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International Journal of Rheumatic... Aug 2023Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge,...
Avacopan is a novel C5a receptor antagonist recently approved for the treatment of microscopic polyangiitis and granulomatosis with polyangiitis. To our knowledge, thrombocytopenia induced by avacopan has not been reported. We report a case of a 78-year-old man with microscopic polyangiitis who developed rapidly progressive glomerulonephritis (RPGN) and vasculitis neuropathy. After developing RPGN, he was treated with prednisolone, which was ineffective. As the dosage of corticosteroids was decreased, he developed impaired dorsiflexion of the left ankle, tingling and numbness in his feet, consistent with vasculitis neuropathy. After a 3-day administration of methylprednisolone, we started avacopan and prednisolone 20 mg/d to reduce the corticosteroid dosage. One week after starting avacopan, platelet counts began to decrease, eventually leading to the cessation of the drug. The possibility of thrombotic microangiopathy and heparin-induced thrombocytopenia was considered unlikely given the clinical course and laboratory studies. After 3 weeks of avacopan cessation, platelet counts began to increase, suggesting avacopan as the most probable cause of thrombocytopenia. Our case highlights the importance of postmarketing surveillance of avacopan to identify its adverse events that were not reported in clinical trials to ensure its safe use. Clinicians should carefully monitor platelet counts when using avacopan.
Topics: Male; Humans; Aged; Microscopic Polyangiitis; Thrombocytopenia; Aniline Compounds; Methylprednisolone; Granulomatosis with Polyangiitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic
PubMed: 36880594
DOI: 10.1111/1756-185X.14645 -
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 -
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 -
Environmental Research Dec 2023The occurrence of glucocorticoids (GCs) in agricultural soils has raised concerns due to their high polarity, widespread biological effects in vertebrates, and their...
The occurrence of glucocorticoids (GCs) in agricultural soils has raised concerns due to their high polarity, widespread biological effects in vertebrates, and their potential to disrupt vital processes such as glucose metabolism and immune function. This study investigated the sorption and transport dynamics of three GCs, namely cortisone (COR), prednisolone (PNL), and triamcinolone acetonide (TCA) in five soil-water systems (S1-S5 systems). The sorption data of the GCs were fitted to a linear sorption model (R = 0.95-0.99), with organic carbon (OC) normalized sorption coefficients ranging from 2.26 ± 0.02 to 3.36 ± 0.02. The sorption magnitudes (K) of the GCs exhibited a nearly linear correlation with their corresponding octanol-water partition coefficients (logK) in the S1-S3 systems. However, some deviations from linearity were observed in the S4 and S5 systems. Furthermore, a strong correlation was observed between the K values of the GCs and the OC% of the soils. These data indicated that specific and hydrophobic partitioning interactions governed the sorption of GCs onto soils. The transport data of the GCs were fitted to a two-site nonequilibrium model using the CXTFIT program (R = 0.82-0.98). The retardation factor (R) for each GC exhibited a positive correlation with the OC% and clay contents of soils. Additionally, the relationships between the logR values and logK values of the GCs deviated slightly from linear correlation in most columns. These results indicated that specific interactions in the columns were more pronounced compared to the batch systems. An initial field-scale simulation demonstrated that frequent precipitation can facilitate the dilution and vertical transport of the GCs through soil profiles. The transport potential of the GCs was affected by the properties and soils and GCs. Overall, these findings provide valuable insights into the transport potential and associated environmental risks of GCs in soil-water systems.
Topics: Soil; Triamcinolone Acetonide; Cortisone; Prednisolone; Soil Pollutants; Glucocorticoids; Carbon; Water; Adsorption
PubMed: 37813136
DOI: 10.1016/j.envres.2023.117287 -
BMJ Case Reports Apr 2024A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung...
A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung adenocarcinoma, for which she was being treated with nivolumab. Filamentary keratitis was evident at the slit-lamp examination. Regardless of ophthalmic reasons, nivolumab was suspended. Prednisolone ointment was started, with a complete remission. We present a case of steroid-responsive filamentary keratitis triggered by nivolumab. We aim to highlight the importance of prompt ophthalmology referral and the use of therapies targeting ocular surface inflammation in immune checkpoint inhibition therapy.
Topics: Humans; Nivolumab; Female; Middle Aged; Keratitis; Antineoplastic Agents, Immunological; Prednisolone; Lung Neoplasms; Immune Checkpoint Inhibitors; Adenocarcinoma of Lung
PubMed: 38688575
DOI: 10.1136/bcr-2023-258013 -
Journal of Equine Veterinary Science Sep 2023This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine...
This research was performed to compare the effects of prednisolone and fluorometholone on intraocular pressure (IOP) and Schirmer tear test (STT) in the normal equine eye. Sixteen normal mares aged between 6 and 10 years were used for this study. Horses were randomly assigned to two groups. Eight horses in the first group received 0.2 mL of topical 1% prednisolone in one eye and the contralateral eye was used as control (0.2 mL of saline was instilled). The second group received 0.2 mL of 0.1% fluorometholone in a randomly selected eye and the contralateral eye served as control and received 0.2 mL of saline. STT values and IOP were determined using STT strips and rebound, respectively, at the baseline, and 30-, 60-, 90-, and 180-minutes post eyedrop instillation. Mean (SD) IOPs at the baseline in the treated eyes of the first and second groups were 28.5 (5.4) and 27.5 (4.9) mm Hg, respectively. STT values at the baseline in the treated eyes of the first and second groups were 26.0 (1.8) mm/min and 24.0 (4.0) mm/min, respectively. Neither prednisolone nor fluorometholone caused significant changes in the IOP during 3 hours of monitoring (P > .05). There were no significant differences in the mean levels of STT in the control and treatment eyes, either between groups or within each group (P > .05). In conclusion, one dose (0.2 mL) of 1% prednisolone or 0.1% fluorometholone after 3 hours did not alter the IOP and STT in healthy horses. Further research for a longer period on normal horses and horses with uveitis is warranted.
