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 235 records · Page 13Linked to original sources
PubMed2002

Dexamethasone impairs insulin signalling and glucose transport by depletion of insulin receptor substrate-1, phosphatidylinositol 3-kinase and protein kinase B in primary cultured rat adipocytes.

OBJECTIVE: Glucocorticoid excess leads to insulin resistance. This study explores the effects of glucocorticoids on the glucose transport system and insulin signalling in rat adipocytes. The interaction between glucocorticoids and high levels of insulin and glucose is also addressed. DESIGN AND METHODS: Isolated rat adipocytes were cultured for 24 h at different glucose concentrations (5 and 15 mmol/l) with or without the glucocorticoid analogue dexamethasone (0.3 micromol/l) and insulin (10(4) microU/ml). After the culture period, the cells were washed and then basal and insulin-stimulated glucose uptake, insulin binding and lipolysis as well as cellular content of insulin signalling proteins (insulin receptor substrate-1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and protein kinase B (PKB)) and glucose transporter isoform GLUT4 were measured. RESULTS: Dexamethasone in the medium markedly decreased both basal and insulin-stimulated glucose uptake at both 5 and 15 mmol/l glucose (by approximately 40-50%, P<0.001 and P<0.05 respectively). Combined long-term treatment with insulin and dexamethasone exerted additive effects in decreasing basal, and to a lesser extent insulin-stimulated, glucose uptake capacity (P<0.05) compared with dexamethasone alone, but this was seen only at high glucose (15 mmol/l). Insulin binding was decreased (by approximately 40%, P<0.05) in dexamethasone-treated cells independently of surrounding glucose concentration. Following dexamethasone treatment a approximately 75% decrease (P<0.001) in IRS-1 expression and an increase in IRS-2 (by approximately 150%, P<0.001) was shown. Dexamethasone also induced a subtle decrease in PI3-K (by approximately 20%, P<0.01) and a substantial decrease in PKB content (by approximately 45%, P<0.001). Insulin-stimulated PKB phosphorylation was decreased (by approximately 40%, P<0.01) in dexamethasone-treated cells. Dexamethasone did not alter the amount of total cellular membrane-associated GLUT4 protein. The effects of dexamethasone per se on glucose transport and insulin signalling proteins were mainly unaffected by the surrounding glucose and insulin levels. Dexamethasone increased the basal lipolytic rate (approximately 4-fold, P<0.05), but did not alter the antilipolytic effect of insulin. CONCLUSIONS: These results suggest that glucocorticoids, independently of the surrounding glucose and insulin concentration, impair glucose transport capacity in fat cells. This is not due to alterations in GLUT4 abundance. Instead dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 and PKB accompanied by a parallel reduction in insulin-stimulated activation of PKB.

Adipocytes↗
PubMed2001

[The effects of dexamethasone on biological characteristics of bone marrow stromal cells].

OBJECTIVE: To investigate the effects of dexamethasone on the proliferation and differentiation of bone marrow stromal cells(MSC). METHODS: MSC were isolated and cultured in vitro. After treatment with different concentrations of dexamethasone (0, 10(-10), 10(-9), 10(-8), 10(-7) and 10(-6) mol/L), the proliferation and alkaline phosphatase (ALP) activity of MSC were measured to evaluate the effect of dexamethasone on the biological characteristics of MSC. RESULTS: Dexamethasone inhibited cell proliferation. With the increase of concentration of dexamethasone, the effect was enhanced, which was more significant when the concentration of dexamethasone was over 10(-8) mol/L. At the same time, dexamethasone promoted the activity of ALP. This effect was enhanced with the increase of concentration of dexamethasone, but the alteration was small when the concentration of dexamethasone was over 10(-8) mol/L. The effects increased with the time. The activity of ALP was enhanced 2 to 4 times with the dexamethasone for 6 days. CONCLUSION: Dexamethasone inhabit the proliferation of MSC, while induce them to differentiate into osteoblasts. The appropriate concentration of dexamethasone was 10(-8) mol/L.

Animals↗
PubMed1983

Dexamethasone stimulates insulin receptor synthesis in cultured rat hepatocytes.

