Different Doses Of Dexamethasone Research Articles

English

INTRODUCTION: To compare the effects of adding two different doses of dexamethasone on the duration and quality of interscalene block in patients undergoing shoulder surgery. METHODOLOGY: A total of 90 patients(age 18-65years) undergoing shoulder surgery under interscalene block were assigned randomly to one of three groups: Control Group-C received injection levobupivacaine (0.5%), 35ml plus 2 ml normal saline Group-L received injection levobupivacaine (0.5%) 35 ml plus dexamethasone 4 mg plus 1 ml normal saline and; Group H received injection levobupivacaine (0.5%) 35 ml plus dexamethasone 8 mg. Assessment of motor and sensory blockade, pulse, systolic blood pressure, respiration and side effects were noted every 5 minutes for first 30 minute and every 10 minute till the end of surgery. Postoperative analgesia was assessed using the numeric rating scores (NRS). RESULTS: The duration of analgesia was significantly prolonged in both Group L (19.2 ± 2.6 h) and Group H (21.3 ± 1.7 h) compared with Group C (11.6 ± 1.1 h) (p<0.05). Similarly, the duration of motor block was longer in both Group L (26.6 ± 2.8 h), and Group H (28.4 ± 2.2 h) compared to Group C (18.6 ± 3.1 h) (p<0.05). Postoperative analgesic consumption for the first 48 hours was significantly lower in Group L (6.5 (4-8) tabs) and in Group H (5.5 (4-7) tabs) vs. 9.5 (8-12) tabs in Group C (p<0.01). CONCLUSION: The addition of dexamethasone to levobupivacaine significantly prolonged the duration of the motor block and improved the quality of analgesia following interscalene block. There was no difference in the duration of analgesia and motor block between low-dose and high-dose dexamethasone.

Effect of different doses of dexamethasone on the duration of single shot interscalene blocks with ropivacaine

Effect of different doses of dexamethasone on the duration of single shot interscalene blocks with ropivacaine

A clinical study of pretreatment with different doses of dexamethasone in the prevention of docetaxel-induced hypersensitivity.

e13514 Background: To evaluate the efficacy and safety of dexamethasone pretreatment regimen with different doses in the prevention of docetaxel-induced hypersensitivity reaction (HSR). Methods: On...

Epidural dexamethasone for post-operative analgesia in patients undergoing abdominal hysterectomy: A dose ranging and safety evaluation study.

Aim:Number of studies revealed that epidural bupivacaine-dexamethasone has the same analgesic potency as bupivacaine-fentanyl with opioid sparing and antiemetic effects. Different doses of dexamethasone were used in different studies. This study was designed to evaluate the optimum dose of epidural dexamethasone for post-operative analgesia.Materials and Methods:In this double-blinded randomized controlled study, we evaluated the efficiency and safety of different doses of epidural dexamethasone for post-operative analgesia in 160 patients aged 45-60 years scheduled for total abdominal hysterectomy. Patient were randomly allocated into four groups to receive a total volume of 10 ml epidural plain bupivacaine 0.25% in the control group (Group D0) with either 4 mg dexamethasone in (Group D4) or 6 mg dexamethasone in (Group D6) or 8 mg dexamethasone in (Group D8). Patients then received general anesthesia. Sedation, satisfaction and visual analog pain scores (VAS) at rest and with effort were measured post-operatively. Meperidine was administered when VAS > or = 4. Intra-operative fentanyl dose, post-operative meperidine consumption and the time to first analgesic requirement were recorded by a blinded observer. Blood glucose was measured pre-operatively and at 4 h and 8 h after study drug administration. Wound healing and infection were assessed after 1 week.Results:Intraoperative fentanyl requirements were comparable among groups. The time to first analgesic requirement was significantly prolonged 5.5 times in D8 Group but only 1.5 times in D6 and D4 Groups more than the analgesic duration in the control Group D0, with a P < 0.01. There was a significant reduction in post-operative meperidine consumption during the first 24 h in the D8 (75%) in comparison with D6 and D4 Groups (50%), respectively, (P < 0.01) and the control Group D0 (0%) (P < 0.01). VAS scores were significantly lower and patient satisfaction score was significantly higher in the D8 and compared with Groups D6 and D4 (P < 0.01) and the control Group D0 (P < 0.01). Post-operative nausea was significantly lower in the D8, D6 and D4 Groups versus the D0 Group (P < 0.05).Conclusion:Epidural dexamethasone in a dose of 8 mg is probably more effective than lower doses to control moderate to severe post-operative pain. This dose is not associated with increased glucose level or delayed wound healing.

