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1.
The impact of intravitreal dexamethasone implant (Ozurdex®) on retrobulbar hemodynamics in patients with diabetic macular edema and retinal vein occlusions.
Gok, M, Altas, H, Kapti, HB
Cutaneous and ocular toxicology. 2019;(3):240-248
Abstract
Objective: To evaluate the effect of single intravitreal dexamethasone implant (Ozurdex®) on ocular blood flow velocities in patients with diabetic macular oedema (DME) and retinal vein occlusions (RVO). Methods: This prospective non-randomized interventional study included injected and fellow eyes of 12 patients with DME and of 16 patients with RVO treated with intravitreal Ozurdex®. Colour Doppler Ultrasonography (CDU) measures of the central retinal artery (CRA), posterior ciliary artery (PCA), ophthalmic artery (OA) those are peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) were performed in both injected and uninjected eyes before injection, at one week, one month after injection, and prior to re-injection. Results: Inter-eye comparison of all the measured CDU data (baseline, first week, first month, reinjection) showed no statistically significant difference in both DME and RVO group. PSV and EDV values of the CRA, OA, and PCA showed a decreasing trend in the first week and first-month visits and then increased at reinjection time. RI and PI measures of the CRA, OA, and PCA measures showed minimal alterations in the follow-up. But all these differences were not statistically significant. Significant visual gain and anatomic recovery were obtained by the intravitreal dex-implant both in the DME and RVO group. Conclusions: Single intravitreal dex-implant did not alter ocular blood flow in the treatment of macular oedema due to RVO and diabetes.
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Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.
Chung, EH, Jia, Y, Ohnishi, H, Takeda, K, Leung, DY, Sutherland, ER, Dakhama, A, Martin, RJ, Gelfand, EW
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014;(3):211-216.e1
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Abstract
BACKGROUND Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity. OBJECTIVE To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma. METHODS CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with anti-CD3/anti-CD28 followed by analysis of BLT1 surface expression and cytokine production. Activation of CD8(+) T cells after ligation of BLT1 by LTB4 was monitored by changes in intracellular Ca(2+) concentrations. RESULTS The number of BLT1-expressing cells was larger in patients with asthma than in controls and larger on activated CD8(+) than on CD4(+) T cells. Addition of LTB4 to activated CD8(+) T cells resulted in increases in intracellular Ca(2+) concentrations. Expansion of activated CD4(+) T cells, unlike CD8(+) T cells, was significantly decreased in the presence of corticosteroid. In patients with SS asthma, numbers of BLT1-expressing CD8(+) T cells were lower in the presence of corticosteroid, unlike in those with SR asthma in whom cell expansion was maintained. Levels of interleukin-13 were highest in cultured CD8(+) T cells, whereas interleukin-10 levels were higher in CD4(+) T cells from controls and patients with SS asthma. Interferon-γ levels were lowest in patients with SR asthma. CONCLUSION Differences in BLT1 expression, steroid sensitivity, and cytokine production were demonstrated in T lymphocytes from patients with SS and SR asthma. The LTB4-BLT1 pathway in CD8(+) cells may play an important role in asthma and serve as an important target in the treatment of patients with SR asthma.
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Theophylline improves steroid sensitivity in acute alcoholic hepatitis.
Kendrick, SF, Henderson, E, Palmer, J, Jones, DE, Day, CP
Hepatology (Baltimore, Md.). 2010;(1):126-31
Abstract
UNLABELLED Corticosteroid therapy has shown some benefit in severe acute alcoholic hepatitis (AAH); however, this is limited by uncertainty in patient selection and variable clinical response. Theophylline has been shown to ameliorate impaired steroid sensitivity in chronic obstructive pulmonary disease by facilitating corticosteroid-induced silencing of proinflammatory genes. We aimed to explore the mechanistic basis of the variable response to corticosteroid therapy seen in patients with AAH and to address the extent to which theophylline can improve this response. The ability of dexamethasone to inhibit phytohemagglutinin-induced lymphocyte proliferation was assessed by (3)H-thymidine incorporation in 12 severe AAH patients and age-matched and sex-matched controls. Steroid sensitivity was measured in terms of I(max), the maximum inhibition of proliferation. The effect of 10(-5) M theophylline and, in survivors, change in I(max) during recovery were observed. Lymphocyte steroid sensitivity was found to be significantly reduced in AAH compared with controls (I(max) 67[+/-4.5]% versus 95[+/-2.3]%, P = 0.0002) and correlated with clinical markers of steroid responsiveness. In survivors, I(max) increased in recovery. Theophylline 10(-5) M significantly increased lymphocyte steroid sensitivity (I(max) 86[+/-6.6]% versus 67[+/-5.0]%, P = 0.027). CONCLUSION Acute alcoholic hepatitis is associated with significant lymphocyte steroid insensitivity, which improves in recovery and can be ameliorated ex vivo by theophylline. This offers potential to rationalize corticosteroid prescribing in AAH and, furthermore, justifies investigation of this novel role for an existing pharmacological agent in this common and frequently fatal condition.
