Role of Stromal Cells in Protecting Young and Aged B-Lineage Precursors from Dexamethasone-Induced Apoptosis
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Lineage (genetic)
We present, to our knowledge, the first case of Cushing's syndrome due to large doses of intramuscular dexamethasone acetate. Dexamethasone levels after intramuscular dexamethasone administration were measured in two patients. Serial determination of the dexamethasone levels demonstrated prolonged serum half-lives of seven and 33 days in the two patients, respectively. Furthermore, pharmacologic levels of dexamethasone were present as long as seven months after the initial injections. The present recommendation for the use of intramuscular dexamethasone acetate is as frequent as every one to three weeks. However, our patients demonstrate that supraphysiologic levels of dexamethasone may still be present well beyond the three-week period.
Intramuscular injection
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To investigate the effects of dexamethasone on the proliferation and differentiation of bone marrow stromal cells(MSC).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.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.Dexamethasone inhabit the proliferation of MSC, while induce them to differentiate into osteoblasts. The appropriate concentration of dexamethasone was 10(-8) mol/L.
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Background In the evaluation for hypercortisolism (Cushing’s syndrome), the 1 mg overnight dexamethasone suppression test has an important role, but false-positive results can occur due to low serum dexamethasone. Given the high intraindividual reproducibility of post-dexamethasone suppression test serum cortisol concentrations, we investigated the chance of success of repeating a non-suppressed dexamethasone suppression test if serum dexamethasone is low. Methods We retrospectively analysed the results of 1901 consecutive dexamethasone suppression tests performed in our laboratory from February 2011 to November 2018. Serum dexamethasone and cortisol were measured by LC-MS/MS, and both were reported. The 2.5 and 5th percentiles of serum dexamethasone in suppressed dexamethasone suppression tests were investigated as cut-off value. Then, we retrospectively determined the success rate of repeating an initial, non-suppressed dexamethasone suppression test in 131 patients, stratified by initial serum dexamethasone. Results At serum dexamethasone concentrations between the 2.5 and 5th percentiles (3.2–3.9 nmol/L), significantly more non-suppressed dexamethasone suppression tests were observed (27/67) than in the control group of 1357 tests having serum dexamethasone ⩾6 nmol/L (40% vs. 30%, P = 0.047), indicating that 3.9 nmol/L is the better cut-off. Overall, 40% of non-suppressed dexamethasone suppression tests were repeated, but repeat testing was performed more often when serum dexamethasone was low. In patients who had initial serum dexamethasone below the cut-off of 3.9 nmol/L, a significantly higher chance of having a suppressed repeat dexamethasone suppression test was observed compared to the control group: 57% (31/54) vs. 26% (15/57), P = 0.001. Conclusions Measuring and reporting serum dexamethasone in dexamethasone suppression tests have added value for the selection of patients who might benefit from a repeat dexamethasone suppression test. We suggest a cut-off for serum dexamethasone of ⩾3.9 nmol/L.
Dexamethasone suppression test
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Intraperitoneal injection
Anti-inflammatory
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Objective
To study the effect of using Dexamethasone in different time for treatment and prevention of bronchopulmonary dysplasia(BPD), in order to provide the clinical reference as to whether dexamethasone can be used to prevent and treat BPD.
Methods
A total of 135 very low birth weight infants hospitalized for 1 week who still survived on mechanical ventilation were studied.The total cases were divided into early Dexamethasone group and none Dexamethasone group.Whether early using dexamethasone could prevent BPD or not were observed.The BPD infants were divided into 3 groups, early Dexamethasone group, later Dexamethasone group and none Dexamethasone group.The effect of using Dexamethasone on BPD in different time were observed.
