a dose-dependent manner. Maximal inhibitory effects were obtained with 0.1 microM isoprenaline. However, the inhibition of histamine release from HLMC by isoprenaline (0.1 microM) was highly variable ranging from 33 to 97% inhibition (mean, 59 +/- 3%, n = 27). 2. Long-term (24 h) incubation of HLMC with isoprenaline led to a subsequent reduction in the ability of a second exposure of isoprenaline to inhibit IgE-mediated histamine release from HLMC. The impairment in the ability of isoprenaline (0.1 microM) to inhibit histamine release following desensitizing conditions (1 microM isoprenaline for 24 h) was highly variable amongst HLMC preparations ranging from essentially negligible levels of desensitization in some preparations to complete abrogation of the inhibitory response in others (mean, 65 +/- 6% desensitization, n = 27). 3. The ability of HLMC to recover from desensitization was investigated. Following desensitizing conditions (1 microM isoprenaline for 24 h), HLMC were washed and incubated for 24 h in buffer and the effectiveness of isoprenaline (0.1 microM) to inhibit IgE-mediated histamine release from HLMC was assessed. The extent of recovery was highly variable with some HLMC preparations failing to recover and others displaying a complete restoration of responsiveness to isoprenaline (mean, 40 +/- 6% recovery, n = 23). 4. The effects of the glucocorticoid, dexamethasone, were also investigated. Long-term (24-72 h) treatments with dexamethasone (0.1 microM) had no effect on IgE-mediated histamine release from HLMC. Additionally, long-term (24-72 h) treatments with dexamethasone (0.1 microM) had no effect on the effectiveness of isoprenaline to inhibit histamine release. However, long-term (24-72 h) treatments with dexamethasone (0.1 microM) protected against the functional desensitization induced by incubation (24 h) of HLMC with isoprenaline (1 microM). The protective effect was time-dependent and pretreatment of HLMC with dexamethasone for either 24, 48 or 72 h prevented desensitization by either 15 +/- 7, 19 +/- 5 or 51 +/- 10%, respectively (n = 5-7). 5. HLMC preparations which were relatively refractory to isoprenaline even after withdrawal (24 h) from desensitizing conditions responded more effectively to isoprenaline (0.1 microM) if dexamethasone (0.1 microM) was also included during the recovery period (19 +/- 9% recovery after 24 h in buffer; 50 +/- 8% recovery after 24 h with dexamethasone, n = 5). 6. These data indicate that the responses of different HLMC preparations to isoprenaline, the susceptibility of HLMC to desensitization and the ability of HLMC to recover from desensitizing conditions varies markedly. Dexamethasone, which itself has no direct effects on IgE-mediated histamine release from HLMC, protected HLMC from the functional desensitization to beta-adrenoceptor agonists. Because beta 2-adrenoceptor agonists and glucocorticoids are important in the therapeutic management of asthma and as the HLMC is probably important in certain types of asthma, these findings may have wider clinical implications.

Adrenergic beta-2 Receptor Agonists↗
PubMed1999

Interleukin-1alpha and tumour necrosis factor-alpha modulate airway smooth muscle DNA synthesis by induction of cyclo-oxygenase-2: inhibition by dexamethasone and fluticasone propionate.

