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Naunyn-Schmiedeberg's Archives of... Feb 2024Clinically, thymoma patients are often complicated with myasthenia gravis (MG). Dexamethasone, a glucocorticoid with anti-inflammatory effects, could be used as an...
Clinically, thymoma patients are often complicated with myasthenia gravis (MG). Dexamethasone, a glucocorticoid with anti-inflammatory effects, could be used as an immunosuppressant for thymoma-associated MG, but the mechanism of action remains to be explored. In this study, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, weighted gene co-expression network analysis (WGCNA) of potential targets was performed by screening the intersection targets of dexamethasone and thymoma-associated MG from the database. Furthermore, the key targets and core active components were identified by topological analysis of the protein-protein interaction (PPI) network. Molecular docking technology was applied to screen the complexes with stable binding of dexamethasone and core targets. Patients with thymoma were divided into two groups according to whether they received dexamethasone before operation, and immunohistochemistry and western blot were used to verify the selected target of dexamethasone in treating thymoma-associated MG. The results showed that the action pathway of dexamethasone on the disease was closely enriched to phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) signaling pathways. The expressions of AKT1 and its downstream molecule mTOR in the thymoma microenvironment of thymoma-associated MG patients who did not receive dexamethasone before operation were higher than those in the group receiving dexamethasone before operation. This study demonstrates that dexamethasone can promote apoptosis through the AKT-mTOR pathway for the treatment of thymoma-associated MG, as validated by network pharmacology predictions and clinical specimen experiments, and can be verified by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.
Topics: Humans; Thymoma; Proto-Oncogene Proteins c-akt; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; TOR Serine-Threonine Kinases; Thymus Neoplasms; Dexamethasone; Tumor Microenvironment
PubMed: 37498332
DOI: 10.1007/s00210-023-02641-z -
American Family Physician Feb 2018
Meta-Analysis Review
Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Pharyngitis; Young Adult
PubMed: 29671527
DOI: No ID Found -
The Journal of Pharmacology and... Aug 2019The plasma and tissue binding properties of two corticosteroids, dexamethasone (DEX) and methylprednisolone (MPL), were assessed in the rat in anticipation of developing...
The plasma and tissue binding properties of two corticosteroids, dexamethasone (DEX) and methylprednisolone (MPL), were assessed in the rat in anticipation of developing physiologically based pharmacokinetic and pharmacokinetic/pharmacodynamic models. The tissue-to-plasma partition coefficients ( ) of DEX and MPL were measured in liver, muscle, and lung in vivo after steady-state infusion and bolus injection in rats. Since is often governed by reversible binding to macromolecules in blood and tissue, an attempt was made to assess values of DEX and MPL by in vitro binding studies using rat tissue homogenates and to compare these estimates to those obtained from in vivo kinetics after dosing. The values of both steroids were also calculated in rat tissues using mechanistic tissue composition-based equations. The plasma binding of DEX and MPL was linear with moderate binding (60.5% and 82.5%) in male and female rats. In vivo estimates of steroid uptake appeared linear across the tested concentrations and was highest in liver and lowest in muscle for both steroids. Assessment of hepatic binding of MPL in vitro was severely affected by drug loss at 37°C in male liver homogenates, whereas DEX was stable in both male and female liver homogenates. With the exception of MPL in liver, in vitro-derived estimates reasonably agreed with in vivo values. The mechanistic equations modestly underpredicted for both drugs. Tissue metabolism, saturable tissue binding, and active uptake are possible factors that can complicate assessments of in vivo tissue binding of steroids when using tissue homogenates. SIGNIFICANCE STATEMENT: Assuming the free hormone hypothesis, the ratio of the unbound drug fraction in plasma and in tissues defines the tissue-to-plasma partition coefficient ( ), an important parameter in physiologically based pharmacokinetic modeling that determines total drug concentrations within tissues and the steady-state volume of distribution. This study assessed the plasma and tissue binding properties of the synthetic corticosteroids, dexamethasone and methylprednisolone, in rats using ultrafiltration and tissue homogenate techniques. In vitro-in vivo and in silico-in vivo extrapolation of was assessed for both drugs in liver, muscle, and lung. Although the extrapolation was fairly successful across the tissues, in vitro homogenate studies severely underpredicted the of methylprednisolone in liver, partly attributable to the extensive hepatic metabolism.
