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The Journal of Dermatological Treatment Dec 2024Dupilumab is a novel treatment agent for moderate to severe atopic dermatitis (AD) with few adverse effects. Drug-induced psoriasiform lesions are rare. We report a...
Dupilumab is a novel treatment agent for moderate to severe atopic dermatitis (AD) with few adverse effects. Drug-induced psoriasiform lesions are rare. We report a 4-year-old boy with AD who developed pustular psoriasis during treatment with dupilumab. Pustular psoriasis appeared within 1 week of treatment and worsened in the second week. After stopping dupilumab administration, topical corticosteroids (desonide and mometasone furoate creams) and oral desloratadine without relief. Pustular psoriasis was confirmed by pathological examination, and thiamphenicol was administered. After 2 weeks of treatment, the lesions nearly resolved without recurrence in 1-year follow-up. Dupilumab-induced pustular psoriasis is rare in children.
Topics: Humans; Male; Psoriasis; Antibodies, Monoclonal, Humanized; Child, Preschool; Dermatitis, Atopic; Mometasone Furoate; Dermatologic Agents
PubMed: 38839072
DOI: 10.1080/09546634.2024.2333016 -
Traffic (Copenhagen, Denmark) Jan 2024Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated...
Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK-293 cells overexpressing NLGN3 of 2662 compounds (FDA-approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full-length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK-293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock-in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism-linked mutation affecting cell surface trafficking of a synaptic protein.
Topics: Animals; Humans; Mice; Autism Spectrum Disorder; Glucocorticoids; HEK293 Cells; Membrane Proteins; Synapses
PubMed: 38272450
DOI: 10.1111/tra.12930 -
Se Pu = Chinese Journal of... Dec 2023Glucocorticoids, which are a class of steroidal hormones secreted by the adrenal cortex, have significant anti-inflammatory, immunosuppressive, and anti-allergic...
Glucocorticoids, which are a class of steroidal hormones secreted by the adrenal cortex, have significant anti-inflammatory, immunosuppressive, and anti-allergic effects. Thus, these compounds are widely used in clinical practice. However, the long-term use of cosmetics containing glucocorticoids can lead to serious consequences, such as hormone-dependent dermatitis, hypertension, and other serious injuries. The Safety and Technical Specification for Cosmetics (2015 edition) and Regulation (EC) No. 1223/2009 of the European Parliament and Council on cosmetic products list glucocorticoids as prohibited raw materials. According to the National Medical Products Administration, reports on the illegal addition of glucocorticoids to cosmetics by manufacturers have increased in recent years. Therefore, establishing high-throughput screening methods to ensure the quality and safety of cosmetics is imperative. In this study, a comprehensive analytical method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the rapid screening of 83 glucocorticoids in cosmetics. A series of conditions were optimized using three matrices that are commonly used in cosmetics: water, lotion, and cream (o/w-type). Four mobile-phase systems and three chromatographic columns were then optimized to achieve the best separation effects. Various MS parameters, such as the capillary voltages, cone voltages, desolvation gas flow rates, and collision energies of the ion pairs of the target compounds, were also optimized. Furthermore, pretreatment was essential for glucocorticoid determination owing to the complex matrix effects of cosmetics. The analytes were divided into two groups, with lg =4 as the limit, to compare the effects of the extraction solvent on recoveries. The extraction recoveries of target analytes with six extraction methods, namely, extraction with acetonitrile, extraction with acetone, extraction with ethyl acetate, dispersion in saturated sodium chloride solution followed by extraction with acetonitrile, dispersion in saturated sodium chloride solution followed by extraction with acetone, and dispersion in saturated sodium chloride solution followed by extraction with ethyl acetate, were compared. The recoveries from QuEChERS and solid-phase extraction (SPE) purification were also compared. Based on the experimental results, the final sample pretreatment method included acetonitrile vortex dispersion, ultrasonic extraction, and sample loading after filtration. The 83 target compounds were separated on a Thermo Accucore PFP column (100 mm×2.1 mm, 2.6 μm) with 0.1% (v/v) acetic acid in acetonitrile and 0.1% (v/v) acetic acid in water as the mobile phases. The analytes were determined by dynamic multiple-reaction monitoring (MRM) in electrospray positive ionization mode (ESI) and quantified using the external standard method. Matrix standard curves were used to reduce matrix effects. The calibration curves of the 83 target compounds were linear in the mass concentration range of 2-200 μg/L (>0.995). At three levels of addition, the recoveries were 74.5%-112.4%, and the relative standard deviations (RSDs, =6) were 0.8%-9.9%. The limits of detection (LODs, ≥3) were 0.001-0.023 μg/g, and the limits of quantification (LOQs, ≥10) were 0.002-0.076 μg/g. The developed method was used to detect glucocorticoids in 41 cosmetic samples. Fluocinolone acetonide, beclomethasone dipropionate, desonide 21-acetate, and desonide were detected in four samples. The content range of glucocorticoids in the positive samples was 0.53-634.27 μg/g. Notably, desonide 21-acetate, which is not included in the scope of the statutory detection method, was detected in two batches of samples. In conclusion, the proposed method is simple, sensitive, reliable, and suitable for the high-throughput analysis of the 83 glucocorticoids in cosmetics with different matrices. This method could provide reliable technical support for the daily supervision of cosmetics and serve as a supplement to current glucocorticoid standards.
