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PubMed2002

Dexamethasone prolongs local analgesia after subcutaneous infiltration of bupivacaine microcapsules in human volunteers.

BACKGROUND: The addition of small amounts of dexamethasone to extended-release formulations of bupivacaine in microcapsules has been found to prolong local analgesia in experimental studies, but no clinical data are available. METHODS: In a double-blinded study, 12 healthy male volunteers were randomized to receive simultaneous subcutaneous injections of bupivacaine microcapsules with dexamethasone and bupivacaine microcapsules without dexamethasone in each calf. Local analgesia was assessed with a validated human pain model; main parameters evaluated were thermal, mechanical, and pain detection thresholds and suprathreshold responses to heat and mechanical stimulation. Measurements were performed every 2 h for the first 8 h and daily for the week after injection. Primary endpoints were evaluation of maximal analgesic effect, time of onset, and duration of analgesia. Summary measures (area under curve [AUC]) were considered best estimate of analgesia. Safety evaluations were performed daily for the first week and at 2 weeks, 6 weeks, and 6 months after injection. RESULTS: The addition of dexamethasone significantly prolonged local analgesia of bupivacaine microcapsules without influence on maximal analgesic effect. AUC in all thermal measurements and the sensory mechanical threshold were significantly increased between 1-7 days after drug injection in the group given dexamethasone compared with the group not given dexamethasone. No serious side effects were observed. CONCLUSIONS: Addition of small amounts of dexamethasone to bupivacaine incorporated in microcapsules prolonged local analgesia compared with microcapsules with plain bupivacaine after subcutaneous administration in humans.

Administration, Cutaneous↗
PubMed2002

Dexamethasone in combination with dolasetron for prophylaxis in the ambulatory setting: effect on outcome after laparoscopic cholecystectomy.

BACKGROUND: Postoperative nausea and vomiting after laparoscopic cholecystectomy remains a common problem despite routine antiemetic prophylaxis. Therefore, the authors investigated the effect of administering 4 mg intravenous dexamethasone as an adjunct to a 5-HT3 antagonist (12.5 mg intravenous dolasetron) with respect to patient outcome. METHODS: Outpatients (N = 140) were enrolled in this prospective, randomized, placebo-controlled, double-blind, institutional review board-approved protocol involving two antiemetic treatment groups. After induction of anesthesia, the control group received 1 ml intravenous saline, whereas the dexamethasone group received 4 mg intravenous dexamethasone. Both groups received 12.5 mg intravenous dolasetron at the time of gallbladder removal. A blinded observer recorded the recovery times, emetic episodes, rescue antiemetics, maximum nausea score, and time to achieve discharge criteria. Postdischarge side effects, as well as patient satisfaction and quality of recovery scores were assessed at 24 h after surgery. RESULTS: Although there was no difference in the incidence of postoperative nausea and vomiting in the early recovery period, the dexamethasone group had a shorter stay in the day-surgery unit (136 +/- 57 vs. 179 +/- 62 min) and more rapidly achieved discharge criteria (161 +/- 32 vs. 209 +/- 39 min). In addition, fewer patients in the dexamethasone group experienced nausea at home within 24 h after discharge (13 vs. 28%, P < 0.05). Finally, the dexamethasone group reported higher quality of recovery and patient satisfaction scores (P < 0.05). CONCLUSIONS: The authors conclude that the adjunctive use of 4 mg intravenous dexamethasone shortened the time to achieve discharge criteria and improved the quality of recovery and patient satisfaction scores after laparoscopic cholecystectomy procedures in outpatients receiving prophylaxis with 12.5 mg intravenous dolasetron.

Adult↗
PubMed1994

Dexamethasone affects platelet aggregation and fibrinolytic activity in rats at different doses which is reflected by their effect on arterial thrombosis.

The effect of oral administration of dexamethasone to rats on the haemostatic system was investigated. Dexamethasone was given once daily for 5 consecutive days. Plasma PAI-1 antigen levels were increased dose dependently (up to 210 +/- 29% of control values at a dose of 3 mg/kg) whereas no significant effects on plasma t-PA antigen levels were observed (131 +/- 6% compared with control values). In addition, treatment with 1 mg/kg dexamethasone decreased t-PA activity in tissue extracts of the aorta, heart and liver (65%, 28% and 58%, respectively) whereas tissue u-PA activity was not influenced. In vivo fibrinolytic activity was significantly decreased after dexamethasone treatment at a dose of 3 mg/kg but not at a dose of 1 mg/kg. The effect of dexamethasone on in vivo platelet aggregation was studied in an arterial thrombosis model. Dexamethasone treatment resulted in a two-fold decrease in arterial thrombosis at a dose of 0.1 mg/kg. At a dose of 1 mg/kg a less pronounced but significant decrease was observed. We conclude that in haemostasis the primary effect of dexamethasone treatment is an inhibition of arterial thrombosis by inhibition of platelet aggregation which is neutralized at higher doses by a decreased fibrinolytic activity.

