-
The American Journal of Sports Medicine Apr 2022Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can...
BACKGROUND
Corticosteroid treatments such as dexamethasone are commonly used to treat tendinopathy but with mixed outcomes. Although this treatment can cause tendon rupture, it can also stimulate the tendon to heal. However, the mechanisms behind corticosteroid treatment during tendon healing are yet to be understood.
PURPOSE
To comprehend when and how dexamethasone treatment can ameliorate injured tendons by using a rat model of Achilles tendon healing.
STUDY DESIGN
Controlled laboratory study.
METHODS
An overall 320 rats were used for a sequence of 6 experiments. We investigated whether the drug effect was time-, dose-, and load-dependent. Additionally, morphological data and drug administration routes were examined. Healing tendons were tested mechanically or used for histological examination 12 days after transection. Blood was collected for flow cytometry analysis in 1 experiment.
RESULTS
We found that the circadian rhythm and drug injection timing influenced the treatment outcome. Dexamethasone treatment at the right time point (days 7-11) and dose (0.1 mg/kg) significantly improved the material properties of the healing tendon, while the adverse effects were reduced. Local dexamethasone treatment did not lead to increased peak stress, but it triggered systemic granulocytosis and lymphopenia. Mechanical loading (full or moderate) is essential for the positive effects of dexamethasone, as complete unloading leads to the absence of improvements.
CONCLUSION
We conclude that dexamethasone treatment to improve Achilles tendon healing is dose- and time-dependent, and positive effects are perceived even in a partly unloaded condition.
CLINICAL RELEVANCE
These findings are promising from a clinical perspective, as the positive effect of this drug was seen even when given at lower doses and in a moderate loading condition, which better mimics the load level in patients with tendon ruptures.
Topics: Achilles Tendon; Animals; Biomechanical Phenomena; Dexamethasone; Disease Models, Animal; Humans; Rats; Tendon Injuries; Wound Healing
PubMed: 35234541
DOI: 10.1177/03635465221077101 -
Journal of Orthopaedic Surgery and... Feb 2022The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of perineural versus intravenous dexamethasone on interscalene block for pain control after shoulder arthroscopy.
METHODS
We have searched PubMed, Embase, Web of science, EBSCO and Cochrane library databases through April 2021 and included randomized controlled trials (RCTs) assessing the effect of perineural and intravenous dexamethasone on interscalene block in patients with shoulder arthroscopy.
RESULTS
Five RCTs were included in the meta-analysis. Overall, compared with intravenous dexamethasone for shoulder arthroscopy, perineural dexamethasone led to similar block duration (SMD = 0.12; 95% CI - 0.12 to 0.35; P = 0.33), pain scores at 12 h (SMD = - 0.67; 95% CI - 1.48 to 0.15; P = 0.11), pain scores at 24 h (SMD = - 0.33; 95% CI - 0.79 to 0.14; P = 0.17), opioid consumption (SMD = 0.01; 95% CI - 0.18 to 0.19; P = 0.95) and incidence of nausea/vomiting (OR = 0.74; 95% CI 0.38-1.44; P = 0.38).
CONCLUSIONS
Perineural and intravenous dexamethasone demonstrated comparable pain relief after shoulder arthroscopy.
Topics: Administration, Intravenous; Analgesics; Arthroscopy; Dexamethasone; Humans; Pain Management; Pain, Postoperative; Randomized Controlled Trials as Topic; Shoulder
PubMed: 35177116
DOI: 10.1186/s13018-022-02952-6 -
MBio Jan 2024Kaposi's sarcoma (KS) is the most common cancer in HIV-infected patients caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Hyperinflammation is the...
Kaposi's sarcoma (KS) is the most common cancer in HIV-infected patients caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Hyperinflammation is the hallmark of KS. In this study, we have shown that KSHV mediates hyperinflammation by inducing IL-1α and suppressing IL-1Ra. Mechanistically, KSHV miRNAs and vFLIP induce hyperinflammation by activating the NF-κB pathway. A common anti-inflammatory agent dexamethasone blocks KSHV-induced hyperinflammation and tumorigenesis by activating glucocorticoid receptor signaling to suppress IL-1α and induce IL-1Ra. This work has identified IL-1-mediated inflammation as a potential therapeutic target and dexamethasone as a potential therapeutic agent for KSHV-induced malignancies.
Topics: Humans; Cell Transformation, Neoplastic; Dexamethasone; Glucocorticoids; Herpesvirus 8, Human; Inflammation; Interleukin 1 Receptor Antagonist Protein; Receptors, Glucocorticoid; Sarcoma, Kaposi
PubMed: 38117084
DOI: 10.1128/mbio.03011-23 -
Journal of Materials Science. Materials... Mar 2022Amniotic membrane (AM) is often applied as a substitute material during ocular surface reconstruction. However, since AM has several disadvantages, alternative materials...
