-
Journal of Orthopaedic Surgery and... Dec 2023Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and...
Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells.
OBJECTIVES
Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model.
METHODS
BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-Exos and BMSC-Exos secreted from such cells were collected. The differences between BMSC-Exos, BMSC-Exos and BMSC-Exos in protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague-Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-Exos or BMSC-Exos were conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model.
RESULTS
Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-Exos could further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-Exos group showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-Exos, could increase microvascular density and enhance bone remodeling of femoral heads.
CONCLUSIONS
BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH.
Topics: Rats; Animals; Glucocorticoids; Endothelial Cells; Femur Head; Exosomes; Hydrocortisone; Rats, Sprague-Dawley; Osteonecrosis; Mesenchymal Stem Cells; Methylprednisolone; MicroRNAs
PubMed: 38062514
DOI: 10.1186/s13018-023-04440-x -
Resuscitation Oct 2023The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC.
METHODS
The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin.
RESULTS
The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs.
CONCLUSION
Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.
Topics: Humans; Methylprednisolone; Cardiopulmonary Resuscitation; Heart Arrest; Vasopressins; Vasoconstrictor Agents; Hemodynamics; Norepinephrine; Hospitals; Gases
PubMed: 37543161
DOI: 10.1016/j.resuscitation.2023.109922 -
The Journal of Maternal-fetal &... Dec 2023There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is ongoing interest in glucocorticoid treatment during oocyte stimulation to treat infertility in women who have undergone Assisted Reproductive Technology (ART).
OBJECTIVE
This meta-analysis was performed to evaluate the efficiency and safety of adjuvant glucocorticoid therapy on pregnancy outcomes in infertile women undergoing ART cycles.
STUDY DESIGN
A literature search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library up to December 2022. To assess the efficacy and safety of additional glucocorticoid treatment during ovulation induction in women who underwent IVF or ICSI treatment, only randomized controlled trials were included.
RESULTS
Overall, glucocorticoid therapy during ovulation showed a nonsignificant effect of prednisolone improving the live birth rate (OR = 1.03, 95% CI [.75, 1.43], I = .0%, = .84), abortion rate (OR = 1.14, 95% CI [.62, 2.08], I = 31%, = .68), and implantation rate (OR = 1.1, 95% CI [.82, 1.5], I = 8%, = .52) of infertile women compared to the control group. The present meta-analysis revealed that the clinical pregnancy rate per cycle tended to increase after glucocorticoid treatment (OR = 1.29, 95% CI [1.02, 1.63], I = 8%, = .52).
CONCLUSIONS
The present meta-analysis suggested that ovarian stimulation prednisolone therapy does not significantly improve clinical outcomes in women undergoing IVF/ICSI. Although the results indicated that adjuvant glucocorticoid therapy during ovarian stimulation may increase the clinical pregnancy rate, subgroup analysis showed that it was affected by infertility factors, dose schedules, and length of treatment. Therefore, these results should be interpreted with caution.
Topics: Female; Pregnancy; Humans; Glucocorticoids; Infertility, Female; Ovulation Induction; Prednisolone; Adjuvants, Pharmaceutic; Dietary Supplements
PubMed: 37385781
DOI: 10.1080/14767058.2023.2227310 -
Human Molecular Genetics Feb 2024Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three...
A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models.
Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn-/-;SMN2 and intermediate Smn2B/- SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone's activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn-/-; SMN2 SMA and Smn+/-; SMN2 healthy mice, we identified molecular targets linked to prednisolone's ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone's potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.
Topics: Mice; Animals; Pharmaceutical Preparations; Drug Repositioning; Muscular Atrophy, Spinal; Muscle, Skeletal; Gene Expression Profiling; Prednisolone; Disease Models, Animal; Survival of Motor Neuron 1 Protein
PubMed: 37947217
DOI: 10.1093/hmg/ddad192 -
Journal of Dental Sciences Oct 2023Delayed healing of the extraction socket is not uncommon when tooth extraction is performed on patients taking prednisolone. This study aimed to identify specific dosage...