Animals↗
PubMed1996

Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether dexamethasone prevents postextubation airway obstruction in young children. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Pediatric intensive care unit of a university teaching hospital. PATIENTS: Sixty-six children, < 5 yrs of age, intubated and mechanically ventilated for > 48 hrs. INTERVENTIONS: Patients were randomized to receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline, every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation. MEASUREMENTS AND MAIN RESULTS: Dependent variables included the presence of stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after extubation; need for aerosolized racemic epinephrine and reintubation. The dexamethasone and placebo groups were similar in age (median 3 months [range 1 to 57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p < .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension. CONCLUSION: Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children.

Airway Obstruction↗
PubMed2002

Effect of dexamethasone on the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids after forebrain ischemia in the rat.

OBJECTIVE: To determine whether a large dose of dexamethasone affected brain damage induced by concurrent cerebral ischemia, we used in situ hybridization to examine the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids (mRNAs) in rats with and without dexamethasone administration after transient forebrain ischemia. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a teaching hospital and university. SUBJECTS: Eighty adult rats. INTERVENTIONS: Twenty minutes of transient forebrain ischemia was induced by occlusion of four vessels in lightly anesthetized rats. Thirty-six animals received dexamethasone (15 mg/kg, intraperitoneally) after initial reperfusion. Thirty-six dexamethasone-control rats were injected with saline, and the remaining animals underwent sham surgery but no ischemia or dexamethasone. MEASUREMENTS AND MAIN RESULTS: Using in situ hybridization, we determined hippocampal brain-derived neurotrophic factor and neurotrophin-3 mRNA expression 2, 4, 6, 12, and 24 hrs and 2, 3, 4, and 7 days after brain ischemia. Additionally, hippocampal CA1 region cell death was measured with Nissl stains. Both brain-derived neurotrophic factor and neurotrophin-3 mRNA exhibited a biphasic response after ischemia. Brain-derived neurotrophic factor mRNA showed two peaks of 4.07-fold and 2.84-fold increases relative to sham operation at 6 hrs and 2 days, respectively. Neurotrophin-3 mRNA initially decreased to 59% of sham levels at 4 hrs and then increased to 146% at 3 days before it returned to basal levels. When the ischemic rats were treated with dexamethasone, the elevation of brain-derived neurotrophic factor mRNA and the reduction of neurotrophin-3 mRNA level were prevented within the first 24 hrs, and hippocampal CA1 neurons were protected from ischemia-induced cell loss 7 days after brain ischemia. The protein levels of both brain-derived neurotrophic factor and neurotrophin-3 in general correspond to the mRNA levels in the hippocampal region. CONCLUSIONS: Dexamethasone modulates the intriguing temporal and spatial expression of brain-derived neurotrophic factor and neurotrophin-3 that predominantly supports neuronal innervation at different times after brain ischemia and also may provide specific trophic support for various neurons in the central nervous system.

Animals↗
PubMed2003

Effect of dexamethasone on root resorption after delayed replantation of rat tooth.

The purpose of this study was to evaluate the effect of dexamethasone after delayed tooth replantation with specific regard to root resorption and ankylosis. In addition, the study was planned to elucidate further the usefulness of the model. Fifty-two maxillary first molar teeth were extracted from 26 Sprague-Dawley white female rats fed 0.4% beta-aminoproprionitrile for 3 days to facilitate the extraction. After extraction, the mesiobuccal root canals were endodontically treated under a microscope to prevent subsequent inflammatory resorption of pulpal origin and were assigned to three groups. Teeth in group 1, the dexamethasone group (n = 22), were demineralized in citric acid (1 min), washed, soaked in 1000 nM dexamethasone solution (3 min), air-dried, and replanted in the original sockets. Total extraoral treatment time for each tooth was controlled to 30 min. Teeth in group 2, the dried-only group (n = 22), were air-dried for 30 min after obturation without any surface treatment and replanted. Teeth in group 3, the immediate group (n = 8), were extracted, not root-filled and replanted immediately into their sockets. All experimental animals were killed at 3 weeks after replantation and evaluated histologically. Forty-three of the 52 teeth were available for histological interpretation. They consisted of six immediate, 18 dried-only, and 19 dexamethasone-treated teeth. The degree of progressive root resorption was significantly less in the dexamethasone-treated group than in the dried-only group (p < 0.05). The dexamethasone-treated group exhibited significantly more bone ankylosis than the dried-only group (p < 0.05). These results indicate that the topical use of dexamethasone may be of value in reducing the degree or rate of progressive root resorption secondary to traumatic avulsion and that the rat is a reasonable model for tooth replantation.