1. Previous studies have established that glucocorticoids inhibit airway smooth muscle DNA synthesis. The effects of a combination of the pro-inflammatory cytokines, interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) on the inhibition of DNA synthesis by glucocorticoids in human cultured airway smooth muscle have now been investigated, since these cytokines are chronically expressed in asthmatic airways. 2. Thrombin (0.3 u ml(-1)) and basic fibroblast growth factor (bFGF, 300 pM) stimulated increases in DNA synthesis which were concentration-dependently inhibited by dexamethasone (1-1000 nM). 3. The cytokine mixture, comprising IL-1alpha (0.01 and 0.1 pM) and TNF-alpha (3 and 30 pM), directly evoked increases in DNA synthesis which were attenuated by dexamethasone. However, the cytokine mixture prevented responses to bFGF or thrombin. 4. Paradoxically, in the presence of the cytokine mixture and bFGF, dexamethasone (1-1000 nM) concentration-dependently increased DNA synthesis. Furthermore, neither dexamethasone (100 nM) nor fluticasone propionate (1 nM) inhibited DNA synthesized in response to bFGF/cytokine mixture combination and dexamethasone was similarly inactive against the thrombin/cytokine mixture. 5. The levels of prostaglandin E2 (PGE2), an established inhibitor of airway smooth muscle DNA synthesis, remained below the limits of assay detection (0.05 nM) under basal conditions or following stimulation with either thrombin or bFGF. In contrast, the cytokine mixture alone, and in the presence of thrombin or bFGF, induced biologically active levels of PGE2. Dexamethasone (100 nM), the non-selective cyclo-oxygenase (COX) inhibitor indomethacin (3 microM) or the selective COX-2 inhibitor L-745,337 (0.3 microM) completely inhibited synthesis of PGE2. 6. Neither indomethacin (3 microM) nor L-745,337 (0.3 microM) influenced thrombin- or bFGF-induced DNA synthesis. However, each COX inhibitor enhanced DNA synthesis in cytokine-treated cells. 7. In unstimulated airway smooth muscle cells, COX-1, but not COX-2 protein was detectable by Western blotting. The induction of COX-2 protein by the cytokine mixture was attenuated by dexamethasone (100 nM), whereas the level of COX-1 protein was unaffected by either the cytokines or by dexamethasone. 8. Cytokine-induced, COX-2-dependent eicosanoid production inhibits DNA synthesis. The paradoxical increase in DNA synthesis observed in glucocorticoid treated airway smooth muscle stimulated by cytokine/bFGF combinations may be explained by the ability of glucocorticoids to repress COX-2 induction and prevent cytokine-induction of the DNA synthesis inhibitor, PGE2.

Administration, Topical↗
PubMed2006

An in vitro study on the compatibility and concentrations of combinations of vancomycin, amikacin, and dexamethasone in human vitreous.

PURPOSE: To investigate the precipitation process of a mixture of vancomycin, amikacin, and dexamethasone by equilibrium dialysis and its subsequent effect on the levels of available-free antibiotics and steroid. METHODS: Concentrations of amikacin, vancomycin, and dexamethasone in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography and fluorescence polarisation immunoassay. Vitreous were used as the medium of dialysis, with the three medications prepared in normal saline (NS) and balanced salt solution plus (BSS Plus) separately. RESULTS: Amikacin showed no measurable loss in NS or BSS Plus, either alone or when mixed with vancomycin or dexamethasone. Vancomycin showed minimal loss in BSS Plus, either alone or when mixed with amikacin or dexamethasone. Dexamethasone showed a median loss of 16 and 15% when incubated alone in NS and BSS Plus, respectively, at 48 h. When mixed with vancomycin or amikacin in BSS Plus, it showed a median loss of 13 and 12%, respectively, at 48 h. There was no statistically significant difference in the loss of dexamethasone under various conditions. In equilibrium dialysis in vitreous, amikacin, vancomycin, and dexamethasone reached equilibrium within 24 h and with no loss up to 192 h. There was no difference observed when the medications were prepared in NS or BSS Plus. CONCLUSIONS: Both amikacin and vancomycin did not show precipitation or decrease in concentration in NS or BSS Plus. Dexamethasone showed relatively small percentage loss. As a result, treatment of endophthalmitis with vancomycin and amikacin combination is preferred.

Amikacin↗
PubMed1999

Acute dexamethasone administration enhances GH responsiveness to GH releasing peptide-6 (GHRP-6) in man.

