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PubMed1984

Effects of dexamethasone in hypoxic-ischemic brain injury in the neonatal rat.

To clarify the effects of corticosteroids in neonatal hypoxic-ischemic brain injury, 7-day-old rats were subjected to unilateral common carotid artery ligation and hypoxia (Levine procedure) after being injected subcutaneously with saline, low-dose dexamethasone (4 mg/kg) or high-dose dexamethasone (40 mg/kg). Neither low-dose nor high-dose dexamethasone ameliorated the brain edema, lactacidemia, or hypoglycemia associated with hypoxia-ischemia. In addition, dexamethasone did not alter the pattern of neuropathologic damage or reduce the fall in brain high-energy phosphates. Finally, high-dose dexamethasone-treated animals experienced significantly more mortality than did either saline- or low-dose dexamethasone-treated animals. In this model of neonatal hypoxia-ischemia, dexamethasone did not confer any significant cerebral protection.

Animals↗

PubMed1991

Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation.

Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.

Animals↗

PubMedDate not supplied

Mesenteric vascular reactivity in dexamethasone-treated hypertensive rats.

Possible alterations in mesenteric vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin and its relationship to prostaglandins in dexamethasone-induced hypertension in rats were investigated. The animals were treated with dexamethasone or its vehicle (sesame oil) for 1 day (1.8 mg/kg) and for 14 days (1.8 mg/kg/wk). The superior mesenteric artery with its branches was isolated and perfused with Tyrode's solution at a constant flow rate of 5 ml/min. Administration of norepinephrine (1-10 nmol), arginine vasopressin (0.03-0.3 nmol), or angiotensin II (0.1-1 nmol) produced vasoconstriction and increased the output of 6-keto-prostaglandin F1 alpha and prostaglandin E2 in a dose-related manner in mesenteric vessels. Administration of 10 nmol bradykinin or 19 nmol A23187 enhanced the output of prostaglandins without altering vascular tone. The vasoconstrictor response to arginine vasopressin, but not norepinephrine or angiotensin II, was enhanced in mesenteric vessels from rats treated with dexamethasone for 14 days but not for 1 day. In contrast, the output of basal as well as norepinephrine, arginine vasopressin, angiotensin II, bradykinin, or A23187-induced prostaglandin output was significantly reduced in mesenteric vessels from rats treated with dexamethasone for 1 or 14 days. Prostaglandin output in mesenteric arteries from rats treated with dexamethasone for 1 and 14 days was not different. These data indicate that dexamethasone treatment for longer but not for shorter periods results in a selective increase in vascular reactivity of mesenteric vessels to arginine vasopressin that is independent of prostaglandin synthesis. The increase in vascular reactivity to arginine vasopressin during long-term dexamethasone treatment may contribute to the development or maintenance, or both, of glucocorticoid-induced hypertension.

Animals↗

PubMed1987

Dexamethasone inhibits the antigen-induced contractile activity and release of inflammatory mediators in isolated guinea pig lung tissue.

Treatment for 24 h in vitro with dexamethasone inhibited the antigen-induced contractile response in guinea pig tracheal rings and parenchymal strips without inhibiting the contractile response of the tissues to either methacholine or histamine, respectively. Antigen-induced histamine release was inhibited by approximately 50% in both tissues by prior treatment with dexamethasone. Dexamethasone treatment also inhibited the release of immunoreactive sulfidopeptide leukotriene from parenchymal strips. In tracheal rings, dexamethasone treatment reduced spontaneous release of all cyclooxygenase metabolites (PGE2, PGF2 alpha, TXB2, PGD2, and 6-k-PGF1 alpha were tested), with the exception of PGD2, and also inhibited the antigen-induced release of all cyclooxygenase metabolites studied. Dexamethasone-treatment did not inhibit the spontaneous release of cyclooxygenase metabolites in the guinea pig lung strips, and only modestly inhibited the antigen-induced release of PGE2, PGF2 alpha, and PGD2. The results suggest that the inhibition of contractile response of guinea pig lung strips and airway tissue to antigen by dexamethasone is the result of a reduced release of inflammatory mediators. The inhibition by dexamethasone of antigen-induced release of mast cell mediators from guinea pig lung parenchyma contrasts with results previously obtained with human parenchymal lung tissue.