BACKGROUND/PURPOSE
Delayed healing of the extraction socket is not uncommon when tooth extraction is performed on patients taking prednisolone. This study aimed to identify specific dosage of prednisolone and factors associated with delayed healing of the extraction socket in patients taking prednisolone.
MATERIALS AND METHODS
This single-center retrospective study included 80 patients who underwent tooth extraction under local anesthesia and were taking prednisolone orally. Patients were divided into the nondelayed healing group ( = 50) and delayed healing group ( = 30), and their background and dosage of prednisolone were compared.
RESULTS
The dosage of prednisolone was significantly higher in the delayed healing group than in the nondelayed healing group. A receiver operating characteristics curve analysis resulted in moderate accuracy when the cutoff value was set at 8.0, with 67% sensitivity, 76% specificity, and 0.765 area under the curve. The multivariate logistic regression analysis revealed that prednisolone dosage >8.0 mg/day (odds ratio [OR], 10.8; 95% confidence interval [CI], 2.79-41.6) and osteosclerotic changes beyond the alveolar bone around the tooth to be extracted (OR, 10.3; 95% CI, 2.81-37.8) in X-ray imaging had significant effects on delayed healing.
CONCLUSION
The results of this study suggested that delayed healing following tooth extractions in patients taking prednisolone was related to a dosage of 8.0 mg/day or higher and osteosclerotic changes.
PubMed: 37799897
DOI: 10.1016/j.jds.2022.08.021 -
Journal of Computer-aided Molecular... Dec 2023Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques...
Theoretical predictions of the solubilizing capacity of micelles and vesicles present in intestinal fluid are important for the development of new delivery techniques and bioavailability improvement. A balance between accuracy and computational cost is a key factor for an extensive study of numerous compounds in diverse environments. In this study, we aimed to determine an optimal molecular dynamics (MD) protocol to evaluate small-molecule interactions with micelles composed of bile salts and phospholipids. MD simulations were used to produce free energy profiles for three drug molecules (danazol, probucol, and prednisolone) and one surfactant molecule (sodium caprate) as a function of the distance from the colloid center of mass. To address the challenges associated with such tasks, we compared different simulation setups, including freely assembled colloids versus pre-organized spherical micelles, full free energy profiles versus only a few points of interest, and a coarse-grained model versus an all-atom model. Our findings demonstrate that combining these techniques is advantageous for achieving optimal performance and accuracy when evaluating the solubilization capacity of micelles. All-atom (AA) and coarse-grained (CG) umbrella sampling (US) simulations and point-wise free energy (FE) calculations were compared to their efficiency to computationally analyze the solubilization of active pharmaceutical ingredients in intestinal fluid colloids.
Topics: Micelles; Molecular Dynamics Simulation; Colloids; Surface-Active Agents
PubMed: 38103089
DOI: 10.1007/s10822-023-00541-1 -
BMC Infectious Diseases Dec 2023Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens.
METHODS
This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared.
RESULTS
In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay.
CONCLUSIONS
Considering the available evidence, this network meta‑analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19.
TRIAL REGISTRATION
PROSPERO CRD42022350407 (22/08/2022).
Topics: Humans; Glucocorticoids; COVID-19; Hydrocortisone; Network Meta-Analysis; Methylprednisolone; Dexamethasone
PubMed: 38124031
DOI: 10.1186/s12879-023-08874-w -
Journal of Human Reproductive Sciences 2023Natural killer T (NKT) cells are influential immune cells in pregnancy failures, including recurrent spontaneous abortion (RSA). Different approaches are used for these...
BACKGROUND
Natural killer T (NKT) cells are influential immune cells in pregnancy failures, including recurrent spontaneous abortion (RSA). Different approaches are used for these disorders due to their effects on maternal immunomodulation.
AIMS
In the present study, we compared the effects of two typical immunotherapies (lymphocyte immunotherapy [LIT] and low-dose prednisolone) on CD3CD56CD16 and CD3CD56CD8 cells as two distinct subsets of NKT cells in Women with RSA.
SETTINGS AND DESIGN
This study was a comparative cohort study conducted from 2021 to 2022. One hundred and five women with RSA were distributed into three treatment groups randomly.