OBJECTIVE: Acute administration of glucocorticoids stimulates GH secretion probably by a decrease in hypothalamic somatostatin release. GHRP-6 is a synthetic hexapeptide that increases GH secretion by a mechanism of action not yet fully known, but apparently not by inhibition of hypothalamic somatostatin release. The aim of this study was to evaluate the effect of acute dexamethasone administration on GH responsiveness to GHRP-6 in man. DESIGN: One group of subjects received iv GHRP-6 (1 microg/kg), GH-releasing hormone (GHRH; 100 microg), GHRH plus GHRP-6 or saline 3.5 h after oral acute dexamethasone administration (4 mg; at 0600 h). A second study group was treated with GHRP-6, GHRH or GHRP-6 plus GHRH after placebo ingestion, following the same protocol. PATIENTS: Sixteen normal subjects (mean age: 29 +/- 3.3 years), with normal BMI (22.4 +/- 2.0 kg/m2), were studied. Eight subjects received dexamethasone and the other eight were treated with placebo. MEASUREMENTS: Serum GH was measured by a two site monoclonal antibody immunofluorometric assay. RESULTS: In the placebo-treated subjects, mean peak GH (mU/l; mean +/- SE) and AUC (mU.min/l) values after GHRP-6 administration (peak: 43.8 +/- 9.0; AUC: 2262.0 +/- 459. 2) did not differ from those observed after GHRH injection (peak: 49. 8 +/- 12.0; AUC: 2903.4 +/- 872.6). The association of the two peptides markedly increased GH levels (peak: 172.4 +/- 34.2; AUC: 10393.0 +/- 1894.8) compared with the isolated administration of GHRP-6 or GHRH. In the subjects who received dexamethasone 3.5 h before saline injection, GH baseline values were significantly higher than those observed after 90 min of sampling (12.4 +/- 9.4 vs. 4.6 +/- 2.0). Mean GH peak and AUC values after GHRP-6 (peak: 78.8 +/- 11.0; AUC: 4114.6 +/- 588.2) and after GHRH administration (peak: 46.8 +/- 16.0; AUC: 3006.8 +/- 1010.0) did not differ significantly in the dexamethasone-treated subjects. In this study group, the administration of the two peptides together caused a significant increase in both peak (119.2 +/- 16.0) and AUC values (7377.0 +/- 937.2) compared with the response obtained after each peptide alone. When the two groups were compared, a significant increase in GH responsiveness to GHRP-6 was observed after dexamethasone administration compared with placebo. No differences in GH response to GHRH, or to the administration of the two peptides together, were seen between the two groups. CONCLUSIONS: Oral dexamethasone, at a dose of 4 mg, enhances GH releasing peptide-6-induced GH release when administered 3.5 h earlier. These results suggest that dexamethasone and GHRP-6 could act at different sites of GH releasing mechanisms. Further studies are necessary to elucidate these findings.

Adult↗
PubMed2001

Effect of vanadate on glycogen synthesis in dexamethasone-treated 3T3 adipocytes: evidence for a novel insulin sensitizing action.

AIM: Type 2 diabetes is characterized by peripheral tissue insulin resistance. The present study was carried out to determine the insulin sensitizing action of vanadium using dexamethasone-treated 3T3 adipocytes as an in-vitro model of insulin resistance. METHODS: Fully differentiated 3T3 adipocytes were incubated with or without 100 nM dexamethasone in the presence or absence of 200 nM insulin for 6 days. Sodium orthovanadate (0-1000 microM) was added on day 2 and was present during the last 4 days. At the end, insulin (100 nM) stimulated glycogen synthesis was determined. RESULTS: Vanadate treatment for 4 days, caused 2-3-fold increase in glycogen synthesis in dexamethasone treated adipocytes. At 100 microM, vanadate completely reversed dexamethasone-induced insulin resistance (by increasing the levels from 9.65 +/- 0.80 to 28.4 +/- 4.9 nmol/h). In cells treated with dexamethasone and insulin, vanadium was partially active and it caused only 30% increase in glycogen synthesis. Exposure of dexamethasone treated cells for 24 h with vanadium did not affect glycogen synthesis. Under identical condition, vanadium had no significant effect in the normal insulin sensitive adipocytes. Vanadium at 100 microM had no effect on 125I-insulin binding to insulin-resistant adipocytes. Glycogen synthesis in the normal and insulin-resistant adipocytes was stimulated by lithium, an inhibitor of glycogen synthase kinase 3 beta, suggesting the involvement of phosphorylation events in dexamethasone-induced insulin resistance. CONCLUSIONS: Since vanadium was active only in the insulin-resistant adipocytes it is likely that vanadium acts by relieving dexamethasone actions rather than having independent effects. These results provide evidence for the novel insulin sensitizing action of vanadium which might be of future clinical relevance.

3T3 Cells↗
PubMed1997

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

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.

