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PubMed1999

The use of dexamethasone in women with preterm premature rupture of membranes--a multicentre, double-blind, placebo-controlled, randomised trial. Dexiprom Study Group.

OBJECTIVE: To assess whether administration of dexamethasone in women with preterm premature rupture of membranes (PPROM) has an effect on the prevalence of maternal sepsis, neonatal respiratory distress syndrome (RDS), perinatal mortality and neonatal sepsis in a developing country. SETTING: Six public hospitals in South Africa that deal mainly with indigent women. METHOD: A multicentre, double-blind, placebo-controlled, randomised trial was performed on women with PPROM and fetuses of 28-34 weeks' gestation or clinically estimated fetal weight between 1,000 and 2,000 g if the gestational age was unknown. Women were randomised to receive either dexamethasone 24 mg intramuscularly or placebo in two divided doses 24 hours apart. All women received amoxycillin and metronidazole and were managed expectantly. Hexoprenaline was administered if contractions occurred within the first 24 hours after admission to the trial. OUTCOME MEASURES: The maternal outcome measures were clinical chorio-amnionitis and postpartum sepsis. The outcome measures for infants were perinatal death, RDS, mechanical ventilation, necrotising enterocolitis, and neonatal infection within 72 hours. RESULTS: One hundred and two women who delivered 105 babies were randomised to the dexamethasone group and 102 women who delivered 103 babies, to the placebo group. The groups were well balanced with regard to clinical features. There was a trend towards fewer perinatal deaths in the dexamethasone group: 4 compared with 10 (P = 0.16, odds ratio 0.37, 95% confidence intervals 0.09-1.34). A subanalysis of mothers who delivered more than 24 hours after admission to the study and their infants revealed a significant reduction in perinatal deaths; 1 death in the dexamethasone group and 7 in the placebo group, P = 0.047 (Fisher's exact test). No woman in either group developed severe sepsis, and the incidence of sepsis in the women did not differ significantly. Eleven infants in each group developed sepsis. CONCLUSION: This is the first randomised trial in women with PPROM to compare the effects of the use of corticosteroids with placebo, where all women received prophylactic antibiotics concomitantly with the corticosteroids. A trend towards an improved perinatal outcome was demonstrated in the women who received dexamethasone. There was no increased risk of infection in the women or their infants where dexamethasone was administered. Administration of corticosteroids to women with PPROM has more advantages than disadvantages in developing countries.

Anti-Inflammatory Agents↗

PubMed1999

The effective dose of dexamethasone for antiemesis after major gynecological surgery.

UNLABELLED: This double-blind, randomized, placebo-controlled study evaluated the minimum effective dose of dexamethasone for postoperative antiemesis. One-hundred fifty women scheduled for major gynecological surgery were randomly assigned to receive dexamethasone 10 mg (D10), 5 mg (D5), 2.5 mg (D2.5), 1.25 mg (D1.25), or placebo (P) before the induction of general anesthesia. A standardized general anesthesia technique was used. Postoperative pain was treated with bolus IV doses of morphine via a patient-controlled analgesia device. Patients were assessed for incidence of vomiting at 4, 8, 12, and 24 h after surgery. A total of 6, 6, 8, 15, and 19 patients in Groups D10, D5, D2.5, D1.25, and Group P experienced vomiting at least once within the first postoperative 24 h, respectively. Dexamethasone 10 mg, 5 mg, and 2.5 mg was more effective than dexamethasone 1.25 mg or placebo for antiemesis (P < 0.05). The difference in antiemetic effect among the 10 mg, 5 mg, and 2.5 mg groups was similar. The results suggest that 2.5 mg is the minimum effective dose of dexamethasone for postoperative antiemesis in patients undergoing general anesthesia for major gynecological surgery. IMPLICATIONS: Although dexamethasone is effective for antiemesis, major side effects may accompany its perioperative use. To achieve the best antiemesis with the fewest side effects, dexamethasone 10 mg, 5 mg, 2.5 mg, and 1.25 mg were compared with placebo in surgical patients. We found 2.5 mg to be the minimum effective dose without discernible side effects.