The protective effect of different doses of dexamethasone on acute kidney injury induced by sepsis in mice

To investigate the effect of different doses of dexamethasone (DEX) on sepsis induced acute kidney injury (AKI). One hundred and thirty healthy male Kunming mice were randomly divided into sham group, sepsis group, physiological-dose DEX group (0.12 mg/kg), stress-dose DEX group (1.2 mg/kg), and high-dose DEX group (12 mg/kg). The sepsis model was reproduced by cecal ligation and puncture (CLP) method. Histopathological changes in the kidney were observed at 24 hours and 48 hours after CLP. The expressions of glucocorticoid receptor-α (GR-α) in the kidney were detected by immunohistochemistry. The levels of GR-α mRNA and nuclear factor-ΚB (NF-ΚB) mRNA were determined by real-time polymerase chain reaction (PCR). The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the plasma were measured by enzyme linked immunosorbent assay (ELISA). Compared with sham group mice, sepsis mice showed serious impairment in renal tubules. The mRNA and protein expression of GR-α were decreased, and NF-ΚB mRNA, plasma TNF-α and IL-1β were elevated. Compared with sepsis group, the histopathological changes in the kidney were mitigated with different levels in groups treated with different doses of DEX. GR-α protein and mRNA were up-regulated, NF-ΚB mRNA and plasma TNF-α, IL-1β were down-regulated obviously. The best effect could be seen in physiological DEX group [AKI score: 24 hours 1.480±0.334 vs. 3.040±0.517, 48 hours 1.840±0.167 vs. 3.400±0.400; GR-α protein (A value): 24 hours 0.102±0.009 vs. 0.088±0.005, 48 hours 0.103±0.008 vs. 0.085±0.006; GR-α mRNA: 24 hours 0.0400(0.0300, 0.0400) vs. 0.0100(0.0093, 0.0100), 48 hours 0.0350(0.0300, 0.0475) vs. 0.0100(0.0010, 0.0138); NF-ΚB mRNA: 24 hours 0.009±0.001 vs. 0.012±0.000,48 hours 0.011±0.000 vs. 0.013±0.001; TNF-α: 24 hours 105.84±3.84 ng/L vs. 135.52±4.49 ng/L, 48 hours 111.35±3.67 ng/L vs. 141.22±4.46 ng/L; IL-1β: 24 hours 45.71±2.93 ng/L vs. 64. 12±3.62 ng/L, 48 hours 57.04±3.04 ng/L vs. 74.87±3.67 ng/L; P<0.05 or P<0.01]. DEX given in physiological-dose could increase renal GR-α level and alleviate the sepsis induced kidney injury. The protective effect was much better than that of high dose DEX.

Effects of Systemic versus Local Administration of Corticosteroids on Mucosal Tolerance

Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperactivity in animal models of asthma. Whereas systemic administration of dexamethasone during the delivery of respiratory Ag has been suggested to prevent the development of mucosal tolerance, the effects of local administration of corticosteroids, first-line treatment for patients with bronchial asthma, on mucosal tolerance remain unknown. To analyze the effects of systemic versus local administration of different types of corticosteroids on the development of mucosal tolerance, mice were exposed to respiratory allergen to induce mucosal tolerance with or without systemic or intranasal application of different doses of dexamethasone or prednisolone. After the induction of mucosal tolerance, proliferation of T cells was inhibited in tolerized mice, whereas systemic applications of corticosteroids restored T cell proliferation and secretion of Th2 cytokines. In contrast, inhaled corticosteroids showed no effect on both T cell proliferation and cytokine secretion. In addition, mice systemically treated with corticosteroids showed an increased airway hyperactivity with a significant lung inflammation, but also an increased T effector cells/regulatory T cells ratio in the second lymphoid organs when compared with mice that receive corticosteroids by inhalation. These results demonstrate that local administration of corticosteroids has no effect on the development of immune tolerance in contrast to systemically applied corticosteroids. Furthermore, although different concentrations of corticosteroids are administered to patients, our results demonstrated that the route of administration rather than the doses affects the effect of corticosteroids on respiratory tolerance induction. Considering the broad application of corticosteroids in patients with allergic disease and asthma, the route of administration of steroid substances seems crucial in terms of treatment and potential side effects. These findings may help elucidate the apparently contradicting results of corticosteroid treatment in allergic diseases.