Administration, Topical↗
PubMed1999

Effect of dexamethasone on the lymphocytic Na+/H+ antiporter activity.

OBJECTIVE: The effects of short-term administration of dexamethasone on sodium/proton antiporter (Na+/H+ antiporter) in human lymphocytes were investigated in vitro. METHODS: Cytosolic pHi in lymphocytes was measured spectrophotometrically using the pH-sensitive fluorescent dye 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein at 530 nm with excitation wavelengths of 440 and 530 nm. The Na+/H+ antiporter activity was determined after intracellular acidification using 100 mmol/l propionic acid. RESULTS: The addition of 1 micromol/l dexamethasone significantly reduced cytosolic pHi from 7.44+/-0.03 to 7.25+/-0.05 (mean +/- SEM; P<0.01). Incubation with dexamethasone for 40 min significantly reduced the Na+/ H+ antiporter activity from (9.19+/-0.61)x10(-3) pHi/s (n = 22) to (7.23+/-0.49)x10(-3) pHi/s (n = 22; P<0.01). The effect of dexamethasone was time and concentration dependent The apparent affinity of the Na+/H+ antiporter was not significantly different in the absence or presence of dexamethasone. The inhibition of the Na+/H+ antiporter by dexamethasone was abolished in the presence of the glucocorticoid receptor blocker, mifepristone. CONCLUSION: Dexamethasone directly inhibits the Na+/H+ antiporter using a receptor-dependent pathway. This effect may be important for pharmacological side effects such as glucocorticoid-induced hypertension.

Cytosol↗
PubMed1997

Increased apoptosis of T lymphocytes and macrophages in the central and peripheral nervous systems of Lewis rats with experimental autoimmune encephalomyelitis treated with dexamethasone.

Using light and electron microscopic histological and immunocytochemical techniques, we investigated the effects of the glucocorticoid dexamethasone on T cell and macrophage apoptosis in the central nervous system (CNS) and peripheral nervous system (PNS) of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP). A single subcutaneous injection of dexamethasone markedly augmented T cell and macrophage apoptosis in the CNS and PNS and microglial apoptosis in the CNS within 6 hours (h). Pre-embedding immunolabeling revealed that dexamethasone increased the number of apoptotic CD5+ cells (T cells or activated B cells), alphabeta T cells, and CD11b+ cells (macrophages/microglia) in the meninges, perivascular spaces, and CNS parenchyma. The induction of increased apoptosis was dose-dependent. Daily dexamethasone treatment suppressed the neurological signs of EAE. However, the daily injection of a dose of dexamethasone (0.25 mg/kg), which, after a single dose, did not induce increased apoptosis in the CNS or PNS, was as effective in inhibiting the neurological signs of EAE as the high dose (4 mg/kg), which induced a marked increase in apoptosis. This indicates that the beneficial clinical effect of glucocorticoid therapy in EAE does not depend on the induction of increased apoptosis. The daily administration of dexamethasone for 5 days induced a relapse that commenced 5 days after cessation of treatment, with the severity of the relapse tending to increase with dexamethasone dosage.

Animals↗
PubMed1996

Effects of prednisolone and dexamethasone on alkali burns of the esophagus in rabbit.

