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FASEB Journal : Official Publication of... Jun 2023Antenatal glucocorticoids accelerate fetal lung maturation and reduce mortality in preterm babies but can trigger adverse effects on the cardiovascular system. The...
Antenatal glucocorticoids accelerate fetal lung maturation and reduce mortality in preterm babies but can trigger adverse effects on the cardiovascular system. The mechanisms underlying off-target effects of the synthetic glucocorticoids mostly used, Dexamethasone (Dex) and Betamethasone (Beta), are unknown. We investigated effects of Dex and Beta on cardiovascular structure and function, and underlying molecular mechanism using the chicken embryo, an established model system to isolate effects of therapy on the developing heart and vasculature, independent of effects on the mother or placenta. Fertilized eggs were treated with Dex (0.1 mg kg ), Beta (0.1 mg kg ), or water vehicle (Control) on embryonic day 14 (E14, term = 21 days). At E19, biometry, cardiovascular function, stereological, and molecular analyses were determined. Both glucocorticoids promoted growth restriction, with Beta being more severe. Beta compared with Dex induced greater cardiac diastolic dysfunction and also impaired systolic function. While Dex triggered cardiomyocyte hypertrophy, Beta promoted a decrease in cardiomyocyte number. Molecular changes of Dex on the developing heart included oxidative stress, activation of p38, and cleaved caspase 3. In contrast, impaired GR downregulation, activation of p53, p16, and MKK3 coupled with CDK2 transcriptional repression linked the effects of Beta on cardiomyocyte senescence. Beta but not Dex impaired NO-dependent relaxation of peripheral resistance arteries. Beta diminished contractile responses to potassium and phenylephrine, but Dex enhanced peripheral constrictor reactivity to endothelin-1. We conclude that Dex and Beta have direct differential detrimental effects on the developing cardiovascular system.
Topics: Chick Embryo; Female; Pregnancy; Animals; Betamethasone; Glucocorticoids; Heart; Arteries; Dexamethasone
PubMed: 37132324
DOI: 10.1096/fj.202200676RR -
BMC Oral Health Oct 2023Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any treatment for RAS and there remains a need for longitudinal randomised clinical trials to evaluate and compare the effectiveness of different therapies in the management of RAS. The aim of the current project was to assess the efficacy of betamethasone mouthwash and colchicine tablets, individually and combined, for the treatment of RAS, and to establish the optimum treatment period necessary for a significant reduction in the disease severity.
METHODOLOGY
A randomised, prospective, parallel-group clinical trial was conducted over one year, to compare the efficacy of three therapies in RAS. One hundred and six patients were randomized into three groups; 35 received betamethasone mouthwash, 35 had colchicine tablets and 36 received both therapies. The response was evaluated quantitatively every 3 months for 1 year, using the Ulcer Severity Score (USS).
RESULTS
For all three treatment regimes, the mean USS decreased by about 30% in the first 3 months (p < 0.001). Further improvement was noted for up to 9 months. At the end of the study, the mean USS had improved by 50% from 34.9 ± 7.2 before treatment to 17.5 ± 8.9 after treatment (p < 0.001). Of included participants, 86% showed significant clinical improvement by the end of the study. There were no significant differences in outcomes between the three regimes (p < 0.05).
CONCLUSIONS
This clinical trial has provided evidence for the efficacy of betamethasone mouthwash and for colchicine tablets in the treatment of RAS and has shown that at least six months of treatment may be required for optimum effect.
CLINICAL TRIAL REGISTRATION NUMBER
ISRCTN3267716. Date of clinical trial registration: 15/04/2018.
Topics: Humans; Stomatitis, Aphthous; Colchicine; Mouthwashes; Prospective Studies; Betamethasone
PubMed: 37789351
DOI: 10.1186/s12903-023-03335-x -
The Journal of Dermatological Treatment Dec 2023Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical...
BACKGROUND
Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown.
METHOD
We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay.