Anesthesia, General↗

PubMed2000

Chronic intrathecal administration of dexamethasone sodium phosphate: pharmacokinetics and neurotoxicity in an animal model.

OBJECTIVE: Although corticosteroids have been used intraspinally for many years, long-term intrathecal administration has not been examined. We have assessed the stability, bioavailability, and safety of continuously delivering the prodrug dexamethasone sodium phosphate into the lumbar subarachnoid space. METHODS: High-performance liquid chromatography studies were performed to determine whether dexamethasone sodium phosphate is degraded either in vials or in an infusion pump at 37 degrees C during a period of weeks. Rats then received implants with a combined intrathecal delivery and microdialysis sampling catheter to determine whether the prodrug is converted to free dexamethasone. A neurotoxicity study was performed in which rats received implants with an intrathecal catheter and were continuously infused with the corticosteroid during a 2-week period. RESULTS: Dexamethasone sodium phosphate, diluted in saline, is stable at body temperature in vials and implantable infusion pumps for at least 2 weeks. When delivered into the cerebrospinal fluid as a bolus, virtually all of the prodrug is converted to free dexamethasone within 40 minutes. When administered continuously, most of the corticosteroid is in its active form at steady state. Low doses of corticosteroid (< or =12.5 ng/h) produced no side effects or neuropathology in the rats, but a higher dose (125 ng/h) was associated with inflammation in the lumbar subarachnoid space. CONCLUSION: Dexamethasone sodium phosphate is a stable prodrug that is efficiently converted to free dexamethasone when delivered intrathecally. Low continuous intrathecal doses seem safe, but higher doses may lead to increased inflammation.

Animals↗

PubMed2000

Dexamethasone differentially regulates expression of carboxylesterase genes in humans and rats.

Carboxylesterases play important roles in the metabolism of endogenous and foreign compounds, therefore, xenobiotic regulation of carboxylesterase gene expression has both physiological and pharmacological significance. We previously reported that liver microsomal esterase activity was significantly decreased in rats treated with dexamethasone accompanied by a decrease in immunoreactive proteins of rat hydrolase A, B, and C. The aim of this study was to determine whether the suppressed expression of these enzymes was linked to the change of the mRNA levels, and whether cultured hepatocytes responded similar to whole animals to this chemical. Northern blotting analyses demonstrated that the levels of the corresponding mRNA were markedly decreased in rats treated with dexamethasone, suggesting that the suppressed expression is achieved through trans-suppression and/or increased degradation of the transcripts. Exposure of cultured rat hepatocytes to nanomolar levels of dexamethasone markedly decreased the levels of immunoreactive proteins of hydrolase A, B, and C. In contrast, exposure of cultured human hepatocytes to dexamethasone caused a slight increase in HCE-1 and HCE-2, two major forms of human liver microsomal carboxylesterases. The inductive effects in human hepatocytes were observed only when micromolar concentrations of dexamethasone were used. These results suggest that a major species difference exists regarding the regulation of carboxylesterase gene expression by dexamethasone. Both the glucocorticoid receptor and the pregnane X receptor are known to mediate dexamethasone action. Differential concentrations required suggest that suppression of rat hydrolases is mediated by the glucocorticoid receptor, whereas the induction of human carboxylesterases is mediated by the pregnane X receptor.

Amino Acid Sequence↗

PubMed2000

Endocrinologic and psychological effects of short-term dexamethasone in anorexia nervosa.

Patients with anorexia nervosa (AN) have hyperactivity of their hypothalamic-pituitary-adrenal (HPA) axis, sometimes accompanied by elevations of cortisol. We examined whether the normal effects of short-term dexamethasone treatment upon HPA axis suppression and appetite stimulation are observed in these patients. Five young women with AN and ten healthy female controls received one week of high-dose oral dexamethasone (2 mg/m2/d) preceded and followed by hormonal evaluation of sensitivity to glucocorticoids and psychological assessments. No differences in hormone levels of the HPA axis were observed between the two groups and control groups at baseline, after dexamethasone suppression, or following ACTH stimulation testing. However, fasting insulin levels were significantly lower in the AN group, both before and after dexamethasone therapy and their serum leptin levels were also significantly lower. The AN group had significantly lower scores on the Anorexia Nervosa Subtest and the Beck Depression Inventory after dexamethasone compared to controls. On daily analog scales, AN patients had higher anxiety scores while on dexamethasone. Normal sensitivity to glucocorticoids was observed in all parameters examined except for mild abnormalities in pancreatic beta-cell function. These data suggest that AN may represent a state of partial glucocorticoid resistance, as in other states of restricted food intake. Furthermore, these pilot data, including the effects of dexamethasone upon psychological outlook in AN, suggest that glucocorticoids are not an effective therapy for these patients.