Topics: Glucocorticoids; Acetone; Chromatography, High Pressure Liquid; Chromatography, Liquid; Desonide; Sodium Chloride; Tandem Mass Spectrometry; Acetic Acid; Acetonitriles; Water; Cosmetics; Solid Phase Extraction
PubMed: 38093538
DOI: 10.3724/SP.J.1123.2023.04009 -
Clinical and Molecular Allergy : CMA Nov 2022Food allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still...
BACKGROUND
Food allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still develops frequent, persistent, and difficult to treat hives (FPDTH) for which there is no curative therapy. Although these cases are rare, these patients are in most need of therapy.
CASE PRESENTATIONS
This is a retrospective review of 3 pediatric patients with highly sensitive food allergies who initially presented with hives daily or every other day, or multiple times a day, but achieved marked remission after traditional Chinese medicine (TCM) therapies. Patient 1 (P1) is a 5-year-old who has experienced 140 reactions in his lifetime. Reactions were mostly hives with 4 episodes of anaphylaxis. P1 had used Prednisone 20 times, had an Epinephrine injection 4 times, and had 3 emergency room (ER) visits. Patient 2 (P2) is a 12-year-old who had experienced hives since age 3. Despite daily antihistamine use, P2 had > 730 reactions in his lifetime at the time of presentation including 2 episodes of anaphylaxis. He had been prescribed prednisone 4 times, an Epinephrine injection 2 times, and had 1 ER visit. Patient 3 (P3) is a 20-month-old girl who had experienced > 120 reactions including 1 episode of anaphylaxis. She was on daily desonide and frequently used an antihistamine, yet still had required a course of prednisone once, an Epinephrine injection once, and had 1 ER visit to manage her reaction. After presenting to our clinic, patients received internal and external TCM treatments, including herbal baths and creams (Remedy A-D) as basic remedies to reduce food reactions, including but not limited to frequent hives. Within 7-9 months of TCM treatment, remarkably all patients had complete remission of atopic symptoms. All three patients also experienced an improvement in other conditions including food intolerance, diarrhea, anxiety, eczema, and environmental allergies. After 1 year of treatment, all three patients had reductions in food-specific IgE levels that had been previously elevated, and additionally, P1 and P3, who initially had high total IgE levels, experienced a marked decrease in total IgE levels as well. All three patients continued to introduce foods into their diet that they previously had reactions to, and all 3 patients remain symptom-free.
CONCLUSIONS
Three pediatric patients with a known history of multiple food sensitivities and physician-diagnosed food allergies that presented with FPDTH underwent a TCM regimen and experienced dramatic improvement in symptoms and reduction in their IgE levels. This regimen appears to be effective in FPDTH population although a further study in a controlled clinical setting is required.
PubMed: 36434719
DOI: 10.1186/s12948-022-00175-y -
BioMed Research International 2022A topological index is a real number derived from the structure of a chemical graph. It is helpful to determine the physicochemical and biological properties of a wide...
