Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8
Published: Feb. 16, 2021
Glucocorticoids therapy has greatly improved the outcome of lupus nephritis patients. Since their discovery, adverse effects have counterbalanced beneficial anti-inflammatory effects. exert through both genomic and non-genomic pathways. Differential activation these pathways is clinically relevant in terms benefit Ongoing aims treatment development focus on a better use glucocorticoids combined with immunosuppressant drugs biologics. Newer regimens aim to decrease peak glucocorticoid dose, allow rapid tapering, intend control disease activity lower cumulative exposure. In this review we discuss mechanisms, recent strategies limit exposure without compromising efficacy.
Language: Английский
Citations
51From NSAIDs to Glucocorticoids and Beyond
Cells, Journal Year: 2021, Volume and Issue: 10(12), P. 3524 - 3524
Published: Dec. 14, 2021
Our interest in inflammation and its treatment stems from ancient times. Hippocrates used willow bark to treat inflammation, many centuries later, salicylic acid derivative aspirin's ability inhibit cyclooxygenase enzymes was discovered. Glucocorticoids (GC) ushered a new era of for both chronic acute inflammatory disease, but their potentially dangerous side effects led the pharmaceutical industry seek other, safer, synthetic GC drugs. The discovery GC-inducible endogenous anti-inflammatory protein annexin A1 (AnxA1) other proresolving mediators has opened therapy. This review aims recapitulate last four decades research on NSAIDs, GCs, AnxA1 effects.
Language: Английский
Citations
50Efficacy and Safety of
Arthritis & Rheumatology, Journal Year: 2022, Volume and Issue: 75(6), P. 879 - 889
Published: Dec. 13, 2022
Objective To assess the efficacy and safety of ABBV‐3373, a novel antibody–drug conjugate (ADC) composed anti–tumor necrosis factor (anti‐TNF) monoclonal antibody adalimumab linked to glucocorticoid receptor modulator (GRM), compared adalimumab, in patients with rheumatoid arthritis (RA). Methods In this randomized, double‐blind, active‐controlled, proof‐of‐concept trial ( ClinicalTrials.gov identifier: NCT03823391), adults moderate‐to‐severe RA receiving background methotrexate were administered intravenously (IV) ABBV‐3373 100 mg every other week for 12 weeks, followed by placebo or subcutaneous 80 24 weeks. The primary end point was change from baseline Disease Activity Score 28 joints using C‐reactive protein (DAS28‐CRP) at 12, 2 prespecified comparisons versus historical (80 equivalent dose) combined in‐trial/historical adalimumab. Secondary points included Clinical Index, Simplified DAS28 erythrocyte sedimentation rate, as well proportion achieving DAS28‐CRP ≤3.2 American College Rheumatology 50% improvement criteria. Results Forty‐eight randomized receive either (n = 31) 17). At demonstrated reduction (−2.65 −2.13; P 0.022) −2.29; probability 89.9%), numerically greater than in‐trial (−2.51). For secondary points, observed adalimumab; predicted 79.3–99.5% be more effective based on data. Of ABBV‐3373–treated who achieved 70.6% maintained response despite switching placebo. Four serious adverse events (SAEs) reported (noncardiac chest pain, pneumonia, upper respiratory tract infection, anaphylactic shock) SAEs (breast abscess bronchitis). After increasing duration IV administration 3 minutes 15–30 minutes, no similar shock reported. Conclusion Data support continued development TNF–GRM ADC treatment RA, potential achieve superior outcomes currently available therapies.
Language: Английский
Citations
30Corticosteroids in COVID-19: pros and cons
Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10
Published: Aug. 14, 2023
The wide and rapid spread of the COVID-19 pandemic has placed an unanticipated burden on global healthcare sector. This necessitated a swift response from international community to reach solution. Efforts were made in parallel develop preventative therapeutic modalities. Since then, drug repurposing blossomed as potentially resolution included various agents with anti-viral anti-inflammatory properties. Corticosteroids, being potent agents, have been under extensive investigation. Various trials recorded beneficial outcome corticosteroids decreasing mortality morbidity COVID-19. With high pace escalating events, quality study design clinical are varied. Therefore, this aims explore role disease. It inspects molecular, pharmacologic, proof behind theory.
