-
Hormone and Metabolic Research =... Jun 2018We previously reported on the lack of utility of the 1 mg overnight dexamethasone (DEX) test in mild and/or periodic Cushing's syndrome, as most patients with the...
We previously reported on the lack of utility of the 1 mg overnight dexamethasone (DEX) test in mild and/or periodic Cushing's syndrome, as most patients with the condition suppressed to 1 mg DEX. It is possible that a lower dose of DEX as part of an overnight DEX test might be able to distinguish between mild and/or periodic Cushing's syndrome and those without the condition. The objective of the current study is to determine the sensitivity and specificity of a 0.25 mg overnight DEX suppression test, the standard 1 mg overnight DEX suppression test, and the two-day low-dose (Liddle test) DEX suppression test with and without correction for DEX levels in patients evaluated for mild and/or periodic Cushing's syndrome. Thirty patients determined to have Cushing's syndrome by biochemical testing and 14 patients determined not to have the condition had the 0.25 mg and standard 1 mg overnight DEX suppression test and the two-day low-dose DEX suppression tests. Our results show that morning serum cortisol and cortisol/DEX ratios following an overnight dexamethasone suppression test were similar in patients with Cushing's syndrome and those not having Cushing's syndrome. However, a morning cortisol value above 7.6 μg/dl following a dose of DEX of 0.25 mg was found in 12 patients with Cushing's syndrome and none in those not having Cushing's syndrome, suggesting that a high cortisol value after this low dose of dexamethasone can indicate that further testing for Cushing's syndrome is warranted. Our data suggest that the traditional 1 mg overnight or the 2 mg/2 day DEX suppression testing should no longer be used as a screening test in patients who could have mild and/or periodic Cushing's syndrome, while the 0.25 mg dose of DEX may pick up some patients with mild Cushing's syndrome.
Topics: Adolescent; Adult; Cushing Syndrome; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Young Adult
PubMed: 29719879
DOI: 10.1055/a-0603-3868 -
Anesthesiology Sep 2011
Topics: Anti-Inflammatory Agents; Dexamethasone; Humans; Pain, Postoperative
PubMed: 21792052
DOI: 10.1097/ALN.0b013e31822a2871 -
PloS One 2023Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is progressive and irreversible chronic lung inflammatory disease. Cigarette smoke, the main cause of COPD, is often associated with double-stranded DNA release which potentially activates DNA-sensing pathways, such as STING. This study, therefore, analyzed the role of STING pathway in inducing pulmonary inflammation, steroid resistance, and remodeling in COPD.
METHODS
Primary cultured lung fibroblasts were isolated from healthy non-smoker, healthy smoker, and smoker COPD individuals. The expression of STING pathway, remodeling, and steroid resistance signatures were investigated in these fibroblasts upon LPS stimulation and treatment with dexamethasone and/or STING inhibitor, at both mRNA and protein levels using qRT-PCR, western blot, and ELISA.
RESULTS
At baseline, STING was elevated in healthy smoker fibroblasts and to a higher extent in smoker COPD fibroblasts when compared to healthy non-smoker fibroblasts. Upon using dexamethasone as monotherapy, STING activity was significantly inhibited in healthy non-smoker fibroblasts but showed resistance in COPD fibroblasts. Treating both healthy and COPD fibroblasts with STING inhibitor in combination with dexamethasone additively inhibited STING pathway in both groups. Moreover, STING stimulation triggered a significant increase in remodeling markers and a reduction in HDAC2 expression. Interestingly, treating COPD fibroblasts with the combination of STING inhibitor and dexamethasone alleviated remodeling and reversed steroid hyporesponsiveness through an upregulation of HDAC2.
CONCLUSION
These findings support that STING pathway plays an important role in COPD pathogenesis, via inducing pulmonary inflammation, steroid resistance, and remodeling. This raises the possibility of using STING inhibitor as a potential therapeutic adjuvant in combination with common steroid treatment.
