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Korean Journal of Anesthesiology Feb 2022Catheter-related bladder discomfort (CRBD) is common in patients with a urinary catheter and is a risk factor for emergence agitation (EA). The mainstay of CRBD... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Catheter-related bladder discomfort (CRBD) is common in patients with a urinary catheter and is a risk factor for emergence agitation (EA). The mainstay of CRBD management is anticholinergics. Dexamethasone inhibits acetylcholine release. This study aimed to evaluate the effects of dexamethasone on postoperative CRBD and EA.
METHODS
In this prospective study, 90 patients undergoing urological surgery requiring urinary catheterization were allocated randomly to one of two groups (each n = 45). Before induction of anesthesia, the dexamethasone group received 10 mg (2 ml) of dexamethasone intravenously, while the control group received 2 ml of saline in the same manner. The incidence and severity of CRBD were assessed 0, 1, 2, and 6 h after the patient arrived in the post-anesthesia care unit (PACU) as the primary outcomes. The incidence and severity of EA were also compared during emergence and recovery from anesthesia as secondary outcomes.
RESULTS
The incidences of CRBD in the control group and dexamethasone group at 0, 1, 2, and 6 h postoperatively were 28.9% and 15.6%, 55.6% and 55.6%, 57.8% and 46.7%, and 53.3% and 51.1%, respectively. The incidence and severity of CRBD assessed at 0, 1, 2, and 6 h postoperatively did not show intergroup differences. The incidence and severity of EA in the operating room and PACU also showed no difference between the groups.
CONCLUSIONS
Dexamethasone (10 mg) administered before induction of anesthesia did not further reduce the incidence or severity of CRBD or EA in patients undergoing urological surgery.
Topics: Dexamethasone; Emergence Delirium; Humans; Pain, Postoperative; Prospective Studies; Urinary Bladder; Urinary Catheters
PubMed: 34551471
DOI: 10.4097/kja.21284 -
Diagnostic evaluation of insulin and glucose dynamics in light-breed horses receiving dexamethasone.The Canadian Veterinary Journal = La... Jun 2022Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS) and increases the risk for development of laminitis. Accurate diagnosis of insulin dysregulation...
OBJECTIVE
Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS) and increases the risk for development of laminitis. Accurate diagnosis of insulin dysregulation is crucial for implementation of preventative strategies in this population. The objective was to assess the effects of dexamethasone administration on insulin and glucose dynamics in light-breed horses and assess the agreement of various diagnostic tests for insulin dysregulation [basal [insulin] (BI), oral sugar test (OST), and combined glucose-insulin test (CGIT)].
ANIMAL
Fourteen adult light-breed horses.
PROCEDURE
Prospective, experimental study to assess insulin and glucose dynamics by performing basal insulin, OST, and CGIT before (baseline) and post-dexamethasone administration (0.08 mg/kg, PO, q24h) for 7 d. Insulin and glucose dynamics were assessed by the BI, OST, CGIT, and insulin sensitivity proxy measurements (RISQI, QUICKI, FGIR, HOMA-IR, IG) at the baseline and post-dexamethasone time points.
RESULTS
The OST area under the insulin and glucose curves were increased following dexamethasone treatment ( < 0.001 and < 0.01, respectively). Basal insulin, OST [insulin] at 60 min and CGIT [insulin] at 45 min were increased at the post-dexamethasone time point ( < 0.001, < 0.001, and < 0.01). Similarly, time spent in the positive glucose phase during the CGIT was longer at the post-dexamethasone time point ( < 0.001). The proxy measurements for insulin sensitivity (RISQI, QUICKI, FGIR) were decreased ( < 0.01) and the proxy measurements for insulin resistance (HOMA-IR) and β-cell function (IG) were increased after dexamethasone administration ( < 0.01). More horses were classified with following dexamethasone administration, based on the diagnostic criteria for basal insulin ( = 0.03), OST ( = 0.01), and CGIT ( < 0.01). coefficients, measuring agreement between basal insulin, OST, and CGIT, showed none to moderate agreement at the baseline time point.
CONCLUSION
Dexamethasone administration at 0.08 mg/kg, PO, q24h for 7 d worsened insulin dysregulation in adult light-breed horses based on findings of a basal insulin, OST, CGIT, and insulin sensitivity proxy measurements. There was none to moderate agreement between the basal insulin, OST, CGIT for the diagnosis of insulin dysregulation.
CLINICAL RELEVANCE
Horses administered dexamethasone at a dose of 0.08 mg/kg, PO, q24h for 7 d should be considered insulin dysregulation and appropriate preventative strategies should be implemented. The variability of diagnostic performance of common tests for insulin dysregulation (basal insulin, OST, CGIT) may affect clinical decisions; therefore, performing multiple tests, including proxy measurements, may improve diagnostic accuracy of insulin dysregulation.
