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PubMed1984

Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide.

Nausea and vomiting remain common and debilitating side effects of therapy with many anticancer drugs. Recent reports have shown that both metoclopramide and dexamethasone are effective drugs for the treatment of severe nausea and vomiting caused by cis-platinum. A double-blind crossover study comparing the antiemetic properties of high-dose oral and intravenous regimens of metoclopramide and dexamethasone in outpatients was carried out. Standardized patient questionnaires and interviews were used to evaluate response. Dexamethasone and metoclopramide protected against more than five episodes of emesis in 48% and 40% of patients, respectively. Nausea persisted for less than six hours in 45% of patients on dexamethasone and in 37% on metoclopramide. The antiemetic efficacy of both regimens was retained through repeated courses of chemotherapy. Side effects were minimal with dexamethasone; however, 33% of patients experienced unacceptable extrapyramidal side effects to metoclopramide. Patient preference was significantly in favor of dexamethasone: 70% of patients chose to continue dexamethasone compared to 22% who preferred metoclopramide and 8% who chose other antiemetics. Dexamethasone was the preferred antiemetic in this patient population due to minimal side effects.

Adult↗
PubMed1985

Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial.

The antiemetic effect of short courses of high-dose dexamethasone was compared with that of placebo in 64 patients receiving cisplatin-based cancer chemotherapy, in a double-blind randomized clinical trial. All patients were receiving cisplatin for the first time. Dexamethasone was given intravenously (IV) at a dose of 20 mg, two hours before and 3, 6, 9, and 12 hours after chemotherapy. Patients were crossed over to dexamethasone on the second cycle of chemotherapy if they experienced unacceptable gastrointestinal (GI) toxicity after initial treatment with placebo. Nine of 32 patients receiving dexamethasone and seven of 32 patients receiving placebo did not vomit. The median duration of nausea was significantly shorter (one-half hour) for the dexamethasone-treated group compared with that of placebo (31/2 hours). The number of patients who experienced unacceptable GI toxicity was significantly greater (53%) for the placebo patients than for those treated with dexamethasone (25%). Patients crossing over to dexamethasone after initially receiving placebo had a median duration of nausea of 11/2 hours and 24% did not vomit, results comparable to the first treatment group. We conclude that high-dose dexamethasone is only minimally effective as an antiemetic agent in patients receiving cisplatin-based chemotherapy.

Adult↗
PubMed1993

Antioxidant enzyme responses to hyperoxia in preterm and term rats after prenatal dexamethasone administration.

Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.

Animals↗
PubMed1994

Two doses of early intravenous dexamethasone for the prevention of bronchopulmonary dysplasia in babies with respiratory distress syndrome.

Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated. We report the results of a phase I study of early i.v. dexamethasone to prevent the development of bronchopulmonary dysplasia in a high-risk population of ventilated premature babies, < 30 wk gestation, with surfactant-treated respiratory distress syndrome. This study used a limited dexamethasone dosing regimen to minimize toxicity but used administration early in the course of acute lung disease to interrupt the injury cycle. Forty babies were enrolled; 19 were randomized to receive dexamethasone (0.5 mg/kg birth weight at 12-18 h of age and a second dose 12 h later) and 21 were randomized to receive placebo (i.v. saline). The dexamethasone group required less ventilatory support (mean airway, peak inspiratory and end expiratory pressures, and intermittent mandatory ventilation) and supplemental oxygen after study d 4 (all p < 0.05, repeated measures analysis of variance). Improved tidal volume in the dexamethasone group, as measured by pulmonary function testing of infants who remained intubated, was seen on study d 7 (p = 0.02, t test). The dexamethasone group required shorter hospitalizations (median of 95 d versus 106 d, p = 0.01) (proportional hazards regression). Survival in the dexamethasone group was 89% versus 67% in the placebo group (p = 0.08, chi 2 analysis). Survival without bronchopulmonary dysplasia, diagnosed at 36 wk corrected gestational age, was 68% in the dexamethasone group versus 43% in the placebo group (p = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchopulmonary Dysplasia↗
PubMed2000

Effects of dexamethasone treatment on bone and collagen turnover in preterm infants with chronic lung disease.