Topics: Humans; Nucleic Acids; Pulmonary Disease, Chronic Obstructive; Lung; Pneumonia; DNA; Dexamethasone; Steroids
PubMed: 37406004
DOI: 10.1371/journal.pone.0284061 -
British Journal of Haematology Jun 2010Glucocorticoids are an integral component of therapy for acute lymphoblastic leukaemia (ALL), but usage differs between cooperative group protocols. All groups use... (Review)
Review
Glucocorticoids are an integral component of therapy for acute lymphoblastic leukaemia (ALL), but usage differs between cooperative group protocols. All groups use glucocorticoids during induction but vary on whether to use dexamethasone or prednisone. Issues to consider in the choice of induction steroid include impact on event-free and overall survival, acute morbidity such as infection risk, diabetes, and behavioural disturbances and long-term complications such as avascular necrosis. It is generally agreed that dexamethasone is the steroid of choice for groups using a delayed intensification phase, but dosing schedules (intermittent versus continuous) vary. There is no consensus on the potential benefit of steroid administration during maintenance therapy. This review will summarize the current available data on steroid use in paediatric ALL, highlighting outcomes as well as major toxicities.
Topics: Adolescent; Child; Child, Preschool; Dexamethasone; Drug Administration Schedule; Glucocorticoids; Humans; Infant; Infant, Newborn; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone
PubMed: 20408842
DOI: 10.1111/j.1365-2141.2010.08192.x -
International Journal of Molecular... Jul 2023(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies...
(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary FeO MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.
Topics: Humans; Mice; Animals; Ascorbic Acid; Cartilage; Osteoarthritis; Dexamethasone; Magnetic Phenomena; Chondrogenesis; Cartilage, Articular
PubMed: 37569290
DOI: 10.3390/ijms241511916 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2016Liposteroid, a lipid emulsion containing dexamethasone, was developed in Japan. This drug is effective against rheumatoid arthritis, and has fewer side effects than... (Review)
Review
Liposteroid, a lipid emulsion containing dexamethasone, was developed in Japan. This drug is effective against rheumatoid arthritis, and has fewer side effects than dexamethasone. Moreover, at high dosage, liposteroid has been effectively used for the treatment of macrophage activation syndrome, because the lipid emulsions are easily taken up by phagocytes, and are retained in macrophages. Its anti-inflammatory effect was found to be 2-5 times higher than that of dexamethasone in arthritis and granuloma rat models. Japanese researchers have reported the clinical efficacy and utility of liposteroid in the treatment of diseases with macrophage activation. These include hemophagocytic lymphohistiocytosis, graft-versus-host disease, and pulmonary hemosiderosis. Here, we describe the clinical effects of liposteroid on macrophage activation syndrome and the hypothalamus-pituitary-adrenal axis in patients.
Topics: Animals; Arthritis; Dexamethasone; Disease Models, Animal; Graft vs Host Disease; Granuloma; Hemosiderosis; Humans; Hypothalamo-Hypophyseal System; Lung Diseases; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Macrophage Activation Syndrome; Pituitary-Adrenal System; Pulse Therapy, Drug; Rats
PubMed: 27320934
DOI: 10.2177/jsci.39.190 -
Molecular Oncology Mar 2022The management of multiple myeloma (MM) is challenging: An assortment of available drug combinations adds complexity to treatment selection, and treatment resistance...
The management of multiple myeloma (MM) is challenging: An assortment of available drug combinations adds complexity to treatment selection, and treatment resistance frequently develops. Given the heterogeneous nature of MM, personalized testing tools are required to identify drug sensitivities. To identify drug sensitivities in MM cells, we established a drug testing pipeline to examine ex vivo drug responses. MM cells from 44 patients were screened against 30 clinically relevant single agents and 44 double- and triple-drug combinations. We observed variability in responses across samples. The presence of gain(1q21) was associated with low sensitivity to venetoclax, and decreased ex vivo responses to dexamethasone reflected the drug resistance observed in patients. Less heterogeneity and higher efficacy was detected with many combinations compared to the corresponding single agents. We identified new synergistic effects of melflufen plus panobinostat using low concentrations (0.1-10 nm and 8 nm, respectively). In agreement with clinical studies, clinically approved combinations, such as triple combination of selinexor plus bortezomib plus dexamethasone, acted synergistically, and synergies required low drug concentrations (0.1 nm bortezomib, 10 nm selinexor and 4 nm dexamethasone). In summary, our drug screening provided results within a clinically actionable 5-day time frame and identified synergistic drug efficacies in patient-derived MM cells that may aid future therapy choices.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Combinations; Drug Evaluation, Preclinical; Drug Resistance; Humans; Multiple Myeloma
PubMed: 35148457
DOI: 10.1002/1878-0261.13191 -
Anaesthesia Sep 2013
Topics: Animals; Antiemetics; Dexamethasone; Humans; Hyperglycemia; Infections; Mental Disorders; Neuralgia; Postoperative Complications; Postoperative Nausea and Vomiting; Stomach Ulcer; Treatment Outcome; Tumor Lysis Syndrome; Wound Healing
PubMed: 23848377
DOI: 10.1111/anae.12309 -
PloS One 2022Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit of high-dose dexamethasone is limited. The goal of this study was to assess the effects of 6 mg daily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia.