Results
(1)Among these 135 infants, there were 65 infants developing BPD.The incidence of BPD was 48.15%.There were no significant differences in the prevalence of BPD, the death rate and the disease index of BPD between the early Dexamethasone group and the none Dexamethasone group(all P>0.05).(2) There were no significant differences in mechanical ventilation time among the 3 BPD groups[(19.81±5.67) d vs(22.32±6.20) d,(21.46±7.02) d, P=0.405]. But the average time of inhaling oxygen and hospital stays of later Dexamethasone BPD group were shorter than early Dexamethasone BPD group and none Dexamethasone BPD group.The differences were significant[(37.27±10.14) d vs(45.96±9.91) d,(43.42±8.73) d, P=0.012;(64.11±8.14) d vs(76.13±7.57) d,(68.59±8.53) d, P=0.000].(3)The incidence of infection(90.90%, 100.00% vs 81.90%), hyperglycemia(27.27%, 30.43% vs 10.00%), hypertension(9.09%, 13.04% vs 0) and neonatal necrotizing enterocolitis(22.73%, 34.78% vs 15.00%) of all the infants who received Dexamethasone were higher than the infants who did not receive Dexamethasone.But the differences showed no significance(all P>0.05).(4) There were no significant differences among the 3 BPD groups in growth[weight:(9.16±1.53) kg vs(8.92±1.13) kg,(9.07±1.46) kg; height:(71.26±8.59) cm vs(69.54±9.32) cm,(70.32±9.07) cm] or been in hospital again because of pulmonary infection during one year(75.00% vs 65.00%, 72.22%)(all P>0.05). The differences of abnormal Chinese children development scale scores among the BPD groups(mental development index 0.05).
Conclusions
Early use of Dexamethasone has no effect to prevent BPD.Dexamethasone therapy on BPD should be used in the later stages, and small doses and short protocol are preferred.
Key words:
Dexamethasone; Bronchopulmonary dysplasia; Very low birth weight infant; Infant, premature
Bronchopulmonary Dysplasia
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AIM To discuss the possibility of using dexamethasone·dextran (average molecular mass 500,000) as a colon specific dexamethasone prodrug. METHODS Dexamethasone·dextran conjugate was synthesized by using succinate as a cross linker. The release of dexamethasone was determined after incubating at 37℃ the prodrug with contents from different parts of gastrointestinal(GI) tract of rats. RESULTS By HPLC analysis, it was found that dexamethasone·dextran contained 9.2 mg dexamethasone per 100 mg dextran conjugate. During the 160 minute incubation, the concentration of dexamethasone released in contents of colon and cecum was 2.7 times of that released in contents of proximal small intestines and distal small intestines. But, there was no dexamethasone released in content of stomach. CONCLUSION Dexamethasone·dextran (average molecular mass 500 000) conjugate can be used as a colon specific dexamethasone prodrug and can selectively deliver dexamethasone to the colon.
Conjugate
Cecum
Proximal colon
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Objective To evaluate the preventive effects of dexamethasone on phlebitis caused by 5-FU chemotherapy. Methods Forty patients receiving the intravenous infusion of 5-FU were randomly divided into two groups (treatment and control groups). In treatment group(n=20), 5 mg dexamethasone was infused into external vein through Murphy's Dropper before the chemotherapy. In control group (n=20), dexamethasone was not used. The incidence rates of phlebitis were compared between both groups. Result The incidence rate of phlebitis in treatment group was significantly higher than that in control group(χ 2=8.287, P0.01). Conclusion Dexamethasone can be used to prevent the peripheral phlebitis caused by dexamethasone therapy.
