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Drug Design, Development and Therapy 2016The introduction of modified-release (MR) prednisone adds a drug with encouraging potential to the armamentarium of the rheumatologist. In particular, for patients... (Review)
Review
The introduction of modified-release (MR) prednisone adds a drug with encouraging potential to the armamentarium of the rheumatologist. In particular, for patients experiencing a reduced quality of life due to prolonged morning stiffness, it is a promising therapeutic approach. Two clinical trials and one open-label observational study investigated the effectiveness of MR prednisone in reducing rheumatoid arthritis-related morning stiffness for both new and current users of corticosteroids. The efficacy and safety of MR prednisone use in rheumatoid arthritis patients are reviewed in this article. This includes pivotal trials as well as pathophysiological considerations and clinical implications.
Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Humans; Prednisone
PubMed: 27022244
DOI: 10.2147/DDDT.S87792 -
Acta Clinica Croatica Dec 2021Epilepsy is one of the most common chronic diseases in children, and cannot be controlled with conventional antiepileptic drugs in 30% of cases. Therefore, in these...
Epilepsy is one of the most common chronic diseases in children, and cannot be controlled with conventional antiepileptic drugs in 30% of cases. Therefore, in these cases, alternative approach such as corticosteroid therapy (CT) is used. The aim of this study was to analyze different types of CT used to treat drug-resistant childhood epilepsies, treated at Rijeka University Hospital Centre during a 5-year period (2016-2020). This retrospective study included 32 patients. The following parameters were analyzed: number of patients with a particular diagnosis, average age (in months) at the onset of epilepsy, average epilepsy duration (in months) prior to CT, average number of antiepileptic drugs used prior to CT, presence of changes on magnetic resonance imaging (MRI), presence of comorbidities, and types of CT. The average age at the onset of epilepsy was 14 months and average epilepsy duration prior to CT was 16 months. On average, 5 antiepileptic drugs were used prior to CT. MRI changes were present in 53.13% and comorbidities in 81.25% of study patients. Prednisone therapy was used in 28.13%, combined therapy with prednisone and methylprednisolone in 65.63%, and methylprednisolone in 6.25% of patients. Study results revealed the use of CT for particular diagnosis to differ among the centers, as well as within the same center, so it is important to highlight the importance of reaching universal guidelines for CT therapy of childhood epilepsies.
Topics: Child; Humans; Anticonvulsants; Prednisone; Retrospective Studies; Epilepsy; Adrenal Cortex Hormones; Methylprednisolone
PubMed: 36405001
DOI: 10.20471/acc.2021.60.s3.04 -
Experimental Physiology Sep 2023What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic... (Review)
Review
NEW FINDINGS
What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic targets in progressive muscle degenerative diseases such as Duchenne muscular dystrophy. What advances does it highlight? Gut microbe-derived metabolites are multifaceted signalling molecules key to muscle function, modifying pathways contributing to skeletal muscle wasting, making them a plausible target for adjunctive therapy in muscular dystrophy.
ABSTRACT
Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut-muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre- and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro-inflammatory phenotype and leaky gut barrier contributing to several of the well-known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota-directed regimen designed to optimise gut-muscle axis signalling, which could alleviate muscle wasting in DMD.
Topics: Animals; Mice; Muscular Dystrophy, Duchenne; Prednisone; Muscle, Skeletal; Glucocorticoids; Inflammation; Mice, Inbred mdx
PubMed: 37269541
DOI: 10.1113/EP091063 -
Journal of Veterinary Internal Medicine May 2020Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects.
BACKGROUND
Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects.
HYPOTHESIS/OBJECTIVES
Determine the effects of clopidogrel and prednisone on platelet function.
ANIMALS
Twenty-four healthy dogs.
METHODS
Double-blinded, placebo-controlled randomized trial. Platelet function was evaluated using a platelet function analyzer and impedance aggregometry (days 0, 14, and 28) for dogs treated with placebo, clopidogrel (2-3 mg/kg/d), prednisone (2 mg/kg/d), or prednisone with clopidogrel PO for 28 days. Results were categorized as nonresponder versus responder (platelet function analyzer), and inadequate, ideal, or excessive response (aggregometry). Results were compared using mixed model, split-plot repeated measures analysis of variance and generalized estimating equation proportional odds models. P < .05 was considered significant.