Language: Английский
Citations
17Precision Medicine in Rheumatic Diseases: Unlocking the Potential of Antibody-Drug Conjugates
Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(4), P. 579 - 598
Published: April 15, 2024
In the era of precision medicine, Antibody-Drug Conjugates (ADCs) have emerged as a cutting-edge therapeutic strategy. These innovative compounds combine monoclonal antibodies with potent cell-killing or immune-modulating abilities attached drug payloads. This unique strategy not only reduces off-target toxicity but also enhances effectiveness drugs. Beyond their well-established role in oncology, ADCs are now showing promising potential addressing unmet needs therapeutics rheumatic diseases. Rheumatic diseases, diverse group chronic autoimmune diseases varying etiologies, clinical presentations, and prognoses, often demand prolonged pharmacological interventions, creating pressing need for novel, efficient low-risk treatment options. ADCs, ability to precisely target immune components, novel this context. review will provide an overview core components mechanisms behind summary latest trials if well discussion on challenges future prospects faced by development next-generation ADCs. Significance Statement There is lack targeted Antibody-drug conjugates, class drugs, disease. While there limited literature summarizing progress antibody-drug conjugates field disease, updating advancements area provides insights into anti-rheumatic
Language: Английский
Citations
6Saussurea lappa Ethanolic Extract Attenuates Triamcinolone Acetonide-Induced Pulmonary and Splenic Tissue Damage in Rats via Modulation of Oxidative Stress, Inflammation, and Apoptosis
Antioxidants, Journal Year: 2020, Volume and Issue: 9(5), P. 396 - 396
Published: May 8, 2020
Background: In this era, worldwide interest has been directed towards using natural antioxidants to guard against drug side effects. Saussurea lappa is a famous medicinal plant with many biologically active compounds. Triamcinolone acetonide (TA) an extensively used glucocorticoid. Hence, study explored, for the first time, possible beneficial effects of S.lappa ethanolic extract on TA-induced oxidative damage in lung and spleen rats. Methods: Five experimental groups were used: control group, S. lappa-treated group (600 mg/kg/day, orally), TA-treated (40 mg/kg/twice/week I/P), + TA co-treated lappa/TA prophylactic group. Results: exposure significantly induced leukocytosis neutrophilia. addition, reduced levels C-reactive protein, interleukin-12, tumor necrosis factor α, immunoglobulins. Lung Caspase-3 overexpression splenic CD8+ downregulation also noted treatment increased malondialdehyde concentration but superoxide dismutase glutathione peroxidase activities. counteracted apoptotic The best results recorded Conclusions:S. remarkable protective effect via its anti-inflammatory, anti-apoptotic, antioxidant capacity. Thus, it could be candidate as face glucocorticoid's harmful
Language: Английский
Citations
46The Role of Glucocorticoids in Breast Cancer Therapy
Current Oncology, Journal Year: 2022, Volume and Issue: 30(1), P. 298 - 314
Published: Dec. 25, 2022
Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland regulated hypothalamic–pituitary–adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their stress conditions. Their mechanism of action can be via receptor-independent or receptor-dependent pathway. The pathway translocates to nucleus, where ligand-receptor complex binds specific sequences in DNA modulate transcription genes. glucocorticoid receptor (GR) its endogenous ligand cortisol (CORT) humans, corticosterone rodents exogenous ligand, dexamethasone (DEX), have been extensively studied breast cancer. Its clinical utility oncology has mainly focused on using DEX as an antiemetic prevent chemotherapy-induced nausea vomiting. In this review, we compile results reported literature recent years, highlighting current trends unresolved controversies field. Specifically, cancer, GR is considered marker poor prognosis, therapeutic target for triple-negative cancer (TNBC) subtype, efforts being made develop better antagonists with fewer side effects. It necessary know type differentiate treatment estrogen (ER)-positive, ER-negative, TNBC, implement therapies that include use GCs.
Language: Английский
Citations
26Circadian Effects of Drug Responses
Annual Review of Biomedical Engineering, Journal Year: 2021, Volume and Issue: 23(1), P. 203 - 224
Published: March 31, 2021
Circadian rhythms describe physiological systems that repeat themselves with a cycle of approximately 24 h. Our understanding the cellular and molecular origins these oscillations has improved dramatically, allowing us to appreciate significant role play in maintaining homeostasis. allow living organisms predict efficiently respond dynamically changing environment, set by repetitive day/night cycles. Since circadian underlie almost every aspect human physiology, it is unsurprising they also influence response organism disease, stress, therapeutics. Therefore, not only do mechanisms maintain health disrupt homeostasis depend on our internal clock, but way drugs are perceived function depends rhythms. We present holistic view therapeutic process, discussing components such as disease state, pharmacokinetics, pharmacodynamics, well adverse reactions critically affected outline challenges opportunities moving toward personalized medicine approaches explore capitalize for benefit patient.
Language: Английский
Citations
28Corticosteroids in oncology: Use, overuse, indications, contraindications. An Italian Association of Medical Oncology (AIOM)/ Italian Association of Medical Diabetologists (AMD)/ Italian Society of Endocrinology (SIE)/ Italian Society of Pharmacology (SIF) multidisciplinary consensus position paper
Critical Reviews in Oncology/Hematology, Journal Year: 2022, Volume and Issue: 180, P. 103826 - 103826
Published: Sept. 30, 2022
Corticosteroids (CSs) are widely used in oncology, presenting several different indications. They useful for induction of apoptosis hematological neoplasms, management anaphylaxis and cytokine release/hypersensitivity reaction the symptomatic treatment many tumour- treatment-related complications. If employment CSs oncological setting results benefits patients satisfaction clinicians, on other hand, potential adverse events (AEs), both during after withdrawal CSs, as well duality effects these compounds recommend being cautious clinical practice. To date, gray zones remain about indications, contraindications, dose, duration treatment. In this article, a panel experts provides critical review therapy focusing mechanisms action pharmacological characteristics, current emerging therapeutic indications/contraindications, AEs related to treatment, impact patient outcome.
Language: Английский
Citations
20Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review
Medicine, Journal Year: 2023, Volume and Issue: 102(32), P. e34614 - e34614
Published: Aug. 11, 2023
The circadian rhythm (CR) is a fundamental biological process regulated by the Earth’s rotation and solar cycles. It plays critical role in various bodily functions, its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, immune response. Immune mediators, proteins, hormones exhibit oscillations, supporting optimal function defence against pathogens. Sleep deprivation disruptions challenge regulatory mechanisms, making responses vulnerable. Altered CR pathways been implicated diseases such as diabetes, neurological conditions, autoimmune (SADs). SADs involve abnormal to self-antigens, with genetic environmental factors disrupting self-tolerance contributing conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, Inflammatory Myositis. Dysregulated may lead increased production of pro-inflammatory cytokines, observed SADs. disturbances significantly quality life patients SADs; however, they are often overlooked. relationship between sleep whether causal or consequential dysregulation, remains unclear. Chrono-immunology investigates immunity, offering potential for targeted therapies conditions. This paper provides an overview connections highlighting importance recognizing need further research into complex diseases.
Language: Английский
Citations
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