Animals↗

PubMed2004

Dexamethasone inhibition of IL-1-induced collagen degradation by corneal fibroblasts in three-dimensional culture.

PURPOSE: Corticosteroids regulate the functions of inflammatory cells. The purpose of the present study was to investigate the effect of dexamethasone on collagen degradation by corneal fibroblasts, an underlying cause of corneal ulceration. METHODS: Rabbit corneal fibroblasts were cultured in three-dimensional gels of type I collagen and in the absence or presence of IL-1beta or dexamethasone. The extent of collagen degradation was determined by measurement of the amount of hydroxyproline generated by acid-heat hydrolysis of culture supernatants. The expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was evaluated by immunoblot analysis, gelatin zymography, and reverse transcription and real-time polymerase chain reaction. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was assessed by immunoblot analysis. RESULTS: Dexamethasone inhibited IL-1beta-induced collagen degradation by corneal fibroblasts in a dose-dependent manner. Both the synthesis and activation of MMPs and the expression of TIMPs were inhibited by dexamethasone, as was the activity of plasmin in culture supernatants. Dexamethasone also inhibited the IL-1beta-induced phosphorylation of the MAPKs extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not that of p38. CONCLUSIONS: Dexamethasone exerted multiple effects on the MMP-TIMP system in corneal fibroblasts and thereby inhibited IL-1beta-induced collagen degradation by these cells. Inhibition of the IL-1beta-induced activation of ERK and JNK may contribute to these effects of dexamethasone.

Animals↗

PubMed1988

Dexamethasone inhibition of interleukin 1 beta production by human monocytes. Posttranscriptional mechanisms.

Dexamethasone is known to have an inhibitory effect on IL-1 production. To determine the mechanism(s) of this inhibition, adherent human blood monocytes were stimulated with Escherichia coli lipopolysaccharide (LPS) (10 micrograms/ml) in the presence of dexamethasone. Nuclear transcription run-off assays showed that LPS induced IL-1 beta gene transcription two- to fourfold and that this induction was unaffected by dexamethasone exposure (10(-5) M). The lack of dexamethasone's transcriptional effects was further supported by the absence of any significant change in IL-1 beta mRNA accumulation between LPS-stimulated monocytes exposed or unexposed to dexamethasone, as determined by Northern blot analysis. Posttranscriptionally, dexamethasone was found to have multiple effects: slight prolongation of IL-1 beta mRNA half-life, moderate inhibition of translation of the IL-1 beta precursor, and profound inhibition of the release of IL-1 beta into the extracellular fluid. The data indicate that IL-1 beta is first translated as the 33,000-D pro-IL-1 beta protein, the predominant intracellular form, and the processed to a 17,500-D IL-1 beta protein before or during extracellular transport. The major inhibitory effects of dexamethasone appear to be directed at the translational and posttranslational steps involved in these events.

Dexamethasone↗

PubMed1988

Gamma-interferon restores listericidal activity and concurrently enhances release of reactive oxygen metabolites in dexamethasone-treated human monocytes.

