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International Journal of Molecular... Mar 2023Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore,...
Skin is a major administration route for drugs, and all transdermal formulations must be tested for their capability to overcome the cutaneous barrier. Therefore, developing highly reliable skin models is crucial for preclinical studies. The current in vitro models are unable to replicate the living skin in all its complexity; thus, to date, excised human skin is considered the gold standard for in vitro permeation studies. However, skin explants have a limited life span. In an attempt to overcome this problem, we used an innovative bioreactor that allowed us to achieve good structural and functional preservation in vitro of explanted human skin for up to 72 h. This device was then used to set up an in vitro inflammatory model by applying two distinct agents mimicking either exogenous or endogenous stimuli: i.e., dithranol, inducing the contact dermatitis phenotype, and the substance P, mimicking neurogenic inflammation. Our in vitro system proved to reproduce inflammatory events observed in vivo, such as vasodilation, increased number of macrophages and mast cells, and increased cytokine secretion. This bioreactor-based system may therefore be suitably and reliably used to simulate in vitro human skin inflammation and may be foreseen as a promising tool to test the efficacy of drugs and cosmetics.
Topics: Humans; Hydrodynamics; Skin; Administration, Cutaneous; Skin Absorption; Inflammation; Pharmaceutical Preparations
PubMed: 37047256
DOI: 10.3390/ijms24076284 -
In Vivo (Athens, Greece) 2023This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIM
This study aimed to research the effects of Harkány healing water on oxidative stress. The study was performed in a randomized, placebo-controlled, double-blind setup.
PATIENTS AND METHODS
Twenty patients with psoriasis who underwent a 3-week-long inward balneotherapy-based rehabilitation were enrolled. Psoriasis Area and Severity Index (PASI) score and Malondialdehyde (MDA) - a marker of oxidative stress - were determined, on admission and before discharge. Patients were treated with dithranol.
RESULTS
The mean PASI score - determined on admission and before discharge - decreased significantly after the 3-week-long rehabilitation 8.17 vs. 3.51 (p<0.001). The baseline MDA value of patients with psoriasis was significantly higher compared to controls (3.0±3.5 vs. 8.4±7.4) (p=0.018). MDA levels of patients receiving placebo water increased significantly compared to MDA levels of patients receiving healing water (p=0.049).
CONCLUSION
The effectiveness of dithranol resides in the formation of reactive oxygen species. No increased oxidative stress was found in the patients treated with healing water, thus healing water seems to be protective against oxidative stress. However, further research is needed to confirm these preliminary results.
Topics: Humans; Pilot Projects; Anthralin; Oxidative Stress; Balneology; Psoriasis; Water
PubMed: 36881082
DOI: 10.21873/invivo.13153 -
Prague Medical Report 2023Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair... (Review)
Review
Alopecia areata is a disease of autoimmune origin which causes non scarring hair loss. The extent of alopecia varies from a small patch to complete scalp and body hair loss, which can have huge psychosocial impact for those affected. Treatment modalities which have been used so far included nonspecific immunosuppressive medications, such as corticosteroids, cyclosporine, and methotrexate, or topical immunomodulators, such as diphencyprone, dithranol, and squaric acid dibutylester. The recognition of the importance of Janus kinase pathway in alopecia areata pathogenesis enabled more specific approaches in treatment. Positive outcomes of Janus kinase inhibitors in several trials granted approval for baricitinib which became the first on-label treatment for alopecia areata. The aim of this review is to summarize the role, efficacy and safety of several Janus kinase inhibitors in alopecia areata.
Topics: Humans; Alopecia Areata; Janus Kinase Inhibitors; Janus Kinases; Adjuvants, Immunologic
PubMed: 36763827
DOI: 10.14712/23362936.2023.1 -
Molecules (Basel, Switzerland) Jan 20231,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in...
1,8-dihydroxy-9-anthrone are tricyclic compounds with a ketone group in the middle ring and two hydroxyl groups substituted in the side-aromatic rings what results in formation of two intramolecular hydrogen bonds in which the oxygen atom from the ketone group is the proton acceptor. 1,8-dihydroxy-9-anthrones in which intramolecular proton transfer between C10 and CO in the middle ring occurs, can exist in a tautomeric keto-enol equilibrium. For anthralin, the most important representative of this group, this equilibrium has been studied previously, but it has not been studied for its derivatives. Substituents in the middle ring change the geometry of 1,8-dihydroxy-9-anthrones so they are also expected to affect the keto-enol equilibrium. It is also important to study the effect of intramolecular hydrogen bonds on the structure of both tautomeric forms. It was found that the nature of the substituent in the middle ring could affect the antioxidant properties of the investigated compound.
Topics: Anthralin; Protons; Electrons; Anthracenes; Alcohols; Ketones
PubMed: 36615539
DOI: 10.3390/molecules28010344 -
NPJ Vaccines Sep 2022Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our...