Adolescent↗

PubMed2000

Determination of dexamethasone in milk of dairy cows by immuno-enzymatic assay.

Eight lactating cows received 3 im injections at 24 h intervals of a commercial formulation containing dexamethasone. Each treatment provided 25 microg/kg bw/d of dexamethasone acetate, equivalent to 22.6 mg of dexamethasone. Milk samples were obtained before treatment (5 d), during the treatment period, and for up to 22 milking after the last injection. The concentrations of dexamethasone in the milk samples were determined by a commercial competitive immunoenzymatic assay for corticosteroids (detection limit 0.15 ng dexamethasone/ml). The conventional therapeutic dose of dexamethasone acetate caused milk drug concentrations exceeding the tolerated maximum residue limit (0.3 mg/kg). A withdrawal time of 3-3.5 d for dexamethasone in milk provided sufficient protection for consumer health. The commercial enzyme immunoassay kit employed in this study was sufficiently sensitive, easy to use, and appropriate to monitor the use of dexamethasone in lactating animals.

Animals↗

PubMed2000

Dexamethasone alone does not prevent postoperative nausea and vomiting in women undergoing dilatation and curettage: a comparison with droperidol and saline.

BACKGROUND: The aim of this study was to evaluate the prophylactic effect of dexamethasone on postoperative nausea and vomiting (PONV) in women undergoing dilatation and curettage. Droperidol and saline were served as control. METHODS: One hundred and sixty women (n = 40 in each group) undergoing dilatation and curettage under intravenous anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Immediately before the induction of anesthesia, group 1 patients received i.v. dexamethasone 8 mg; group 2 patients received i.v. droperidol 1.25 mg; group 3 patients received i.v. droperidol 1.25 mg and dexamethasone 8 mg, and group 4 received i.v. saline. RESULTS: We found that dexamethasone alone did not reduce the incidence of PONV in a 24 h postoperative period. Droperidol was effective for this purpose with incidence of PONV of 25% (P < 0.05). A combination of droperidol and dexamethasone was also effective and was the most effective regimen during the postoperative period of 2-24 h. CONCLUSIONS: We conclude that dexamethasone (8 mg) alone does not prevent PONV in women undergoing dilatation and curettage. Droperidol is effective. Dexamethasone enhances the antiemetic effect of droperidol.

Adult↗

PubMed2001

Binding of dexamethasone by alpha-crystallin.

PURPOSE: Long-term steroid therapy is a known risk factor for the development of posterior subcapsular cataract. Previous work in this laboratory has found soluble lens proteins to bind dexamethasone, but this binding is not due to a glucocorticoid receptor. This study was undertaken to identify the soluble protein or proteins involved in lens glucocorticoid binding. METHODS: Bovine lens extract was incubated with 5.2 x 10(-)(8) M [(3)H]-dexamethasone for 3 hours, and the distribution of label assessed in the soluble and insoluble fractions after centrifugation. Soluble lens extract was fractionated using gel permeation chromatography to isolate and identify proteins involved in the binding. Total lens proteins, high-molecular-weight proteins, or alpha-crystallin were exposed to dexamethasone and the protein bound steroid measured after separation of free and bound ligand on a gel chromatography column. Scatchard analysis was used to determine dexamethasone-binding parameters. Sequence comparisons between bovine alphaA- and alphaB-crystallins and glucocorticoid-binding proteins were performed using a sequence-alignment program. RESULTS: Of the total dexamethasone bound in lens extract, soluble proteins were found to account for 52%. The majority of the soluble protein-bound dexamethasone coeluted with the high-molecular-weight proteins that consisted mainly of alpha-crystallin. Binding studies with isolated proteins showed that alpha-crystallin accounted for more than 98% of total soluble dexamethasone binding in the lens. Scatchard analysis of steroid binding showed it to be a nonspecific partitioning event. Sequence comparisons between alphaA- and alphaB-crystallins and various glucocorticoid-binding proteins showed the lens proteins to have three regions of sequence homology with yeast corticosteroid-binding protein. CONCLUSIONS: alpha-Crystallin is the principal soluble glucocorticoid binding protein in the lens. The steroid association is described by nonspecific partitioning and may be related to the unique structural characteristics of the protein. The nonspecific association with alpha-crystallin is not thought to be functional; however, it may aid in the increased covalent steroid modification observed for this protein.