3-Hydroxybutyric Acid↗
PubMed2000

Prenatal dexamethasone rescues heart hypoplasia in fetal rats with congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Patients and rats with congenital diaphragmatic hernia (CDH) have lung and heart hypoplasia. Prenatal steroids improve lung hypoplasia in CDH rats. The current study tests the hypothesis that prenatal dexamethasone could rescue heart hypoplasia in rats with CDH. METHODS: Timed pregnant rats received intragastrically either 100 mg nitrofen or oil on day 9.5, and other animals had the same treatment with, in addition, either 0.25 mg/kg dexamethasone intraperitoneally or no treatment on days 19 and 20. Fetuses were recovered on day 21, and heart weight to body weight ratios, heart DNA, protein, and glycogen were measured in fresh specimens. Left-to-right ventricular diameter and aortic-to-pulmonary diameter ratios were measured after formalin fixation. RESULTS: Wet heart weight to body weight, left-to-right ventricular diameter, and aortic-to-pulmonary root diameter ratios, which were lower in fetuses exposed only to nitrofen than in their oil controls, were similar in those exposed to nitrofen plus dexamethasone than in their corresponding oil plus dexamethasone controls. Total heart DNA, which was decreased in fetuses exposed to nitrofen with CDH in comparison with their controls, was increased in those receiving nitrofen and dexamethasone in comparison with theirs. Protein to DNA ratio was decreased in all rats with CDH irrespective of their exposure or not to dexamethasone. Glycogen to DNA ratio was higher in all dexamethasone-treated fetuses than in those without this treatment. No gross histologic differences were seen among groups. CONCLUSIONS: Heart hypoplasia in rats with CDH is in part rescued by prenatal dexamethasone treatment as expressed by increased number of smaller myocytes with higher glycogen content. Prenatal steroids could modify heart involvement in human fetuses with CDH as well.

Animals↗
PubMed1996

Response to dexamethasone in ventilated preterm infants: effect of radiographic subtype of chronic lung disease.

We compared the response to prolonged treatment with dexamethasone in two groups of ventilated preterm infants: one whose chest radiographs showed homogenous opacity, and one whose radiographs showed cystic changes and hyperinflation. Forty-nine infants were treated with dexamethasone for 42 days, beginning when they were 15 to 27 days old, had no evidence of sepsis or patent ductus arteriosus, and had experienced no decrease in ventilator support for 24 hours. Forty-nine controls were selected who met these criteria for dexamethasone treatment. All had birthweights of 500 to 1250 g. Two radiographs made between 14 and 28 days of age were reviewed. Among infants with homogeneous opacity (19 dexamethasone, 26 controls), dexamethasone was associated with fewer days on assisted ventilation (median [interquartile range]: 7 [3-11] versus 23 [9-40]; p = 0.001). Among those with cystic changes and hyperexpansion (30 dexamethasone, 23 controls), no difference was found between dexamethasone treated infants and controls (17 [7-34] versus 32 [16-47]; p = 0.9). Thus, the effect of dexamethasone on days of ventilation was attenuated in infants with cystic changes and hyperinflation.

Bronchopulmonary Dysplasia↗
PubMed1996

Effects of maternal dexamethasone therapy on fetal lung development in the rhesus monkey.

A large body of evidence demonstrates that antenatal glucocorticoids can accelerate fetal lung maturation. The purpose of this study was to delineate the optimal dose of dexamethasone and to determine whether a single- or multiple-injection regimen of the same total dexamethasone dosage was more effective in accelerating pulmonary development. Pregnant rhesus monkeys were injected with varying doses of dexamethasone or vehicle as either a single-bolus injection or as four separate injections, each spaced 12 hours apart. All maternal treatments were begun exactly 72 hours prior to delivery, and all fetuses were delivered by cesarean section at 135 +/- 1 days gestation. When a single injection of dexamethasone was used, fetal liver weight increased in a dose-related fashion. Fetal and maternal cortisol and fetal blood glucose concentrations were also influenced by increasing dexamethasone dosages. Fetal pulmonary phospholipids, however, were unchanged at all steroid doses examined. Multiple injections of dexamethasone generally produced more pronounced effects, even though the total dexamethasone dose remained the same. Thus, liver weight and fetal and maternal cortisol, glucose, and insulin levels were significantly influenced by the multiple administration of dexamethasone. In addition, total lung phosphatidylcholine, surfactant phosphatidylcholine, the surfactant-phosphatidylcholine-to-total-phosphatidylcholine ratio, and the surfactant-disaturated-phosphatidylcholine-to-total-lung-disaturated- phosphatidylcholine ratio were elevated after the multiple-injection regimen. A total dose of 0.5 mg dexamethasone/kg maternal body weight given in four separate injections appeared to produce the most beneficial results. These data suggest that low-dose, antenatal glucocorticoid treatment can effectively accelerate the biochemical maturation of the fetal lung.

Animals↗
PubMed1989

A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia.

