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Medical Archives (Sarajevo, Bosnia and... Feb 2023Proximal femoral fractures (PrFF) are one of the most common causes of emergency admission in the elderly population. The majority of patients have pre-existing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Proximal femoral fractures (PrFF) are one of the most common causes of emergency admission in the elderly population. The majority of patients have pre-existing conditions that get worsened by unplanned surgery.
OBJECTIVE
Purpose of this article was to evaluate if a is single shot of dexamethasone with levobupivacaine administered intrathecally reduces postoperative pain and cognitive complications in patients with proximal femoral fractures.
METHODS
The study was performed at a level II trauma center which is a part of a teaching hospital with a catchment population of around 300,000 patients, the first author's affiliation. Around 500 PrFF are performed yearly in the center. All participants gave oral and written informed consent before randomization.
RESULTS
In total, 60 patients with a PrFF, ASA status 2 or 3 were randomized into two groups for spinal anaesthesia as DLSA study group (received 8 mg of dexamethasone and 12.5 mg of 0.5 % levobupivacaine) or LSA control group (received 12.5 mg of 0,5 % levobupivacaine). Postoperative cognitive disturbance was evaluated using simplified Confusion Assessment Method (CAM) scale, pain intensity was measured using Visual Analogue Scale (VAS) and blood samples for defining cortisol concentrations were taken before and after the surgical procedure. The primary outcomes were effects of intrathecal dexamethasone on plasma cortisol affecting cognitive disturbances. Secondary outcomes included pain scores and length of hospital stay. The DLSA group demonstrated a reduced incidence of postoperative cognitive dysfunction (POCD), p=0.043, longer analgesia duration, p<0.001, decreased cortisol levels and shorter hospitalization p=0.045. Intrathecal dexamethasone was the only significant predictor of postoperative delirium, OR 7.76, p=0.019.
CONCLUSION
Single shot intrathecal administration of dexamethasone with levobupivacaine used in anaesthesia for proximal femoral fractures reduces the stress response by decreasing plasma cortisol concentrations prolonging analgesia. Complications such as delirium and POCD occurred with significantly lower frequency allowing better postoperative rehabilitation and shortening the hospitalization.
Topics: Humans; Aged; Levobupivacaine; Hydrocortisone; Cognition Disorders; Cognitive Dysfunction; Dexamethasone
PubMed: 36919129
DOI: 10.5455/medarh.2023.77.18-23 -
PloS One 2022Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Clinical practice guidelines recommend administering antenatal corticosteroids (ACS), either betamethasone or dexamethasone, to women at risk of preterm birth at less than 35 weeks' gestation. If women remain at risk of preterm birth seven or more days after an initial course of ACS, most guidelines recommend administration of a repeat dose(s). No randomised trials have assessed the efficacy of dexamethasone as a repeat steroid compared to betamethasone.
AIM
We aimed to determine if there were differences between the use of dexamethasone or betamethasone as repeat ACS, for women who remain at risk of preterm birth after an initial course, on maternal, infant, and childhood health outcomes.
METHODS
We performed a secondary analysis of data from the ASTEROID randomised trial, where women at risk of preterm birth were allocated to either betamethasone or dexamethasone. Infant, childhood, and maternal outcomes were compared according to whether women received a repeat dose(s) of dexamethasone or betamethasone. The primary outcome was a composite outcome of death or any neurosensory disability at age two years (corrected for prematurity). The ASTEROID trial is registered with ANZCTR, ACTRN12608000631303.
RESULTS
168 women and their infants were included, with 86 women receiving dexamethasone and 82 women receiving betamethasone as a repeat dose. Women in the two ACS groups had similar baseline characteristics. We observed little to no difference in the incidence of death or any neurosensory disability at age two years (OR 0.89, 95% CI 0.39 to 2.06, p = 0.79) or in the incidence of other infant, childhood, and maternal adverse health outcomes between women who received dexamethasone and those who received betamethasone.
CONCLUSION
Use of dexamethasone for a repeat dose(s) compared to betamethasone did not result in any differences in infant, childhood, and maternal health outcomes. These results can be used to support clinical practice guideline recommendations.
Topics: Adult; Betamethasone; Dexamethasone; Female; Glucocorticoids; Humans; Infant; Infant Mortality; Infant, Newborn; Maternal Mortality; Premature Birth
PubMed: 35192656
DOI: 10.1371/journal.pone.0263927 -
Steroids Feb 2019Cellular effects of glucocorticoids can be separated into classical transcriptional regulation via activation of the canonical nuclear glucocorticoid receptor and rapid...