The ability of the glucocorticoid dexamethasone to modulate the insulin receptor was examined directly in primary cultures of hepatocytes prepared from adult male rats. Hepatocytes were cultured in a defined medium in the presence and absence of dexamethasone, 0.1 microM. The exposure of hepatocytes to dexamethasone resulted in a time-dependent (steady state by 32 h) increase in insulin binding in both intact hepatocytes and Triton X-100-soluble extracts (total insulin receptor content). The enhanced insulin binding found in soluble extracts of dexamethasone-treated hepatocytes was the result of an increase in insulin receptor number without a change in receptor affinity. In order to assess the mechanism by which dexamethasone "up-regulates" the insulin receptor, the heavy isotope density-shift technique was used to analyze insulin receptor turnover in control and dexamethasone-treated hepatocytes. Hepatocytes were initially cultured for 32 h in standard culture media containing only "light" (14C, 12C, 1H) amino acids. In hepatocytes exposed to dexamethasone, a 417% increase in insulin binding in Triton X-100-soluble extracts was observed. After 32 h, when steady state binding is achieved in dexamethasone-treated cultures, parallel cultures of hepatocytes incubated in the absence and presence of dexamethasone were washed and subsequently cultured in media containing "heavy" amino acids (15N, 13C, 2H). The time-dependent disappearance of light insulin receptor (receptor degradation) and appearance of heavy insulin receptor (receptor synthesis) were monitored using CsCl gradients to resolve the two density species of receptor. At steady state, the rate of receptor synthesis (k8) was 2.94 and 0.62 fmol of insulin bound h-1 in dexamethasone-treated and control hepatocytes, respectively. In contrast to this large increase in the rate of receptor synthesis observed in dexamethasone-treated cells, the first order rate constant for decay (k d) was the same in dexamethasone-treated (0.074 h-1) and in control (0.077 h-1) hepatocytes. We therefore conclude that glucocorticoid-induced up-regulation of the insulin receptor in the liver is due to stimulation of insulin receptor synthesis.

Animals↗
PubMedDate not supplied

Severe retinopathy of prematurity in extremely low birth weight infants after short-term dexamethasone therapy.

With advances in neonatal intensive care survival of extremely low birth weight (< 1 kg) infants has increased significantly over the past decade. Dexamethasone is used increasingly for the prevention and treatment of chronic lung disease in these infants. The impact of dexamethasone therapy on the incidence or severity of retinopathy of prematurity (ROP) remains controversial. We conducted a retrospective study to evaluate the association between short-term dexamethasone treatment and severe ROP in extremely low birth weight infants. From October 1989 to December 1992, 309 very low birth weight infants were admitted to the neonatal intensive care unit. A total of 266 infants (86%) survived until hospital discharge. Of these, 90 weighed less than 1 kg. Thirty-eight of 90 infants received short-term dexamethasone therapy for chronic lung disease and the remaining 52 infants did not. Infants treated with dexamethasone and those not treated with dexamethasone were comparable in birth weight (820 vs 828 gm), gestational age (26.5 vs 26.9 weeks), inborn (11 vs 14), and occurrence of sepsis (13/38 vs 21/52). Infants treated with dexamethasone required longer periods of mechanical ventilation (44 +/- 23 vs 26 +/- 15 days, p < 0.001), had longer duration of supplemental oxygen (57 +/- 28 vs 29 +/- 23 days, p < 0.001), had higher incidence of patent ductus arteriosus (28/38 vs 18/52, p < 0.0003), and required surfactant therapy more often for respiratory distress syndrome (17/38 vs 11/52, p < 0.01), when compared with infants who did not receive dexamethasone. Severe ROP developed in 16 infants (stage III or higher); 12 of these were in the dexamethasone-treated group (p < 0.003). Thirteen infants required cryotherapy; nine were from the dexamethasone-treated group (p < 0.13). This study demonstrates an apparent association between the incidence of severe ROP and dexamethasone therapy. Prospective, randomized, controlled studies are needed to correct for differences in severity of cardiorespiratory illness to establish whether a causal role exists for steroid therapy in ROP. Until such studies are available, careful consideration must be given to indications, dosage, time of initiation, and duration of treatment with dexamethasone in extremely low birth weight infants.

