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Journal of the American Academy of... May 2024Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study.
BACKGROUND
Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis.
OBJECTIVE
To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD).
METHODS
In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment.
RESULTS
Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole.
LIMITATIONS
Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists.
CONCLUSION
Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.
Topics: Humans; Boron Compounds; Bridged Bicyclo Compounds, Heterocyclic; Dermatitis, Atopic; Double-Blind Method; Eczema; Leg Dermatoses; Ointments; Skin; Treatment Outcome; Proof of Concept Study
PubMed: 38340127
DOI: 10.1016/j.jaad.2023.12.048 -
Biomedicine & Pharmacotherapy =... Oct 2023The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is...
The chronic disease psoriasis is associated with severe inflammation and abnormal keratinocyte propagation in the skin. Tranexamic acid (TXA), a plasmin inhibitor, is used to cure serious bleeding. We investigated whether TXA ointment mitigated Imiquimod (IMQ)-induced psoriasis-like inflammation. Furthermore, this study investigated the effect of noncytotoxic concentrations of TXA on IL-17-induced human keratinocyte (HaCaT) cells to determine the status of proliferative psoriatic keratinocytes. We found that TXA reduced IMQ-induced psoriasis-like erythema, thickness, scaling, and cumulative scores (erythema plus thickness plus scaling) on the back skin of BALB/c mice. Additionally, TXA decreased ear thickness and suppressed hyperkeratosis, hyperplasia, and inflammation of the ear epidermis in IMQ-induced BALB/c mice. Furthermore, TXA inhibited IMQ-induced splenomegaly in BALB/c mouse models. In IL-17-induced HaCaT cells, TXA inhibited ROS production and IL-8 secretion. Interestingly, TXA suppressed the IL-17-induced NFκB signaling pathway via IKK-mediated IκB degradation. TXA inhibited IL-17-induced activation of the NLRP3 inflammasome through caspase-1 and IL1β expression. TXA inhibited IL-17-induced NLRP3 inflammasome activation by enhancing autophagy, as indicated by LC3-II accumulation, p62/SQSTM1 expression, ATG4B inhibition, and Beclin-1/Bcl-2 dysregulation. Notably, TXA suppressed IL-17-induced Nrf2-mediated keratin 17 expression. N-acetylcysteine pretreatment reversed the effects of TXA on NFκB, NLRP3 inflammasomes, and the Nrf2-mediated keratin 17 pathway in IL-17-induced HaCaT cells. Results further confirmed that in the ear skin of IMQ-induced mice, psoriasis biomarkers such as NLRP3, IL1β, Nrf2, and keratin 17 expression were downregulated by TXA treatment. TXA improves IMQ-induced psoriasis-like inflammation in vivo and psoriatic keratinocytes in vitro. Tranexamic acid is a promising future treatment for psoriasis.
Topics: Humans; Animals; Mice; Interleukin-17; Tranexamic Acid; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Keratin-17; NF-E2-Related Factor 2; Psoriasis; Dermatitis; Skin; Keratinocytes; Inflammation; Imiquimod; NF-kappa B; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37573659
DOI: 10.1016/j.biopha.2023.115307 -
BioMed Research International 2024In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with...
MATERIALS AND METHODS
In a research experiment, 48 male Wistar rats were anesthetized and second-degree burns were induced on their backs. The rats' wounds were then uniformly inoculated with MRSA. Various treatments were applied to the burn wounds daily, including Myrtus ointment, silver nanoparticles, silver nanoparticles-Myrtus ointment, silver sulfadiazine-Myrtus ointment, silver sulfadiazine 1%, mupirocin ointment, and a positive control. The study measured the antimicrobial effects, wound area, percentage of wound healing, antioxidant capacities, malondialdehyde, and nitric oxide concentrations in the serum of the rats. Data analysis was performed using GraphPad software, with one-way ANOVA and Tukey's tests used to determine the statistical significance of the results.
RESULTS
Rats treated with Myrtus ointment, silver nanoparticles-Myrtus ointment, and mupirocin had reduced bacterial growth compared to the positive control group, nanoparticle ointment, and silver sulfadiazine ( < 0.05). The wound area of the Myrtus ointment group decreased significantly on the seventh and fourteenth days, as well as the level of MDA and nitric oxide, compared to the other groups. In Myrtus and silver sulfadiazine-Myrtus ointment increased the thickness of the epidermis and dermis compared to the other groups.
CONCLUSION
Based on the anti-inflammatory, antimicrobial, and wound healing properties of Myrtus, with further studies, an ointment of this plant may be used as a main or complementary treatment for burn wound infections caused by MRSA.
Topics: Animals; Wound Healing; Methicillin-Resistant Staphylococcus aureus; Burns; Plant Extracts; Male; Ointments; Rats; Rats, Wistar; Anti-Inflammatory Agents; Plant Leaves; Myrtus; Anti-Infective Agents; Wound Infection; Staphylococcal Infections; Metal Nanoparticles; Silver Sulfadiazine
PubMed: 38899039
DOI: 10.1155/2024/6758817 -
Health Technology Assessment... Oct 2023Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing.
OBJECTIVE
To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema.