Impact of cell culture methods on the outcomes of the in vitro inflammatory response in nasal polyps

In vitro culture of nasal polyp cells is frequently used in the investigation of inflammatory mechanisms and effect of treatments in nasal polyposis. Research outcomes may, however, be influenced by the culture methodology used. Nasal polyp and nasal mucosa in vitro fibroblast cultures were pre-treated with foetal bovine serum (FBS)-free culture medium or medium supplemented with either FBS or charcoal-stripped (cs) FBS. Cells were then stimulated with FBS or csFBS, with or without different doses of dexamethasone for 4 and 24h. IL-6, IL-8, GM-CSF and VEGF release and cell viability were measured. The highest cytokine levels were found in growth-arrested cells stimulated with 10% FBS. csFBS poorly stimulated cytokine release. Nasal polyp released larger IL-8 amounts than nasal mucosa fibroblasts. Dexamethasone decreased cytokine production dose- and time-dependently in both nasal mucosa and nasal polyp fibroblasts. The IC25 of IL-8 inhibition by dexamethasone was higher in nasal polyp than in nasal mucosa fibroblasts. Cell viability did not differ among treatments. Cytokine production by in vitro cultured nasal fibroblasts is affected by the culture conditions used and is inhibited by dexamethasone in both fibroblast types. Our results highlight the importance of culture methodology on nasal polyp research outcomes.

Adjuvant dexamethasone with bupivacaine prolongs the duration of interscalene block: a prospective randomized trial

To identify the effects of adding two different doses of dexamethasone on the duration and quality of interscalene block in patients undergoing shoulder surgery in ambulatory surgery settings. The study design was reviewed and approved by the University at Buffalo Institutional Review Board for Human Subjects. After obtaining informed consent, a total of 90 patients undergoing shoulder surgery using interscalene block with 0.5% bupivacaine (40mL) were assigned randomly to one of three groups: control patients, "Group C," who received no additive; low dose, "Group L," who received additional dexamethasone 4mg; and high dose, "Group H," who received dexamethasone 8mg in addition to 0.5% bupivacaine. Postoperative analgesia was assessed using the numeric rating scores of pain and the postoperative consumption of acetaminophen 325mg+hydrocodone 7.5mg tablets. Analysis was by intention to treat. Statistical significance was tested using a two-way analysis of variance and a nonparametric analysis of variance for consumption of analgesics. Four patients were excluded from the study due to either a failed block or inadequate follow-up. The duration of analgesia was significantly prolonged in both Group L (21.6±2.4h) and Group H (25.2±1.9h) compared with Group C (13.3±1.0h) (p<0.05). Similarly, the duration of motor block was longer in both Group L (36.7±4.1h), and Group H (39.2±3.9h) compared to Group C (24.6±3.3h) (p<0.05). Postoperative analgesic consumption for the first 48h was significantly lower in Group L (6.5 [4-8] tabs) and in Group H (5.5 [4-7] tabs) vs. 9.5 [8-12] tabs in Group C (p<0.01). There were no adverse events related to dexamethasone during the 4-week follow-up period. The addition of dexamethasone to bupivacaine significantly prolonged the duration of the motor block and improved the quality of analgesia following interscalene block. There was no difference in the duration of analgesia and motor block between low-dose and high-dose dexamethasone.