Case-Control Studies↗
PubMed1982

5'-deoxypyridoxal interaction with dexamethasone receptor: a new probe for structure and function of steroid receptors.

5'-Deoxypyridoxal, a vitamin B-6 analogue, increased the rate of dissociation of [3H]dexamethasone from HeLa S3 cytoplasmic glucocorticoid receptor complexes in vitro. This effect was achieved at millimolar concentrations of 5'-deoxypyridoxal, suggesting a low-affinity interaction of 5'-deoxypyridoxal with receptor. Loss of [3H]dexamethasone-receptor binding in the presence of 5'-deoxypyridoxal was pH dependent, and a plot of Kdiss vs. pH fit a simple sigmoidal titration curve with an inflection point at pH 7.8, suggesting that deprotonation of a single functional group on 5'-deoxypyridoxal increases Kdiss. Loss of [3H]dexamethasone binding in the presence or absence of unlabeled steroid also increased with pH, but no inflection point occurred over the range of pH tested. A titration of 5'-deoxypyridoxal indicated a pK of 7.94 for the pyridinium proton, suggesting deprotonation of the pyridinium nitrogen may account for the pH dependence of Kdiss of dexamethasone from receptor. 5'-Deoxypyridoxal also caused a decrease in nuclear [3H]-dexamethasone-receptor binding when incubated with whole HeLa S3 cells at 37 degrees C. Furthermore, 5'-deoxypyridoxal was effective in reducing nuclear binding of dexamethasone when added either simultaneously with [3H]dexamethasone or after achievement of equilibrium of steroid with receptor. The reduction in nuclear [3H]dexamethasone binding is highly specific for 5'-deoxypyridoxal. Several analogues of this compound, including 5'-deoxypyridoxamine, were ineffective. In addition, this effect was reversible following removal of extracellular 5'-deoxypyridoxal. Under these conditions, 5'-deoxypyridoxal was competitive with dexamethasone for binding to nuclear receptor, with KI = 8.1 X 10(-6) M. Scatchard plot analysis of dexamethasone-receptor binding in the presence or absence of 5'-deoxypyridoxal was consistent with an apparent reduced affinity of [3H]dexamethasone for receptor, which again suggests competitive interaction or allosteric interaction mediated dissociation. Glucocorticoids are known to stimulate alkaline phosphatase activity within HeLa S3 cells. In whole cell incubations, 5'-deoxypyridoxal was effective in reducing the dexamethasone-induced increase in alkaline phosphatase activity by 60% under conditions in which cell viability and cell growth were not affected.

Alkaline Phosphatase↗
PubMed1997

Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988.

OBJECTIVE: To evaluate the effectiveness of dexamethasone in bacterial meningitis in the subcategories of causative organism and timing and nature of antibiotic therapy. DATA SOURCES: MEDLINE, HEALTHLINE, and AIDSLINE were searched with the Medical Subject Headings "dexamethasone" and "meningitis" in any language. Bibliographies, conference abstracts, and the authors of identified studies were consulted. STUDY SELECTION: Randomized, concurrently controlled trials of dexamethasone therapy in childhood bacterial meningitis published from 1988 to November 1996 were selected. Of 16 studies identified, 5 were not eligible. DATA EXTRACTION: Data were extracted by means of standard outcomes in a protocol sent to all principal authors. DATA SYNTHESIS: Random-effects meta-analysis models were used to obtain summary estimates. As the incidence of severe hearing loss differed significantly by organism among control subjects, organism-specific estimates were used. In Haemophilus influenzae type b meningitis, dexamethasone reduced severe hearing loss overall (combined odds ratio [OR], 0.31; 95% confidence interval [CI], 0.14-0.69). Similar ORs were obtained after studies were stratified by the timing of administration of dexamethasone (before or with antibiotics vs later) or by type of antibiotic (cefuroxime vs other). In pneumococcal meningitis, only studies in which dexamethasone was given early suggested protection, which was significant for severe hearing loss (combined OR, 0.09; 95% CI, 0.0-0.71) and approached significance for any neurological or hearing deficit (combined OR, 0.23; 95% CI, 0.04-1.05). For all organisms combined, the pooled OR suggested protection against neurological deficits other than hearing loss but was not significant (OR, 0.59; 95% CI, 0.34-1.02). Outcomes were similar in studies that used 2 vs more than 2 days of dexamethasone therapy. Adverse effects were not significantly increased with dexamethasone except for secondary fever. The incidence of gastrointestinal tract bleeding increased with longer duration of dexamethasone treatment (0.5% in controls, 0.8% with 2 days of treatment, 3.0% with 4 days of treatment). CONCLUSIONS: The available evidence on adjunctive dexamethasone therapy confirms benefit for H influenzae type b meningitis and, if commenced with or before parenteral antibiotics, suggests benefit for pneumococcal meningitis in childhood. Limiting dexamethasone therapy to 2 days may be optimal.