Topics: Animals; Blood Glucose; Dexamethasone; Glucose; Glucose Tolerance Test; Horse Diseases; Horses; Insulin; Insulin Resistance; Prospective Studies
PubMed: 35656529
DOI: No ID Found -
Journal of Pharmacokinetics and... Jun 2021Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and... (Observational Study)
Observational Study
Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and betamethasone (BET) in 48 healthy nonpregnant Indian women in a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM) where each woman enrolled in a two-period cross-over study. Plasma concentrations collected over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Overall, BET exhibited slower clearance, similar volume of distribution, faster absorption, and longer persistence than DEX with BET acetate producing extremely slow absorption but full bioavailability of BET. Six biomarkers were assessed over a 24-h baseline period with four showing circadian rhythms with complex baselines. These baselines and the strong responses seen after drug dosing were fitted with various indirect response models using the Laplace estimation methods in NONMEM 7.4. Both the PK and six biomarker responses were well-described with modest variability likely due to the homogeneous ages, weights, and ethnicities of the women. The drugs either inhibited or stimulated the influx processes with some models requiring joint inclusion of drug effects on circadian cortisol suppression. The biomarkers and order of sensitivity (lowest IC/SC to highest) were: cortisol, T-helper cells, basophils, glucose, neutrophils, and T-cytotoxic cells. DEX sensitivities were generally greater than BET with corresponding mean ratios for these biomarkers of 2.86, 1.27, 1.72, 1.27, 2.69, and 1.06. Overall, the longer PK (e.g. half-life) of BET, but lesser PD activity (e.g. higher IC), produces single-dose response profiles that appear quite similar, except for the extended effects from BET-PA. This comprehensive population modeling effort provides the first detailed comparison of the PK profiles and six biomarker responses of five commonly used dosage forms of DEX and BET in healthy women.
Topics: Administration, Oral; Adult; Betamethasone; Biomarkers; Chronopharmacokinetics; Circadian Rhythm; Cross-Over Studies; Dexamethasone; Dose-Response Relationship, Drug; Female; Half-Life; Healthy Volunteers; Humans; India; Inhibitory Concentration 50; Injections, Intramuscular; Models, Biological; Young Adult
PubMed: 33954911
DOI: 10.1007/s10928-021-09755-y -
BMC Developmental Biology Nov 2021Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their...
BACKGROUND
Human Mesenchymal Stem Cells (hMSCs) represent a promising cell source for cell-based therapy in autoimmune diseases and other degenerative disorders due to their immunosuppressive, anti-inflammatory and regenerative potentials. Belonging to a glucocorticoid family, Dexamethasone (Dex) is a powerful anti-inflammatory compound that is widely used as therapy in autoimmune disease conditions or allogeneic transplantation. However, minimal immunomodulatory effect of hMSCs may limit their therapeutic uses. Moreover, the effect of glucocorticoids on the immunomodulatory molecules or other regenerative properties of tissue-specific hMSCs remains unknown.
METHOD
Herein, we evaluated the in vitro effect of Dex at various dose concentrations and time intervals, 1000 ng/ml, 2000 ng/ml, 3000 ng/ml and 24 h, 48 h respectively, on the basic characteristics and immunomodulatory properties of Bone marrow derived MSC (BM-MSCs), Adipose tissue derived MSCs (AD-MSCs), Dental Pulp derived MSC (DP-MSCs) and Umbilical cord derived MSCs (UC-MSCs).
RESULTS
The present study indicated that the concentration of Dex did not ramify the cellular morphology nor showed cytotoxicity as well as conserved the basic characteristics of tissue specific hMSCs including cell proliferation and surface marker profiling. However, quite interestingly it was observed that the stemness markers (Oct-4, Sox-2, Nanog and Klf-4) showed a significant upregulation in DP-MSCs and AD-MSCs followed by UC-MSCs and BM-MSCs. Additionally, immunomodulatory molecules, Prostaglandin E-2 (PGE-2), Indoleamine- 2,3-dioxygenase (IDO) and Human Leukocyte Antigen-G (HLA-G) were seen to be upregulated in a dose-dependent manner. Moreover, there was a differential response of tissue specific hMSCs after pre-conditioning with Dex during mixed lymphocyte reaction, wherein UC-MSCs and DP-MSCs showed enhanced immunosuppression as compared to AD-MSCs and BM-MSCs, thereby proving to be a better candidate for therapeutic applications in immune-related diseases.
CONCLUSION
Dex preconditioning improved the hMSCs immunomodulatory property and may have reduced the challenge associated with minimal potency and strengthen their therapeutic efficacy. Preconditioning of tissue specific hMSCs with dexamethasone biomanufacturers the enhanced potential hMSCs with better stemness and immunomodulatory properties for future therapeutics.
Topics: Adipose Tissue; Cell Proliferation; Cells, Cultured; Dexamethasone; Humans; Immunomodulation; Mesenchymal Stem Cells
PubMed: 34736395
DOI: 10.1186/s12861-021-00246-4 -
Journal of the Association For Research... Dec 2022The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment...
The synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48 h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that the afferent processes beneath neuromasts also regenerated in the presence of dexamethasone and formed an appropriate number of synapses, indicating that innervation of hair cells was not inhibited by dexamethasone. In addition to regeneration, we also explored the effects of prolonged dexamethasone exposure on lateral-line homeostasis and function. Following dexamethasone treatment, we observed hyperpolarized mitochondrial membrane potentials (ΔΨm) in neuromast hair cells and supporting cells. Hair cells exposed to dexamethasone were also more vulnerable to neomycin-induced cell death. In response to a fluid-jet delivered saturating stimulus, calcium influx through hair cell mechanotransduction channels was significantly reduced, yet presynaptic calcium influx was unchanged. Cumulatively, these observations indicate that dexamethasone enhances hair cell regeneration in lateral-line neuromasts, yet also disrupts mitochondrial homeostasis, making hair cells more vulnerable to ototoxic insults and possibly impacting hair cell function.
Topics: Animals; Zebrafish; Mechanotransduction, Cellular; Calcium; Hair; Dexamethasone; Lateral Line System
PubMed: 36261670
DOI: 10.1007/s10162-022-00875-x -
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 -
Pain Research & Management 2022Postendodontic pain is one of the problems of root canal therapy. This clinical study aimed to evaluate the effect of infiltration injection of dexamethasone and... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the Efficacy of Dexamethasone and Methylprednisolone in Infiltration Injection for Postendodontic Pain in Patients with Necrotic Pulp: A Randomized Controlled Clinical Trial.
PURPOSE
Postendodontic pain is one of the problems of root canal therapy. This clinical study aimed to evaluate the effect of infiltration injection of dexamethasone and methylprednisolone on postendodontic pain in patients with necrotic pulp.
METHODS
A total of 80 volunteers with necrotic pulp teeth were included and assigned to two groups ( = 40). After the administration of local anesthesia and before root canal therapy, in group 1, an infiltration injection of 1 ml of dexamethasone was done and in group 2, an infiltration injection of 1 ml of methylprednisolone was done in the buccal vestibule of each tooth. Patients' pain was reported using a visual analogue scale at pretreatment and 6, 12, 24, and 48 hours after treatment.
RESULTS
There was no significant difference between the two groups receiving dexamethasone and methylprednisolone at pretreatment and 6, 12, 24, and 48 hours after endodontic treatment.
CONCLUSIONS
Infiltration injection of dexamethasone and methylprednisolone had a significant effect in reducing pain after the endodontic treatment in necrotic pulp teeth, but between 6 and 12 hours, methylprednisolone had significantly more effect on pain relief than dexamethasone. Overall, the use of any of these drugs to reduce postendodontic pain is recommended.
Topics: Dexamethasone; Double-Blind Method; Humans; Methylprednisolone; Pain, Postoperative; Root Canal Therapy
PubMed: 35251416
DOI: 10.1155/2022/4163120 -
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 -
Pharmacology Research & Perspectives Oct 2021Dexamethasone has antitumor activity in metastatic castration resistant prostate cancer (mCRPC). We aimed to investigate intravenous liposome-encapsulated dexamethasone...
An exploratory first-in-man study to investigate the pharmacokinetics and safety of liposomal dexamethasone at a 2- and 1-week interval in patients with metastatic castration resistant prostate cancer.
Dexamethasone has antitumor activity in metastatic castration resistant prostate cancer (mCRPC). We aimed to investigate intravenous liposome-encapsulated dexamethasone disodium phosphate (liposomal dexamethasone) administration in mCRPC patients. In this exploratory first-in-man study, patients in part A received a starting dose of 10 mg followed by five doses of 20 mg liposomal dexamethasone at 2-week intervals. Upon review of part A safety, patients in part B received 10 weekly doses of 18.5 mg. Primary outcomes were safety and pharmacokinetic profile, secondary outcome was antitumor efficacy. Nine mCRPC patients (5 part A, 4 part B) were enrolled. All patients experienced grade 1-2 toxicity, one (part B) patient experienced grade 3 toxicity (permanent bladder catheter-related urosepsis). No infusion-related adverse events occurred. One patient had upsloping glucose levels ≤9.1 mmol/L. Trough plasma concentrations of liposomal- and free dexamethasone were below the lower limit of quantification (LLOQ) in part A, and above LLOQ in three patients in part B (t ~50 h for liposomal dexamethasone), trough concentrations of liposomal- and free dexamethasone increased toward the end of the study. In seven of nine patients (78%) patients, stable disease was observed in bone and/or CT scans at follow-up, and in one (part B) of these seven patients a >50% PSA biochemical response was observed. Bi- and once weekly administrations of IV liposomal dexamethasone were well-tolerated. Weekly dosing enabled trough concentrations of liposomal- and free dexamethasone >LLOQ. The data presented support further clinical investigation in well-powered studies. Clinical trial registration: ISRCTN 10011715.
Topics: Adenocarcinoma; Aged; Bone Neoplasms; Dexamethasone; Drug Delivery Systems; Humans; Liposomes; Male; Middle Aged; Prostatic Neoplasms, Castration-Resistant
PubMed: 34414692
DOI: 10.1002/prp2.845