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Transient Receptor Potential Channels and Itch
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Mahar Fatima, Jingyi Liu, Bo Duan
Contact hypersensitivity in allergic contact dermatitis is a cutaneous immune response elicited by hapten sensitization. Squaric acid dibutylester (SADBE), a small molecule hapten, is commonly used in the treatment of alopecia areata and warts but often causes contact hypersensitivity in patients. TRPV1 does not affect SADBE-mediated acute itch. By contrast, TRPV1 is a crucial mediator of chronic itch in the mouse model of SADBE-induced contact hypersensitivity. Genetic deletion of Trpv1 or pharmacological ablation of TRPV1+ sensory nerves reduces SADBE-induced persistent scratching in mice (40). Strikingly, Trpv1 deficiency promotes skin inflammation in SADBE-induced contact hypersensitivity. Furthermore, the study shows that TRPV1 modulates skin inflammation by regulating the function of dermal macrophages (40). These results indicate distinct roles of TRPV1 channels in the pathogenesis of skin inflammation and chronic itch.
Topical Contact Immunotherapy in Alopecia Areata
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Andrea Combalia, Juan Ferrando
Squaric acid dibutyl ester (SADBE) or dibutyl squarate derives from a squaric acid and is also used for treating alopecia areata through topical immunotherapy. Contact immunotherapy with SADBE is a relatively safe and effective alternative treatment, both in adult and children [11]. It acts as an ideal immunogen because it is not found in the natural environment and is not mutagenic by the Ames test, unlike other topical sensitizers such as DNCB.
Alopecia areata: Pathogenesis, clinical features, diagnosis, and management
Published in Jerry Shapiro, Nina Otberg, Hair Loss and Restoration, 2015
SADBE has been shown to be Ames-assay-negative. No mutagenic contaminants were detected on gas chromatography–mass spectrometry [267]. Furthermore, lifetime subcutaneous injections of squaric acid into ICR/Ha Swiss mice resulted in a low incidence of tumors at the injection site, equaling that of control animals [268]. SADBE is an ideal immunogen in that it is a strong topical sensitizer, it is used only rarely in industry, is not found in the natural environment, and does not react with other chemicals. However, it loses its stability in the presence of water.
Shiitake dermatitis: experience of the Poison Control Centre Network in France from 2014 to 2019
Published in Clinical Toxicology, 2022
David Boels, Chloé Greillet, Jérôme Langrand, Magali Labadie, Gaël Le Roux, Luc de Haro, Juliette Bloch, Sandra Sinno-Tellier
Nguyen et al. propose another mechanism and postulate that genetically susceptible individuals with certain human leukocyte antigen alleles require exposure to large amounts of lentinan in order to be sensitised [10]. The immunomodulating properties of lentinan have been shown to induce vasodilation and haemorrhage, skewing the immune system towards a Th1-type response [21–23]. This is also consistent with proposed mechanisms of bleomycin-induced flagellate erythema [24]. This phenomenon has been noted in the sensitisation process of individuals using squaric acid, in which a cutaneous hypersensitivity reaction has been found to be dose dependent [25]. Our study suggests a dose-dependent response which could be explained by a partial toxic mechanism, but also a th1-type hypersensitivity mechanism proposed by Nguyen et al. Experimental research as well as future investigations regarding potential genetic considerations in patients, and information on the culture conditions of shiitake (media, region), will be needed to confirm these hypotheses.
Recent advances in lipopolysaccharide-based glycoconjugate vaccines
Published in Expert Review of Vaccines, 2021
Henderson Zhu, Christine S. Rollier, Andrew J. Pollard
Squaric acid chemistry presents a relatively quick and convenient way of conjugation. The use of squaric acid chemistry was first demonstrated in the synthesis of glycoconjugates from synthetic carbohydrates [136]. To carry out conjugation via squaric acid chemistry, the carbohydrate component is linked with a monoamide to the squaric diester. The squarate intermediate can then be reacted with lysine residues in borate buffer (pH = 9) through the formation of 1,2-bisamide of the squaric acid [137].