Adolescent↗
PubMed1985

Opposing effects of dexamethasone on the clonal growth of granulocyte and macrophage progenitor cells and on the phagocytic capability of mononuclear phagocytes at different stages of differentiation.

Dexamethasone, a synthetic glucocorticosteroid, was shown to modulate the colony-stimulating factor-dependent clonal growth of myeloid progenitor cells in semisolid agar cultures, enhancing the formation of granulocyte colonies (50-100%) and suppressing the formation of macrophage colonies (75-97%). Modulation of the pattern of myeloid colony formation by dexamethasone (12-125 nM) was brought about when the steroid was administered to 6-day cultures at the time of culture initiation and up to 72 hr later. Dexamethasone inhibited myeloid cell proliferation when administered to 5-day liquid cultures at culture initiation and up to 96 hr later. Dexamethasone (12-250 nM) also enhanced the phagocytic activity of bone marrow-derived mononuclear phagocytes toward heat-killed (HK) yeast cells (up to 100%) and IgG-coated sheep red blood cells (up to 60%). Enhancement of the phagocytic capability depended critically on the stage in culture at which dexamethasone was administered. Exposure to dexamethasone for 28 hr up to 96 hr of 96-hr cultures of bone marrow cells did not lead to a modulation of phagocytic activity of the developing mononuclear phagocytes. The presence of dexamethasone during the critical period of 96 hr to 120 hr after culture initiation led to an enhanced phagocytic capability, which was statistically significant already 12 hr after the administration of the glucocorticoid. Dexamethasone induced an enhanced phagocytic activity when administered at any time after culture initiation provided that it was in culture during this critical period. When added at 120 hr of culture, dexamethasone no longer enhanced the phagocytic capability of mononuclear phagocytes and when added later than 156 hr of culture suppressed it. Dexamethasone also suppressed (up to 68%) the phagocytic capability of resident and elicited peritoneal macrophages. The results suggest that glucocorticoids shift the balance of granulocyte vs. macrophage formation at early stages of precursor cell differentiation. Reduction in mononuclear phagocyte growth and enhancement of its phagocytic capability might reflect accelerated differentiation/maturation steps. The inhibitory effect of dexamethasone on macrophage formation and on the phagocytic capability of mature mononuclear phagocytes and peritoneal macrophages might be a relevant aspect of the in vivo immune suppression encountered after glucocorticoid administration.

Animals↗
PubMed1987

Effects of dexamethasone on selected parameters of the bovine immune system.

The synthetic glucocorticoid, dexamethasone, has been used by investigators studying bovine immune mechanisms to either exacerbate infectious processes or stimulate stress-induced steroid-influenced immunosuppression. Considerable differences exist in the literature concerning the effect of dexamethasone on the bovine immune response. The purpose of our study was to clarify the reported effects of dexamethasone on bovine T-lymphocyte function. Therefore, we designed experiments to evaluate cellular and humoral aspects of the bovine immune response under the influence of dexamethasone. The experiments took into consideration the pharmacokinetics of dexamethasone and optimal and suboptimal doses of selected mitogens. The data suggest little variation in hematological parameters that occurred with the administration of dexamethasone. Leukocyte counts were slightly elevated at two observations, and this was believed to be the result of an increase in peripheral blood neutrophils. T-lymphocytes (erythrocyte rosetting) were not selectively depleted. However, suppression of T-lymphocyte function was noted, particularly in response to suboptimum doses of phytohaemagglutinin (PHA) and Concanaval in A (Con A). Antibody production to the T-dependent antigen, KLH, was suppressed in those animals receiving dexamethasone. These data suggest that the immunosuppressive effect of dexamethasone in the bovine is dependent upon the dose of dexamethasone administered, the pharmacological level of dexamethasone in vivo, physiological adaptation of the host, mitogen dose used in evaluation, and the time of evaluation post drug administration. The study points out the importance of considering these variables when interpreting the effects of dexamethasone on the bovine immune response.