Intravenous Infusions
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Objective To investigate the mechanism of therapeutic action of dexamethasone on asthmatic mice by detecting the levels of IL-25 and IFN-γ in bronchoalveolar lavage fluid( BALF). Methods Balb /c mice with SPF grade were randomly divided into normal control group,asthma group and dexamethasone group. Asthma group and dexamethasone group were sensitized and challenged with ovalbumin( OVA). Dexamethasone group was intraperitoneally injected with dexamethasone one hour before challenging. The mice were executed 24 hours after the last challenge,and the HE stained pathological sections of the right lung were made. Pathological sections of lung were observed. BALF in the left lung was also collected. The total white blood cell count and absolute eosinophile( EOS) count were observed,and the percentage of EOS was calculated. The levels of IL-25 and IFN-γ were measured with ELISA,and correlation analyses were made. Results The counts of total white blood cell and EOS,and the percentage of EOS were significantly higher in the asthma group than in the normal control group and dexamethasone group( P 0.05). No differences were found between the normal control group and dexamethasone group. The IL-25 level was higher in the asthma group than in the normal control group and dexamethasone group( P 0. 05),and its level in the dexamethasone group was also higher than that in the normal control group. The IFN-γ level was lower in the asthma group than in the normal control group and dexamethasone group( P 0. 05),while there was no significant difference between the normal control group and dexamethasone group. IL-25 was negatively correlated with IFN-γ in each group. Conclusion Part of the mechanisms of dexamethasone acting on asthma are related to its inhibition on the pulmonary inflammation and promotion on the expression of IFN-γ,and possible inhibition of IL-25 expression.
White blood cell
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Summary Reasons for performing study : Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. Objectives : To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. Methods: Protocol 1 used 8 RAO‐affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary function over 4 h. Protocol 2 used 6 similar horses to compare, in a crossover design, the effects of dexamethasone i.v. (0.1 mg/kg bwt), dexamethasone per os (0.164 mg/kg bwt) with and without prior fasting, and dexamethasone per os (0.082 mg/kg) with fasting. Results : Dexamethasone i.v. caused significant improvement in lung function within 2 h with a peak effect at 4–6 h. Dexamethasone per os was effective within 6 h with peak effect at 24 h at a dose of 0.164 mg/kg bwt prior to feeding. The duration of effect was, for all dexamethasone treatments, statistically significant for 30 h when compared to saline and tended to have a longer duration of effect when used orally. Dexamethasone per os at a dose of 0.164 mg/kg bwt to fed horses had mean effects comparable to dexamethasone at a dose of 0.082 mg/kg bwt per os given to fasted horses, indicating that feeding decreases bioavailability. Conclusions : Dexamethasone administered i.v. has a rapid onset of action in RAO‐affected horses. Oral administration of a bioequivalent dose of the same solution to fasted horses is as effective as i.v. administration and tends to have longer duration of action. Fasting horses before oral administration of dexamethasone improves the efficacy of treatment. Potential relevance : Oral administration to fasted horses of a dexamethasone solution intended for i.v. use provides an effective treatment for RAO‐affected animals.
Crossover study
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To evaluate the efficacy of topical 1% cyclosporin A (CsA), 0.1% dexamethasone or 1% CsA combined with 0.1% dexamethasone in preventing and treating immune rejection after penetrating keratoplasty (PKP).Eighty-six eyes from 86 PKP patients were randomly divided into 3 groups: (1) Thirty-one eyes were treated with 1% CsA and dexamethasone for 3 months. (2) Twenty-nine eyes were treated with 1% CsA for 3 months; (3) Twenty-six eyes were treated with 0.1% dexamethasone for 3 months. The rejected eyes of postoperation were given with the dexamethasone injection under conjunctiva and increased the frequency of CsA and dexamethasone eye drops. All patients were followed up for 1 to approximately 2 years.There was a statistical difference in the 3 groups in the postoperative immune rejection which occurred in 5 out of 29 (17.3% ) eyes treated with 1% CsA, 7 out of 26 (26.9%) treated with 0.1% dexamathasone, and 3 out of 31 (9.7%) with 1% CsA and dexamethasone. The immune rejection after PKP occurred in 15 eyes and 13 eyes were cured by sub-conjunctiva injection of dexamethasone combined with eye drops of 1% CsA and 0. 1% dexamethasone.The efficacy of CsA combined with dexamethasone topically is better than that of 1% CsA or 0.1% dexamethasone alone in preventing rejection episodes. It is effective to cure the graft rejection after PKP with sub-conjunctiva injection of dexamethasone combined with the eye drop of 1% CsA and 0.1% dexamethasone.
Eye drop
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