Dexamethasone is used commonly in the treatment of chronic lung disease of prematurity, but there are concerns about possible deleterious effects on growth and bone. Our aim in this study was to examine the effects of dexamethasone treatment on bone and collagen turnover in preterm infants. Bone-specific alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP, reflecting whole-body type I collagen synthesis), and the N-terminal propeptide of type III procollagen (P3NP, reflecting soft tissue collagen turnover), together with the C-terminal telopeptide of type I collagen (ICTP), urinary pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown) were measured at weekly intervals over the first 12 wk of life in 14 preterm infants with chronic lung disease treated with dexamethasone. Results were expressed as SD scores relative to preterm control infants not treated with dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (-2.1 to -3.7 SD scores) during the first week of treatment (p < 0.001), returning to pretreatment levels after stopping dexamethasone. In the group as a whole, these collagen markers were negatively correlated with dexamethasone dose (p < 0.0001); negative correlations were also seen in most individual babies, although the slopes of individual regression lines varied by a factor of 2. Weight gain at 12 wk was correlated with PICP, expressed as the mean SD score over 12 wk for each baby, (r = 0.69, p < 0.01) but not with other markers or cumulative dose of dexamethasone. We conclude that dexamethasone markedly suppressed collagen turnover in preterm infants in a dose-dependent fashion, although some babies were more affected than others. The degree of suppression of type I collagen synthesis was a strong independent predictor of overall weight gain over the first 12 wk of life.

Alkaline Phosphatase↗
PubMed2005

Effect of dexamethasone on B7 regulation and T cell activation in neonates and adults.

The safety of dexamethasone for neonates has been questioned, partly because of its multiple unspecific effects on the immune system. Specific effects of dexamethasone on co-stimulatory and immune suppressive functions of neonatal compared with adult macrophages (MPhi) are not known. We evaluated the effect of dexamethasone on the expression and regulation of MPhi B7 family receptors (B7-1, CD80; B7-2, CD86) and on their ability to co-stimulate T cells. Cord blood macrophages (CBMPhi) and MPhi from healthy adults (PBMPhi) were isolated, and cell surface markers were phenotyped by flow cytometry. In tissue culture, cells were exposed to dexamethasone, interferon-gamma (IFN-gamma), cAMP, or a T cell mitogen (alphaCD3) and examined for their capacity to activate or destroy T cells. CBMPhi were less able to up-regulate CD80 and CD86 than PBMPhi (p < 0.05). Dexamethasone inhibited the up-regulation of CD80, CD86, and HLA-DR on PBMPhi and even more so on CBMPhi (p < 0.05 versus PBMPhi for CD80 and CD86). In the presence of dexamethasone, stimulation with alphaCD3 MAb enhanced cytotoxic functions of PMBMPhi and CB(mu)phi with an increase in deleted T cells, a reduced fraction of enlarged T cells, and an inhibition of T cell CD28 up-regulation, which again were more pronounced with CBMPhi (p < 0.05 versus PBMPhi). In conclusion, neonatal MPhi are exquisitely sensitive to the inhibitory effects of dexamethasone on B7 expression. Although perhaps producing the desired therapeutic effect, dexamethasone may do so in newborns at the expense of a near complete paralysis of MPhi-dependent T cell function.

Adult↗
PubMed1983

Growth hormone secretion by cultured rat anterior pituitary cells. Effects of culture conditions and dexamethasone.