Animals↗
PubMed2000

Dexamethasone does not affect vasopressin release in bronchopulmonary dysplasia.

Elevated levels of vasopressin (AVP) have been found in premature infants with bronchopulmonary dysplasia (BPD), and may be related to abnormalities of water handling, and to non-pulmonary signs of edema. Dexamethasone treatment improves pulmonary function in infants with BPD, and is frequently associated with a significant increase in diuresis and a decrease in weight gain. To determine whether this diuresis is primarily the result of AVP inhibition (potentially induced by steroid treatment), we measured endogenous AVP levels in nine premature babies with BPD [birth weight 802 +/- 141 (SD) g; gestation 26 +/- 2 weeks, age 26 +/- 17 days], before initiation, and 3 and 7 days after the start of dexamethasone therapy (0.5 mg/kg/day). All study infants required mechanical ventilation, and none was receiving diuretics or cardiac inotropes during the study. Results indicated that premature infants with BPD have functionally unmodified AVP levels after 3 and 7 days of dexamethasone therapy (pre-dexamethasone 5.9 +/- 2.1 ng/l vs post-dexamethasone 7.0 +/- 3.0 and 8.0 +/- 1.9 ng/l at 3 and 7 days, respectively). Pulmonary function improved with oxygenation indexes decreasing (pre-dexamethasone 14 +/- 7 vs post-dexamethasone 9 +/- 7 and 7 +/- 4 at 3 and 7 days, respectively). A concurrent reduction in weight gain occurred (pre-dexamethasone 12 +/- 10 g/kg/day vs post-dexamethasone 7 +/- 3 g/kg/day and 3 +/- 1.5 g/kg/day on days 3 and 7, respectively). These data suggest that the improvement in lung function with dexamethasone treatment for BPD in premature infants does not correlate with a diuresis that results from vasopressin inhibition, and potentially induced by dexamethasone.

Anti-Inflammatory Agents↗
PubMed2002

Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects?

In order to minimize neurological symptoms and treatment-related side-effects, patients with primary or secondary brain tumors receive dexamethasone. The goal of this study was to analyze dosage and duration of dexamethasone intake and to compare the advantages and disadvantages of this medication during the course of radiation therapy (RT). Data from 138 consecutive patients were therefore analyzed retrospectively. During the course of therapy, the dosage of dexamethasone was evaluated, as were the indications for and duration of this treatment, its side-effects and any clinical changes reported during dexamethasone intake. The dosage of dexamethasone was higher at the outset and during RT (median 7-12 mg/day) than at the end of RT (median 1-6 mg/day). The average duration of dexamethasone intake was 23 weeks for patients with primary, and 7 weeks for patients with secondary brain tumors. The most frequent side-effects were a rise in serum glucose level, peripheral edema, psychiatric disorders, and Cushing's syndrome. Life-threatening complications remained rare. Initially, dexamethasone led to good clinical improvement with few side-effects of RT, whereas by the end of RT the symptom relief was slight and toxicity increased. In a group of 13 patients who received no dexamethasone during RT, 12 showed neither RT-related side-effects nor of neurological impairment. Dexamethasone effectively minimizes neurological symptoms and RT-related side-effects in patients with primary and secondary brain tumors. Nevertheless, the side-effects of dexamethasone itself increase over time. For this reason, a generalized dose scheme should not be used. Instead, dosage should be adapted to each patient's individual needs. Future prospective studies will have to determine whether dexamethasone is advantageous on balance or not.