By preventing macrophages from destroying phagocytized microorganisms, glucocorticoids lower natural resistance of the host against many pathogens. gamma-Interferon has an opposite effect and restores activity of dexamethasone-treated mononuclear phagocytes against some but not all microorganisms. In the present studies we show that dexamethasone impairs activity of human blood monocytes kept in culture for 36 h against Listeria monocytogenes, without impairing H2O2 or O2- secretion. Likewise dexamethasone does not interfere with activation of systems generating oxygen metabolites by lymphokines. Thus gamma-interferon increases three- to fivefold the capacity of dexamethasone-treated monocytes to secrete O2- or H2O2 upon stimulation by opsonized zymosan, live bacteria, or phorbol myristate acetate. Concurrently gamma-interferon restores listericidal activity of dexamethasone-treated monocytes. After gradual activation by exposure to gamma-interferon for progressive time periods, listericidal activity becomes tightly correlated (r = 0.922-0.994) with the amount of H2O2 or O2- secreted by dexamethasone-treated monocytes. Activation of oxidative systems by the lymphokine is, however, not correlated with the restoration of activity against Aspergillus spores, lost during dexamethasone treatment, which does not depend on antimicrobial oxygen metabolites. Taken together, these observations lend to the hypothesis that glucocorticoids impair nonoxidative defense mechanisms of "resting" macrophages, while gamma-interferon restores macrophage function impaired by glucocorticoids by activating alternate killing systems, which are at least partly of oxidative nature.

Blood Bactericidal Activity↗

PubMed1993

Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder.

OBJECTIVE: The authors investigated the possibility of enhanced negative feedback sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in posttraumatic stress disorder (PTSD) by using a low dose of dexamethasone. METHOD: Baseline blood samples were obtained at 8:00 a.m., and 0.5 mg of dexamethasone was administered to 21 male patients with PTSD and 12 normal age-comparable men at 11:00 p.m. Cortisol and dexamethasone levels were measured 9 and 17 hours after dexamethasone administration. RESULTS: After correction for differences in dexamethasone levels, the PTSD patients showed greater suppression of cortisol in response to dexamethasone than did the normal subjects. This was true even in patients meeting concurrent diagnostic criteria for major depression. CONCLUSIONS: The data support earlier studies showing that HPA abnormalities in PTSD are different from those seen in depression and suggest that the low-dose dexamethasone suppression test may be a potentially useful tool for differentiating the two syndromes and further exploring differences in their pathophysiology.

Adult↗

PubMed2004

The ACTH response to dexamethasone in PTSD.

OBJECTIVE: Enhanced negative feedback and reduced adrenal output are two different models that have been put forth to explain the paradoxical observations of increased release of corticotropin-releasing factor in the face of low cortisol levels in posttraumatic stress disorder (PTSD). To discriminate between these models, the authors measured levels of adrenocorticopic hormone (ACTH) and cortisol at baseline and in response to dexamethasone in medically healthy subjects with and without PTSD. Under conditions of enhanced negative feedback inhibition, ACTH levels would not be altered relative to cortisol levels, but the ACTH response to dexamethasone would be augmented, in concert with the enhanced cortisol response to dexamethasone. In contrast, under conditions of reduced adrenal output, ACTH levels would be expected to be higher at baseline relative to cortisol levels, but the ACTH response to dexamethasone would be unchanged in PTSD relative to healthy comparison subjects. METHOD: The ACTH and cortisol responses to 0.50 mg of dexamethasone were assessed in 19 subjects (15 men and four women) with PTSD and 19 subjects (14 men and five women) without psychiatric disorder. RESULTS: The ACTH-to-cortisol ratio did not differ between groups before or after dexamethasone, but the subjects with PTSD showed greater suppression of ACTH (as well as cortisol) in response to dexamethasone. CONCLUSIONS: The data support the hypothesis of enhanced cortisol negative feedback inhibition of ACTH secretion at the level of the pituitary in PTSD. Pituitary glucocorticoid receptor binding, rather than low adrenal output, is implicated as a likely mechanism for this effect.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

A randomized open-label parallel-group study comparing ondansetron with ondansetron plus dexamethasone in patients with metastatic breast cancer receiving high-dose epirubicin. A Hellenic Cooperative Oncology Group study.