Cellular effects of glucocorticoids can be separated into classical transcriptional regulation via activation of the canonical nuclear glucocorticoid receptor and rapid actions mediated by activation of one or more putative membrane-associated glucocorticoid receptors that regulate both transcriptional and non-transcriptional signaling. Dexamethasone-bovine serum albumin (Dex-BSA) is one of several membrane-limited steroid receptor agonists. Dex-BSA and other steroid conjugates such as corticosterone-, estradiol- and testosterone-BSA have been used to study rapid steroid effects initiated by putative membrane receptors. The purity and stability of the steroid-BSA conjugate is crucial, therefore, since any steroid that is not bound to or that dissociates from the BSA conjugate could penetrate into the intracellular compartment and confound the experiment. We used fluorine NMR to determine if free Dex could be detected in a commercially available Dex-BSA dissolved in HO. Non-covalently bound Dex was detected in the Dex-BSA solution, but the level of free Dex remained constant over time and with increasing temperature, indicating that the free Dex was not a result of instability of the Dex-BSA conjugate. The free Dex was lost when the Dex-BSA was denatured and subjected to dialysis, which suggested that it was trapped in the Dex-BSA three-dimensional structure and not covalently bound to the BSA. The purified, renatured Dex-BSA retained its rapid activity, which confirmed that the observed effects of Dex-BSA are not caused by non-covalently-bound Dex. Therefore, the Dex contaminant found in the Dex-BSA solution is likely to be tightly, but non-covalently, bound to BSA, and the Dex-BSA activity remains membrane-limited. Our findings indicate that Dex-BSA remains a suitable membrane-restricted glucocorticoid receptor agonist, but suggest that denaturing purification is a useful control for the study of membrane-initiated steroid-BSA actions.
Topics: Animals; Cattle; Cell Membrane; Cell Nucleus; Cells, Cultured; Dexamethasone; Drug Contamination; Drug Stability; Hypothalamus; Mice; Rats; Receptors, Glucocorticoid; Serum Albumin, Bovine
PubMed: 28939328
DOI: 10.1016/j.steroids.2017.09.004 -
Veterinary Medicine and Science Jul 2023Thymus, bursa of Fabricius and spleen are the major lymphoid organs of avian species that plays a crucial role in their immunity. Though glucocorticoids are reportedly...
BACKGROUND
Thymus, bursa of Fabricius and spleen are the major lymphoid organs of avian species that plays a crucial role in their immunity. Though glucocorticoids are reportedly used as growth promoters, they also suppress the immune system.
OBJECTIVES
The objective of this study was to investigate the morphologic and morphometric adaptations in the lymphoid organs as well as the mortality rate in broilers in response to long-term treatment with dexamethasone (DEX).
METHODS
A total of 80 one-day-old broiler chicks (Cobb 500) were randomly divided into four homogenous groups (control - C and treatment groups - T1, T2, and T3). The treatment groups received DEX at the rate of 3, 5, and 7 mg/kg commercial feed. Samples, i.e. thymus, bursa of Fabricius, and spleen, were collected on 7, 14, 21, and 28 days of the experiment. Relative weight of the organs was calculated on each sampling day. The tissues were then processed and stained with haematoxylin and eosin stain for morphological and morphometric study.
RESULTS
The relative weight of lymphoid organs was found substantially (p < 0.05) less in the DEX-treated groups. Significant (p < 0.05) reduction in lobular size and the cortical-medullary ratio was observed in the thymus of the DEX-treated broilers. Follicular atrophy and massive depletion of lymphocytes were evident in the bursa of Fabricius. The mortality rate was also increased which was largely dependent on the dose and duration of DEX treatment.
CONCLUSIONS
The study results indicate that DEX treatment can alter the morphology and morphometry of lymphoid organs which might result in severe immunosuppression and increased mortality rate in broilers.
Topics: Animals; Chickens; Diet; Thymus Gland; Spleen; Dexamethasone
PubMed: 37067539
DOI: 10.1002/vms3.1139 -
Cells Jan 2023The NLRP3 inflammasome is a multimolecular complex that processes inactive IL-1β and IL-18 into proinflammatory cytokines. OLT1177 is an orally active small compound...