DESIGN
Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks.
SETTING
Primary care (78 general practitioner surgeries) in England.
PARTICIPANTS
Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents.
INTERVENTIONS
Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked.
MAIN OUTCOME MEASURES
The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks.
RESULTS
A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study ( = 44 parents, = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial.
LIMITATIONS
Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds.
CONCLUSIONS
The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them.
FUTURE WORK
Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and 'novel' emollients.
TRIAL REGISTRATION
This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34.
FUNDING
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in ; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.
Topics: Child; Female; Humans; Male; Cost-Benefit Analysis; Dermatitis, Atopic; Eczema; Emollients; Ointments; Quality of Life; Severity of Illness Index; Child, Preschool
PubMed: 37924282
DOI: 10.3310/GZQW6681 -
Frontiers in Immunology 2023Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer....
INTRODUCTION
Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer. Previously, we reported on the combined application of the TLR7 agonist imiquimod (IMQ) together with the anti-psoriatic drug dithranol as novel TCI platform DIVA (dithranol/IMQ based vaccination). In extension of this work, we further optimized DIVA in terms of drug dose, application pattern and established a new IMQ formulation.
METHODS
C57BL/6 mice were treated on the ear skin with dithranol and IMQ-containing ointments together with ovalbumin-derived peptides. T cell responses were determined by flow cytometry and IFN-ɤ ELISpot assay, local skin inflammation was characterized by ear swelling.
RESULTS
Applying the adjuvants on separate skin sites, a reduced number of specific CD8 T cells with effector function was detectable, indicating that the local concurrence of adjuvants and peptide antigens is required for optimal vaccination. Likewise, changing the order of dithranol and IMQ resulted in an increased skin inflammatory reaction, but lower frequencies of antigen-specific CD8 T cells indicating that dithranol is essential for superior T cell priming upon DIVA. Dispersing nanocrystalline IMQ in a spreadable formulation (IMI-Sol+) facilitated storage and application rendering comparable immune responses. DIVA applied one or two weeks after the first immunization resulted in a massive increase in antigen-specific T cells and up to a ten-fold increased memory response. Finally, in a prophylactic tumor setting, double but no single DIVA treatment enabled complete control of tumor growth, resulting in full tumor protection.
DISCUSSION
Taken together, the described optimized transcutaneous vaccination method leads to the generation of a strong cellular immune response enabling the effective control of tumor growth and has the potential for clinical development as a novel non-invasive vaccination method for peptide-based cancer vaccines in humans.
Topics: Mice; Humans; Animals; Mice, Inbred C57BL; Imiquimod; Anthralin; CD8-Positive T-Lymphocytes; Immunization; Vaccination; Adjuvants, Immunologic; Neoplasms; Dermatitis
PubMed: 37727790
DOI: 10.3389/fimmu.2023.1238861 -
Gels (Basel, Switzerland) Nov 2023The purpose of this work was to develop a novel topical formulation of econazole nitrate based on gel that can be easily scaled up in one pot for the potential treatment...
The purpose of this work was to develop a novel topical formulation of econazole nitrate based on gel that can be easily scaled up in one pot for the potential treatment of fungal and yeast infections. Econazole nitrate, a topical antifungal, is used to treat tinea versicolor, tinea pedis, and tinea cruris. Compared to applying cream or ointment, topical gels offer numerous advantages, one of which is that the drug is released more quickly to the intended site of action. A viscous mixture of propylene glycol, Capmul MCM C8, methyl and propyl paraben, and econazole nitrate were mixed together before being formulated into the optimized Carbopol gel bases. The gel's color, appearance, and homogeneity were assessed visually. For every formulation, the drug content, pH, viscosity, spreadability, and gel strength were characterized. The cup plate diffusion method was used to evaluate the anti-fungal activity of the prepared formulations. To assess the behavior of the developed system, studies on in vitro release and mechanism were conducted. The manufactured formulations were transparent, pale yellow, and exhibited excellent homogeneity. The pH of each formulation was roughly 6.0, making them suitable for topical use. The concentration of Carbopol 940 resulted in a significant increase in viscosity and gel strength but a significant decrease in spreadability. It was demonstrated that the prepared formulations inhibited the growth of and . In contrast, the standard blank gel showed no signs of antifungal action. By increasing the concentration of Carbopol 940, the in vitro release profile of econazole nitrate significantly decreased. Following the Korsmeyer-Peppas model fitting, all formulations exhibited n values greater than 0.5 and less than 1, indicating that diffusion and gel swelling control econazole nitrate release.
PubMed: 38131915
DOI: 10.3390/gels9120929 -
Journal of Inflammation Research 2023Phlebitis is a common complication of intravenous administration and greatly affects clinical outcomes, patient satisfaction, and health-care expenditure. Numerous... (Review)
Review
BACKGROUND
Phlebitis is a common complication of intravenous administration and greatly affects clinical outcomes, patient satisfaction, and health-care expenditure. Numerous studies have revealed venous injuries only through visual and histopathological examination. Although sporadic studies have explored the cellular and molecular biological mechanisms of phlebitis and the outcomes of pharmacological interventions, an updated review over the last decade is not available.