AIMS AND BACKGROUND: The purpose of this multicenter randomized, open-label, parallel-group study was to assess whether the addition of low-dose dexamethasone to ondansetron results in improved control of chemotherapy-induced emesis in patients undergoing first-line chemotherapy with high-dose epirubicin. METHODS & STUDY DESIGN: Patients were randomized to receive either 24 mg of ondansetron or 24 mg of ondansetron plus 8 mg of dexamethasone administered as an intravenous infusion 30 minutes prior to administration of chemotherapy. Both groups of patients received 8 mg of ondansetron given orally from day 2 to 5 two times daily. Fifty-three patients received ondansetron and 50 received ondansetron plus dexamethasone. The patients recorded nausea and the number of vomits and retches daily on diary cards. RESULTS: Significantly more patients in the ondansetron plus dexamethasone group experienced neither vomiting nor retching during the first day of the first course of chemotherapy compared to those receiving ondansetron alone (79.6% vs 53.8%, P = 0.0062). Furthermore, there was a trend in favor of ondansetron plus dexamethasone in the control of nausea. There was no statistically significant difference between ondansetron plus dexamethasone versus ondansetron alone in protecting patients from emesis between days 2 and 5 of the first course of chemotherapy (66.7% vs 62.7%, P = 0.68). This was probably due to the small sample size. Ondansetron was well tolerated, with 15 patients (15%) reporting adverse events such as headache or constipation. CONCLUSIONS: It appears that ondansetron given intravenously in combination with dexamethasone is more effective than ondansetron alone in the control of acute emesis in patients undergoing their first course of chemotherapy with high-dose epirubicin. No difference between the regimens was found with regard to nausea and delayed emesis control.

Antibiotics, Antineoplastic↗

PubMed1994

Stability of diluted dexamethasone sodium phosphate injection at two temperatures.

OBJECTIVE: Premature neonates with bronchopulmonary dysplasia frequently are treated with intravenous dexamethasone for their chronic lung disease. The injection volumes of the commercially available products often are too small to measure accurately. The objective of this study was to evaluate the stability over 28 days of dexamethasone sodium phosphate injection 4 mg/mL diluted with bacteriostatic NaCl 0.9% to 1 mg/mL. DESIGN: Ten vials of dexamethasone 1 mg/mL were prepared from dexamethasone sodium phosphate injection, USP 4 mg/mL and bacteriostatic NaCl 0.9% injection. Five vials were stored at 4 degrees C and five at 22 degrees C. Dexamethasone was measured on days 0, 1, 3, 7, 14, 21, and 28 by an accurate, reproducible, and stability-indicating HPLC method. Samples were also inspected visually for precipitation or discoloration on each study day. RESULTS: The samples retained at least 97.7 percent of the original concentration of dexamethasone sodium phosphate when stored at either 4 or 22 degrees C for 28 days. No discoloration or precipitation was observed. CONCLUSIONS: Dexamethasone sodium phosphate injection 1 mg/mL in bacteriostatic NaCl 0.9% was stable for 28 days at 4 and 22 degrees C.

Chromatography, High Pressure Liquid↗

PubMed2003

Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone (6 mg/m(2)/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m(2)/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system-directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7% +/- 0.8%, compared with 7.1% +/- 1.1% for prednisone (P =.01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% +/- 2% for dexamethasone and 77% +/- 2% for prednisone (P =.002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.

Administration, Oral↗

PubMed2006

5-hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: a placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19).

PURPOSE: To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy. PATIENTS AND METHODS: Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (> or = 15 fractions) to the upper abdomen were randomly assigned to receive ondansetron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided. RESULTS: During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite. CONCLUSION: The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.

Antiemetics↗

PubMed1991

Effect of dexamethasone on pulmonary surfactant metabolism in hyperoxia-treated rat lungs.