Antineoplastic Agents, Hormonal↗
PubMed1978

Evaluation of dexamethasone acetate as a topical ophthalmic formulation.

Penetration of an ophthalmic suspension of 0.1% dexamethasone acetate into the rabbit cornea and aqueous humor was unaffected by the status of the corneal epithelium or by the presence or absence of intraocular inflammation. However, the total quantity of this corticosteroid that could be measured in the cornea or aqueous humor was significantly less than that produced by either dexamethason alcohol or dexamethasone sodium phosphate. Despite this, dexamethasone acetate was the most effective of the three dexamethasone derivatives in suppressing inflammation in the cornea, which indicates that following topical administration to the eye it is the most potent of the dexamethasone derivatives studied. This greater therapeutic effect does not seem to be accompanied by a greater propensity to increase intraocular pressure. Comparison of the intraocular pressureincreasing effect in known corticosteroid responders of dexamethasone acetate with that of dexamethasone sodium phosphate, the least effective of the dexamethasone products studied, demonstrated no difference between the two drugs. These data support the conclusion that dexamethasone acetate is superior to the commercially available dexamethasone derivatives for use as a topical ocular anti-inflammatory agent.

Animals↗
PubMed1985

Effect of growth factors with dexamethasone on healing of rabbit corneal stromal incisions.

Treatment of rabbit corneal wounds with topical corticosteroid retards both epithelial regeneration and healing of penetrating stromal wounds. Currently, no clinical agent is available which accelerates the rate of stromal wound healing. Epidermal growth factor (EGF, 0.5 mg ml-1), fibroblast growth factor (FGF, 20 micrograms ml-1), and insulin (0.5 mg ml-1) were tested for their ability to accelerate healing of totally penetrating wounds in rabbit corneas when the hormones were administered alone or in combination with dexamethasone (1 mg ml-1). After 5 days of treatment with eye drops, the tensile strengths of corneal wounds treated with EGF (54 +/- 4 g mm-1) or treated with EGF and dexamethasone (32 +/- 9 g mm-1) were significantly higher than the tensile strengths of corneal wounds treated with only saline vehicle (3 +/- 1 g mm-1) or dexamethasone (1 +/ 0 g mm-1) (P less than 0.001). The combination of dexamethasone with EGF significantly (P less than 0.025) reduced the strength of corneal wounds compared to treatment with EGF alone. Similarly, the tensile strength of corneal wounds after 5 days of insulin treatment alone (28 +/- 8 g mm-1) or in combination with dexamethasone (25 +/- 7 g mm-1) was significantly increased compared with saline- or dexamethasone-treated corneas (P less than 0.001). In the absence of dexamethasone, EGF increased the tensile strength of corneal wounds significantly better than insulin (P less than 0.01). However, when EGF or insulin were given in combination with dexamethasone there was no significant difference between the tensile strength produced by the peptide hormones. In comparison to the tensile strength of corneal wounds treated by EGF or insulin, treatment with FGF alone (5 +/- 4 g mm-1) or in combination with dexamethasone (2 +/- 1 g mm-1) produced poor wound healing. The in vitro actions of EGF or FGF alone or in combination with dexamethasone were tested for ability to stimulate [3H]-thymidine incorporation into pure cultures of human corneal fibroblasts (HCF) in defined culture medium. EGF (5 mM) or FGF (100 ng ml-1) alone stimulated [3H]-thymidine incorporation approximately 2.5-fold compared to control cultures, whereas in combination with dexamethasone (10 nM), the stimulatory action of FGF, but not EGF, was abolished. Dose-response curves indicated that HCF in culture were very sensitive to EGF, insulin, and FGF with maximum stimulation of [3H]-thymidine incorporation occurring at approximately 1 nM for EGF and insulin and at 100 micrograms ml-1 for FGF. Binding of 125I-EGF to HCF reached maximum after 2 hr at 37 degrees C and was specific, saturable, and of high affinity (half saturation at 1 nM). (ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Detection of adenovirus by rapid 24-well plate centrifugation and conventional cell culture with dexamethasone.