The NLRP3 inflammasome is a multimolecular complex that processes inactive IL-1β and IL-18 into proinflammatory cytokines. OLT1177 is an orally active small compound that specifically inhibits NLRP3. Here, B16F10 melanoma were implanted in mice and treated with OLT1177 as well as combined with the glucocorticoid dexamethasone. At sacrifice, OLT1177 treated mice had significantly smaller tumors compared to tumor-bearing mice treated with vehicle. However, the combined treatment of OLT1177 plus dexamethasone revealed a greater suppression of tumor growth. This reduction was accompanied by a downregulation of nuclear and mitochondrial STAT3-dependent gene transcription and by a significant reduction of STAT3 Y705 and S727 phosphorylations in the tumors. In vitro, the human melanoma cell line 1205Lu, stimulated with IL-1α, exhibited significantly lower levels of STAT3 Y705 phosphorylation by the combination treatment, thus affecting the nuclear functions of STAT3. In the same cells, STAT3 serine 727 phosphorylation was also lower, affecting the mitochondrial functions of STAT3. In addition, metabolic analyses revealed a marked reduction of ATP production rate and glycolytic reserve in cells treated with the combination of OLT1177 plus dexamethasone. These findings demonstrate that the combination of OLT1177 and dexamethasone reduces tumor growth by targeting nuclear as well as mitochondrial functions of STAT3.
Topics: Humans; Animals; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammasomes; Melanoma; Dexamethasone; STAT3 Transcription Factor
PubMed: 36672229
DOI: 10.3390/cells12020294 -
Frontiers in Immunology 2022Current evidence highlights the critical role of the gut-kidney axis in the pathogenesis of IgA nephropathy (IgAN). However, few attempts have been made to explore...
Orange-derived and dexamethasone-encapsulated extracellular vesicles reduced proteinuria and alleviated pathological lesions in IgA nephropathy by targeting intestinal lymphocytes.
Current evidence highlights the critical role of the gut-kidney axis in the pathogenesis of IgA nephropathy (IgAN). However, few attempts have been made to explore targeted intestinal immunity therapy. This research aims to develop an oral intestine targeting medication based on extracellular vesicles (EVs) and investigate its therapeutic efficacy in IgAN. EVs were isolated from orange juice and electroporated with dexamethasone sodium phosphate (DexP). After oral administration, EVs-DexP was picked up by lymphocytes in the submucosal area of ileocecum. EVs-DexP outperformed DexP not only in suppressing lymphocyte stimulation but also in alleviating renal pathological lesions in the IgAN mouse model. Clinical improvement was accompanied by a reducing IgA secreted by the intestine and a decreasing IgA + B220 + lymphocytes in Peyer's patches. The present study develops a cost-effective, biofriendly EVs-based glucocorticoid strategy for IgAN.
Topics: Animals; Citrus sinensis; Dexamethasone; Extracellular Vesicles; Glomerulonephritis, IGA; Glucocorticoids; Immunoglobulin A; Lymphocytes; Mice; Proteinuria
PubMed: 36119039
DOI: 10.3389/fimmu.2022.900963 -
Turkish Journal of Ophthalmology Apr 2020We present patient characteristics and follow-up results of cases with anterior chamber dexamethasone implant migration. The common feature of all six presented cases...
We present patient characteristics and follow-up results of cases with anterior chamber dexamethasone implant migration. The common feature of all six presented cases was vitrectomized eyes. Four of the patients had sutured intraocular lens (IOL) implantation due to complicated cataract surgery, one had combined retinal detachment surgery with sutured IOL implantation, and one had vitrectomy for diabetic intravitreal hemorrhage cleaning and uncomplicated cataract surgery. Anterior chamber implant migration caused corneal edema in all cases and elevated intraocular pressure in three cases. In two cases, the dexamethasone implant was directed into the vitreous cavity after maximum pupillary dilation and corneal manipulation with cotton tip applicator with the patient in reverse Trendelenburg position. There was no other complication until dexamethasone implant degradation, with clear cornea at final examination. In two cases, the implant was removed from the anterior chamber by aspiration, but keratoplasty surgery was planned due to endothelial cell loss and persistent corneal edema during follow-up. In the last two cases, the dexamethasone implant was redirected into the vitreous chamber with a 23-gauge catheter and anterior chamber maintainer but they migrated into the anterior chamber again. In one of these patients, the implant was aspirated by catheter and corneal transplantation was performed due to corneal edema, while the other patient's implant was redirected into the vitreous chamber with no further anterior migration. The risk of dexamethasone implants migrating into the anterior chamber of vitrectomized eyes and those with sutured IOL implantation should be kept in mind and the patient should be informed and advised to see an ophthalmologist immediately before permanent corneal endothelial damage occurs.