Optimal conditions were sought for the study of GH secretion by cultured normal pituitary cells. Dispersed rat pituitary cells were cultured for 1 week in four different media supplemented with 10% fetal calf serum. Minimal essential medium resulted in high GH content and secretion during a 4-h incubation period, whereas GH secretion was lower (P less than 0.05) for cells cultured in medium 199, Ham's F-10, and RPMI-1640. GH secretion/24 h declined gradually with time. After 2 weeks in culture hormone secretion amounted to 30% of secretion on day 1, but after 3 weeks GH secretion was still measurable. GH recovery during the 3-weeks culture period was more than 600% of the amount initially plated. GH secretion was positively correlated with the bicarbonate concentration between 0.85 and 2.2 g/liter NaHCO3. When pituitary cells were cultured in concentrations varying from 0.5 X 10(5) to 10 X 10(5) cells per dish, GH secretion and content per cell were constant, suggesting that no direct autofeedback occurred in cultures with high cell densities and thus high medium GH. Dexamethasone stimulated GH secretion and content in a dose-dependent way (0.1 nM-10 microM). The stimulatory effect of 100 nM dexamethasone occurred within 24-48 h. After 7 days of treatment with 100 nM dexamethasone, GH secretion had increased to 190% and GH content to 230% of control. In contrast to the effects on GH, dexamethasone suppressed PRL secretion in a dose-dependent way, but this effect was seen only after 7 days of treatment and not after 4 days of treatment. Cycloheximide and actinomycin D prevented the stimulatory effect of dexamethasone on GH secretion. However, 24 h after cessation of cycloheximide treatment GH secretion was stimulated by dexamethasone. Four days of treatment with 100 nM dexamethasone did not affect the GH response to somatostatin, prostaglandin E1, and theophylline, nor the PRL response to dopamine, TRH, and theophylline. Thus, culture conditions may affect GH production, and dexamethasone can be used to culture somatotrophs for longer periods with steady GH production and normal responsiveness.

Alprostadil↗
PubMed1984

Effect of dexamethasone on triiodothyronine production in the perfused rat liver and kidney.

Dexamethasone administration to rats decreases T4-5'-deiodinase activity in liver homogenates and slices and in isolated rat renal tubules. To determine if this decreased T4-5'-deiodinase activity results in decreased T3 production, rat livers and kidneys of control and dexamethasone-treated rats were perfused with medium containing free T4 concentrations approximating euthyroid rat serum, and net T3 production was measured by RIA. Dexamethasone administration decreased body weight by 14% but did not affect liver weight, kidney weight, or serum concentrations of T4 or T3. When livers were perfused with T4 concentrations of 10 micrograms/dl (free T4 = 6.5 ng/dl), hepatic T3 production, T4 uptake, and the conversion of T4 to T3 were similar in dexamethasone-treated rats and saline-treated controls. However, when livers were perfused at a T4 concentration of 125 micrograms/dl (free T4 = 81 ng/dl), dexamethasone-treated livers produced significantly less T3 than controls because of decreased conversion of T4 to T3. Hepatic deiodination of T3 and excretion of T3 into bile were not affected by dexamethasone. Renal T3 production, T4 uptake, and conversion of T4 to T3 was likewise unaffected by dexamethasone treatment when kidneys were perfused at near-normal free T4 concentrations. These studies indicate that dexamethasone treatment does not alter T3 production in the perfused liver and kidney and underscore the importance of using free T4 concentrations approximating physiologic levels when studying regulation of T3 production in individual organs.

Animals↗
PubMed1976

Dexamethasone: increased weights and decreased [3H] estradiol retention of uterus, vagina and pituitary in the ovariectomized rat.