Amino Acid Sequence↗

PubMed2001

Effect of Garcinia cambogia extract on lipids and lipoprotein composition in dexamethasone administered rats.

Dexamethasone (10 mg/kg body weight/day, s.c.) administered rats were treated with or without Garcinia cambogia fruit extract (1 g/kg body weight/day, orally) for 8 days. The administration of dexamethasone resulted in marked increase in the levels of triglycerides and cholesterol and free acids in both plasma and liver. The level of phospholipids increased in the plasma but decreased significantly in liver tissue after dexamethasone administration as compared to those in normal rats. The activities of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase were lowered significantly after dexamethasone per se administration. The levels of HDL-triglycerides and HDL-cholesterol remained unchanged, while the LDL and VLDL increased significantly in dexamethasone administered rats. The lipid levels were maintained at near normalcy when co-treated with Garcinia cambogia extract in dexamethasone administered rats. This study reveals the undesirable changes in lipid profile on dexamethasone administration and the hypolipidemic property of Garcinia cambogia extract.

Animals↗

PubMed2002

[In vitro effects of low-molecular weight heparin and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria patients].

OBJECTIVE: To study the in vitro effects of low-molecular weight heparin (LMWH) and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria (PNH) patients. METHODS: By Ham's test and micro-complement lysis sensitive test (mCLST), the changes of hemolysis of red blood cells from 6 PNH patients were tested by adding different doses of LMWH and dexamethasone into the test mixture. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied by activated partial thromboplastin time (APTT). RESULTS: (1) Either LMWH or dexamethasone could dose-dependently inhibit the hemolysis of PNH red blood cells, and the effects were synergistic when added together. The same dose of LMWH induced a less than 100% prolongation of APTT. (2) Dexamethasone could inhibit the hemolysis in Ham's test and had different effects on the hemolysis by different adding methods in mCLST. LMWH could inhibit the hemolysis in both Ham's test and mCLST. CONCLUSION: Both LMWH and dexamethasone could inhibit the hemolysis of PNH red cells and showed a synergistic effect. The mechanisms of the inhibition of hemolysis were different. Furthermore, a tolerable dose of LMWH induced only a limited prolongation of APTT, which might be useful for controlling acute hemolysis and reducing the dose of dexamethasone.

Anti-Inflammatory Agents↗

PubMed2002

Enhancing and suppressing effects of dexamethasone on transgene expression in vitro.

Gene therapy is becoming an important treatment modality against various diseases including cancer, genetic disorders, infectious diseases and inflammatory diseases. For achieving successful gene therapy, it is extremely important to control the expression of a transduced therapeutic gene. However, there have been few studies examining the effect of glucocorticoid on transgene expression. We demonstrate here that the synthetic glucocorticoid dexamethasone significantly affected transgene expression in vitro. Bone marrow cells freshly prepared from rats and murine fibroblasts were infected with retroviruses carrying the neomycin phosphotransferase gene under the transcriptional control of the retroviral long terminal repeat promoter and the reporter lacZ gene under the transcriptional control of the simian virus 40 (SV40) early promoter. Retrovirus-infected cells were selected by G418. When retrovirus-infected bone marrow cells were cultured in the presence of dexamethasone, lacZ expression was markedly decreased. This suppressive effect of dexamethasone on transgene expression in bone marrow cells appeared to be mediated by a methylation-independent mechanism, because the suppressive effect was also observed in bone marrow cells that were supposed to contain a considerable number of methylated cells. In marked contrast, when retrovirus-infected fibroblasts were cultured in the presence of dexamethasone, lacZ expression was significantly increased. The enhancing and suppressing effects of dexamethasone on transgene expression were considered to be independent on promoter types, because the SV40 early promoter used to control lacZ expression does not contain a glucocorticoid-responsive element. Therefore, the different effects of dexamethasone on transgene expression appeared to be dependent on cell types. These results indicate that dexamethasone may play an important role for achieving successful gene therapy. Furthermore, these observations may also have important implications for future clinical applications of gene therapy.

