@article{fukuyama_martel_linder_ehling_ganchingco_baeumer_2018, title={Hypochlorous acid is antipruritic and anti-inflammatory in a mouse model of atopic dermatitis}, volume={48}, ISSN={["1365-2222"]}, DOI={10.1111/cea.13045}, abstractNote={SummaryBackgroundIt has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis; however, the specific antipruritic mechanism of action remains unclear.ObjectiveTo confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action.MethodsIn this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis‐like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow‐derived dendritic cells (mBMDCs) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively and therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application.ResultsTreatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL‐12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre‐incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl.Conclusions and Clinical RelevanceThese data indicate a direct reduction in sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.}, number={1}, journal={CLINICAL AND EXPERIMENTAL ALLERGY}, author={Fukuyama, T. and Martel, B. C. and Linder, K. E. and Ehling, S. and Ganchingco, J. R. and Baeumer, W.}, year={2018}, month={Jan}, pages={78–88} }
 @misc{fukuyama_ganchingco_mishra_olivry_rzagalinski_volmer_baeumer_2017, title={Janus kinase inhibitors display broad anti-itch properties: A possible link through the TRPV1 receptor}, volume={140}, ISSN={["1097-6825"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85013487374&partnerID=MN8TOARS}, DOI={10.1016/j.jaci.2016.12.960}, abstractNote={Janus kinase (JAK) inhibitors are being proposed for the treatment of cancer and inflammatory diseases, such as atopic dermatitis. Their mechanism of action, especially that to reduce itch, remains speculative. The JAK inhibitor oclacitinib is currently approved for the treatment of lesions and pruritus in dogs with atopic dermatitis,1,2 whereas tofacitinib is under clinical development for the treatment of the homologous human disease (https://www.clinicaltrials.gov/ct2/show/NCT02001181). In rodent and canine models of allergic dermatitis and in human patients with psoriasis and atopic dermatitis, the antipruritic effect of JAK inhibitors is rapidly visible.}, number={1}, journal={JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY}, author={Fukuyama, Tomoki and Ganchingco, Joy Rachel and Mishra, Santosh K. and Olivry, Thierry and Rzagalinski, Ignacy and Volmer, Dietrich A. and Baeumer, Wolfgang}, year={2017}, month={Jul}, pages={306-+} }
 @article{fukuyama_ganchingco_baumer_2017, title={Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib}, volume={794}, ISSN={["1879-0712"]}, DOI={10.1016/j.ejphar.2016.11.020}, abstractNote={The janus kinase-inhibitor oclacitinib is licensed for the control of pruritus associated with allergic skin diseases in dogs. Strikingly, it has been clinically reported that abrupt withdrawal of oclacitinib leads to a rebound pruritus in dogs. Therefore, the primary objective of this study was to mimic the rebound phenomenon of oclacitinib using a chronic pruritic mouse model of allergic contact dermatitis. Chronic allergic contact dermatitis was induced by repetitive toluene-2,4-diisocyanate (TDI) challenge in BALB/c mice. Oclacitinib was orally administered twice daily at 45mg/kg for 7 days, with concurrent TDI challenge, and then treatment of oclacitinib was abruptly discontinued. Scratching bouts following TDI challenge were evaluated to day 15. Additionally, dorsal root ganglia (DRG) and affected skin were isolated from mice receiving oclacitinib and from mice 24h after oclacitinib withdrawal and were used to determine pruritogen induced Ca2+ signals in sensory neurons, the number of activated dendritic cells (DCs) within DRG, and the cytokine profiles of affected skin. Mice treated with oclacitinib showed a significant decrease in scratching bouts during treatment, then following abrupt withdrawal scratching bouts were significantly increased. Furthermore, following abrupt withdrawal more DRG neurons were activated by pruritogenic cytokines, TNFα positive DCs were significantly increased, and affected skin revealed a significant increase of TNFα and TSLP. In conclusion, while oclacitinib significantly reduced itch during treatment the abrupt withdrawal led to a rapid rebound phenomenon which can be explained by an increase in pruritogenic cytokines and fast peripheral sensitization.}, journal={EUROPEAN JOURNAL OF PHARMACOLOGY}, author={Fukuyama, Tomoki and Ganchingco, Joy Rachel and Baumer, Wolfgang}, year={2017}, month={Jan}, pages={20–26} }