Ovariectomized rats given 100 mug dexamethasone per day for 5 days had significantly heavier dry weights for uterus, vagina and pituitary, indicating a growth promoting activity of dexamethasone on these tissues in which estrogen normally promotes growth changes. The dexamethasone treated animals also retained significantly less [3H]estradiol per mug dry weight of tissue for uterus, vagina and pituitary. When[3H]estradiol retention was examined in vitro for the nuclear fraction, a significant decrease in retention was found for uterus, vagina and pituitary but not for hypothalamus or cerebral cortex. The decreased ability to bind [3H]estradiol, shown by the estrogen target tissues of the dexamethasone-treated rats, along with the increased growth of the estrogen target tissues, demonstrates that these tissues were able to show trophic responses even when greater levels were one-third of normal. Dexamethasone-treated animals tested for sexual receptivity in the presence or absence of progesterone priming did not show induction of facilitation of sexual receptivity. However, estrogen plus progesterone injections induced sexual receptivity in the presence of dexamethasone. When dexamethasone was combined with a dosage of estrogen, which by itself did not induce sexual receptivity, there was a significant response with 6 to 10 animals showing a low level of receptivity. Thus, dexamethasone can apparently synergize with estrogen to facilitate sexual receptivity.

Animals↗
PubMed1995

Effects of dexamethasone and forskolin on neurotensin production in rat hypothalamic cultures.

In the present study, the effects of glucocorticoids and forskolin, an activator of adenylate cyclase, were examined on neurotensin (NT) production from rat hypothalamic neurons in primary culture. Treatment with dexamethasone induced a dose-dependent increase in NT content. The maximum was reached at 1 microM dexamethasone, which induced a 100% increase in NT levels. The effect of dexamethasone was mimicked by the glucocorticoid agonist RU28362 and blocked by the antiglucocorticoid RU38486, suggesting that this effect was mediated through the glucocorticoid receptor. The treatment with dexamethasone also enhanced the number of immunoreactive NTergic cells (92% increase). In contrast to dexamethasone, forskolin affected neither the NT content nor the number of immunoreactive NTergic cells. However, when cells were treated with both dexamethasone and forskolin, a 285% increase in NT content and a 430% increase in the number of immunoreactive NTergic cells were observed, representing 2.8- and 4.7-fold increases, respectively, compared to the effect of dexamethasone alone. Moreover, this combined treatment increased the accumulation of NT in the culture medium (160% increase) as well as the abundance of NT messenger RNA. We conclude from the present findings that dexamethasone and forskolin act synergistically to enhance NT production in hypothalamic neurons.

Amino Acid Sequence↗
PubMed1998

Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice.

Mice with a genetic disruption of the multiple drug resistance (mdr1a) gene were used to examine the effect of the absence of its drug-transporting P-glycoprotein product from the blood-brain barrier on the distribution and cell nuclear uptake of [3H]-dexamethasone in the brain. [3H]-dexamethasone (4 microg/kg mouse) was administered s.c. to adrenalectomized mdr1a (-/-) and mdr1a (+/+) mice. One hour later, the mice were decapitated, and the radioactivity was measured in homogenates of cerebellum, blood, and liver following extraction of the radioactive steroid. The frontal brain was cut in sections for autoradiography. In the cerebellum of the mdr1a mutants, the amount of [3H]-dexamethasone relative to blood was about 5-fold higher than observed in the controls, whereas the ratio in blood vs. liver was not different. Using autoradiography, it was found that brain areas expressing the glucocorticoid receptor (GR) in high abundance, such as the hippocampal cell fields and the paraventricular nucleus (PVN), showed a 10-fold increase in cell nuclear uptake of radiolabeled steroid. The amount of retained steroid increased toward levels observed in the pituitary, which contains a similar density of GRs. The [3H]-dexamethasone concentration in pituitary was not affected by mdr1a gene disruption. The GR messenger RNA expression pattern in hippocampus was not different between the wild types and mdr1a mutants, which rules out altered receptor expression as a cause of the enhanced dexamethasone uptake. In conclusion, the present study demonstrates that the brain is resistant to penetration by dexamethasone because of mdr1a activity at the level of the blood-brain barrier. The data support the concept of a pituitary site of action of dexamethasone in blockade of stress-induced ACTH release. Dexamethasone poorly substitutes for depletion of the endogenous glucocorticoid from the brain and therefore, in this tissue, may cause a condition resembling that of adrenalectomy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1975

Opposite effects of dexamethasone on serum concentrations of 3,3',5'-triiodothyronine (reverse T3) and 3,3'5-triiodothyronine (T3).