We have examined the effect of dexamethasone on the metabolism of pulmonary surfactant in normal and hyperoxia-treated rats. The relative abundance of the surfactant-specific apoprotein A (SP-A) mRNA in lung tissues and the contents of disaturated phosphatidylcholine (DSPC) and SP-A were measured in bronchoalveolar lavage fluids and in lung tissues in 4-wk-old rats exposed to room air or greater than 90% oxygen for 7 d with or without simultaneous treatment with dexamethasone (0.5 mg/kg body wt for 7 d). The relative abundance of the SP-A mRNA was marginally increased by hyperoxia (1.3-fold over controls). Dexamethasone increased the relative abundance of the SP-A mRNA to a level comparable to that with hyperoxia treatment (1.5-fold over controls). In lavage fluids, the contents of DSPC and SP-A were increased by 4- and 6-fold over controls by hyperoxia, respectively, but they were increased only by 2-fold by dexamethasone. In lung tissues, the contents of DSPC and SP-A were increased by 3- and 2-fold over controls by hyperoxia, respectively. These values in lung tissues in the air-exposed rats were not significantly increased by dexamethasone. In hyperoxia-treated rats, dexamethasone did not significantly affect the relative abundance of the SP-A mRNA level and the contents of DSPC and SP-A in lavage fluids and lung tissues. These results indicate that mechanisms other than increased synthesis of SP-A are involved in hyperoxia-induced SP-A accumulation and that dexamethasone does not affect the abnormal accumulation of pulmonary surfactant induced by hyperoxia.

Animals↗

PubMed2000

Low doses of dexamethasone suppress pituitary-adrenal function but augment the glycemic response to acute hypoxemia in fetal sheep during late gestation.

Despite the widespread use of antenatal glucocorticoid therapy in obstetric practice, little is known about the effects of synthetic glucocorticoids on the fetal capacity to respond to episodes of acute hypoxemia, such as may occur during labor and delivery. This study investigated the effects of prolonged fetal exposure to low concentrations of dexamethasone on the fetal ACTH, cortisol, and glycemic responses to an episode of acute hypoxemia during the period of dexamethasone treatment in sheep. At 118 d of gestation (term is approximately 145 d), 11 fetal sheep had catheters implanted under halothane anesthesia. From 124 d, five fetuses were infused i.v. continuously with dexamethasone (1.80 +/- 0.15 microg x kg(-1) x h(-1) in 0.9% saline at 0.5 mL/h) for 48 h, and the other six fetuses received saline solution i.v. at the same rate. At 45 h of infusion, acute hypoxemia was induced in all fetuses for 1 h by reducing the maternal inspired fraction of oxygen. During glucocorticoid treatment, fetal plasma dexamethasone concentrations increased to 3.9 +/- 0.2 nM by 24 h and remained elevated for the rest of the infusion period. During hypoxemia, a similar fall in fetal arterial PO2 occurred in both saline-infused and dexamethasone-treated fetuses. In control fetuses, significant increases in plasma ACTH and cortisol concentrations and in blood glucose concentrations occurred during hypoxemia. Dexamethasone treatment prevented the increases in fetal plasma ACTH and cortisol, and augmented the blood glucose response, induced by hypoxemia. These data indicate that prolonged fetal exposure to low concentrations of dexamethasone suppresses pituitary-adrenal function, but augments the glycemic response, to acute hypoxemia in fetal sheep during late gestation.

Acid-Base Equilibrium↗

PubMed2001

Dexamethasone treatment attenuates pulmonary injury in piglet meconium aspiration.