Two methods for rapid detection of adenovirus were tested: (i) 24-well plate centrifugation followed by staining with a monoclonal antibody after incubation for 24 h and 48 h, and (ii) pretreatment of A549 cells used in conventional cell culture and 24-well plate centrifugation with 10(-5)M dexamethasone. Twenty-seven clinical isolates of adenovirus and 12 specimens from which adenovirus had been recovered were included in the analysis. Both isolates and specimens had been frozen at -70 degrees C for up to 6 months. By 24-well plate centrifugation both with and without dexamethasone, 21 (78%) and 27 (100%) isolates were positive for adenovirus at 24 h and 48 h, respectively. Of the specimens, 6 (50%) and 8 (67%) were positive by 24-well plate centrifugation without dexamethasone at 24 h and 48 h, respectively, whereas with dexamethasone 3 (25%) were positive at 24 h and 7 (58%) were positive at 48 h. Overall, combining isolates and specimens, the sensitivity of 24-well plate centrifugation for detection of adenovirus at 24 h was 69% without dexamethasone and 62% with dexamethasone, and at 48 h the sensitivity was 90% without dexamethasone and 87% with dexamethasone. The specificity under all conditions tested was 100%. In conventional tissue culture dexamethasone inhibited recovery of adenovirus. Without dexamethasone, adenovirus was recovered from all 39 samples within 7 days after inoculation; however with dexamethasone pretreatment, the virus was detected in only 31 (79%) of the samples tested in the same period of time.

Adenoviridae↗
PubMed1990

Dexamethasone inhibition of rat hepatoma cell growth and cell cycle traverse is reversed by insulin.

(1) The growth of 7800 C1 Morris hepatoma cells was inhibited by dexamethasone. The inhibition was detectable at 1 nM and half-maximal effect was obtained with approx. 13 nM dexamethasone. About 80% growth inhibition was obtained with 250 nM of the hormone and the growth rate was normalized on cessation of treatment. (2) These hepatoma cells contain dexamethasone receptors with equilibrium dissociation constant of 0.24 nM and a capacity of 24 fmol/mg cell protein. Treatment of the cells with insulin did not change these dexamethasone binding properties. Binding experiments showed that 2, 10 and 100% of the receptors were occupied when the cells were incubated with 1 nM, 7 nM and 250 nM dexamethasone, respectively. (3) Insulin completely counteracted the growth inhibition by dexamethasone and antagonized the induction of peroxisomal acyl-CoA oxidase and tyrosine aminotransferase caused by the glucocorticoid. (4) Micro-flow fluorometry showed that the cultures had a major diploid DNA stem line and a minor tetraploid stem line. Changes in diploid, tetraploid and S phase cells of the diploid stem line were scored. Dexamethasone reduced the proportion of cells in S phase and of tetraploid cells. Insulin partly reversed the action of dexamethasone in S phase, but prevented the reduction in tetraploid cells caused by dexamethasone. (5) The mitotic rate was significantly reduced by dexamethasone and this effect was reversed by insulin. (6) Continuous [3H]methyl-thymidine labelling showed a growth fraction of unity in all treatment groups. (7) It is concluded that dexamethasone induces growth inhibition by reducing the G1-S transition. Insulin is able to counteract this effect and increase the rate of DNA synthesis.

Animals↗
PubMed1989

Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes.

Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10(-6) and 10(-4) M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 x 10(-5) M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements.

Animals↗
PubMed1982

Reduced tumorigenicity of cultured neuroblastoma cells after treatment in vitro with dexamethasone.