Dexamethasone, 2 mg every 6 hours for 4 doses, was given to 4 hypothyroid patients receiving treatment with synthetic thyroxine (T4) and to 8 untreated hyperthyroid patients with Graves' disease, and serum concentrations of thyroid hormones were measured by radioimmunoassays. Serum concentration of 3,3'5'-triiodothyronine (reverse T3, rT3) increased appreciably within 8 hours after the first dose of dexamethasone, was maximum at 24-32 hours after beginning dexamethasone, and remained elevated for about 24 hours after discontinuing the steroid. The mean baseline serum rT3 was 58 ng/per 100 ml in treated hypothyroid patients and 119 ng per 100 ml in patients with Graves' disease; the corresponding maximal post-dexamethasone serum rT3 values were 87 and 170 serum concentration of 3,3',5-triiodothyronine (T3) decreased. The decrease in serum T3 was significant at about 24 hours after beginning dexamethasone and was maximal at about 30 hours in both groups of cases under study. The decrease in serum T3 persisted in treated hypothyroid cases for about 24-48 hours and in Graves' disease cases as long as studied, at least 5 days after discontinuing hexamethasone. The changes in serum rT3 and T3 could not be attributed to the effect of dexamethasone on serum protein binding of the iodothyronines because the dialyzable fractions of rT3 and T3 following steroid administration were not different from those before it. Serum T4 did not change appreciably in treated hypothyroid cases, but decreased in Graves' disease cases from a mean baseline value of 23.5 mug per 100 ml to 18.4 mug per 100 ml 3 days after beginning dexamethasone. In addition, 3 hyperthyroid cases were studied before, during, and after administration of dexamethasone, 2 mg every 6 h for 5 days. Serum rT3 increased again as noted above and the increase persisted until about 24 hours after the last dose of the steroid. Serum T3 decreased considerably and remained decreased as long as studied, at least 4 days after discontinuing the steroid. Serum T4 decreased appreciably in 2 of the 3 cases studied. The data suggest that 1) conversion of T4 to T3 and to rT3 may occur via two distinct pathways in the metabolism of T4; 2) the changes in serum rT3 and T3 observed in our study may be due in part at least to a steroid-induced 'shift' in the metabolism of T4 whereby conversion of T4 to T3 is diminished and that to rT3 is enhanced; 3) in addition to the effect on peripheral metabolism of T4, steroids appear to reduce the circulating thyroid hormones in Graves' disease by another mechanism, probably by reduction in thyroid secretion.

Adult↗
PubMed1979

Virilizing adrenal adenoma stimulated by dexamethasone in a middle-aged woman.

In a middle-aged woman with virilizing adenoma, 2 mg dexamethasone increased urinary excretion of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids, whereas 8 mg dexamethasone increased urinary excretion only of 17-KS. With discontinuation of dexamethasone, 17-KS excretion returned to the predexamethasone level. Dexamethasone depressed the basal level of cAMP synthesis and basal testosterone production by the normal adrenal tissue in vitro. Dexamethasone also depressed the increase of cAMP produced by ACTH in the normal tissue. In contrast, dexamethasone increased basal cAMP synthesis and stimulated testosterone secretion in the tumor tissue. ACTH and dexamethasone were additive in their effects on cAMP and testosterone in the tumor tissue. It is suggested that dexamethasone acted directly on the adrenal tumor to stimulate steroid secretion in this patients.

11-Hydroxycorticosteroids↗
PubMed1992

Pulsatile human corticotropin-releasing hormone prevents dexamethasone-induced suppression of the plasma cortisol response to hypoglycemia in normal men.