Transcutaneous immunization (TCI) utilizing the TLR7 agonist imiquimod (IMQ-TCI) induces T cell-driven protective immunity upon application onto intact skin. In our present work, we combine the anti-psoriatic agent dithranol with IMQ-TCI to boost vaccination efficacy (Dithranol/IMQ-based transcutaneous vaccination (DIVA)). Using ovalbumin-derived peptides as model antigens in mice, DIVA induced superior cytolytic CD8 T cells and CD4 T cells with a T cytokine profile in the priming as well as in the memory phase. Regarding the underlying mechanisms, dithranol induced an oxidant-dependent, monocyte-attracting inflammatory milieu in the skin boosting TLR7-dependent activation of dendritic cells and macrophages leading to superior T cell priming and protective immunity in vaccinia virus infection. In conclusion, we introduce the non-invasive vaccination method DIVA to induce strong primary and memory T cell responses upon a single local treatment. This work provides relevant insights in cutaneous vaccination approaches, paving the way for clinical development in humans.
PubMed: 36153349
DOI: 10.1038/s41541-022-00530-9 -
JAMA Dermatology Oct 2022Alopecia areata (AA) is an autoimmune disorder of hair loss with a complex and evolving treatment landscape, making it an ideal setting for shared decision-making (SDM)...
IMPORTANCE
Alopecia areata (AA) is an autoimmune disorder of hair loss with a complex and evolving treatment landscape, making it an ideal setting for shared decision-making (SDM) between patients and physicians. Given the varying efficacy, experience, and risks of treatments for AA, we sought to evaluate patient preferences for SDM and the association of SDM with decisional regret.
OBJECTIVE
To evaluate patient preferences for SDM and the association of SDM with decisional regret.
DESIGN, SETTING, AND PARTICIPANTS
A cross-sectional online survey using the validated SDMQ9 scale for shared decision-making and Decisional Regret Scale (DRS) was distributed using the National Alopecia Areata Foundation (NAAF) with the aim of assessing (1) patient preferences in SDM when making treatment decisions, (2) how patients perceived the last decision to have been made, (3) which components of SDM were incorporated into the last decision, and (4) decisional regret related to their last treatment decision. The survey was distributed from July 12, 2021, to August 2, 2021, and data analysis occurred from October 2021 to March 2022.
MAIN OUTCOMES AND MEASURES
Primary outcomes included (1) patient preferences in incorporation of SDM, (2) how patients made their most recent treatment decision, (3) which components of SDM were incorporated into their most recent treatment decision measured with the validated SDMQ9, and (4) an assessment of decisional regret in relation to SDM components and the most recent treatment modality used by the patient as measured by the validated DRS.
RESULTS
Of 1387 individuals who initiated the survey, 1074 completed it and were included in the analysis (77.4% completion rate). Overall, 917 respondents were women (85.4%). There were 5 American Indian or Alaska Native respondents (0.5%), 33 were Asian (3.1%), 112 Black or African American (10.4%), 836 White (77.8%), and 36 were multiracial (3.4%) or other (36 [3.4%]). The mean age (SD) was 49.3 (15.4) years. Most respondents preferred making the final treatment decision themselves after considering their physician's opinion (503 [46.8%]). Of those who preferred to make treatment decisions using SDM, most made the last AA treatment decision with their physician (596 [55%]; 95% CI, 53%-58%; P < .001). The components of SDM implemented by the patients' dermatologists most identified were the physician "explained the advantages and disadvantages of treatment options" (472 [44%]), and the physician "asked me which treatment option I prefer" (494 [45.9%]). Incorporation of SDM by physicians was generally associated with decreased decisional regret (all ORs with 95% CIs greater than 1.1; P < .01). The treatments associated with the lowest decisional regret were Janus kinase (JAK) inhibitors, followed by biologics, and deciding not to treat; whereas, the highest decisional regret was reported with anthralin and minoxidil.
CONCLUSIONS AND RELEVANCE
The findings of this cross-sectional survey study suggest that patients with AA prefer to make treatment decisions with their dermatologist using SDM. When SDM is used, patients report less decisional regret, indicating that SDM may help improve the patient-reported quality of treatment decisions. Newer, more efficacious therapies such as JAK inhibitors may be related to lower decisional regret. Future studies should seek to devise solutions to implement SDM as the AA treatment landscape continues to evolve.
Topics: Female; Humans; Male; Middle Aged; Alopecia Areata; Anthralin; Biological Products; Cross-Sectional Studies; Decision Making; Emotions; Janus Kinase Inhibitors; Minoxidil; Patient Participation
PubMed: 35976667
DOI: 10.1001/jamadermatol.2022.3025 -
International Journal of Trichology 2022The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA).
Topical diphenylcyclopropenone plus topical 0.5% anthralin versus topical diphenylcyclopropenone alone for the treatment of chronic extensive alopecia areata: A split-scalp, double-blind, controlled study.
