Stasis Dermatitis: An Overview of Its Clinical Presentation, Pathogenesis, and Management

American Journal of Clinical Dermatology, Journal Year: 2023, Volume and Issue: 24(2), P. 275 - 286

Published: Feb. 17, 2023

Stasis dermatitis is a chronic inflammatory skin disease of the lower extremities. It typically occurs in older individuals and cutaneous manifestation venous hypertension caused by reflux. Such retrograde blood flow result incompetent valves, valve destruction, or obstruction. eczematous. The associated impairment valves may cause swelling legs, leading to serious conditions including ulcerations. Diagnosis can be challenging because its clinical resemblance other poor recognition physicians. cornerstones stasis treatment are compression therapy ameliorate pain swelling, topical treatments alleviate secondary changes, interventional options correct underlying causes Given central role inflammation extremities driving changes characteristic dermatitis, new therapeutic approaches that target under evaluation patients with dermatitis. affect person for long time. affects legs people who have called insufficiency. This when person's veins difficulty sending from their limbs back heart. increased pressure inside veins. Its signs symptoms discoloration, itch, dryness, scaling similar cellulitis allergic contact Cellulitis common infection bacteria. redness, pain. Allergic an itchy rash something irritates skin. usually diagnosed after healthcare provider has looked at medical history. Treatment should treat insufficiency disease. also lesions One way reduce swelling. done applying stockings bandages. Minor surgery No been approved New ways such need developed.

Language: Английский

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Comorbidities in COPD: Current and Future Treatment Challenges

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(3), P. 743 - 743

Published: Jan. 27, 2024

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition, primarily characterized by the presence of limited airflow, due to abnormalities airways and/or alveoli, that often coexists with other chronic diseases such as cancer, cardiovascular diseases, and metabolic disorders. Comorbidities are known pose challenge in assessment effective management COPD also acknowledged have an important health economic burden. Local systemic inflammation been proposed having potential role explaining association between these comorbidities. Considering number patients expected rise, understanding mechanisms linking its comorbidities may help identify new targets for therapeutic purposes based on multi-dimensional assessments.

Language: Английский

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PDE4 inhibitors: potential protective effects in inflammation and vascular diseases

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 10, 2024

Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases. Roflumilast, apremilast, and crisaborole have been developed approved the treatment of chronic obstructive pulmonary disease psoriatic arthritis, atopic dermatitis. Inflammation underlies many vascular diseases, yet role PDE4 in these diseases remains inadequately explored. This review elucidates clinical applications anti-inflammatory mechanisms inhibitors, as well their potential protective effects on Additionally, strategies to mitigate adverse reactions discussed. article emphasizes need further exploration

Language: Английский

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The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10616 - 10616

Published: Sept. 13, 2022

Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the its respective 5'-nucleotide to control intracellular cAMP and/or cGMP levels maintain physiological state. However, many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly organs tissue failures related uncontrolled phosphorylation cascade. Among these, PDE4 represents greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular subcellular levels, allowing different fine-tuned regulations. Since 1980s, pharmaceutical companies have developed inhibitors (PDE4-I) overcome cardiovascular diseases. Since, they encountered undesired problems, (emesis), focused their research on other PDEs. Today, increases knowledge complex regulations tissues evolution drug design, resulted renewal PDE4-I development. The present review describes recent development targeting diseases, obesity, diabetes, ulcerative colitis, Crohn's disease, malignancies, fatty liver osteoporosis, depression, as well COVID-19. direct therapeutic approach extended developing allosteric protein/protein interactions act PDE interactome.

Language: Английский

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The regulatory role of PDE4B in the progression of inflammatory function study

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when are persistent, they tend trigger chronic inflammation. The presence inflammation an important component tumor microenvironment produced by variety inflammatory cells macrophages, neutrophils, leukocytes, etc.). relationship between cancer development has been widely accepted, associated with many cancers, including bronchitis lung cancer, cystitis inducing bladder cancer. Moreover, colorectitis more likely develop into colorectal Therefore, specific cellular mechanisms hot topic research. Recent studies have identified phosphodiesterase 4B (PDE4B), member (PDEs) protein family, as major cyclic AMP (cAMP) metabolizing enzyme in cells, therapeutic role PDE4B inflammation, In this review, we will present tumors potential clinical application.

Language: Английский

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Novel pharmacological approaches in abdominal aortic aneurysm

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1167 - 1194

Published: Aug. 1, 2023

Abstract Abdominal aortic aneurysm (AAA) is a severe vascular disease and major public health issue with an unmet medical need for therapy. This featured by progressive dilation of the abdominal aorta, boosted atherosclerosis, ageing, smoking as risk factors. Aneurysm growth increases rupture, life-threatening emergency high mortality rates. Despite increasing progress in our knowledge about etiopathology AAA, effective pharmacological treatment against this disorder remains elusive surgical repair still unique available therapeutic approach high-risk patients. Meanwhile, there no alternative patients small aneurysms but close surveillance. Clinical trials assessing efficacy antihypertensive agents, statins, doxycycline, or anti-platelet drugs, among others, failed to demonstrate clear benefit limiting AAA growth, while data from ongoing clinical addressing metformin on progression are eagerly awaited. Recent preclinical studies have postulated new targets strategies paving way implementation future exploring these novel strategies. review summarises some most relevant search approaches AAA.