METHODS
Progress in research on the mechanisms and interventions of phlebitis was summarized from the perspective of endothelial cells and signaling pathways by retrieving the PubMed, Web of Science Core Collection, MEDLINE, Embase, and CNKI.
RESULTS
Phlebitis involves multiple signaling pathways (eg, nuclear factor kappa B, Wnt/β-catenin, focal adhesion kinase/protein kinase B, Toll-like receptor, protein kinase C beta/NADPH oxidase, PI3K/AKT/TNF, and JAK2/STAT3), upregulation of E-selectin, GBP5/NLRP3 inflammasome axis, cell apoptosis, intracellular ROS generation, SOD reduction, stimulation of angiogenesis, and induction of autophagy-associated cell death. Preventive and curative interventions included α-solanine, baicalein, escin, intermedin, Y15, micro-ribonucleic acid-223, sotrastaurin, cimetidine, aescin, resveratrol, α-chaconine, Chahuang ointment, QingLuoTongMai, Mailuo Shutong, and N-acetylcysteine. Laboratory models included vascular endothelial cells, real-time cell-monitoring analysis, network pharmacology analysis and experimental verification in vivo, animal models of phlebitis (rat, rabbit, and mouse), rabbit models with peripherally inserted central catheters (PICC) catheterization, models of PICC/central venous catheter indwelling with combined drugs in human umbilical vein endothelial cells, and compatibility with endothelial cells. Factors affecting vascular endothelial cell injury include difference in the same class of drugs, concentration and exposure time of precipitant, and infusion strategy.
CONCLUSION
Phlebitis is accompanied by endothelial dysfunction and may involve multiple molecular and cellular mechanisms. These findings improve our understanding of the molecular targets of interventions and help identify effective candidates for the prophylaxis and treatment of phlebitis. Vascular health and risk management should be considered when initiating intravenous administration.
PubMed: 38170089
DOI: 10.2147/JIR.S450149 -
Journal of Clinical Medicine Jul 2023Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation....
BACKGROUND
Actinic keratosis (AK) is a cutaneous lesion resulting from the proliferation of atypical epidermal keratinocytes caused by long-term exposure to ultraviolet radiation. AK may progress to cutaneous squamous cell carcinoma (cSCC) and therefore is often treated with topical agents such as 5-fluorouracil, diclofenac, imiquimod, and photodynamic therapy. Tirbanibulin has been approved based on two phase III trials in the USA. However, real-world evidence for tirbanibulin is absent.
METHODS
This was a single-centre study of adult patients with clinically typical, visible AK on the face or scalp treated with tirbanibulin 1% ointment. Treatment was administered as per label once daily for 5 consecutive days on the same lesions or field. Treatment outcomes were assessed 4 weeks after treatment, with additional optional assessments conducted at later time points. Efficacy was measured using the actinic keratosis area and severity index (AKASI) and digital dermoscopy.
RESULTS
A total of 33 patients were treated of whom 30 were analysed. The median AKASI score was 5.6 (1.4-11) pre-treatment and 1.2 (0-7.4) post-treatment ( < 0.0001). Complete clearance as defined by AKASI scores less than 1 was achieved in 47% ( = 14) and 57% ( = 13) at the first and second follow-up, respectively. All local reactions resolved spontaneously and without sequelae. The most common local reactions were erythema (80%, = 26) and flaking or scaling (43%, = 13).
CONCLUSIONS
Tirbanibulin 1% ointment significantly and rapidly reduced the AKASI score in a real-world setting. The complete clearance rates were in line with those observed in the two pivotal trials.
PubMed: 37510952
DOI: 10.3390/jcm12144837 -
Heliyon Sep 2023Herbal extracts are a well-known source of therapeutically important bioactive chemicals since they are widely available, relatively inexpensive, and have fewer adverse...
Herbal extracts are a well-known source of therapeutically important bioactive chemicals since they are widely available, relatively inexpensive, and have fewer adverse effects. The three plants' leaves have been used to treat a variety of illnesses in Ghana, including skin conditions and wound infections. Their effectiveness as an ointment in treating the aforementioned illnesses has not yet been shown, though. The extracts were made into an ointment with polyethylene glycol (PEG), and both the ointment and the raw extracts were examined for in vitro antibacterial activity. The three (3) chosen bacterial isolates were subjected to potential activities of the plant extracts from different extractants. The minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) values for the plant extracts were both low. The herbal ointment made with extract from both extractants showed significantly different activity (P < 0.05), against the test pathogens when compared to the reference medication (Madecassol®). However, the activities of formulated herbal ointment from both and extracts were comparable at higher concentrations to the standard drug used. Notably, both plant extracts and extract-PEG manufactured ointments exhibit significant in vitro efficacy against the disease-causing bacterial species. The current study is the first in-depth account of species with regard to an examination of herbal ointments made from leaves extract obtained utilizing solvents such as water and ethanol. Our research findings have important implications for the pharmaceutical industry in terms of providing a suitable, workable, and alternative supply of bioactive compounds and anti-infective agents.
PubMed: 37681151
DOI: 10.1016/j.heliyon.2023.e19316