The effect of dexamethasone on tumorigenicity of cultured neuroblastoma and on de novo synthesis of DNA and protein was determined. Within 12 hr dexamethasone caused a dose-dependent inhibition of [3H]-thymidine incorporation into DNA. Incorporation of [3H]-leucine into protein was not affected by dexamethasone. Neurite formation was interrupted by actinomycin D or cycloheximide. Cells treated with dexamethasone before inoculation into A/J mice produced fewer tumors with longer latent periods than controls. About 2.6 times as many neuroblastoma cells treated with 50 micrograms/ml dexamethasone for 4 days were required for tumor development in 50% of recipient animals as compared to controls. Reduced tumorigenicity was dependent upon the length of treatment and the concentration of dexamethasone used. Cortexolone did not mimic the effects of dexamethasone. If, instead of inoculation, cells were replated and grown without dexamethasone, cellular aggregations appeared among the cells cultured in the absence of dexamethasone. By autoradiography, replated cells previously treated with ethanol displayed uniform incorporation of [3H]-thymidine, whereas replated cells from dexamethasone-treated cultures exhibited no incorporation in differentiated cells. However, incorporation was noted among the clusters. We hypothesize that tumors arising after dexamethasone treatment may be due to the presence of an unresponsive subpopulation of cells.

Animals↗
PubMed2006

The favorable clinical and angiographic outcomes of a high-dose dexamethasone-eluting stent: randomized controlled prospective study.

BACKGROUND: Previous studies with dexamethasone-eluting stents could not elucidate the role of dexamethasone in the prevention of neointimal hyperplasia because they did not compare their results with a control group. We prospectively evaluated the clinical and angiographic outcomes of dexamethasone-eluting stents, comparing them with unloaded stents of an identical design. METHODS: A total of 92 patients (98 lesions) were randomly assigned to the dexamethasone group (67 patients, 71 lesions) or control group (25 patients, 27 lesions). The inclusion criteria for a stent implantation were a de novo lesion with a diameter of 2.60 to 4.0 mm. BiodivYsio Drug Delivery phosphorylcholine-coated stents (Biocompatibles Ltd, Galway, Ireland) were immersed in a 20-mg/mL dexamethasone solution, yielding a total dexamethasone dose of 0.5 microg/mm2 per stent. RESULTS: The total major adverse cardiac events rate at 12 months was significantly lower in the dexamethasone group, as compared with the control group (10.4% [7/67] vs 28.0% [7/25], P = .037). The binary restenosis rate at 6 months was 11.9% (7/59) in the dexamethasone group and 42.9% (9/21) in the control group (P = .002). The use of dexamethasone-eluting stents was the only independent predictor for the major adverse cardiac event at 12 months (relative risk 0.20, 95% CI 0.06-0.68, P = .009) and binary restenosis at 6 months (relative risk 0.17, 95% CI 0.05-0.60, P = .006) by multivariate analysis. CONCLUSIONS: Dexamethasone-eluting stents exhibited an improvement in the clinical and angiographic outcomes, as compared with the control stents. These results suggest that dexamethasone may play an important role in the inhibition of the polymer-induced inflammation in the era of drug-eluting stents.

Aged↗
PubMed2006

Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice.

OBJECTIVE: The aim of this study was to assess whether the anti-inflammatory agent dexamethasone can inhibit vein graft thickening without the occurrence of serious side effects. METHODS: Venous interposition grafting was performed in the common carotid artery of hypercholesterolemic ApoE3Leiden transgenic mice. Mice were treated with dexamethasone (0.15 mg.kg(-1).d(-1) orally), and after 28 days, vein graft thickening was quantified. RESULTS: Treatment with dexamethasone resulted in a significant 43% reduction in lesion area without changes in lesion composition when compared with nontreated controls. However, dexamethasone, when administered for a prolonged period of time, is known for its potentially serious side effects. To overcome these potential side effects of prolonged dexamethasone treatment, the effect of a short-term 7-day dexamethasone treatment was studied. This short dexamethasone treatment resulted in a 49% decrease of vein graft thickening at 28 days. Furthermore, it was demonstrated that dexamethasone treatment led to reduced local expression of several proinflammatory cytokines and factors in the vein grafts 24 hours after surgery. Finally, observations in mice were verified in human saphenous organ cultures. Exposure to dexamethasone for either 7 or 28 days significantly reduced intimal hyperplasia formation on cultured saphenous vein segments. CONCLUSIONS: Short-term anti-inflammatory treatment with dexamethasone leads to a significant reduction in vein graft thickening over an extended period, possibly by the reduction of early expression of proinflammatory cytokines. This 7-day treatment minimizes the risk of unwanted side effects of long-term dexamethasone treatment and may be a new approach to prevent graft failure.

Animals↗