RESULTS
We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline ( < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs ( < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets.
CONCLUSION
In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.
Topics: Humans; Proteomics; Psoriasis; Betamethasone; Biomarkers; Computational Biology
PubMed: 37621164
DOI: 10.1080/09546634.2023.2248318 -
Pharmaceuticals (Basel, Switzerland) Sep 2023Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid...
Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient's adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.
PubMed: 37765130
DOI: 10.3390/ph16091322 -
Dermatology and Therapy Oct 2023Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol... (Review)
Review
Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) represents the first-line choice in topical psoriasis treatment. A CAL/BDP cream based on polyaphron dispersion (PAD) Technology has emerged as a novel formulation for a more convenient topical treatment of psoriasis. This article aims to summarize the most relevant published evidence about CAL/BDP PAD-cream and its underlying PAD Technology. The PAD Technology enables CAL and BDP stability in an aqueous cream through a multimolecular shell structure, as well as it increases the penetration of both active ingredients into the epidermis and dermis. This technology also demonstrated to increase the cosmetic acceptability and to provide the desirable sensory properties for a topical psoriasis treatment. Two phase III clinical trials have been conducted so far with CAL/BDP PAD-cream. Findings from both trials revealed high efficacy with a fast onset of action, a favourable safety and tolerability profile and convenience for CAL/BDP PAD-cream compared to CAL/BDP gel. In the trial including patients with psoriasis affecting the scalp (MC2-01-C7), results support the use of CAL/BDP PAD-cream in scalp psoriasis. An anchored matching-adjusted indirect comparison (MAIC) was conducted to compare CAL/BDP PAD-cream and CAL/BDP foam, as both products had been previously compared to CAL/BDP gel. CAL/BDP PAD-cream and CAL/BDP foam showed equivalent efficacy and quality of life at their recommended treatment duration, whereas greater treatment satisfaction for CAL/BDP PAD-cream was found after one week of treatment. Overall, the high patient acceptability and treatment satisfaction observed with CAL/BDP PAD-cream in clinical trials may lead to improved adherence and hence higher efficacy in clinical practice.
PubMed: 37740858
DOI: 10.1007/s13555-023-01003-0 -
Inflammopharmacology Oct 2023Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional...
Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-β1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-β1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-β1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-β1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-β1 and improved mouth opening in OSF rat model.
Topics: Humans; Animals; Rats; Oral Submucous Fibrosis; Transforming Growth Factor beta1; Polyphenols; Collagen; Hydrogels
PubMed: 37106237
DOI: 10.1007/s10787-023-01212-1 -
Dermatology and Therapy Nov 2023Several comprehensive and updated guidelines are available on the management of psoriasis with systemic treatments. However, there is a lack of updates in... (Review)
Review
Several comprehensive and updated guidelines are available on the management of psoriasis with systemic treatments. However, there is a lack of updates in recommendations and guidelines on topical treatments, particularly regarding the latest evidence and developments in treatment formulations. Consequently, a comprehensive literature review on this topic, considering the continuous evolution of knowledge and evaluation of the relevance of the available literature evidence, represents a current need to improve the topical management of psoriasis. This study critically appraises the available literature on all topical treatments of psoriasis from the past 20 years to address some relevant issues, such as the vehicle associated with the highest effectiveness, the best vehicle for improving patient adherence, and the best strategy in terms of efficacy and safety for long-term treatment. The greater effectiveness of the foam formulation was demonstrated for calcipotriene/betamethasone dipropionate (Cal/BD) administration compared with the gel and ointment. Without a direct comparison, matching-adjusted indirect comparison analyses support the superiority of the foam versus the cream overall. In addition, the reduced treatment period required by the Cal/BD foam (4 weeks) may favor this formulation over cream (8 weeks). The literature evidence, supported by a broad clinical experience, reported high rates of acceptability and adherence for the foam vehicle. A growing consensus is shared among dermatologists sustaining the proactive approach as the best option for the long-term topical treatment of psoriasis in adults. The Cal/BD foam is the only treatment for which the approved label allows biweekly maintenance use (proactive management), thus representing the first option for long-term topical treatment.