Steroids have been widely used to prevent the severe secondary strictures that inevitably follow accidental ingestion of caustic substances by children, though with controversial results. To confirm the efficacy of large early doses of dexamethasone, we conducted an experimental study in rabbits. A cotton swab soaked in sodium hydroxide was placed on the esophageal mucosa of 30 rabbits. The rabbits were then treated with antibiotics and randomly allocated to one of three groups. One group received no steroids; the second group was treated with prednisolone; and the third was given dexamethasone. After 21 days, the rabbits were killed and the severity of the lesion was evaluated by radiological, anatomical, and histological examination. Rabbits with moderate or severe stricture, as defined on the basis of radiological examination, made up 80% of the control group, 70% of the prednisolone-treated group, and 40% of the dexamethasone-treated group. Rabbits with third-degree burns, with or without macroscopic ulcers, made up 60% of the control group, 40% of the prednisolone-treated group, and 30% of the dexamethasone-treated group. On histological examination, rabbits with third-degree lesions made up 70% of the control group, 40% of the prednisolone-treated group, and only 20% of the dexamethasone-treated group. Only the difference between the control and dexamethasone-treated group was statistically significant. Taken together, our results clearly indicate that, in rabbits, rapid postburn administration of dexamethasone leads to significant reductions in the frequency and severity of strictures and in the severity of burns.

Animals↗
PubMed1998

Dexamethasone modulates the expression of endothelin-1 and -A receptors in A7r5 vascular smooth muscle cells.

Endothelin-1 (ET-1) is synthesized and released by vascular smooth-muscle cells (VSMCs). Glucocorticoids induce the release of ET-1 from VSMCs into the medium. We investigated whether glucocorticoids modulate ET-1 action by an autocrine production of ET-1 in A7r5 VSMCs. Dexamethasone (100 nM) stimulated the release of ET-1 into the medium. Treatment with 100 nM dexamethasone for 24 h reduced the peak increase of intracellular free Ca2+ induced by ET-1 (100 nM) by 50%, an effect that was dose-dependently inhibited by the specific ET(A)-receptor antagonist FR139317. Scatchard plots of [125I]-ET-1 binding revealed that dexamethasone reduced the number of maximal ET-1 binding sites without altering their binding affinity. FR139317 reversed the decrease in ET-1 binding capacity induced by dexamethasone. Northern blot analysis revealed that dexamethasone increased the level of prepro-ET-1 messenger RNA (mRNA) and decreased the level of ET(A)-receptor mRNA. FR139317 prevented the decrease in the level of ET(A)-receptor mRNA induced by dexamethasone. Results indicate that dexamethasone downregulates ET(A) receptors in A7r5 VSMCs at the mRNA level, in part by the autocrine production of ET-1.

Animals↗
PubMed1997

The protective effect of dexamethasone against radiation damage induced by interstitial irradiation in normal monkey brain.

OBJECTIVE: The protective effect of dexamethasone against radiation damage is unclear. We examined the effect of early treatment of high-dose dexamethasone on iridium-192-induced damage to normal brain tissue. METHODS: Brain damage induced by interstitial irradiation with iridium-192 was evaluated with sequential magnetic resonance imaging and proton magnetic resonance spectroscopy in 11 adult monkeys, with or without short-term high-dose dexamethasone treatment. Dexamethasone (1 mg/kg of body weight/d) was administered intramuscularly to five irradiated animals every 24 hours, beginning 2 days before and ending 7 days after irradiation. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed 1 week, 1 month, and 3 months after irradiation. RESULTS: Magnetic resonance imaging performed 1 week after irradiation revealed marked edema in five nontreated animals. In dexamethasone-treated animals, the volume of edema was reduced significantly, compared to that of nontreated animals, 1 week and 1 month after irradiation. The volume of ring enhancement in dexamethasone-treated animals was also reduced significantly, compared to that of nontreated animals, 3 months after the irradiation. Proton magnetic resonance spectroscopy spectra revealed that N-acetylaspartate and choline peaks were reduced 1 week after irradiation in both groups. However, there were no statistically significant differences between the two groups at any time points. CONCLUSION: These results suggest that dexamethasone treatment may have an antiedema effect at an early stage and may modify subsequent development of vascular and inflammatory changes but may have no effect of preventing radiation-induced necrosis and the reduction of N-acetylaspartate after brachytherapy.

Animals↗
PubMed1997

Therapy for neurocysticercosis: pharmacokinetic interaction of albendazole sulfoxide with dexamethasone.

Albendazole is considered the drug of choice for neurocysticercosis. It is frequently used in combination with dexamethasone to prevent the acute inflammatory reaction due to cysticercal death. It has been reported that dexamethasone increases the plasma level of albendazole sulfoxide, the active metabolite of albendazole. The pharmacokinetic interaction of albendazole sulfoxide with dexamethasone, associated or not with cimetidine, was investigated in 24 patients with active intraparenchymal brain cysticercosis. Eight of these patients received albendazole alone, eight received it in combination with dexamethasone, and eight received it in combination with both dexamethasone and cimetidine. The pharmacokinetic parameters maximum plasma concentration, time to maximum plasma concentration, absorption half-life, and absorption rate constant did not differ between groups, suggesting that the formation of albendazole sulfoxide was not altered by the administration of dexamethasone, combined or not with cimetidine. There were significant differences, however, in the parameters plasma concentration-time curve, oral clearance, elimination half-life, and elimination rate constant, suggesting that dexamethasone, combined or not with cimetidine, decreases the rate of elimination of albendazole sulfoxide.