Language: Английский

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Topical Application of a PDE4 Inhibitor Ameliorates Atopic Dermatitis through Inhibition of Basophil IL-4 Production

Journal of Investigative Dermatology, Journal Year: 2023, Volume and Issue: 144(5), P. 1048 - 1057.e8

Published: Oct. 11, 2023

Phosphodiesterase (PDE) 4 inhibitors have been approved for the treatment of atopic dermatitis (AD). However, cellular and molecular mechanisms underlying their therapeutic effect remain to be fully elucidated. Here we addressed this unsolved issue by analyzing action difamilast, a novel PDE4 inhibitor, on an oxazolone (OX)-induced skin allergic inflammation commonly used as mouse model AD. Topical application difamilast ameliorated in association with reduced IL-4 expression even when commenced days after initiation OX challenge, showing its IL-4-deficient mice displayed milder than did WT mice, had little or no further effect. This was also case depleted basophils, predominant producers lesion, suggesting that may act basophils. Of note, basophils accumulating lesion showed highly upregulated Pde4b encoding B subtype family. Difamilast suppressed production from activated vitro, at least part, through inhibition ERK phosphorylation. Taken together, appeared ameliorate AD suppression basophil lesion.

Language: Английский

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Targeting PDE4A for therapeutic potential: exploiting drug repurposing approach through virtual screening and molecular dynamics

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Jan. 29, 2024

cAMP-specific 3′,5′-cyclic phosphodiesterase 4 A (PDE4A) holds a pivotal role in modulating intracellular levels of cyclic adenosine monophosphate (cAMP). Targeting PDE4A with novel therapeutic agents shows promise addressing neurological disorders (e.g. Alzheimer's and Parkinson's diseases), mood (depression, anxiety), inflammatory conditions (asthma, chronic obstructive pulmonary disease), even cancer. In this study, we present comprehensive approach that integrates virtual screening molecular dynamics (MD) simulations to identify potential inhibitors from the existing pool FDA-approved drugs. The initial compound selection was conducted focusing on binding affinity scores, which led identification several high-affinity compounds properties. From refined process, two promising compounds, Fluspirilene Dihydroergocristine, emerged as strong candidates, displaying substantial specificity for site. Interaction analysis provided robust evidence their capabilities. To gain deeper insights into dynamic behavior Dihydroergocristine complex PDE4A, 300 ns MD simulations, principal components (PCA), free energy landscape (FEL) analysis. These analyses revealed stabilized structure induced minimal conformational changes, highlighting potent binders. conclusion, our study systematically explores repurposing drugs through pipeline. identified exhibit characteristics support suitability further development associated dysfunction.

Language: Английский

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Artesunate inhibits PDE4 leading to intracellular cAMP accumulation, reduced ERK/MAPK signaling, and blockade of influenza A virus vRNP nuclear export

Antiviral Research, Journal Year: 2023, Volume and Issue: 215, P. 105635 - 105635

Published: May 15, 2023

Language: Английский

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Narrative Review of the Pathogenesis of Stasis Dermatitis: An Inflammatory Skin Manifestation of Venous Hypertension

Dermatology and Therapy, Journal Year: 2023, Volume and Issue: 13(4), P. 935 - 950

Published: March 22, 2023

Stasis dermatitis (SD), also known as venous dermatitis, is a form of inflammatory the lower extremities that typically occurs in older individuals and represents cutaneous manifestation hypertension. Venous hypertension (also sustained ambulatory pressure) most often due to retrograde blood flow, which calf muscle pump failure. This failure commonly secondary incompetent valves, valve destruction, or obstruction system. Many common symptoms associated with SD are caused by processes. review summarizes pathogenesis key role inflammation reviewing biomarkers SD. The literature was selected though high-level PubMed search focusing on keywords relating reflux at causes hypertension, leads chronic insufficiency. High pressure promotes local accumulation extravasation cells across vascular endothelium. Leukocyte trapping microcirculation perivascular space trophic skin changes. Cell adhesion molecules linked perpetuated influx activated leukocytes into sites. Here, may influence remodeling extracellular matrix inducing secretion proteinases such metalloproteinases (MMPs). increased expression MMPs formation leg ulcers lesions. Phosphodiesterase 4 activity has been shown be elevated dermatoses compared healthy individuals. Because driver signs SD, several highlighted represent potential opportunities target interrupt molecular pathways and, therefore, remediate Understanding help clinicians identify drivers use targets for development new treatment options. disease affects legs, people, Chronic insufficiency when veins cannot return from legs back heart. high those flow backwards. If stasis left untreated, complications, including ulcers, can result. Other include itchiness, scaling, discoloration. Such have negative effect person's quality life. Inflammation lasts long time likely main link between changes seen people veins. Several observed white cells, metalloproteinases, phosphodiesterase 4, interleukin-31. Treatment should focus both underlying issues. Identifying markers could treat symptoms.

Language: Английский

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