Topics: Horses; Animals; Female; Intraocular Pressure; Fluorometholone; Prednisolone; Tears; Ophthalmic Solutions
PubMed: 37348824
DOI: 10.1016/j.jevs.2023.104840 -
Aquatic Toxicology (Amsterdam,... Mar 2024Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects...
Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.
Topics: Animals; Larva; Prednisone; Prednisolone; Water Pollutants, Chemical; Oxidative Stress
PubMed: 38387247
DOI: 10.1016/j.aquatox.2024.106869 -
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 -
Theriogenology Sep 2023While captivity-related stress and the associated rise in baseline glucocorticoid (GC) concentrations have been linked to ovarian quiescence in some felid species, no...
While captivity-related stress and the associated rise in baseline glucocorticoid (GC) concentrations have been linked to ovarian quiescence in some felid species, no study has examined the effects of elevated GC on oocyte quality. This study examined the effects of exogenous GC administration on the ovarian response and oocyte quality of domestic cats after an ovarian stimulation protocol. Entire mature female cats were divided into treatment (n = 6) and control (n = 6) groups. Cats in the GC treatment (GCT) group were given 1 mg kg oral prednisolone daily from Day 0-45. All cats (n = 12) were given 0.088 mg kg day progesterone orally from Day 0-37, before treatment with 75 IU eCG im to induce follicular growth on Day 40, followed by 50 IU hCG im 80 h later to induce ovulation. Cats were ovariohysterectomised 30 h after the hCG treatment. Blood samples were collected on Days 0, 10, 30 and 40 (prior to eCG treatment), 80 h after eCG treatment, and on Day 45 for cortisol, glucose, prednisolone, oestradiol, and progesterone analysis. Cortisol concentrations did not differ between treatment groups throughout the study. Mean glucose concentrations were higher in the GCT cats (P = 0.004). Prednisolone was undetectable in all samples. Oestradiol and progesterone concentrations confirmed that the eCG treatment stimulated follicular activity and ovulation in all cats. Following ovariohysterectomy, the ovarian responses were graded (1 = excellent, 4 = poor) and oocytes retrieved from the oviducts. Each oocyte was given a total oocyte score (TOS: using an 9-point scale, 8 = best) based on four parameters: oocyte morphology, size, ooplasm uniformity and granularity, and zona pellucida (ZP) thickness and variation. Ovulation was confirmed in all cats, with a mean of 10.5 ± 1.1 ovulations per cat. Ovarian mass, ovarian response, number of ovulations, and oocyte recovery did not differ between groups. Oocyte diameter did not differ between the groups, but the ZP was thinner in the GCT group (3.1 ± 0.3 μm vs. 4.1 ± 0.3 μm, P = 0.03). The TOS was similar between treatment and control cats, but the ooplasm grade was lower (1.5 ± 0.1 vs. 1.9 ± 0.1, P = 0.01) and there was a tendency for ZP grade to be poorer (0.8 ± 0.1 vs. 1.2 ± 0.2; P = 0.08) in the treatment group. In conclusion, the GC treatment resulted in morphological changes to oocytes collected following ovarian stimulation. Whether these changes would affect fertility warrants further investigation.
Topics: Female; Cats; Animals; Glucocorticoids; Hydrocortisone; Progesterone; Oocytes; Prednisolone; Estradiol; Glucose
PubMed: 37302246
DOI: 10.1016/j.theriogenology.2023.05.024 -
Cornea Nov 2023The aim of this study was to report a case of peripheral ulcerative keratitis (PUK) associated with lichen planus.
PURPOSE
The aim of this study was to report a case of peripheral ulcerative keratitis (PUK) associated with lichen planus.
METHODS
A 42-year-old woman with histological confirmation of lichen planus from an oral buccal mucosa biopsy presented with bilateral peripheral stromal thinning and an epithelial defect, in keeping with PUK.
RESULTS
All screening for known causes of PUK were negative, and lichen planus was presumed as the etiological factor. Oral prednisolone 1 mg/kg was initiated, alongside topical steroids and topical ciclosporin. The PUK resolved after 3 months, and a slow-tapering regimen of oral prednisolone was needed to prevent a relapse of ocular surface inflammation. Topical steroids were also tapered and discontinued after 5 months, and the ocular surface remained stable with topical ciclosporin with no relapse after 1 year.
CONCLUSIONS
Ocular manifestations of lichen planus are rare and mostly involve the conjunctiva; however, PUK might also develop, presumably due to its similar mechanisms with other T-cell autoimmune diseases. Systemic immunosuppression is required initially but further control of the ocular surface can be achieved successfully with topical ciclosporin.
Topics: Female; Humans; Adult; Cyclosporine; Corneal Ulcer; Lichen Planus; Prednisolone; Conjunctiva
PubMed: 37318141
DOI: 10.1097/ICO.0000000000003323