To investigate the pulmonary effects of steroid treatment in neonates with meconium aspiration, 25 10- to 12-d-old piglets were studied for 6 h after an intratracheal bolus of human meconium. Dexamethasone (0.5 mg/kg) was given in two treatment schedules, either 1 h before (n = 6) or 1 h after meconium instillation (n = 8). Eight piglets served as controls. Three additional piglets were given dexamethasone without meconium instillation. Pulmonary hemodynamics and oxygenation were followed, and lung tissue samples investigated for signs of inflammation and ultrastructural injury, including apoptosis. Pulmonary artery pressure and vascular resistance increased after meconium instillation, but this rise was significantly prevented after prophylactic dexamethasone. This treatment also improved the acutely deteriorated oxygenation of the piglets after meconium insufflation. Prophylactic, but not early, dexamethasone treatment further protected the lungs from the ultrastructural changes caused by meconium instillation. Additionally, the increase of apoptotic epithelial cell deaths was significantly prevented by both dexamethasone treatments. These results show that prophylactic dexamethasone treatment significantly attenuates the early pulmonary hemodynamic deterioration and structural lung damage caused by meconium aspiration. Further studies on the apoptosis-inhibiting effect of dexamethasone administration in neonatal lungs exposed to heavy meconium are warranted.

Animals↗

PubMed2004

Pituitary-adrenal responses to acute hypoxemia during and after maternal dexamethasone treatment in sheep.

The effects of maternal dexamethasone treatment on hypothalamic-pituitary-adrenal axis function were determined during basal and hypoxemic conditions in maternal and fetal sheep. Under halothane, ewes and their fetuses were catheterized at 117 d gestation (term = 145 d). Starting at 124 d, the ewes received i.m. injections of two doses of either dexamethasone (12 mg) or saline at 24-h intervals. All animals experienced one episode of hypoxemia when the dexamethasone was present in the maternal and fetal circulations [125 +/- 1 d (H1)] and a second episode of hypoxemia when the steroid was no longer detectable in either the maternal or fetal circulations [128 +/- 1 d (H2)]. The fall in partial pressure of oxygen in arterial blood in response to hypoxia was similar in the two episodes in both the fetal and the maternal blood. Maternal dexamethasone treatment diminished maternal and fetal basal plasma cortisol but not ACTH during the normoxic period of H1 but not H2. In control animals, hypoxemia induced increases in fetal but not maternal ACTH and cortisol concentrations. In dexamethasone-treated animals, maternal ACTH and cortisol concentrations also remained unchanged from baseline in both H1 and H2. In contrast, fetal plasma ACTH and cortisol responses to hypoxemia were significantly suppressed during H1 but not H2. Correlation of fetal plasma ACTH and cortisol concentrations suggested diminished cortisol output without a change in adrenocortical responsiveness in dexamethasone-treated fetuses during H1 but not H2. Maternal treatment with dexamethasone transiently suppressed maternal and fetal basal hypothalamic-pituitary-adrenal axis function and the fetal plasma ACTH and cortisol responses to acute hypoxemia in sheep.

Acute Disease↗

PubMed2006

Dexamethasone increases hippocampal neuronal apoptosis in a rabbit model of Escherichia coli meningitis.

Mortality and long-term sequelae rates are high among adults and children with acute bacterial meningitis. Adjunctive treatment with dexamethasone has been shown to reduce systemic complications in bacterial meningitis patients, but corticosteroid treatment may have detrimental effects on hippocampal function. We evaluated the effect of dexamethasone treatment in addition to antibiotic therapy in a rabbit model of Escherichia coli meningitis. A moderate anti-inflammatory effect of dexamethasone could be demonstrated with respect to the inflammatory mediator prostaglandin E2, whereas no significant effect of dexamethasone on tumor necrosis factor-alpha, cerebrospinal fluid pleocytosis, protein, lactate, indicators of global neuronal damage, or blood gas analysis was found. Dexamethasone, however, increased the rate of apoptotic neurons in the granular layer of the hippocampal dentate gyrus. In view of the proapoptotic effect of adjunctive dexamethasone on hippocampal neuronal cells in animal models of Gram-positive and Gram-negative meningitis, the application of dexamethasone should be considered carefully in those forms of bacterial meningitis for which no evidence-based data of beneficial effect in humans are available, such as neonatal meningitis, bacillary Gram-negative meningitis or nosocomial forms of meningitis (e.g. following neurosurgery).

Animals↗