Topics: Animals; Blood Proteins; Computer Simulation; Dexamethasone; Drug Stability; Female; Male; Methylprednisolone; Models, Biological; Rats; Rats, Wistar; Tissue Distribution
PubMed: 31197020
DOI: 10.1124/jpet.119.257519 -
The Primary Care Companion For CNS... Sep 2022
Topics: Dexamethasone; Humans; Mental Health; Suicide, Attempted; COVID-19 Drug Treatment
PubMed: 36067504
DOI: 10.4088/PCC.22cr03296 -
Nature Communications May 2021Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have...
Polymeric drug carriers are widely used for providing temporal and/or spatial control of drug delivery, with corticosteroids being one class of drugs that have benefitted from their use for the treatment of inflammatory-mediated conditions. However, these polymer-based systems often have limited drug-loading capacity, suboptimal release kinetics, and/or promote adverse inflammatory responses. This manuscript investigates and describes a strategy for achieving controlled delivery of corticosteroids, based on a discovery that low molecular weight corticosteroid dimers can be processed into drug delivery implant materials using a broad range of established fabrication methods, without the use of polymers or excipients. These implants undergo surface erosion, achieving tightly controlled and reproducible drug release kinetics in vitro. As an example, when used as ocular implants in rats, a dexamethasone dimer implant is shown to effectively inhibit inflammation induced by lipopolysaccharide. In a rabbit model, dexamethasone dimer intravitreal implants demonstrate predictable pharmacokinetics and significantly extend drug release duration and efficacy (>6 months) compared to a leading commercial polymeric dexamethasone-releasing implant.
Topics: Adrenal Cortex Hormones; Animals; Cells, Cultured; Delayed-Action Preparations; Dexamethasone; Dimerization; Disease Models, Animal; Drug Delivery Systems; Drug Implants; Drug Liberation; Polymers; Rabbits; Rats; Uveitis
PubMed: 34001908
DOI: 10.1038/s41467-021-23232-7 -
Nature Reviews. Endocrinology Jun 2022
Topics: Blood Glucose; Dexamethasone; Diabetes Mellitus; Humans
PubMed: 35414023
DOI: 10.1038/s41574-022-00676-5 -
The Cochrane Database of Systematic... 2000Endotracheal tubes are foreign bodies that may injure the upper airway causing laryngeal edema. This in turn may result in failure of extubation in preterm infants.... (Review)
Review
BACKGROUND
Endotracheal tubes are foreign bodies that may injure the upper airway causing laryngeal edema. This in turn may result in failure of extubation in preterm infants. Corticosteroids have been used prophylactically to reduce upper airway obstruction and facilitate extubation.
OBJECTIVES
In newborn infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation (IPPV), what are the effects of intravenous corticosteroids on the incidence of endotracheal reintubation, stridor, atelectasis and adverse side effects?
SEARCH STRATEGY
Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH search terms "dexamethasone", "extubat*" and "exp infant, newborn"), previous reviews including cross references, abstracts of conferences and symposia proceedings, expert informants, journal handsearching mainly in the English language and expert informant searches in the Japanese language by Prof. Y. Ogawa.
SELECTION CRITERIA
Trials were included which used random or quasi-random patient allocation, and which compared intravenous steroids given immediately prior to a planned extubation with placebo.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by the two authors and analysed in Revman for all trials. Prespecified subgroup analyses were performed to examine differences in response between infants at high risk for upper airway edema and those receiving routine prophylaxis prior to extubation.
MAIN RESULTS
Administration of dexamethasone prior to extubation significantly reduced the need for reintubation of the trachea. This result applies to both the high risk group and to the total population of infants enrolled. However, the incidence of extubation failure was zero in the trial that attempted to exclude infants at high risk of airway edema. The side effects of higher blood sugar levels and glycosuria were found in the 2 trials where these were sought.
REVIEWER'S CONCLUSIONS
Implications for practice Dexamethasone reduces the need for endotracheal reintubation of neonates after a period of IPPV. In view of the lack of effect in low risk infants and the documented and potential side effects, it appears reasonable to restrict its use to infants at increased risk for airway edema and obstruction, such as those who have received repeated or prolonged intubations. Implications for research Issues of dosage and applicability to the extremely low birthweight population could be addressed in future trials. Longer term outcomes such as chronic lung disease, duration of assisted ventilation and length of hospital stay should also be examined.
Topics: Anti-Inflammatory Agents; Dexamethasone; Humans; Infant, Newborn; Intermittent Positive-Pressure Ventilation; Intubation, Intratracheal
PubMed: 10796193
DOI: 10.1002/14651858.CD000308 -
American Journal of Veterinary Research Jul 2010To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution...