A topological index is a real number derived from the structure of a chemical graph. It is helpful to determine the physicochemical and biological properties of a wide range of drugs, and it better reflects the theoretical properties of organic compounds. This is accomplished using degree-based topological indices. Vitiligo is a common, acquired skin pigmentation disorder that significantly impacts the quality of life. It frequently embodies a therapeutic challenge, resulting in interest in alternative treatments based on vitamin and herbal supplements. In this article, azathioprine, clobetasol, desonide, hydrocortisone valerate, and other drugs utilized to cure vitiligo have discoursed, and the goal of QSPR revision is to determine the mathematical relationship between properties under investigation (e.g., polarity and enthalpy) and diverse descriptors associated with the drugs' molecule. The QSPR model will help to predict physical properties. In this study, topological indices (TIs) imposed on said drugs were found to have a good correlation with physicochemical properties in this course. Finally, this work can be helpful to design and synthesize new vitiligo treatments and other disease drugs.
Topics: Humans; Vitiligo; Quantitative Structure-Activity Relationship; Quality of Life; Autoimmune Diseases; Restraint, Physical
PubMed: 36425334
DOI: 10.1155/2022/6045066 -
Proceedings of the National Academy of... Mar 2022Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders...
Identifying inhibitors of pathogenic proteins is the major strategy of targeted drug discoveries. This strategy meets challenges in targeting neurodegenerative disorders such as Huntington’s disease (HD), which is mainly caused by the mutant huntingtin protein (mHTT), an “undruggable” pathogenic protein with unknown functions. We hypothesized that some of the chemical binders of mHTT may change its conformation and/or stability to suppress its downstream toxicity, functioning similarly to an “inhibitor” under a broader definition. We identified 21 potential mHTT selective binders through a small-molecule microarray–based screening. We further tested these compounds using secondary phenotypic screens for their effects on mHTT-induced toxicity and revealed four potential mHTT-binding compounds that may rescue HD-relevant phenotypes. Among them, a Food and Drug Administration–approved drug, desonide, was capable of suppressing mHTT toxicity in HD cellular and animal models by destabilizing mHTT through enhancing its polyubiquitination at the K6 site. Our study reveals the therapeutic potential of desonide for HD treatment and provides the proof of principle for a drug discovery pipeline: target-binder screens followed by phenotypic validation and mechanistic studies.
Topics: Animals; Desonide; Disease Models, Animal; Huntingtin Protein; Huntington Disease; Mice; Mice, Transgenic; Mutation; Protein Stability
PubMed: 35238684
DOI: 10.1073/pnas.2114303119 -
Contact Dermatitis Aug 2020
Topics: Anti-Inflammatory Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Dermatitis, Allergic Contact; Desonide; Facial Dermatoses; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Isocyanates; Loratadine; Masks; Pandemics; Patch Tests; Pneumonia, Viral; SARS-CoV-2; Young Adult
PubMed: 32390190
DOI: 10.1111/cod.13599 -
JAMA Dermatology Jul 2020This cohort study uses data from a medical record review of a dermatogynecology practice to describe the association between reduced recurrence of vulvar squamous cell...
This cohort study uses data from a medical record review of a dermatogynecology practice to describe the association between reduced recurrence of vulvar squamous cell carcinoma and use of topical corticosteroids in the treatment of vulvar lichen sclerosus.
Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Betamethasone; Carcinoma in Situ; Carcinoma, Squamous Cell; Clobetasol; Desonide; Female; Humans; Hydrocortisone; Methylprednisolone; Middle Aged; Neoplasm Recurrence, Local; Vulvar Lichen Sclerosus; Vulvar Neoplasms
PubMed: 32374363
DOI: 10.1001/jamadermatol.2020.1074 -
Indian Journal of Dermatology 2020A 50-year-old woman had suffered from chronic pruritic plaque located on right retroauricular area for around 16 years, which was diagnosed as lichen simplex chronicus....
A 50-year-old woman had suffered from chronic pruritic plaque located on right retroauricular area for around 16 years, which was diagnosed as lichen simplex chronicus. Seventeen years ago, patient had multiple scalded areas distributed throughout the body and underwent autologous skin flap transplantation for the right retroauricular wound. After the wound healed, patient started experiencing paresthesia continuously on the skin grafted area and could not resist scratching. To our knowledge, this is the first reported case of lichen simplex chronicus secondary to scald injury and skin flap transplantation. We successfully treated this patient with dyclonine hydrochloride cream 1% and desonide cream 0.05%.
PubMed: 32029940
DOI: 10.4103/ijd.IJD_88_19