METHODS
We conducted a single-center, randomized, clinical trial involving hospitalized patients with COVID-19 pneumonia. Participants were randomized 1:1 to dexamethasone 6 mg daily or dexamethasone 20 mg daily, and were stratified by the WHO-Ordinal Scale for Clinical Improvement (OSCI). The primary outcome was clinical improvement equal to or greater than 2 points by OSCI on day 28. Secondary outcomes were 28-day mortality, intensive care unit-free days, and ventilator-free days on day 28.
RESULTS
Of the 107 patients who enrolled and completed the follow up, 55 patients enrolled in the low-dose group and 52 patients enrolled in the high-dose group. Treatment with dexamethasone 20 mg daily compared with dexamethasone 6 mg daily did not result in better clinical improvement based on OSCI on day 28 (71.2% vs. 78.2%; odds ratio, 1.45 [0.55-3.86]; p = 0.403). For participants who required high-flow oxygen or noninvasive ventilation at randomization, the 6-mg group had better survival than the 20-mg group on day 28 (100% vs. 57.1%; p = 0.025). Although more participants in the 6-mg group received immune modulators (40% vs. 21.2%; p = 0.035), 50% of death cases in the 20-mg group who required high-flow oxygen or noninvasive ventilation at randomization received immune modulators.
CONCLUSIONS
Dexamethasone 20 mg daily did not result in better clinical outcome improvement, and was probably associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation, compared with dexamethasone 6 mg daily.
TRIAL REGISTRATION
Clinialtrials.gov number, NCT04707534, registered January 13, 2021.
Topics: Dexamethasone; Humans; Oxygen; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36190994
DOI: 10.1371/journal.pone.0275217 -
Translational Vision Science &... Feb 2024This study aims to assess the efficacy of two aprepitant formulations (X1 and X2), in a preclinical model of dry eye disease (DED) induced by benzalkonium chloride (BAK).
PURPOSE
This study aims to assess the efficacy of two aprepitant formulations (X1 and X2), in a preclinical model of dry eye disease (DED) induced by benzalkonium chloride (BAK).
METHODS
Two aprepitant formulations were tested on 7 to 8-week-old male mice for their efficacy. In vivo corneal fluorescein staining assessed epithelial damage as the primary end point on days 0, 3, 5, 7, 9, 12, and 14 using slit-lamp microscopy. The DED model was induced with 0.2% BAK twice daily for the first week and once daily for the next week. Mice were randomly assigned to 5 treatment groups: Aprepitant X1 (n = 10) and X2 (n = 10) formulation, 2 mg/mL dexamethasone (n = 10), control vehicle X (n = 10), 0.2% hyaluronic acid (n = 10), or no treatment (n = 10). Eye wiping, phenol red, and Cochet Bonnet tests assessed ocular pain, tear fluid secretion, and nerve function. After 7 days, the mice were euthanized to quantify leukocyte infiltration and corneal nerve density.
RESULTS
Topical aprepitant X1 reduced BAK-induced corneal damage and pain compared to gel vehicle X (P = 0.007) and dexamethasone (P = 0.021). Aprepitant X1 and X2 improved corneal sensitivity versus gel vehicle X and dexamethasone (P < 0.001). Aprepitant X1 reduced leukocyte infiltration (P < 0.05) and enhanced corneal nerve density (P < 0.001). Tear fluid secretion remained statistically unchanged in both the X1 and X2 groups.
CONCLUSIONS
Aprepitant formulation X1 reduced pain, improved corneal sensitivity and nerve density, ameliorated epitheliopathy, and reduced leukocyte infiltration in male mouse corneas.
TRANSLATIONAL RELEVANCE
Aprepitant emerges as a safe, promising therapeutic prospect for the amelioration of DED's associated symptoms.
Topics: Male; Mice; Animals; Aprepitant; Cornea; Fluorescein; Pain; Dexamethasone
PubMed: 38345550
DOI: 10.1167/tvst.13.2.9