We evaluated the use of dexamethasone in preterm infants to decrease morbidity associated with bronchopulmonary dysplasia in a randomized, double-blind, placebo-controlled trial. Thirty-six preterm infants (birth weight, less than or equal to 1250 g and gestational age, less than or equal to 30 weeks) who were dependent on oxygen and mechanical ventilation at two weeks of age received a 42-day course of dexamethasone (n = 13), an 18-day course of dexamethasone (n = 12), or saline placebo (n = 11). The starting dose of dexamethasone was 0.5 mg per kilogram of body weight per day, and it was progressively lowered during the period of administration. Infants in the 42-day dexamethasone group, but not those in the 18-day group, were weaned from mechanical ventilation significantly faster than control infants (medians 29, 73, and 84 days, respectively; P less than 0.05), and from supplemental oxygen (medians 65, 190, and 136 days, respectively; P less than 0.05). No clinical complications of steroid administration were noted. Follow-up of all 23 survivors at 6 and 15 months of age showed good outcome (normal neurologic examinations and Bayley Developmental Indexes greater than or equal to 84) in 7 of the 9 infants in the 42-day dexamethasone group, but in only 2 of the 9 infants in the 18-day dexamethasone group and 2 of the 5 in the placebo group (P less than 0.05). We conclude that dexamethasone therapy for 42 days improves pulmonary and neurodevelopmental outcome in very-low-birth-weight infants at high risk for bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed2002

In vitro osteogenic differentiation of rat bone marrow cells subcultured with and without dexamethasone.

The aim of our study was to investigate the osteogenic potential of subcultured rat bone marrow cells. Rat bone marrow (RBM) cells were cultured with or without dexamethasone. Subsequently, osteogenic differentiation and expression was studied. When cells were cultured continuously in the presence of dexamethasone, cultures initially showed high alkaline phosphatase expression and abundant mineralization. Expression of differentiation markers decreased with passaging. After cells were passaged three times, no alkaline phosphatase activity and calcification were found. Primary cells cultured without dexamethasone showed low alkaline phosphatase and no calcification, and remained fibroblast-like. When these cells were subcultured in the presence of dexamethasone, the cells did show osteogenic differentiation. Nevertheless, this occurred at a significant lower level than with cells continuously cultured with dexamethasone. In addition, no differentiation was found after second passage. Our results indicate that subcultured undifferentiated RBM cells show osteogenic differentiation after addition of dexamethasone. Expression of alkaline phosphatase and mineralization is higher in cells continuously supplemented with dexamethasone. Still, even when dexamethasone is added continuously, RBM cells loose their osteogenic potential after several passages. Therefore, we conclude that subculture of undifferentiated rat bone marrow cells results in the loss of osteogenic potential of these cells.

Alkaline Phosphatase↗
PubMed1996

Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting.

We studied 100 ASA I-II females undergoing general anaesthesia for major gynaecological surgery, in a prospective, double-blind, placebo-controlled, randomized study. Patients received one of four regimens for the prevention of postoperative nausea and vomiting (PONV): ondansetron 4 mg (n = 25), dexamethasone 8 mg (n = 25), ondansetron with dexamethasone (4 mg and 8 mg, respectively, n = 25) or placebo (saline, n = 25) There were no differences in background factors or factors related to operation and anaesthesia, morphine consumption, pain or side effects between groups. The incidence of nausea and emetic episodes in the ondansetron with dexamethasone group was lower than in the placebo (P < 0.01), ondansetron (P < 0.05) and dexamethasone (P = 0.057) groups. There were no differences between ondansetron and dexamethasone, and both were more effective than placebo (P < 0.05 and P < 0.01, respectively). Dexamethasone appeared to be preferable in preventing nausea than emetic episodes. Fewer patients in the ondansetron with dexamethasone group needed antimetic rescue (P < 0.01 vs placebo and P < 0.05 vs ondansetron). We conclude that prophylactic administration of combined ondansetron and dexamethasone is effective in preventing PONV.

Adolescent↗
PubMed1998

The effect of dexamethasone administration at different stages of gestation on maternal plasma steroid concentrations in the baboon (Papio cynocephalus).