3T3 Cells↗

PubMed2002

A prospective randomized trial of megadose methylprednisolone and high dose dexamethasone for traumatic optic neuropathy.

PURPOSE: To determine whether the improvement in visual acuity obtained when using high dose dexamethasone in the treatment of traumatic optic neuropathy was comparable to that of megadose methylprednisolone. METHOD: A total of forty-four patients with traumatic optic neuropathy were prospectively randomized and selected to receive intravenous high dose dexamethasone or megadose methylprednisolone within 2 weeks of injury. Age, gender, cause of injury, interval from injury to treatment, initial, post-pulse, and final visual acuity were analysed statistically to compare the dexamethasone and methylprednisolone groups. RESULTS: The mean interval to treatment was not significantly different (p=0.28) for the dexamethasone group at 5.5 days compared to the methylprednisolone group at 4.1 days. Visual improvement of at least two lines of the Snellen chart or two levels of unmeasured visual acuity was shown in 9 patients (37.5%) of the dexamethasone group and 10 patients (50%) of the methylprednisolone group. There was no statistically significant difference between the initial and post-pulse visual acuity (p=1.0) and the initial and final visual outcome (p=0.60) in the dexamethasone group compared with the methylprednisolone group. CONCLUSION: There was no significant difference in the visual acuity obtained after treatment with intravenous dexamethasone or methylprednisolone for traumatic optic neuropathy.

Adolescent↗

PubMed2002

Role of dexamethasone in acute bacterial meningitis in adults.

OBJECTIVE: To evaluate the role of dexamethasone as adjunctive therapy in adult acute bacterial meningitis (ABM) in two groups of patients treated with antibiotics alone or a combination of antibiotics and dexamethasone. DESIGN: Systematic sampling interventional open cohort study. SETTING: Department of Medicine (Medical Unit II), Jinnah Postgraduate Medical Centre, Karachi. PATIENTS: Sixty eight patients aged 12-85 years admitted in Medical Unit II and diagnosed to have ABM. Patients were divided into two groups. Group A received anti-microbial therapy for 14 days (a combination of benzyl penicillin 6 million units I/V 6 hourly and chloramphenicol 1 gm I/V 6 hourly) and group B received the same antimicrobial therapy with dexamethasone 0.6 mg/kg/day in 3 divided doses for 4 days. MAIN OUTCOME MEASURES: Differences in mortality and morbidity in the two groups and differences in the CSF inflammatory parameters between the two groups of patients. RESULTS: There was early resolution of fever, headache and altered consciousness in group B as compared to group A. Cranial nerves involvement was lower in group B. There was no difference in the occurrence of other focal neurological deficits between the two groups. CSF inflammatory parameters (glucose, protein and WBC count) were significantly better in group B by day 5. No complications attributable to dexamethasone were seen in group B. CONCLUSION: There was early resolution of symptoms and CSF inflammatory parameters in the group that received dexamethasone as adjuvant therapy. Mortality was lower in the group treated with dexamethasone but the difference was not statistically significant. Dexamethasone should be administered to all adults patients with ABM.

Adolescent↗

PubMed2001

[Study on the enzyme dependant colon targeting prodrug--dexamethasone succinate dextran and its tablets].