OBJECTIVE
To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses.
ANIMALS
6 adult horses.
PROCEDURES
Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concentrations were assessed at predetermined intervals.
RESULTS
Maximum plasma dexamethasone concentration after PO administration of powdered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexamethasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses.
CONCLUSIONS AND CLINICAL RELEVANCE
PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Area Under Curve; Circadian Rhythm; Dexamethasone; Female; Half-Life; Horses; Hospitalization; Hospitals, Animal; Hydrocortisone; Kinetics; Male; Orchiectomy
PubMed: 20594087
DOI: 10.2460/ajvr.71.7.831 -
Scientific Reports Oct 2023Stress can be one of the leading causes of hair loss. Stress related hormones, glucocorticoids (GCs), secretion by hair follicle have been mentioned in literature and...
Stress can be one of the leading causes of hair loss. Stress related hormones, glucocorticoids (GCs), secretion by hair follicle have been mentioned in literature and proven to exert an inhibitory effect on hair follicle cells growth by modulating the expression of target genes related to cell proliferation and cycling. The gene modulating effect of the synthetic GC, dexamethasone (DEX), in human dermal papilla (DP) cells has been outlined in this study by mediating a contradictory effect on the expression of secreted frizzled related protein 2 (SFRP2) and SFRP3. The SFRP2 and SFRP3 possess a regulating effect on wnt signaling pathway. Their structural similarities to the cysteine-rich-domain of the frizzled receptors (FZD) allow their binding to the wnt ligands causing the blocking of the wnt ligands-receptors complex. The SFRP family members have been known as inhibitors of the wnt signaling modulating the proliferation and development of various cells. In hair follicle cells, SFRP2 activity has been reported positively on the proliferation of keratinocytes. However, the SFRP3 effect hasn't been well addressed. Under stress, the investigation of the mRNA and protein expressions of SFRP members in human DP cells revealed opposite expressions where SFRP2 decreased while SFRP3 increased by DEX. The proliferation rate of hair keratinocytes outer root sheath was detected via immunofluorescence highlighting the stimulatory effect of SFRP2 and the inhibitory effect of SFRP3. Here, we sought to determine the effect of GC agonist on SFRPs expression and their effect on hair follicle growth.
Topics: Humans; Hair Follicle; Hair; Keratinocytes; Wnt Signaling Pathway; Dexamethasone; Membrane Proteins
PubMed: 37783752
DOI: 10.1038/s41598-023-43688-5 -
Clinical Biomechanics (Bristol, Avon) Dec 2022Several pathological conditions (atrophy, dystrophy, spasticity, inflammation) can change muscle biomechanical parameters. Our previous works have shown that...
BACKGROUND
Several pathological conditions (atrophy, dystrophy, spasticity, inflammation) can change muscle biomechanical parameters. Our previous works have shown that dexamethasone treatment changes skeletal muscle tone, stiffness, elasticity. Exercise training may oppose the side effects observed during dexamethasone treatment. The purpose of this study was to examine the changes in biomechanical parameters (tone, stiffness, elasticity) of skeletal muscle occurring during dexamethasone treatment and subsequent short-time recovery from glucocorticoid-induced muscle atrophy and weakness, as well as the effect of mild therapeutic exercise.
METHODS
17 old female rats, aged 22 months were used in this study. The hand-held and non-invasive device (MyotonPRO, Myoton Ltd., Tallinn, Estonia) was used to study changes in biomechanical properties of muscle. Additionally, body and muscle mass, hind limb grip strength were assessed.
FINDINGS
Results showed that dexamethasone treatment alters muscle tone, stiffness and elasticity. During 20-day recovery period all measured parameters gradually improved towards the average baseline, however, remaining significantly lower than these values. The body and muscle mass, hind limb grip strength of the rats decreased considerably in the groups that received glucocorticoids. After 20 days of recovery, hind limb grip strength of the animals was slightly lower than the baseline value and mild therapeutic exercise had a slight but not significant effect on hind limb grip strength. Biomechanical parameters improved during the recovery period, but only dynamic stiffness and decrement retuned to baseline value.
INTERPRETATION
The study results show that monitoring muscle biomechanical parameters allows to assess the recovery of atrophied muscle from steroid myopathy.
Topics: Female; Rats; Animals; Inflammation; Muscle, Skeletal; Atrophy; Dexamethasone
PubMed: 36368193
DOI: 10.1016/j.clinbiomech.2022.105808