Dexamethasone administration at different stages of gestation in the baboon was studied for its effect on maternal steroid hormone concentrations. Dexamethasone (2 mg i.m. at 12 h intervals for three doses) was administered at early (days 37-39), mid (days 76-85) or late (days 112-123) gestation and morning blood samples were collected before, during and after dexamethasone suppression for 6 consecutive days. Dexamethasone treatment, at all stages of pregnancy, resulted in a significant decline in maternal serum cortisol concentrations, which rapidly return to normal concentrations after treatment. Progesterone concentrations were not affected by dexamethasone at any stage of gestation. Serum concentrations of oestradiol, testosterone and androstenedione were unchanged following dexamethasone administration in early pregnancy. A trend toward lower serum oestradiol was observed following dexamethasone administration in both mid and late gestation, but this was not significant. Both testosterone and androstenedione were significantly decreased following dexamethasone in both mid and late pregnancy and recovered to pretreatment concentrations within a few days after cessation of treatment. These results confirm other studies which demonstrate that adrenal precursors (maternal or fetal) are a major contributor to maternal serum concentrations of oestradiol. They also demonstrate that these adrenal precursors increase serum concentrations of testosterone and androstenedione in the pregnant baboon. Since these changes are only evident after that time (>40 days) when the fetal adrenal is steroidogenically competent, a role for fetal adrenal involvement in maternal serum androgen concentrations is suggested.

Adrenal Glands↗
PubMed1998

Dexamethasone enhances macrophage colony stimulating factor- and granulocyte macrophage colony stimulating factor-stimulated proliferation of bone marrow-derived macrophages.

Glucocorticoids are effective repressors of the immune system. We have examined the effect of glucocorticoids on the proliferation of murine macrophages. Dexamethasone by itself did not affect proliferation of differentiated or undifferentiated bone marrow-derived macrophages (BMM) and elicited peritoneal macrophages. However, dexamethasone enhanced the proliferation induced by macrophage colony stimulating factor (M-CSF) of these cells. The effect of dexamethasone was not restricted to M-CSF-dependent proliferation. Similarly, dexamethasone enhanced granulocyte macrophage colony stimulating factor (GM-CSF)-dependent proliferation of BMM. In agreement, macrophages transfected with the glucocorticoid receptor showed an enhancement of M-CSF-dependent proliferation. The enhancement of proliferation by dexamethasone or the glucocorticoid receptor was abolished by RU 486, an antagonist of the glucocorticoid receptor. Moreover, the addition of antibodies against M-CSF inhibits the effect of dexamethasone, suggesting that dexamethasone increases the autocrine production of M-CSF. This only occurs when M-CSF or GM-CSF, which induce M-CSF, are present in the media. In tissues, dexamethasone may enhance macrophage proliferation and contribute to the resolution of the inflammatory states.

Animals↗
PubMed1995

A single intracerebroventricular injection of dexamethasone elevates food intake and plasma insulin and depresses metabolic rates in adrenalectomized obese (ob/ob) mice.

A single intracerebroventricular (ICV) injection of dexamethasone rapidly (within 30 min to 3 h) increases plasma insulin and suppresses oxygen consumption in adrenalectomized ob/ob mice with minimal effects in lean mice. Food intake of these adrenalectomized ob/ob mice was unaffected by ICV dexamethasone during these short-term studies. However, in a longer-term study with adrenalectomized gold thioglucose-lesioned obese mice, food intake increased fourfold 6-8 d after a single ICV injection of dexamethasone. We have now further examined the time course of dexamethasone actions in adrenalectomized ob/ob and lean mice in the 96-h post-injection period. A single ICV injection of dexamethasone increased food intake 32% and plasma insulin 81%, and depressed oxygen consumption 11%, in adrenalectomized ob/ob mice during the 24-h period after injection, without increasing food intake or plasma insulin in lean mice. Oxygen consumption was 14% lower in lean mice 24 and 48 h after dexamethasone injection relative to saline-injected lean mice. Food intake and oxygen consumption in ob/ob mice returned to levels in saline-injected controls at 48 and 72 h after injection, respectively. Oxygen consumption of lean mice also returned to control levels at 72 h post-injection. Plasma insulin concentrations were similar in dexamethasone- and saline-treated ob/ob and lean mice at 96 h post-injection (the only time point examined other than 24 h). A single ICV injection of dexamethasone exerts both rapid (within 30 min to 3 h) and sustained (days) metabolic actions in ob/ob mice.

Adrenalectomy↗
PubMed1998

Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone.