AIM: To develop an orally administered colon targeting drug delivery system dexamethasone succinate dextran (DSD) tablets. METHODS: Dexamethasone succinate dextran was synthesized in an anhydrous environment. Using 4-dimethyl aminopyridine and 1,1'-carbonyldiimidazole as the catalyzer. The chemical structure was identified by UV, IR, NMR and MS. The contents of dexamethasone in various samples were determined by HPLC. RESULTS: Dexamethasone was distributed mainly in plasma and gastric contents after the oral administration of common tablets. In contrast, after oral administration of DSD tablets, the recovery of dexamethasone in plasma and gastric contents decreased significantly, while the percentage of dexamethasone in cecum and colon increased obviously. CONCLUSION: The experimental results showed the good colon targeting property of DSD prodrug compared with free dexamethasone.

Administration, Oral↗

PubMed2002

Establishment of a rat long-term culture expressing the osteogenic phenotype: dependence on dexamethasone and FGF-2.

Rat stromal bone-marrow cells cultured in the presence of dexamethasone, ascorbic acid, beta-glycerophosphate, and fibroblast growth factor-2 (FGF-2) express the osteogenic phenotype (Pitaru et al., J. Bone Miner. Res. 8:919-929, 1993). The purpose of this study was to establish a long-term homogeneous culture expressing the osteogenic phenotype. The cultures were routinely passaged every 5 days in the absence or presence of either or both dexamethasone and FGF-2, and the cumulative doubling number and the expression of the osteogenic phenotype were determined. Cultures treated with dexamethasone (10(-7) M) ceased proliferation and only upon addition of FGF-2 (3 ng/ml) was a spontaneous immortalization achieved, as expressed by sustained proliferation for about 1 year, with a doubling time of 22 h and more than 300 doublings in 72 passages. Both FGF-2 and dexamethasone are required and act synergistically to maintain cell propagation, alkaline phosphatase expression, and osteocalcin secretion; however, protein content was FGF-2 dependent and the mineralization was dexamethasone dependent. Repetitive single-cell cloning tested the homogeneity and stability of the cells expressing the osteogenic phenotype in these long-term cultures. It was shown that 25% to 50% of subclones derived from clones with an osteogenic phenotype do not further express the osteogenic phenotype. In conclusion, we have established a spontaneously immortalized dexamethasone- and FGF-2-dependent rat stromal bone-marrow-derived long-term culture expressing the osteogenic phenotype. The cultures tend to lose the osteogenic phenotype, and dexamethasone supports the long-term preservation of the osteogenic phenotype.

Alkaline Phosphatase↗

PubMed1992

Dexamethasone down-regulates the expression of endothelin receptors in vascular smooth muscle cells.

Steroid hormones have been shown to modulate a number of physiological processes in addition to their potent antiinflammatory effects. Endothelin (ET) is a newly discovered vasoconstrictor that is synthesized and released by endothelial cells and acts on adjacent vascular smooth muscle cells by interacting with specific cell surface receptors. Proinflammatory agents such as thrombin and transforming growth factor beta have been shown to up-regulate ET gene expression in vascular endothelial cells. We wondered whether the anti-inflammatory steroids might have any regulatory effect on the ET receptors present in the vascular smooth muscle cells. Rat vascular smooth muscle cells (A-10 cell line, ATCC.CRL 1476) were used as a model system to study the effects of glucocorticoids on ET receptor expression and function. These cells display high density and high affinity ET receptors that belong to the ETA subtype. Pretreatment of these cells with dexamethasone reduced the number of ET receptors by 50-60% without changing the affinity. Of the steroids tested, dexamethasone was most effective followed by prednisolone and hydrocortisone. Aldosterone, a mineralocorticoid, was 5000-fold less potent than dexamethasone. This effect of dexamethasone was dependent on the time of pretreatment and concentration of the steroid used. This down-regulation of ET receptors was also accompanied by an attenuated response to ET-1 in dexamethasone-pretreated cells. The inhibitory effect of dexamethasone was selective for ET receptors because the vasopressin-mediated response was unaffected. In addition, dexamethasone pretreatment of these cells resulted in 50-60% reduction in the steady-state level of ETA receptor mRNA as revealed by Northern analysis. These results suggest that glucocorticoid pretreatment of smooth muscle cells resulted in the down-regulation of the ETA receptor at the mRNA level.