Experimental study of the mechanism of tolerance induction in dexamethasone-treated dendritic cells

SummaryBackgroundThe aim of this study was to investigate the mechanisms underlying tolerance induction of dexamethasone (Dex)-treated dendritic cells (DCs).Material/MethodsWell-grown DC2.4 cells were randomly assigned to receive control, 50 μg/L, 100 μg/L, or 200 μg/L of dexamethasone and then were cultured for 6 days. The expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells were analyzed with flow cytometry and the level of IL-12 secreted by DC2.4 cells was determined by ELISA. The stimulating activity of DC2.4 cells on allogeneic T cells was assessed with mixed lymphocyte reaction. Dexamethasone-treated DC2.4 cells were co-cultured with allogeneic splenic lymphocytes and the Foxp3 expression in naive T lymphocytes was determined with flow cytometry.ResultsCompared with the control group, the expressions of CD80, CD86, galectin-9, and PD-L1 on the surface of DC2.4 cells exposed to different doses of dexamethasone showed no significant changes; however, dexamethasone treatment significantly reduced IL-12 secretion and inhibited DC2.4’s stimulation on the proliferation of allogeneic T lymphocytes. Moreover, dexamethasone-treated DC2.4 cells effectively promoted FOXP3 expression in naive T lymphocytes.ConclusionsDC2.4 is a stable cell line with high expressions of CD80, CD86, and PD-L1. Dexamethasone does not significantly change the cell phenotype of DC2.4 cells, but inhibits the secretion of IL-12 cytokine and attenuates DC2.4’s stimulation of the proliferation of allogeneic T cells. Dexamethasone-treated DC2.4 cells also effectively promote FOXP3 expression in naive T lymphocytes.

Preliminary experimental research on glucocorticoid for treatment of nitrogen dioxide induced acute pulmonary edema in rats

To investigate the therapeutic effect of glucocorticoids on the acute pulmonary edema in rats induced by nitrogen dioxide (NO₂). Thirty SD female rats were randomly equally divided into 5 groups: normal control group, NO₂ exposed group, high-, middle- and low-dose of glucocorticoids treated group (6 rats per group). 6 rats in the normal control group were exposed to room air for 30 min, and the other rats to NO₂. 18 rats in the glucocorticoids group were treated with different doses of dexamethasone (6.0, 3.0, 1.0 mg/kg), while the rats in the NO₂ poisoning group were treated with normal saline (2.5 mg/kg). The lung wet/dry (W/D) weight ratio was calculated, and plasma atrial natriuretic peptide (ANP) levels, superoxide dismutase (SOD) activity from whole blood, plasma interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α) and Interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay (ELISA). The lung W/D ratios were increased significantly in glucocorticoids treated group and NO₂-exposed group compared with normal control group (P < 0.05), while they were significantly reduced in glucocorticoids treated group as compared with NO₂-exposed group (P < 0.05). SOD activity in whole blood in glucocorticoids treated group and NO₂-exposed group was significantly lower than that of normal control group (P < 0.05), while it was no significant difference between that of glucocorticoids treated group and NO₂-exposed group (P > 0.05). Plasma ANP was significantly increased in NO₂-exposed group compared with normal control group (P < 0.05), while it was significantly decreased in glucocorticoids treated group compared with NO₂-exposed group (P > 0.05). Plasma TNF-α of high-, middle- and low-dose of glucocorticoids treated group [(27.04 ± 8.19), (40.10 ± 9.09), (39.76 ± 9.60) pg/ml] was decreased significantly as compared with NO₂-exposed group (68.55 ± 27.84 pg/ml) (P < 0.05). Plasma IL-6 in high- and middle-dose of glucocorticoids treated group [(15.97 ± 6.18), (19.69 ± 5.52) pg/ml] was significantly decreased as compared to NO₂-exposed group [(29.29 ± 9.31) pg/ml] (P < 0.05). Plasma IL-10 in high-, middle- and low-dose of glucocorticoids treated group [(23.24 ± 5.14), (27.78 ± 8.17), (33.29 ± 10.42) pg/ml] was significantly reduced compared with NO₂-exposed group [(44.38 ± 9.19) pg/ml] (P < 0.05). Plasma IFN-γ in high- and middle-dose of glucocorticoids treated group [(7.21 ± 4.55), (19.23 ± 4.35) pg/ml] was reduced compared with NO₂-exposed group [(30.83 ± 6.82) pg/ml] (P < 0.05). High-, middle-, low-dose glucocorticoids all can improve the permeability of alveolar wall and capillary, and have nonspecific anti-inflammatory effects. The therapeutic effects on pulmonary edema are significant. High and middle dose of glucocorticoids treated group are more useful for decreased inflammatory factors.