Adolescent↗
PubMed2003

Salivary cortisol responses to dexamethasone in adolescents with posttraumatic stress disorder.

OBJECTIVE: Previous studies of adults with posttraumatic stress disorder (PTSD) have found various abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis, including enhanced suppression of cortisol following low-dose dexamethasone. The purpose of the present study was to investigate salivary cortisol responses to low-dose dexamethasone in adolescents with PTSD. METHOD: Forty-eight adolescents (20 with current PTSD, 9 trauma controls without PTSD, and 19 healthy nontraumatized controls) were enrolled in the study. On day 1, baseline saliva samples were obtained at 8 a.m. and 0.5 mg of dexamethasone was administered at 11 p.m. Cortisol and dexamethasone levels were assessed at 8 a.m. the following day. RESULTS: Adolescents with current PTSD showed no difference in the suppression of salivary cortisol in response to low-dose (0.5 mg) dexamethasone compared to trauma controls without PTSD and nontraumatized controls. More severely affected PTSD subjects with co-occurring major depression showed higher pre- and post-dexamethasone salivary cortisol levels compared to controls. CONCLUSIONS: The present study did not find evidence for enhanced suppression of salivary cortisol at 8 a.m. following low-dose dexamethasone in multiply traumatized adolescents with PTSD. This result differs from findings in adults with PTSD. Further investigations of hypothalamic-pituitary-adrenal axis abnormalities in traumatized children and adolescents are needed.

Adolescent↗
PubMed2003

Double blind, randomized, placebo-controlled study of dexamethasone therapy for hematogenous septic arthritis in children.

BACKGROUND: Septic arthritis is associated with residual dysfunction in 10 to 25% of affected children. Concentrations of cytokines detected in synovial fluid of children with bacterial arthritis correlate with the severity of inflammation. Treatment with dexamethasone decreased cartilage degradation in experimental Haemophilus influenzae b and Staphylococcus aureus arthritis. ENDPOINTS: To decrease the number of patients with residual dysfunction of the affected joint at the end of therapy and at 6 and 12 months and to speed clinical recovery by the administration of dexamethasone. METHODS: In a double blind manner we randomly selected 123 children with suspected hematogenous bacterial arthritis to receive dexamethasone or saline for 4 days. Antibiotic therapy was tailored according to age and the recovered pathogen. RESULTS: Of the 123 children enrolled, 61 were assigned to the dexamethasone group and 62 to the placebo group. Only 50 and 50 patients in each group were evaluable. The 2 groups of patients were comparable with respect to age, sex, duration of symptoms, pathogen, affected joint and therapeutic and diagnostic procedures. Staphylococcus aureus accounted for 67% of the isolates, Haemophilus influenzae type b for 13% and Streptococcus pneumoniae for 9%. Dexamethasone therapy reduced residual dysfunction at the end of therapy, P = 0.000068; at 6 months, P = 0.00007; and at 12 months, P = 0.00053 of follow-up and shortened the duration of symptoms (P = 0.001) during the acute phase. The 26% incidence of residual dysfunction in the control patients was similar to the 25% found in other series. CONCLUSIONS: A short course of dexamethasone reduced residual joint dysfunction and shortened significantly the duration of symptoms in children with documented hematogenous septic arthritis. These results suggest that a 4-day course of low dose dexamethasone given early benefits children with hematogenous septic arthritis.

Anti-Bacterial Agents↗
PubMed2005

Effects of dexamethasone on antral mucosal protein and gastric development in postnatal rats.