Insulin-induced hypoglycemia causes a sequential stimulation of all three components of the hypothalamic-pituitary-adrenal axis. States of acute glucocorticoid excess, such as the overnight (1 mg) dexamethasone suppression test (DST), inhibit both the basal cortisol level and the response to an insulin tolerance test (ITT). However, whether this negative feedback effect is exerted primarily at the hypothalamic or the pituitary level is not clear. To explore this question further we have examined the cortisol response to insulin-induced hypoglycemia in three experimental settings, in the following order: 1) a control ITT performed at 0900 h after an overnight hospital stay (cITT); 2) an ITT at 0900 h after oral dexamethasone, 1 mg, at 2300 h on the previous evening (DST + ITT); and 3) an ITT at 0900 h after dexamethasone, 1 mg, at 2300 h and hCRH, 1 microgram/kg iv, at 90 min intervals from 0100-0700 h (DST+hCRH + ITT). The response to ITT was defined as the peak cortisol increment (peak minus baseline). Since the study objective was to test whether overnight pulsatile hCRH could prevent dexamethasone-induced suppression of the response to a morning ITT, only subjects that demonstrated a greater than 25% decrease in the cortisol response to DST + ITT vs. cITT received the full protocol (five of nine normal men). Basal ACTH and cortisol secretion remained suppressed throughout the night during both the Dex + ITT and Dex + hCRH + ITT studies when compared to the control study (cITT, P < 0.05). However, the cortisol response to hypoglycemia during DST + hCRH + ITT was significantly greater than during DST+ITT (P < 0.05) and was similar to the cITT response. Thus, pulsatile hCRH, administered during the 10 h between dexamethasone and the subsequent hypoglycemic stimulus, prevented acute suppression by dexamethasone of the cortisol response to hypoglycemia. We conclude that the dexamethasone-induced inhibition of the cortisol response to hypoglycemia results primarily from suppression by dexamethasone of basal hypothalamic corticotropin-releasing factor and the consequent impairment of corticotroph responsiveness to exogenous and endogenous corticotropin-releasing factor.

Adrenocorticotropic Hormone↗
PubMed1989

Dexamethasone acts as a negative regulator of epidermal growth factor receptor synthesis in fetal rat lung cells.

125I-Epidermal growth factor (EGF) binding capacity in fetal rat lung cells is decreased by approximately 50% following 24-h dexamethasone treatment. Ligand binding assays identified an average of 30,000 receptors per cell in untreated FRL cells, while analysis of dexamethasone treated cells showed a decrease to about 16,000 receptors per cell. No substantial changes in receptor affinities were detected. Immunoprecipitation of 35S-methionine-labeled EGF receptor protein demonstrated a 50% decrease in total EGF receptor protein after 24-h dexamethasone treatment. Brief pulse labeling with 35S-methionine showed that the reduction in total EGF receptor protein content was due to a decrease in EGF receptor synthesis. Receptor synthesis declined about 25% after 1 h of dexamethasone treatment and at 3 h, EGF receptor synthesis was maximally decreased to nearly 50% that of cells not exposed to dexamethasone. Dexamethasone treatment was also effective in reducing EGF receptor synthesis in cells pretreated with retinoic acid, an agent which enhances receptor synthesis. These data are the first to document a dexamethasone-induced decrease in EGF receptor synthesis. Furthermore, these findings may provide a plausible mechanism by which dexamethasone could regulate EGF responsiveness.

Animals↗
PubMed1989

Expression of a glucose transporter gene cloned from brain in cellular models of insulin resistance: dexamethasone decreases transporter mRNA in primary cultured adipocytes.