BACKGROUND
The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA).
OBJECTIVE
The objective of the study was to compare the efficacy of the combination therapy of topical DCP and topical 0.5% anthralin versus topical DCP alone for the treatment of chronic extensive AA.
MATERIALS AND METHODS
Ten patients were included in the study. Of these, 1, 2, and 7 patients were diagnosed with alopecia totalis, severe AA (>50% hair loss), and alopecia universalis, respectively. For each patient, one side of the scalp was treated with a DCP solution and 0.5% anthralin for 6 months, while the other side was treated with DCP and a cream base for the same duration. The clinical responses were assessed at baseline and then monthly until the end of the 6-month study period using the Severity of Alopecia Tool score. The side effects were evaluated at each follow-up visit.
RESULTS
The difference in the efficacies of the combination treatment and DCP alone was not statistically significant ( = 0.59). Regarding the side effects, DCP plus 0.5% anthralin caused significantly more excessive dermatitis than DCP alone (7 patients vs. 2 patients; = 0.02). Eight patients reported temporary hyperpigmentation at the combination-treatment site, whereas no hyperpigmentation was reported at the DCP-alone site of any patient ( < 0.001).
CONCLUSIONS
The combination of DCP and 0.5% anthralin was not superior to DCP alone for the treatment of chronic extensive AA. An increase in side effects - excessive dermatitis and hyperpigmentation - was observed in the combination-treatment group.
PubMed: 35755959
DOI: 10.4103/ijt.ijt_72_21 -
World Journal of Plastic Surgery Mar 2022A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She...
A 16-year-old female with psoriasis presented to our Plastic Surgery Department with a significant chemical burn to the neck, upper torso and left cheek (TBSA 6%). She applied a concoction of cream prescribed by her dermatologist in her native country, Poland when she returned to the United Kingdom. A few hours after application she developed a burn with pH of 5. A review of the cream revealed a mixture of 19% dithranol and 5% salicylic acid. This combination is recognized for managing psoriasis, however the strength of dithranol in the combination given is of a high concentration (normally <3%). This alone can cause a burn to the skin if left for a prolonged period of time. Salicylic acid is an enhancer which augments the stability of dithranol and increases its penetration and efficacy. The concentration of 5% is also on the higher end. Our patient was admitted for pain relief and further irrigation till normalization of the pH which was achieved after 3 days. A worrying aspect in our patients' case is that she was given the cream to commence at home. High concentration preparation is normally commenced in a controlled setting under medical supervision.
PubMed: 35592224
DOI: 10.52547/wjps.11.1.138 -
European Journal of Mass Spectrometry... Oct 2021Butyl-terminated poly(2-vinylpyridine) (P2VP), CH(CHN)H, is evaluated for use as an external and internal mass calibrant in positive-ion matrix-assisted laser...
Poly(2-vinylpyridine) as a reference compound for mass calibration in positive-ion matrix-assisted laser desorption/ionization-mass spectrometry on different instrumental platforms.
Butyl-terminated poly(2-vinylpyridine) (P2VP), CH(CHN)H, is evaluated for use as an external and internal mass calibrant in positive-ion matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). P2VP oligomers covering the 450-4500 range are employed to calibrate a time-of-flight (TOF) mass spectrometer in linear and reflector mode, an ion mobility-quadrupole-time-of-flight (IM-Q-TOF) mass spectrometer, and a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The proton affinity of P2VPs introduced by the numerous pyridyl groups leads to the almost exclusive formation of [M + H] ions with common acidic matrices like α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) as well as with the non-acidic and aprotic matrices 1,8-dihydroxy-10-anthracen-9-on (dithranol) and 2-[(2)-3-(4--butylphenyl)-2-methylprop-2-enylidene]malonitrile (DCTB). This prevalence of [M + H] ions evenly spaced at Δ() = 105.0578 renders butyl-terminated P2VP oligomers as convenient mass calibrants. The mass accuracies achieved across various ranges with different mass analyzers and modes of operation are evaluated by using established standard compounds. Results as obtained by internal or external calibration are presented. Further, the compilation of mass reference lists tailored to suit the respective analyzer modes is discussed and those reference files are provided.
PubMed: 34738841
DOI: 10.1177/14690667211055701 -
Journal of the American Academy of... Jun 2022Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist;... (Review)
Review
BACKGROUND
Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking.
OBJECTIVE
To evaluate the evidence of current treatment modalities for pediatric AA.
METHODS
We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available.
RESULTS
Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab.
LIMITATIONS
English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed.
CONCLUSION
Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.
Topics: Adolescent; Adrenal Cortex Hormones; Alopecia; Alopecia Areata; Autoimmune Diseases; Child; Humans; Janus Kinase Inhibitors; Prospective Studies
PubMed: 33940103
DOI: 10.1016/j.jaad.2021.04.077