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Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis.
Ichiyama, T, Matsushige, T, Kajimoto, M, Tomochika, K, Matsubara, T, Furukawa, S
Brain & development. 2008;(2):95-9
Abstract
It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1-3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.
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Differential modulation of cytokine production in major depressive disorder by cortisol and dexamethasone.
Heiser, P, Lanquillon, S, Krieg, JC, Vedder, H
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2008;(12):860-70
Abstract
In major depressive disorder (MDD), there is increasing evidence of a relationship between neuroendocrine and immunological alterations. Therefore, we investigated the influence of cortisol and dexamethasone on the in vitro production of TNF-alpha and IL-6 in blood cells of depressed inpatients at admission, in the course of MDD and in healthy controls. Patients were psychopathologically classified as responders and non-responders after a 6-week antidepressant treatment. At admission in the responder subgroup, incubation with both steroids under basal conditions resulted in an increase of TNF-alpha levels, which decreased after treatment. After stimulation with phytohemagglutinin, an enhancement of TNF-alpha suppression by steroids was detectable after successful antidepressive treatment. A significant relationship was seen between the cortisol-induced modulation of TNF-alpha levels and the psychopathology in this subgroup. Under basal conditions, IL-6 levels were increased after treatment with both steroids. The data suggest a normalization of the altered effects of glucocorticoids on TNF-alpha production in the responder subgroup only.
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Effectiveness of dexamethasone and low-power laser in minimizing oedema after third molar surgery: a clinical trial.
Markovic, A, Todorovic, Lj
International journal of oral and maxillofacial surgery. 2007;(3):226-9
Abstract
UNLABELLED Postoperative oedema is common following removal of impacted lower third molars. Several types of drug therapy (corticosteroids, non-steroidal anti-inflammatory drugs, enzymes) have been tried. The aim of this study was to compare the effectiveness of low-power laser (LPL) and dexamethasone after surgical removal of impacted lower third molars under local anaesthesia (2% lidocaine/epinephrine). MATERIAL AND METHODS There were 120 healthy patients divided into four groups of 30 each. Group 1 received LPL irradiation immediately after operation (energy output 4 J/cm2 with constant power density of 50 mW, wavelength 637 nm); group 2 also received i.m. injection of 4 mg dexamethasone (Dexason) into the internal pterygoid muscle; group 3 received LPL irradiation supplemented by systemic dexamethasone (Dexason), 4 mg i.m. in the deltoid region, followed by 4 mg of dexamethasone intraorally 6h postoperatively; and the fourth (control) group received only the usual postoperative recommendations (cold packs, soft diet, etc.). RESULTS LPL irradiation with local use of dexamethasone (group 2) resulted in a statistically significant reduction of postoperative oedema in comparison to the other groups. No adverse effects of the procedure or medication were observed. CONCLUSION LPL irradiation after lower third molar surgery can be recommended to minimize swelling. The effect is enhanced by simultaneous local intramuscular use of dexamethasone.
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A pulse of insulin and dexamethasone stimulates serum leptin in fasting human subjects.