BACKGROUND: The rat stomach undergoes major developmental changes postnatally. An antral mucosal protein (AMP-18) with in vitro mitogenic activity has recently been found in the mammalian stomach. METHODS: To evaluate the role of AMP-18 in gastric development in postnatal rats, the AMP-18 content of glandular stomach extracts from postnatal rats at different ages were measured by Western blots using anti-AMP-18 specific serum. Dexamethasone administration was used to evaluate the corticosteroid regulation of AMP-18 expression. RESULTS: AMP-18 was detected only in glandular stomach homogenate and gastric mucus. AMP-18 and pepsin levels were high at birth. Both decreased postnatally to low levels at 7 days of age, then increased at 10-15 days of age and reached peak levels around weaning (18-21 days of age). The glandular stomach showed stepwise growth relative to body weight, with a significant increase at 18-20 days of age. The forestomach showed a decrease in growth relative to body weight during the same period. Dexamethasone given to pups before 7 days of age induced the accumulation of AMP-18 and pepsin. Induction of AMP-18 by dexamethasone was evident by 7 hours with a delayed increase in glandular stomach mass 30 hours after dexamethasone injection. Induction of AMP-18 by dexamethasone was attenuated by RU-486 but not by spironolactone. CONCLUSION: Increases in AMP-18, pepsin and glandular stomach mass during normal postnatal development suggest that AMP-18 might be involved in gastric maturation, at least in the glandular portion. Dexamethasone induction of pepsin and AMP-18 and the subsequent increase in glandular stomach mass also suggest a possible role for AMP-18 in glandular stomach maturation. Dexamethasone apparently acts through the type II corticosteroid receptor to induce AMP-18.

Aging↗
PubMed2004

Dual synergistic effect: the effect of dexamethasone plus carnitine on skin flap survival.

Dexamethasone has well-known useful effects in dealing with the progression of necrosis. Carnitine is an endogenous cofactor, for having a regulatory action on the energy flow from different oxidative sources. The aim of this study was to determine whether combined local dexamethasone and systemic carnitine administration would result in an additive enhancement of skin flap survival in the rat model. A rectangular (3 cm x 11 cm) dorsal random skin flap was elevated on the rats and then sutured back into its original site with separate sutures. Overall, 40 rats were allocated randomly into 4 groups: Group 1 (control group, n = 10), group 2 (Dexamethasone group, n = 10, 2.5 mg/kg), group 3 (carnitine group, n = 10, 100 mg/kg), group 4 (dexamethasone plus carnitine group, n = 10).The mean flap survival area was 57.50 +/- 5.2% (mean survival area +/- SD) in control group (group 1), 71.5 +/- 4.8% in the dexamethasone group (group 2), 73.0 +/- 5.5% in the carnitine group (group 3), 85.30 +/- 6.1% in the dexamethasone plus carnitine group (group 4). In conclusion, based on the findings of this experimental study, the synergistic effect of carnitine and dexamethasone on skin flap viability is determined.

Animals↗
PubMed1994

Multiple cytochrome P450 isozymes in murine skin: induction of P450 1A, 2B, 2E, and 3A by dexamethasone.

Cytochrome P450s (P450s) are a supergene family of enzymes responsible for the metabolism of a wide range of endogenous and foreign compounds. P450 isozymes possess overlapping substrate specificity. Systemic administration of dexamethasone, a widely used topical agent in dermatologic practice, to animals is known to result in the induction of multiple P450 isozymes in liver. In this study the effect of topical application of dexamethasone to mice on P450-dependent monooxygenase activities, expression of P450 isozymes, and P450 mRNA levels in skin was assessed. The treatment of mice with dexamethasone resulted in significant induction of 7-ethoxyresorufin O-deethylase (2.3 times), 7-pentoxyresorufin O-depentylase (19.2 times), para-nitrophenol hydroxylase (7.5 times), and erythromycin N-demethylase (2.2 times) activities; the monooxygenases catalyzed preferentially by P450 isozymes 1A1, 2B1, 2E1, and 3A, respectively. Immunoblot analysis of cutaneous microsomes, employing antibodies directed against purified P450s 1A1/2, 2B1/2, 2E1, and 3A, showed that dexamethasone treatment results in an increased immunoreactivity (1.8-13.9 times). In immunohistochemical staining of skin with antibody against P4502B1/2, topical application of dexamethasone resulted in an increased reactivity towards microsomal protein in the suprabasal layer of the epidermis and with the cells of the hair follicles. Whereas constitutive expression of mRNAs for CYP1A1 and CYP2E1 was evident in murine skin, any change in the levels of these mRNAs following treatment with dexamethasone was not apparent. The results of our study indicate that the application of dexamethasone to murine skin results in the induction of several families of P450 isozymes, suggesting that murine skin contains multiple inducible P450 isozymes capable of participating in the metabolism of a wide range of xenobiotics and endogenous compounds.

Administration, Topical↗
PubMed1977

Development of Neutrophilia by serially increasing doses of dexamethasone.

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.

Adult↗