Effects of different doses of dexamethasone on bone qualities in rats

This study was aimed to investigate the effects of different doses of dexamethasone (Dex) on bone quality in rats. Thirty-one SD rats were randomly divided into 4 groups, Control (7 with saline), Dex-L (8 with 1 mg Dex. / kg), Dex-M (8 with Dex. 2.5 mg/kg), Dex-H (8 with Dex. 5 mg/kg), with tail injection, twice per week for 8 weeks. All the rats were killed then. Their proximal tibia were processed into undecalcified sections and measured for bone histomorphometry. The content of Ca2+ and hydroxyproline in their left ulnars were tested. Bone mineral density (BMD) and biomechanical property of the thigh bone were tested to observe the qualities of bone. Compared to the control group, the bodyweights of the rats in different Dex treatment Groups decreased remarkably. Percent labeled perimeter (%L. Pm), Mineral apposition rate(MAR), Bone formation rate (BFR/BV) and so on reduced significantly. Percent trabecular area (%Tb. Ar) and Trabecular number (Tb. N) were obviously higher while Trabecular separation (Tb. sp) was remarkablely lower than those of the control group. BMD in Dex-L and the content of hydroxyproline in Dex-M reduced notablely. Biomechanical property of Dex groups decreased significantly. Dex suppressed bone formation and reduced bone turnover significantly. As the increase doses of Dex, %Tb. Ar increased, and, on the contrary, BMD and biomechanical property decreased with the reduced matrix in bone at the same time. It suggested that non-mineralized bone formation increased and biomechanical property deceased. The doses of 1 mg/kg Dex had the most obvious effect on bone quality. This dose slightly increased %Tb. Ar, however, bone formation, bone biomechanical property and matrix in bone decreased obviously. Diffferent doses of Dex have different effects on bone qualities. However the dose has no direct influcing ratio to the bone qualities.

High doses of dexamethasone induce increased β-cell proliferation in pancreatic rat islets

Activation of insulin signaling and cell cycle intermediates is required for adult beta-cell proliferation. Here, we report a model to study beta-cell proliferation in living rats by administering three different doses of dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0, respectively) for 5 days. Insulin sensitivity, insulin secretion, and histomorphometric data were investigated. Western blotting was used to analyze the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats, which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1-fold increase in beta-cell proliferation and an increase (17%) in beta-cell size, with significant increase in beta-cell mass, compared with control rats. The hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the lowest degree of insulin resistance, compensate for insulin demand by improving only islet function. Activation of the insulin receptor substrate 2/phosphatidylinositol 3-kinase/serine-threonine kinase/ribosomal protein S6 kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX 0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of dexamethasone induce three different degrees of insulin requirement in living rats, serving as a model to investigate compensatory beta-cell alterations. Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent, beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to a lesser extent, glucose levels could be the major stimuli for beta-cell proliferation in the dexamethasone-induced insulin resistance.