Amniotic membrane (AM) is often applied as a substitute material during ocular surface reconstruction. However, since AM has several disadvantages, alternative materials must be considered for this application. Keratin films made from human hair (KFs) have previously been presented as a promising option; they exhibited suitable characteristics and satisfactory biocompatibility in an in vivo rabbit model. Nevertheless, dexamethasone (DEX) eye drops are necessary after surgery to suppress inflammation. Since eye drops must be administered frequently, this might result in poor patient compliance, and the release of DEX at the transplant site would be clinically beneficial. Therefore, we aimed to incorporate DEX into KFs without hindering the positive film characteristics. Drug-loaded KFs were generated either by suspension technique or by the addition of solubilizing agents. The resulting specimens were analyzed regarding appearance, loading capacity, transparency, mechanical characteristics, swelling behavior and in vitro release. Furthermore, biocompatibility was assessed in vitro by determining the cell viability, seeding efficiency and growth behavior of corneal epithelial cells. The amount of incorporated DEX influenced the transparency and biomechanical properties of the films, but even highly loaded films showed properties similar to those of AM. The suspension technique was identified as the best incorporation approach regarding chemical stability and prolonged DEX release. Moreover, suspended DEX in the films did not negatively impact cell seeding efficiencies, and the cell-growth behaviors on the specimens with moderate DEX loads were satisfactory. This suggest that these films could comprise a suitable alternative material with additional anti-inflammatory activity for ocular surface reconstruction. Graphical abstract.
Topics: Amnion; Animals; Anti-Inflammatory Agents; Dexamethasone; Inflammation; Keratins; Ophthalmology; Rabbits; Tissue Scaffolds
PubMed: 35244790
DOI: 10.1007/s10856-021-06638-z -
PloS One 2022Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue...
INTRODUCTION
Liver sinusoidal endothelial cells (LSECs) are specialized fenestrated scavenger endothelial cells involved in the elimination of modified plasma proteins and tissue turnover waste macromolecules from blood. LSECs also participate in liver immune responses. A challenge when studying LSEC biology is the rapid loss of the in vivo phenotype in culture. In this study, we have examined biological processes and pathways affected during early-stage primary culture of rat LSECs and checked for cell responses to the pro-inflammatory cytokine interleukin (IL)-1β and the anti-inflammatory drug dexamethasone.
METHODS
LSECs from male Sprague Dawley rats were cultured on type I collagen in 5% oxygen atmosphere in DMEM with serum-free supplements for 2 and 24 h. Quantitative proteomics using tandem mass tag technology was used to examine proteins in cells and supernatants. Validation was done with qPCR, ELISA, multiplex immunoassay, and caspase 3/7 assay. Cell ultrastructure was examined by scanning electron microscopy, and scavenger function by quantitative endocytosis assays.
RESULTS
LSECs cultured for 24 h showed a characteristic pro-inflammatory phenotype both in the presence and absence of IL-1β, with upregulation of cellular responses to cytokines and interferon-γ, cell-cell adhesion, and glycolysis, increased expression of fatty acid binding proteins (FABP4, FABP5), and downregulation of several membrane receptors (STAB1, STAB2, LYVE1, CLEC4G) and proteins in pyruvate metabolism, citric acid cycle, fatty acid elongation, amino acid metabolism, and oxidation-reduction processes. Dexamethasone inhibited apoptosis and improved LSEC viability in culture, repressed inflammatory and immune regulatory pathways and secretion of IL-1β and IL-6, and further upregulated FABP4 and FABP5 compared to time-matched controls. The LSEC porosity and endocytic activity were reduced at 24 h both with and without dexamethasone but the dexamethasone-treated cells showed a less stressed phenotype.
CONCLUSION
Rat LSECs become activated towards a pro-inflammatory phenotype during early culture. Dexamethasone represses LSEC activation, inhibits apoptosis, and improves cell viability.
Topics: Animals; Dexamethasone; Endothelial Cells; Liver; Male; Proteome; Rats; Rats, Sprague-Dawley; Secretome
PubMed: 36054185
DOI: 10.1371/journal.pone.0273843 -
Cytotherapy Mar 2023We have previously demonstrated the safety and feasibility of adoptive cell therapy with CD45RA memory T cells containing severe acute respiratory syndrome coronavirus...
Donor selection for adoptive cell therapy with CD45RA memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release.
BACKGROUND AIMS
We have previously demonstrated the safety and feasibility of adoptive cell therapy with CD45RA memory T cells containing severe acute respiratory syndrome coronavirus 2-specific T cells for patients with coronavirus disease 2019 from an unvaccinated donor who was chosen based on human leukocyte antigen compatibility and cellular response. In this study, we examined the durability of cellular and humoral immunity within CD45RA memory T cells and the effect of dexamethasone, the current standard of care treatment, and interleukin-15, a cytokine critically involved in T-cell maintenance and survival.
METHODS
We performed a longitudinal analysis from previously severe acute respiratory syndrome coronavirus 2-infected and infection-naïve individuals covering 21 months from infection and 10 months after full vaccination with the BNT162b2 Pfizer/BioNTech vaccine.