Topics: Anterior Chamber; Dexamethasone; Drug Implants; Foreign-Body Migration; Humans; Macular Edema; Male; Middle Aged; Tomography, Optical Coherence
PubMed: 32367704
DOI: 10.4274/tjo.galenos.2019.43778 -
European Journal of Drug Metabolism and... 1991Dexamethasone phosphate (DXM-PHO) is an ester which is quickly hydrolysed by the bovine and the dexamethasone (DXM) plasma half-life was 5.16 h. It has been demonstrated...
Dexamethasone phosphate (DXM-PHO) is an ester which is quickly hydrolysed by the bovine and the dexamethasone (DXM) plasma half-life was 5.16 h. It has been demonstrated that 54 h after DXM-PHO injection, DXM concentrations were lower than 0.1 mg/ml. Tritiated dexamethasone was also administered twice to an another young bull for metabolite investigation. The elapsed time required to recover, in plasma, half of the radioactivity injected was 8.8 h. Radioactivity recovery in the urine reached 36.4% and 22.6% for the first and the second injections respectively.
Topics: Animals; Cattle; Dexamethasone; Half-Life; Hydrolysis; Injections, Intramuscular; Injections, Intravenous; Male; Regression Analysis
PubMed: 1814739
DOI: 10.1007/BF03189963 -
Ambiguous Contribution of Glucocorticosteroids to Acute Neuroinflammation in the Hippocampus of Rat.International Journal of Molecular... Jul 2023Effects of modulation of glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) on acute neuroinflammatory response were studied in the dorsal (DH) and...
Effects of modulation of glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) on acute neuroinflammatory response were studied in the dorsal (DH) and ventral (VH) parts of the hippocampus of male Wistar rats. Local neuroinflammatory response was induced by administration of bacterial lipopolysaccharide (LPS) to the DH. The modulation of GR and MR was performed by dexamethasone (GR activation), mifepristone, and spironolactone (GR and MR inhibition, respectively). Experimental drugs were delivered to the dentate gyrus of the DH bilaterally by stereotaxic injections. Dexamethasone, mifepristone, and spironolactone were administered either alone (basal conditions) or in combination with LPS (neuroinflammatory conditions). Changes in expression levels of neuroinflammation-related genes and morphology of microglia 3 days after intrahippocampal administration of above substances were assessed. Dexamethasone alone induced a weak proinflammatory response in the hippocampal tissue, while neither mifepristone nor spironolactone showed significant effects. During LPS-induced neuroinflammation, GR activation suppressed expression of selected inflammatory genes, though it did not prevent appearance of activated forms of microglia. In contrast to GR activation, GR or MR inhibition had virtually no influence on LPS-induced inflammatory response. The results suggest glucocorticosteroids ambiguously modulate specific aspects of neuroinflammatory response in the hippocampus of rats at molecular and cellular levels.
Topics: Rats; Male; Animals; Spironolactone; Mifepristone; Rats, Wistar; Neuroinflammatory Diseases; Lipopolysaccharides; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Dexamethasone; Hippocampus
PubMed: 37446324
DOI: 10.3390/ijms241311147 -
Molecules (Basel, Switzerland) Feb 2022Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of...
Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of fibrous tissue. The current study aimed at the development of a dual drug release from a PLLA coating and from the bulk material to address short-term and long-lasting release of anti-inflammatory drugs. Inner-ear cytocompatibility of drugs was studied in vitro. A PLLA coating (containing diclofenac) of medical-grade silicone (containing 5% dexamethasone) was developed and release profiles were determined. The influence of different coating thicknesses (2.5, 5 and 10 µm) and loadings (10% and 20% diclofenac) on impedances of electrical contacts were measured with and without pulsatile electrical stimulation. Diclofenac can be applied to the inner ear at concentrations of or below 4 × 10 mol/L. Release of dexamethasone from the silicone is diminished by surface coating but not blocked. Addition of 20% diclofenac enhances the dexamethasone release again. All PLLA coatings serve as insulator. This can be overcome by using removable masking on the contacts during the coating process. Dual drug release with different kinetics can be realized by adding drug-loaded coatings to drug-loaded silicone arrays without compromising electrical stimulation.
Topics: Animals; Anti-Inflammatory Agents; Coated Materials, Biocompatible; Cochlear Implants; Dexamethasone; Diclofenac; Drug Delivery Systems; Drug Liberation; Rats; Rats, Sprague-Dawley
PubMed: 35209205
DOI: 10.3390/molecules27041417