Laferrère, B, Caixas, A, Fried, SK, Bashore, C, Kim, J, Pi-Sunyer, FX
European journal of endocrinology. 2002;(6):839-45
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Abstract
OBJECTIVES We have previously shown that dexamethasone increases serum leptin in fed but not in fasted human subjects. We hypothesized that insulin and/or glucose mediated the effect of food intake. The primary aim of this study was to determine whether the administration of a pulse of insulin with dexamethasone was sufficient to increase serum leptin in vivo in fasted human subjects. Whether the presence of transient hyperglycemia and the dose of insulin were important was tested as a secondary aim. METHODS Twenty-nine normal subjects were studied. In experiment 1 (meal-like), a pulse of insulin (0.03 U/kg s.c.) and of dexamethasone (2 mg i.v.) was given, and the blood glucose transiently elevated to 50 mg/dl above baseline for the first 2 h. In experiments 2 and 3 (dose-response), the effect of two doses of insulin (0.03 U/kg in experiment 2 and 0.06 U/kg in experiment 3) was tested in combination with dexamethasone, this time without transient hyperglycemia. Nine subjects were studied under fasting conditions, with or without dexamethasone, as a control experiment. RESULTS A meal-like transient hyperinsulinemia and hyperglycemia, with a pulse of dexamethasone, increased serum leptin levels from baseline by 54+/-21% at 9 h (P=0.038). In the absence of transient hyperglycemia, leptin increased significantly after doses of both insulin and dexamethasone. The effect of insulin was dose-dependent, with a larger increment of serum leptin at 9 h after the highest dose of insulin (75.2+/-15.7% vs 21.3+/-8.5%, P=0.013). Fasting, with or without dexamethasone, resulted in a significant 20% decrease in leptin from morning basal levels. Conversely, the administration of a pulse of insulin and glucose, in the absence of dexamethasone, prevented the drop in serum leptin observed during fasting, regardless of the insulin dose or the serum glucose elevation. CONCLUSIONS With the permissive effect of dexamethasone, a single pulse of insulin triggered a rise in serum leptin in humans, even in the absence of transient hyperglycemia. A single pulse of insulin with glucose can prevent the drop in serum leptin normally observed during fasting.
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Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia.
Reilly, JJ, Brougham, M, Montgomery, C, Richardson, F, Kelly, A, Gibson, BE
The Journal of clinical endocrinology and metabolism. 2001;(8):3742-5
Abstract
Despite a widespread belief that glucocorticoid therapy is associated with positive energy balance and excess weight gain there is a dearth of quantitative evidence about its effects and the underlying mechanisms of any effects. The primary aim of the present study was to quantify the effect of dexamethasone and prednisone treatment on energy intake in children treated for childhood acute lymphoblastic leukemia. A secondary aim was to test for differences in excess weight gain between patients treated using the 2 glucocorticoids. We measured energy intake in 26 patients (mean +/- SD age, 6.3 +/- 2.3 yr) during a 5-d period "on" steroids and again in the week before steroid treatment. Changes in body mass index from diagnosis to 1 and 2 yr postdiagnosis were expressed as SD scores. Steroid treatment was associated with a significant increase in energy intake of approximately 20% (mean paired difference, 1.7 MJ/d; SD, 2.8; 95% confidence interval, 0.7-2.8 MJ/d), with no significant difference between the 2 steroids. The mean change in body mass index SD score was +0.38 (SD, 1.10; P < 0.05) to 1 yr and +0.68 (SD, 1.38; P < 0.05) to 2 yr, with no significant difference between the 2 groups of patients. Glucocorticoid treatment in childhood acute lymphoblastic leukemia increases energy intake markedly, and this effect contributes to the excess weight gain and obesity characteristic of patients being treated for acute lymphoblastic leukemia.
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Influence of prophylactic dexamethasone on edema following prostate brachytherapy.
Merrick, GS, Butler, WM, Dorsey, AT, Lief, JH, Totterd, , Coram, RJ
Techniques in urology. 2000;(2):117-22
Abstract
PURPOSE This work evaluates the prophylactic administration of dexamethasone as an adjunct to prostate brachytherapy to determine the effect of dexamethasone on postimplant edema, dosimetric quality, catheter dependency, and clinical outcome as assessed by serial American Urological Association (AUA) symptom score determinations. MATERIALS AND METHODS In a controlled study, 22 unselected patients were placed alternately into either a dexamethasone or control arm. RESULTS There was no statistically significant difference in volume between the experimental and control groups on either day 0 or day 28. Accordingly, the day 0 dosimetric parameters, short-term catheter dependency, and serial AUA symptom score determinations were equivalent in both patient groups. However, the patients receiving dexamethasone had a markedly smaller volume on day 3, but 9 of 11 experienced rebound edema with a volume on day 14 significantly greater than day 3. CONCLUSIONS Because of the small number of patients evaluated, additional studies are essential to confirm these findings. At the present time, we do not recommend this dexamethasone schedule as a routine component of prostate brachytherapy.