RESULTS
Closure times differed by treatment (F [3, 20] = 10.5; P < .001), time (F [2, 40] = 14.3; P < .001), and treatment-by-time (F [6, 40] = 3.4; P = .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P < .001), time (F [2, 40] = 35.4; P < .001), and treatment-by-time (F [6, 40] = 13.5; P < .001). Based on closure times, 5/6 dogs each in the clopidogrel and prednisone/clopidogrel groups were responders. All dogs in the prednisone/clopidogrel group were overcontrolled based on AUC (days 14 and 28), whereas 5/6 (day 14) and 2/6 (day 28) dogs treated with clopidogrel were overcontrolled. Compared to clopidogrel, dogs receiving prednisone/clopidogrel were 11 times (P = .03) more likely to have an excessive response.
CONCLUSIONS AND CLINICAL IMPORTANCE
Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs.
Topics: Animals; Blood Platelets; Clopidogrel; Dogs; Drug Interactions; Female; Glucocorticoids; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prednisone
PubMed: 32246893
DOI: 10.1111/jvim.15759 -
British Medical Journal Apr 1977
Topics: Aged; Arteritis; Female; Humans; Polymyalgia Rheumatica; Prednisolone; Prednisone
PubMed: 858041
DOI: No ID Found -
The Netherlands Journal of Medicine 2011
Topics: Aged; Cushing Syndrome; Diabetes Mellitus, Type 2; Female; Humans; Hypoaldosteronism; Prednisone
PubMed: 22173367
DOI: No ID Found -
Postgraduate Medical Journal Feb 1965
Topics: Diagnosis, Differential; Drug Therapy; Genetic Diseases, X-Linked; Histiocytosis, Langerhans-Cell; Humans; Infant; Leukemia, Hairy Cell; Lymphatic Diseases; Mandibular Neoplasms; Neoplasms; Prednisone; Severe Combined Immunodeficiency
PubMed: 14270750
DOI: 10.1136/pgmj.41.472.93 -
Annals of the Rheumatic Diseases May 2023Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term...
OBJECTIVES
Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects.
METHODS
We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics.
RESULTS
With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including T2, T17 and circulating T cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed.
CONCLUSIONS
Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.
Topics: Humans; Retroperitoneal Fibrosis; Prednisone; Sirolimus; Fibrosis; Inflammation; TOR Serine-Threonine Kinases
PubMed: 36720581
DOI: 10.1136/ard-2022-223736 -
Archives of Disease in Childhood Feb 1985
Topics: Adrenocorticotropic Hormone; Child; Humans; Infant; Prednisone; Spasms, Infantile
PubMed: 2983624
DOI: 10.1136/adc.60.2.94 -
Journal of Neuromuscular Diseases 2022Glucocorticoid steroids are standard of care in Duchenne Muscular Dystrophy (DMD) to slow disease course. Use of glucocorticoids in other muscular dystrophies, including... (Clinical Trial)
Clinical Trial
BACKGROUND
Glucocorticoid steroids are standard of care in Duchenne Muscular Dystrophy (DMD) to slow disease course. Use of glucocorticoids in other muscular dystrophies, including Becker (BMD) and Limb Girdle (LGMD), has been less explored. Recently, preclinical studies conducted in DMD and LGMD mouse models showed once-weekly prednisone was associated with improved muscle performance without activation of muscle atrophy genes.
OBJECTIVE
To determine safety and tolerability of once-weekly prednisone in patients with LGMD and BMD.
METHODS
We conducted an open label, exploratory single center study of of once-weekly prednisone at 0.75-1 mg/Kg in LGMD (n = 19) and BMD (n = 1) (mean age 35, range 18-60). The LGMD participants represented multiple different LGMD subtypes, and the study included ambulatory and non-ambulatory participants. Participants were assessed at baseline and 24 weeks for vital signs, blood biomarkers, and for patient-reported side effects. As secondary endpoints, functional muscle testing and body composition were measured.
RESULTS
Over the 24-week study, there were no significant changes in blood pressure, HgbA1C, or lipid profiles. We observed a reduction in serum creatine kinase over the study interval. Whole body DEXA scanning suggested a possible increase in lean mass and a reduction in adiposity. Functional measures suggested trends in improved muscle performance.
CONCLUSIONS
In this single center, open label pilot study, once-weekly prednisone was safe and well tolerated. Additional investigation of once-weekly prednisone in a larger cohort and for a longer period of time is warranted.
Topics: Drug Administration Schedule; Humans; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Duchenne; Pilot Projects; Prednisone
PubMed: 35124660
DOI: 10.3233/JND-210741