Effects of different doses of dexamethasone plus flunixin meglumine on survival rate in lethal endotoxemia

Effects of different doses of dexamethasone plus flunixinmeglumine on survival rate were investigated in lethal endotoxemia. Atotal of 60 Balb/C female mice were divided into 4 equal groups. Lethalendotoxemia (80-100%) was induced by lipopolysaccharide injection(Group 1, 1 mg, intraperinoneally). At 4 hours after the lipopoly-saccharide injection; low-dose dexamethasone (0.6 mg/kg, SID, 5days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days,subcutaneously), normal-dose dexamethasone (2 mg/kg, SID, 5 days,intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days,subcutaneously) and high-dose dexamethasone (10 mg/kg, SID, 5days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days,subcutaneously) were injected to Group 2, 3 and 4, respectively. Afterthe injections, survival was monitored at 7 days and 13.3%, 13.3%,33.3% and 73.3% survival rates were observed in Groups 1, 2, 3 and 4,respectively. As results, high-dose dexamethasone plus flunixinmeglumine may be the treatment of choice for endotoxaemia inanimals.Key words: lethal endotoxaemia, dexamethasone, flunixin,survival rate

The role of MAP kinase phosphatase-1 in the protective mechanism of dexamethasone against endotoxemia

Aims We have previously shown that glucocorticoids induce the expression of MAP kinase phosphatase (Mkp) a-1 in innate immune cells. Since Mkp-1 is a critical negative regulator of the innate immune response, we hypothesize that Mkp-1 plays a significant role in the anti-inflammatory action of glucocorticoids. The specific aim of the present study is to understand the role of Mkp-1 in the anti-inflammatory function of glucocorticoids. Main methods Wild-type and Mkp-1 −/− mice were treated with different doses of dexamethasone and then challenged with different doses of lipopolysaccharide (LPS). The survival and blood cytokines were assessed. The effects of dexamethasone on cytokine production in wild-type and Mkp-1 −/− primary macrophages ex vivo were also examined. Key findings We found that dexamethasone induced the expression of Mkp-1 in vivo. Dexamethasone treatment completely protected wild-type mice from the mortality caused by a relatively high dose of LPS. However, dexamethasone treatment offered only a partial protection to Mkp-1 −/− mice. Dexamethasone attenuated TNF-α production in both wild-type and Mkp-1 −/− mice challenged with LPS, although TNF-α production in Mkp-1 −/− mice was significantly more robust than that in wild-type mice. Dexamethasone pretreatment shortened the duration of p38 and JNK activation in LPS-stimulated wild-type macrophages, but had little effect on p38 or JNK activation in similarly treated Mkp-1 −/− macrophages. Significance Our results indicate that the inhibition of p38 and JNK activities by glucocorticoids is mediated by enhanced Mkp-1 expression. These results demonstrate that dexamethasone exerts its anti-inflammatory effects through both Mkp-1-dependent and Mkp-1-indepent mechanisms.

The Short-Term Effects of Different Doses of Dexamethasone on the Numbers of some Bacteria in the Ileum

Glucocorticoids are known to affect intestinal biota both directly or indirectly. The aim of the study reported here was to determine the short-term effects of different doses of dexamethasone on the numbers of various ileal bacteria populations. Rats were randomly put into groups, and each group was administered a single-dose injection of dexamethasone at either 0.1, 0.5, 1, 2.5, 5, or 10 mg/kg body weight. At 48-h post-injection, the numbers of total aerobe, anaerobe, lactobacilli and coliform bacteria in the ileum were determined. The numbers of total aerobes and lactobacilli were higher in the groups receiving 5 and 10 mg/kg dexamethasone than in the control and other dose groups (P < 0.01 and P < 0.001, respectively). The number of ileal anaerobic bacteria was higher in group receiving 5 mg/kg than in the other groups (P < 0.01). There were more coliform bacteria in the group receiving 0.1 mg/kg than in the groups receiving 0.5, 1 and 10 mg/kg (P < 0.05). In light of these results, the effects of dose-dependent increases in the number of different bacterial groups affecting gut functions have still to be determined in future studies.