Animals↗

PubMed2003

[Modulation of matrix metalloproteinase by dexamethasone in airway remodeling in asthmatic rats].

OBJECTIVE: To observe the effect of dexamethasone on airway remodeling and to explore the significance of the balance between matrix metalloproteinase and the tissue inhibitor of metalloproteinase. METHODS: Thirty male Wistar rats were randomly divided into asthmatic group (n = 10), dexamethasone group (n = 10) and control group (n = 10). Lung tissues were sliced and stained with H. E. The parameters such as bronchial basement membrane perimeter(Pbm), total bronchial wall area(WAt), inner wall area(WAi) and smooth muscle area(WAm), which reflect the thickness of airway wall, were measured by image analysis system. The expression levels of MMP-2 and TIMP-1 mRNA in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: 1. WAt/Pbm, WAi/Pbm and WAm/Pbm in asthmatic group (25.3 +/- 2.1 microns 2/micron, 20.4 +/- 2.3 microns 2/micron, 4.2 +/- 2.0 microns 2/micron, respectively) were significantly higher than those in control group (20.8 +/- 1.3 microns 2/micron, 15.3 +/- 2.1 microns 2/micron, 3.1 +/- 1.1 microns 2/micron) (P < 0.01). The differences between those in control group and those in dexamethasone group (21.3 +/- 2.4 microns 2/micron, 14.2 +/- 2.5 microns 2/micron, 3.2 +/- 1.0 microns 2/micron) were not statistically significant (P > 0.05). 2. MMP-2 and TIMP-1mRNA levels in asthmatic group (0.68 +/- 0.14, 0.56 +/- 0.10) and dexamethasone group (0.37 +/- 0.11, 0.31 +/- 0.10) were significantly higher than those in control group (0.14 +/- 0.03, 0.11 +/- 0.05). The differences between asthmatic group and dexamethasone group were also significant (P < 0.01). 3. There was a significant positive correlation between MMP-2 and TIMP-1 mRNA in control group and dexamethasone group (r = 0.67, 0.58, P < 0.05), but not in asthmatic group (r = 0.24, P > 0.05). CONCLUSION: Dexamethasone could prevent airway remodeling by downregulating the expression of MMP-2 and TIMP-1 and restoring the balance between MMP-2 and TIMP-1.

Animals↗

PubMed1992

Use of enzyme immunoassay and reverse-phase high-performance liquid chromatography to detect and confirm identity of dexamethasone in equine blood.

An enzyme immunoassay (EIA) was developed for detection of dexamethasone in equine blood. Dexamethasone 21-hemisuccinate-bovine serum albumin was used for immunization of rabbits, and prednisolone 21-hemisuccinate-horseradish peroxidase was used as enzyme conjugate. The assay had sensitivity in the low-picogram range (detection limit, 0.3 pg/well, 50% inhibition of binding at 4.5 +/- 0.7 pg/well). Apart from cortisol, which was recognized by the antiserum at concentration > 8.5 ng/ml, the dexamethasone antiserum failed to interfere with endogenous steroids, but cross-reacted with triamcinolone, flumethasone, and betamethasone. Thus, the antiserum was used to perform simultaneous screening for these synthetic glucocorticoids and to confirm their identity by combining reverse-phase high-performance liquid chromatography (RP-HPLC) and EIA. The immunoreactivity obtained by direct serum measurements was characterized by means of 2 independent RP-HPLC systems. Serum extracts were submitted to RP-HPLC systems I and II, and the fractions were tested by EIA. Immunoreactive peaks were identified by comparing their retention time with that of the standard glucocorticoids used for calibration. Coinjection of an internal standard (methylprednisolone) in RP-HPLC system II yielded reproducible relative retention times. The effectiveness of the test system was evaluated, using blood from a horse treated with commonly used veterinary preparations of dexamethasone. Administration of the free alcohol of dexamethasone and of dexamethasone 21-trioxaundecanoate, both given IV, was detected, and the identity of each was confirmed for up to 48 hours. Intramuscular administration of dexamethasone 21-isonicotinate was continued for at least 14 days after injection of a therapeutic dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