BACKGROUND: The active metabolite of vitamin D, i.e., 1,25-dihydroxycholecalciferol (1,25-D3), inhibits the growth of murine SCCVII/SF squamous cell carcinoma cells, both in vitro and in vivo. However, in vivo use of 1,25-D3 is hampered as a result of hypercalcemia (i.e., elevated levels of calcium in the blood). Glucocorticoids, such as dexamethasone, affect calcium absorption and modulate vitamin D receptor binding and have been used to treat hypercalcemia. In this study, we examined the effect of dexamethasone on tumor growth inhibition by 1,25-D3. METHODS: The effects of 1,25-D3 and dexamethasone, alone and in combination, on the growth of SCCVII/SF cells in in vitro culture or in vivo in female C3H/HeJ mice were determined by clonogenic tumor cell assay and/or by actual changes in tumor volume. Vitamin D receptor-ligand-binding activities in whole-cell extracts from cells (in culture), tumors, and normal tissues were assayed by single-point saturation analysis and equilibrium binding. RESULTS: Treatment of cultured SCCVII/SF cells with 500 nM dexamethasone for 24 hours before addition of 1,25-D3 reduced their survival. The growth of SCCVII/SF tumors was inhibited in mice treated simultaneously with dexamethasone and 1,25-D3 (as compared with no treatment or single-agent treatment); hypercalcemia was also reduced. Total vitamin D receptor content in SCCVII/SF cells was increased after treatment with dexamethasone. Treatment of tumor-bearing animals with dexamethasone (9 microg/day) for 7 days led to increased vitamin D receptor-ligand-binding activities in whole-cell extracts from tumor or kidneys and decreased activity in intestinal mucosa. CONCLUSIONS: Dexamethasone may enhance the antitumor effect of 1,25-D3 by increasing vitamin D receptor-ligand-binding activity.

Animals↗
PubMed1985

Dexamethasone inhibits alpha-fetoprotein gene transcription in neonatal rat liver and isolated nuclei.

The effect of dexamethasone on rat alpha-fetoprotein (AFP) expression has been further examined. Quantitation of serum AFP levels from newborns treated with dexamethasone showed a dose-response relationship between the quantity of dexamethasone administered and the reduction in AFP serum level. RNA blots, utilizing cloned AFP cDNA as probe, showed a marked reduction in AFP mRNA in dexamethasone treated livers. The extent of AFP mRNA depletion was correlated with dexamethasone dosage. The effect of dexamethasone on AFP mRNA concentration was relatively rapid; a substantial reduction occurred 12 hours after a single injection. The effect of dexamethasone appeared to be irreversible as hormone withdrawal did not cause AFP mRNA levels to rise. One putative AFP nuclear RNA precursor was identified which rapidly disappeared following dexamethasone treatment. AFP mRNA synthesis was also diminished in nuclei transcribed in vitro. The direct inhibitory effect of glucocorticoid hormone on AFP gene transcription was demonstrated in a reconstituted cell-free nuclear system.

Animals↗
PubMed2002

A cyclooxygenase-2 (COX-2) inhibitor compared with dexamethasone in a survival study of rats with intracerebral 9L gliosarcomas.

Although dexamethasone is very effective for controlling peritumoral cerebral edema, it is associated with distressing side effects that decrease the quality of life for many patients. One potential mechanism to explain the ability of dexamethasone to repair blood-brain barrier dysfunction is through the inhibition of cyclooxygenase-2 (COX-2). The purpose of this study was to determine in a rat brain tumor model whether SC-236, a selective COX-2 inhibitor, is as effective as dexamethasone. Twenty-nine adult male Fischer 344 rats were implanted with intracerebral 9L gliosarcomas and divided into 3 treatment groups. One group (n = 9) served as controls, another (n = 9) was treated with dexamethasone (3 mg/kg p.o. daily), and a third group (n = 11) received SC-236 (3 mg/kg p.o. daily). A survival study was performed. The median survival in the control group was 16 days, compared with 23 days for the dexamethasone group and 23 days for the COX-2 inhibitor group. Kaplan-Meier analysis on pairwise group comparisons showed improved survival that was statistically significant for each treatment group compared with the control group (log-rank test P = 0.009 for dexamethasone to control and P = 0.005 for COX-2 to control), and no significant difference in survival for the COX-2 compared with dexamethasone (log-rank test P = 0.2). These results suggest that a selective COX-2 inhibitor appears to be as effective as dexamethasone in prolonging survival in a rat brain tumor model.

Animals↗