Pneumothorax‐associated pleural eosinophilia is tumour necrosis factor‐alpha‐dependent and attenuated by steroids

The pathogenesis and the optimal treatment of eosinophilic pleural effusions are unknown. We aimed to examine whether pneumothorax-associated pleural eosinophilia in mice is dependent on tumour necrosis factor (TNF)-alpha, and whether it is affected by systemic administration of corticosteroids. Mice were injected intrapleurally with 0.4 mL air to create pneumothoraces. Animals were sacrificed 24 or 48 h later, and pleural lavage (PL) was performed. In the first experiment, comparisons were made between wild-type and TNF-alpha knockout mice with pneumothorax. In the second experiment, wild-type mice were injected intraperitoneally with different doses of dexamethasone (0, 0.25, 0.5 and 1 mg/kg), 5 min before and 24 h after the induction of pneumothorax. After induction of a pneumothorax, TNF-alpha knockout mice had significantly fewer total number of cells (P = 0.004), mononuclear cells (P = 0.01), neutrophils (P = 0.017) and eosinophils (P = 0.002) in their PL compared with wild-type animals. TNF-alpha was detected in the PL of most of the control mice but not in TNF-alpha knockouts. Dexamethasone induced a significant, dose-dependent reduction of PL total cells (P < 0.001), eosinophils (P < 0.001), mononuclear cells (P = 0.007) and lymphocytes (P = 0.04) at 48 h, and significantly reduced the number of PL total cells (P = 0.045) and eosinophils (P = 0.005) at 24 h. Furthermore, dexamethasone prevented eosinophil infiltration of lung and pleural tissue. Pneumothorax-associated pleural eosinophilia in mice is TNF-alpha-dependent and is significantly attenuated by corticosteroid treatment. In addition, both TNF-alpha deficiency and dexamethasone treatment were associated with a significant reduction of other types of inflammatory cells in PL.

A combined dexamethasone/corticotropin-releasing hormone test in patients with chronic PTSD – First preliminary results

Background Reports about alterations of hypothalamic-pituitary-adrenocortical (HPA) function in patients with chronic posttraumatic stress disorder (PTSD) are inconsistent and controversial. More refined laboratory tests and subgrouping of PTSD patients might help to decrease variance of findings. Methods 14 subjects with chronic PTSD and 14 healthy controls were examined between 13:00 and 17:00 using a modified combined dexamethasone/CRH test (0.5 mg dexamethasone at 23:00, 100 μg CRH at 15:00). Plasma adenocorticotropic hormone (ACTH), cortisol and blood pressure were measured every 15 min from 14:45 until 17:00. Results No significant differences between patients and controls were found in the analyses of ACTH and cortisol levels, but a significantly elevated systolic and diastolic blood pressure in PTSD. Severity of depressive symptoms had no influence. However, explorative analyses showed that patients with a history of childhood traumatization had significantly higher post-dexamethasone-ACTH levels and a significantly lower diastolic blood pressure in comparison to patients without early trauma. Conclusions In this first pilot study in a typical clinical sample of patients with chronic PTSD we found effects of severe adverse events in childhood on HPA axis regulation. Maybe, childhood traumatization could influence HPA axis findings in PTSD. Further research is needed, especially dose-response studies with different doses of dexamethasone in dexamethasone/CRH tests in PTSD.

Alterations of seizure-induced c- fos immunolabelling and gene expression in the rat cerebral cortex following dexamethasone treatment

We examined the effects of dexamethasone on the expression of the inducible transcription factor c-fos in 4-aminopyridine (4-AP) seizures. Induction of c-fos mRNA due to 4-AP-elicited convulsion was detected by means of the polymerase chain reaction (PCR) in samples from the neocortex. Adult male rats were pretreated with different doses of dexamethasone (0.5, 1, 3, 5mg/kg body weight); 1h later 5mg/kg 4-AP was injected intraperitoneally. Controls received the solvent of dexamethasone. Pretreatment with dexamethasone provided significant symptomatic protection against 4-AP-induced convulsions. Immunohistochemistry was used to evaluate the presence of the c-fos protein. The number of Fos-immunoreactive nuclei per section area was measured in the neocortex and hippocampus. Pretreatment with dexamethasone resulted in a dose-dependent, significant decrease of seizure-induced Fos-protein immunoreactivity in the neocortex, in the hilum of the dentate fascia, as well as in regions CA1-3 of the hippocampus, compared to control animals. Brains processed for mRNA isolation and PCR, displayed a significant increase of c-fos mRNA following the 4-AP treatment, while pretreatment with dexamethasone did not prevent or decrease this boosted c-fos mRNA expression. We conclude that seizure-induced c-fos expression and intracellular Fos-protein localization are mediated by transmitter and receptor systems, and dexamethasone significantly decreases Fos immunoreactivity, probably by regulating the intracellular traffic of the protein. We also conclude that dexamethasone does not interfere with the genomic regulation of c-fos mRNA synthesis.