PubMed: 37737941
DOI: 10.1007/s13555-023-01024-9 -
Lasers in Medical Science Jan 2024The purpose of this review is to consolidate and summarize laser-assisted drug delivery (LADD) for nail diseases, particularly onychomycosis and psoriasis. A PubMed... (Review)
Review
The purpose of this review is to consolidate and summarize laser-assisted drug delivery (LADD) for nail diseases, particularly onychomycosis and psoriasis. A PubMed search was conducted in June 2023 using search terms (1) "laser assisted drug delivery" AND "nail," (2) "laser" AND "nail," and (3) "nail disorder" AND "laser treatment." References of papers were also reviewed, yielding 15 papers for this review. Fractional ablative CO laser (FACL) and Er:YAG laser can be used for LADD of topical medications such as amorolfine, terbinafine, and tioconazole to treat onychomycosis. A fungal culture should be performed to determine the type of dermatophyte, which will help determine which topical will be most effective. Laser settings varied between studies, but overall LADD tended to be more effective than topical treatments alone. Laser-assisted photodynamic therapy (PDT) was also found to be effective in treating onychomycosis. For psoriatic nails, LADD was used to deliver calcipotriol-betamethasone dipropionate foam, tazarotene, triamcinolone, or methotrexate into the nail. Again, LADD was found to be significantly more effective than topical treatment alone. FACL was the only laser noted for use for LADD in both diseases. Laser-assisted drug delivery for nail disease is a newer approach for onychomycosis and nail psoriasis with several benefits and drawbacks. Dermatologists should discuss the option of LADD with their patients who have recalcitrant onychomycosis or nail psoriasis.
Topics: Humans; Onychomycosis; Pharmaceutical Preparations; Antifungal Agents; Nail Diseases; Psoriasis; Administration, Topical; Lasers, Gas; Treatment Outcome
PubMed: 38240827
DOI: 10.1007/s10103-024-03992-6 -
Dermatology Practical & Conceptual Oct 2023Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body... (Review)
Review
INTRODUCTION
Alopecia areata (AA) is a common, non-scarring, autoimmune hair loss disorder, varying in severity from small round hairless patches to the total loss of scalp or body hair. As steroid pulse therapy outcomes for AA vary, this study aimed to review the related literature regarding the efficacy, relapse rates, side effects, and prognostic factors associated with the response to different pulse corticosteroid treatments.
METHODS
We performed a literature search on August 29, 2022, to provide an overview of the efficacy of pulse steroid therapy in patients with AA. The terms "pulse steroid therapy AND alopecia areata" and "pulse corticosteroid therapy AND alopecia areata" were searched on PubMed and Google Scholar.
RESULTS
A total of 24 articles were assessed. There was no difference in outcomes and side effects between intravenous and oral pulse corticosteroid therapy. The relapse rate and efficacy depended on the time of AA onset, age, and AA type: improved outcomes and decreased relapse were linked with recent onset (<6 months), a younger age (<10 years), and the multifocal type of AA. Patients with a past medical history of atopy, nail pitting, or thyroid disease and those with severe forms of AA like alopecia totalis and alopecia universalis had the least improvement.
CONCLUSIONS
All kinds of mentioned systemic pulse corticosteroids effectively induce hair regrowth in AA. Betamethasone pulse seems to be the most effective agent (followed by intramuscular triamcinolone), especially in severe cases, but more side effects may accompany it. Combining this agent with other medications can reduce the dosage and side effects. Pulses of prednisolone and methylprednisolone are less effective but safer, as they have low relapse rates and adverse effects. A combination of them with other drugs can increase their efficacy.
PubMed: 37992355
DOI: 10.5826/dpc.1304a255