MATERIALS AND METHODS
Fifty women in the group of low-dose prednisolone therapy, fifty women in the LIT group and five women without any treatment as the control group were included in the study. NK and NKT cell subsets were assessed using flow cytometry. Furthermore, the concentration of interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) was measured quantitatively using the enzyme-linked immunosorbent assay technique.
STATISTICAL ANALYSIS USED
Normality and comparisons between study groups were performed by non-parametric unpaired Mann-Whitney, Kruskal-Wallis rank sum test, and one-way ANOVA.
RESULTS
The percentage of CD56 NK cells was increased after prednisolone therapy, while this population significantly decreased in the LIT group. In contrast to the LIT group, the administration of prednisolone increased CD3CD8CD56 NKT cells ( < 0.0001), which is helpful for pregnancy. The effect of the investigated treatment approaches on the population of peripheral CD3CD56CD16 NKT cells of women with RSA was not adequately significant. The same situation was also observed regarding the serum level of IFN-γ. However, a significant decrease in serum levels of IL-10 and TGF-β was observed after prednisolone therapy.
CONCLUSION
The lower capability of LIT in changing the population of NKT cells compared to prednisolone therapy may be due to its mechanism of action, which is related to the production of blocking antibodies. These treatment approaches had different effects on NKT cells, indicating that NKT cell population and function can be affected using LIT and prednisolone therapy distinctly. In addition, prednisolone therapy and LIT in women with normal serum levels of IFN-γ have no harmful effects in changing the production of this critical cytokine.
PubMed: 38045499
DOI: 10.4103/jhrs.jhrs_8_23 -
Cureus Sep 2023Renal transplantation is a life-saving procedure and contributes to a better quality of life in patients with end-stage renal disease. The discovery and use of...
BACKGROUND
Renal transplantation is a life-saving procedure and contributes to a better quality of life in patients with end-stage renal disease. The discovery and use of immunosuppressants to prevent and treat allograft rejection are responsible for the improved outcome after the transplant. Long-term usage of these drugs warrants special monitoring and follow-up of the adverse drug reactions developed during the post-transplant period. This study analyzes the prescribing pattern and severity and outcome of adverse drug reactions of immunosuppressants in renal transplant patients.
MATERIALS AND METHODS
A cross-sectional, observational study was done in patients more than 18 years of age who have undergone renal transplantation and receiving immunosuppressants in the Department of Nephrology in a tertiary care hospital.
RESULTS
During the two-month study period, 150 post-transplant patients were screened for adverse drug reactions, and the prescription pattern was also studied. Immunosuppressive therapy was given as induction and maintenance therapy. The short-term induction therapy regimen was based on the type of donor (injection basiliximab or anti-thymocyte globulin). The long-term maintenance therapy comprises triple therapy of tacrolimus, mycophenolate mofetil, and prednisolone in 102 (68%) patients and cyclosporine, mycophenolate mofetil, prednisolone in 37 (25%) patients. A total of 116 adverse drug reactions were reported in 82 patients. The pattern of the adverse drug reactions showed urinary tract infections in 26 (17.3%) patients on tacrolimus-based regimen and hypertension in 20 (13.3%) patients on tacrolimus and cyclosporine-based regimen. Causality assessment using the World Health Organization causality assessment scale showed that the observed reactions were of probable 42 (36%) and possible 74 (64%) categories.
CONCLUSIONS
Long-term intake of immunosuppressive drugs is essential to improve the quality of life in renal transplant individuals and it is essential to monitor adverse drug reactions of these drugs through vigilant self-reporting and pharmacovigilance practices.
PubMed: 37905288
DOI: 10.7759/cureus.46200 -
Archives of Razi Institute Jun 2023Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the...
Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.
Topics: Rats; Female; Animals; Rats, Wistar; Ketorolac; Methylprednisolone Acetate; Estrous Cycle; Seizures; Inflammation; Anti-Inflammatory Agents
PubMed: 38028823
DOI: 10.22092/ARI.2022.360115.2553