Effects of postnatal steroids on Na+/K+-ATPase activity and α1- and β1-subunit protein expression in the cerebral cortex and renal cortex of newborn lambs

Na(+)/K(+)-ATPase is a membrane-bound enzyme responsible for Na(+)/K(+) translocation across cell membranes. It is essential for the generation of electrochemical gradients, which control the ionic environment necessary for electrical activity and water and electrolyte balance. Newborn infants who are at risk of developing bronchopulmonary dysplasia (BPD) are frequently treated with corticosteroids. Although these infants are at risk for neurological, water and electrolyte abnormalities, there is little information regarding the effects of clinically relevant doses of corticosteroids on Na(+)/K(+)-ATPase activity and protein isoform expression in the brain and kidney of newborns. In the present study, we examined the effects of dexamethasone on cerebral cortical and renal cortical Na(+)/K(+)-ATPase activity and alpha1- and beta1-protein isoform expression in newborn lambs. Lambs were given four injections of a placebo (n = 11) or one of three different doses of dexamethasone (0.01 mg kg(-1), n = 9; 0.25 mg kg(-1), n = 11; or 0.50 mg kg(-1), n = 9) 12 h apart on Postnatal Days 3 and 4 up to 18 h before harvest of the cerebral cortex and renal cortex. We selected doses in a range to approximate those used to treat infants with BPD. Na(+)/K(+)-ATPase activity was measured in membrane preparations as ouabain-sensitive inorganic phosphate liberation from ATP and alpha1- and beta1-subunit abundance by Western immunoblot. Postnatal treatment of lambs with dexamethasone resulted in a 21.4% increase in Na(+)/K(+)-ATPase activity and a 30.4% increase in catalytic alpha1-protein expression in the cerebral cortex at a dose of 0.50 mg kg(-1) dexamethasone, but not at the lower doses. Dexamethasone treatment was not associated with changes in beta1-isoform expression in the cerebral cortex. In the kidney, dexamethasone treatment was not associated with significant changes in Na(+)/K(+)-ATPase activity or alpha1- or beta1-isoform expression for the doses we examined. Therefore, clinically relevant corticosteroid treatment exerts dose-related, differential organ-specific effects on Na(+)/K(+)-ATPase activity and protein isoform expression in newborn lambs.

Prophylactic Dexamethasone for Postoperative Nausea and Vomiting in Pediatric Strabismus Surgery: A Dose Ranging and Safety Evaluation Study

In this double-blind, randomized, placebo-controlled study, we evaluated the efficacy and safety of different doses of prophylactic IV dexamethasone for postoperative nausea and vomiting (PONV) in 168 children (aged 2-15 yr) scheduled for strabismus surgery. Patients received IV dexamethasone 0.25 mg/kg (D 0.25), 0.5 mg/kg (D 0.5), 1.0 mg/kg (D 1), or saline (S) immediately after induction of general anesthesia. Patients were discharged 24 h after surgery. Nausea and vomiting were assessed at 0-2, 2-6, and 6-24 h after surgery. Blood glucose was measured preoperatively and at 4 h after study drug administration. Wound healing and infection were assessed after 1 wk. More patients in group S had vomiting at 0-2, 2-6, and 6-24 h (P = 0.001, P = 0.003, and P = 0.04, respectively) and required larger doses of rescue antiemetics compared with the dexamethasone groups. Fewer patients in the dexamethasone groups (6, 3, and 6 in D 0.25, D 0.5, and D 1, respectively) had severe PONV compared with group S (P = 0.001). No significant increase in postoperative blood glucose levels was observed and wound healing was satisfactory in all four groups. The results suggest that dexamethasone 0.25 mg/kg is more effective than saline and equally effective compared with larger doses for preventing PONV for pediatric strabismus surgery.