RESULTS
We observed that cellular responses are maintained over time. Humoral responses increased after vaccination but were gradually lost. In addition, dexamethasone did not alter cell functionality or proliferation of CD45RA T cells, and interleukin-15 increased the memory T-cell activation state, regulatory T cell expression, and interferon gamma release.
CONCLUSIONS
Our results suggest that the best donors for adoptive cell therapy would be recovered individuals and 2 months after vaccination, although further studies with larger cohorts would be needed to confirm this finding. Dexamethasone did not affect the characteristics of the memory T cells at a concentration used in the clinical practice and IL-15 showed a positive effect on SARS-CoV-2-specific CD45RA T cells.
Topics: Humans; Interferon-gamma; Interleukin-15; Memory T Cells; Donor Selection; BNT162 Vaccine; COVID-19; SARS-CoV-2; COVID-19 Drug Treatment; Leukocyte Common Antigens; Phenotype; Dexamethasone; Cell Proliferation; Antibodies, Viral; Vaccination
PubMed: 36585293
DOI: 10.1016/j.jcyt.2022.12.001 -
Platelets Dec 2023This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with...
This retrospective study aimed to evaluate whether anti-glycoproteins (GPs) autoantibodies can be used as predictors of response to high-dose dexamethasone combined with rituximab (DXM-RTX) in the treatment of primary immune thrombocytopenia (ITP) patients. One-hundred twenty-six ITP patients were included and retrospectively analyzed, 66.7% of anti-GPIb/IX and 65.9% of anti-GPIIb/IIIa autoantibodies. Results showed that overall response (OR) and complete response (CR) rates of patients without anti-GPIb/IX autoantibodies to DXM-RTX were significantly higher than those with anti-GPIb/IX autoantibodies at 4 weeks (OR: 73.8% . 47.6%, CR: 50.0% . 26.2%; < 0.05) and 6 months (OR: 71.4% . 45.2%, CR: 42.9% . 25.0%; < .05). Furthermore, patients with anti-GPIb/IX single-positivity exhibited higher resistance to DXM-RTX than patients with anti-GPIIb/IIIa single-positivity at 4 weeks (OR: 37.5% . 78.3%; < .05) and 6 months (OR: 29.2% . 78.3%; < .05). Multivariable logistic regression analysis revealed that anti-GPIb/IX autoantibodies and megakaryocytes were associated with the OR rate of patients at both 4 weeks and 6 months, and anti-GPIb/IX autoantibodies at 4 weeks represented the only significant factor affecting OR rate with DXM-RTX (F = 9.128, = .003). Therefore, platelet anti-GPIb/IX autoantibodies might predict poor response to DXM-RTX in ITP patients.
Topics: Humans; Retrospective Studies; Rituximab; Purpura, Thrombocytopenic, Idiopathic; Autoantibodies; Platelet Glycoprotein GPIIb-IIIa Complex; Dexamethasone
PubMed: 37722393
DOI: 10.1080/09537104.2023.2258988 -
International Journal of Molecular... Dec 2022As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a...
As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.
Topics: Animals; Female; Male; Pregnancy; Rats; Antioxidants; Dexamethasone; Maternal Exposure; Oxidation-Reduction; Placenta; Thiobarbituric Acid Reactive Substances
PubMed: 36613982
DOI: 10.3390/ijms24010540 -
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 -
BMC Pregnancy and Childbirth Aug 2021To evaluate the effect of dexamethasone administration on the interval between initiation of labor induction and active phase of labor. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the effect of dexamethasone administration on the interval between initiation of labor induction and active phase of labor.
METHODS
The databases including PubMed, Cochrane Library, Embase, Scopus and Web of Science were searched for studies published up to June 27, 2021. Two types of articles were included: a) full-text articles published in English or any other languages, and b) Randomized Controlled Trials (RCTs). Participants were primi- or multigravida women with term or post-term pregnancy. The intervention group received parenteral or extra-amniotic dexamethasone whereas the control group received normal saline or no treatment before initiation of labor induction. All data were analyzed using Review Manager 5.3.
RESULTS
Seventeen studies involving 1879 patients were included in the meta-analysis. Administration of dexamethasone reduced the interval between the initiation of labor induction and the beginning of active phase by about 70 min [MD: - 1.17 (- 1.37, - 1.00); P < 0.00001]. Duration of the first stage of labor in the dexamethasone group was about 88 min shorter than that in the control. There were no maternal and fetal adverse effects.
CONCLUSIONS
Dexamethasone could significantly reduce the length of induction-active phase interval, and length of the first stage of labor, with no difference in maternal or fetal adverse effects.
Topics: Adolescent; Adult; Dexamethasone; Female; Glucocorticoids; Humans; Labor, Induced; Pregnancy; Pregnancy Outcome; Time; Young Adult
PubMed: 34404372
DOI: 10.1186/s12884-021-04010-1