In two cellular models of insulin resistance we measured glucose transport activity, total glucose transporter number using the cytochalasin B binding assay, and expression of a transporter mRNA species specifically hybridizing with cDNA cloned from brain. In primary cultured adipocytes, chronic exposure to glucose plus insulin (24 h), but neither agent alone, markedly decreased (less than 50%) glucose transport activity; however, neither glucose nor insulin regulated the number of glucose transporters or levels of transporter mRNA whether normalized per total RNA, RNA per cell, or as a fraction of CHO-B mRNA. On the other hand, chronic treatment with 30 nM dexamethasone (24 h) decreased basal and maximal transport rates (approximately 75%), led to a 40% depletion in total cellular glucose transporters, and decreased transporter mRNA by 57-59% (t 1/2 = 10 h; ED50 = 4-5 nm). Dexamethasone's effects to decrease transport rates, transporter protein, and mRNA were inhibited by coincubation with insulin. Dexamethasone did not alter the degradation rate of transporter mRNA relative to that in control cells indicating a lack of effect on mRNA stability. Also, suppression of transporter mRNA did not appear to require ongoing protein synthesis since the effect was observed when dexamethasone was added to cycloheximide-treated cells; however, cycloheximide per se specifically increased transporter mRNA 4-fold. We conclude in adipocytes: 1) glucose and insulin (24 h) do not regulate the total number of glucose transporters or expression of mRNA encoding a transporter species cloned from brain. 2) Long-term dexamethasone treatment reduces the cellular abundance of both glucose transporters and the specific transporter mRNA; these effects may be due to inhibition of gene transcription since dexamethasone does not influence transporter mRNA stability. 3) Insulin heterologously inhibits regulation of the glucose transport system by dexamethasone. 4) Dexamethasone-mediated insulin resistance is due in part to regulation of a glucose transporter species encoded by cDNA cloned from brain. These observations may be relevant to mechanisms of insulin resistance in clinical states of hypercortisolism.

Adipose Tissue↗
PubMed2002

Dexamethasone reduces morphine-induced Straub reaction in mice.

This study examined the effect of dexamethasone on morphine-induced straub reaction in mice. When morphine was administered in doses of 7.5, 15 and 30 mg kg(-1) intraperitoneally, a dose-dependent straub reaction was produced. Dexamethasone per-se (0.1-10 mg kg(-1) i.p.) did not modify the tail of control mice. Pre-treatment with dexamethasone 120 min before morphine injection caused a dose-dependent reduction of straub reaction. Cycloheximide (15 mg kg(-1) i.p.) administered 2 h before morphine did not change morphine-induced straub reaction, but was able to prevent the effects of dexamethasone on morphine-induced straub reaction. The glucocorticoid receptor antagonist RU-38486 (15 mg kg(-1) i.p.) did not affect morphine-induced straub reaction, whereas it was able to block the effects of dexamethasone on morphine-induced straub reaction. Results of this study indicate that dexamethasone reduced morphine-mediated straub reaction in mice, indicating a further important functional interaction between dexamethasone and the opioid system. The ability of cycloheximide and RU-38486 to block dexamethasone's effects indicates that the steroid's interference with morphine-mediated straub reaction involves a protein-synthesis-dependent mechanism via glucocorticoid receptors.

Animals↗
PubMed2005

Hyperglycemia in patients administered dexamethasone for craniotomy.

Hyperglycemia should be avoided during neurosurgery in order to decrease the risk of neurological injury. Dexamethasone has been associated with increased blood glucose during surgery. In this prospective, nonrandomized study, we documented the blood glucose concentration changes for 12 h in 34 nondiabetic patients undergoing craniotomy and compared patients who received intraoperative dexamethasone (10 mg IV on induction and 4 mg IV 6 h later), with or without preoperative dexamethasone, with patients who did not receive dexamethasone. Blood glucose concentrations increased from the preinduction value in all groups. Patients not taking dexamethasone before surgery, but who were given it intra- and postoperatively, had the largest peak blood glucose concentrations (11.0 +/- 2.0 mmol/L, mean +/- sd; P < 0.01) compared with patients who received no dexamethasone (7.8 +/- 2.1 mmol/L) or those who had been taking dexamethasone before surgery and continued it during surgery (8.5 +/- 1.2 mmol/L). The peak blood glucose concentrations in this group occurred 9 +/- 2 h after the induction of anesthesia. We recommend that the blood glucose concentration be monitored for at least 12 h in nondiabetic patients having neurosurgery who are newly administered dexamethasone.

Anti-Inflammatory Agents↗