J. Lenn

INTRODUCTION/PURPOSE: Fish oils (FO) have been shown to modulate the inflammatory response through alteration of the eicosanoid pathway. Isoflavones (ISO) appear to reduce the inflammatory pathway through their role as a tyrosine kinase inhibitor. Delayed onset muscle soreness (DOMS) develops after intense exercise and has been associated with an inflammatory response. Therefore, we hypothesized that physical parameters associated with DOMS could be decreased via the modulation of the inflammatory response by supplementing subjects with either FO or ISO. METHODS: 22 subjects were recruited and randomly assigned to one of three treatment groups: FO (1.8 g of omega-3 fatty acids x d(-1)), ISO (120 mg soy isolate x d(-1)), or placebo (PL) (Western fat blend and/or wheat flour). All treatment groups received 100-IU vitamin E x d(-1) to minimize lipid peroxidation of more highly unsaturated fatty acids. Subjects were supplemented 30 d before the exercise and during the week of testing and were instructed to refrain from unusual exercise. DOMS was induced by 50 maximal isokinetic eccentric elbow flexion contractions. Strength parameters, pain, arm circumference, and relaxed arm angle (RANG) were measured at 48, 72, and 168 h post exercise. Cortisol, creatine kinase (CK), interleukin-6 (IL-6), tumor necrosis factor (TNFalpha), malondialdehyde (MDA), and serum iron were measured before supplementation, after supplementation, and post exercise. RESULTS: Significant decreases were observed in RANG and strength 48 h postexercise among all groups, and there were significant increases in pain and arm circumference. There were no significant changes among all groups from baseline at 168 h (7 d) post exercise. There were no significant treatment effects between groups for the physical parameters or for cortisol, CK, IL-6, TNFalpha, MDA, or serum iron. CONCLUSION: These data indicate FO or ISO, at the doses supplemented, were not effective in ameliorating DOMS with the above-cited protocol.

To the Editor: Atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous lesions and pruritus, is prevalent worldwide.1Weidinger S. Beck L.A. Bieber T. et al.Atopic dermatitis.Nat Rev Dis Primers. 2018; 4: 1Crossref PubMed Scopus (209) Google Scholar Crisaborole ointment 2% is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate AD.2Eucrisa [package insert]. Pfizer Labs, New York, NY2017Google Scholar Although moisturizers are often used in combination with topical therapies to reduce xerosis and aid in skin barrier repair,3Eichenfield L.F. Tom W.L. Berger T.G. et al.Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.J Am Acad Dermatol. 2014; 71: 116-132Abstract Full Text Full Text PDF PubMed Scopus (711) Google Scholar their effect on topical drug permeation and penetration when coapplied is not well understood. The objective of this study was to assess the effect of over-the-counter (OTC) cream and ointment moisturizers on the permeation and penetration of crisaborole. Crisaborole was applied (10 mg/cm2) to ex vivo healthy abdominal human skin (3 donors, 4 replicates, sliced to a thickness of 500 ± 50 μm with a dermatome) either alone, 15 minutes before, immediately after, or 15 minutes after application of OTC cream (Cetaphil; Galderma Inc, Baie d'Urfé, Montréal, Canada) or OTC ointment (Aquaphor; Beiersdorf Inc, Wilton, CT). The skin was mounted in a flow-through diffusion cell, and the receptor solution (phosphate-buffered saline) was collected at 2-hour intervals up to 24 hours. The amount of crisaborole delivered into the skin and through the skin into the receptor solution was determined by liquid chromatography–tandem mass spectrometry. When crisaborole was applied 15 minutes before either OTC cream or ointment, there were no statistical differences in the concentration of crisaborole in the receptor solution or the dermis (Figs 1 and 2). However, when crisaborole was applied immediately after OTC cream, the concentration of crisaborole was significantly decreased by approximately 3-fold in the receptor solution (Fig 1, A) and 2-fold in the dermis (Fig 2, A) compared with crisaborole alone (P < .05 for both). Similar results were observed for the epidermis. Application of crisaborole 15 minutes after OTC cream resulted in no statistical difference in the concentration of crisaborole in the receptor solution (Fig 1, A) or in the epidermis and dermis (Fig 2, A). When crisaborole was applied immediately after OTC ointment, there was no statistical difference in the concentration of crisaborole in the receptor solution (Fig 1, B) or in the epidermis and dermis (Fig 2, B). However, when crisaborole was applied 15 minutes after OTC ointment, the concentration of crisaborole decreased by approximately 2-fold in both the receptor solution (Fig 1, B) and the epidermis (Fig 2, B) (P < .05 for both).Fig 2Mean concentration of crisaborole recovered from epidermis and dermis 24 hours after application alone, 15 minutes before, immediately after, and 15 minutes after application of (A) OTC cream and (B) OTC ointment. ∗P < .05 versus crisaborole alone. OTC, Over the counter.View Large Image Figure ViewerDownload Hi-res image Download (PPT) There are limited data regarding the effect of coapplication of moisturizers and topical treatments.4Del Rosso J.Q. Lehman P.A. Raney S.G. Impact of order of application of moisturizers on percutaneous absorption kinetics: evaluation of sequential application of moisturizer lotions and azelaic acid gel 15% using a human skin model.Cutis. 2009; 83: 119-124PubMed Google Scholar,5Ng S.Y. Begum S. Chong S.Y. Does order of application of emollient and topical corticosteroids make a difference in the severity of atopic eczema in children?.Pediatr Dermatol. 2016; 33: 160-164Crossref PubMed Scopus (11) Google Scholar Here, we show, using an ex vivo model, that the time between applications can affect drug penetration and permeation. The current findings in an ex vivo model suggest that crisaborole should be applied at least 15 minutes before OTC ointments and creams to minimize the impact on dermal absorption of crisaborole. The current study was limited by the use of ex vivo skin from patients without AD, although this approach is a suitable tool for demonstrating the bioequivalence of topical dosage forms.6European Medicines AgencyDraft guideline on quality and equivalence of topical products.https://www.ema.europa.eu/en/documents/scientific-guideline/draft-guideline-quality-equivalence-topical-products_en.pdfDate: 2018Date accessed: August 21, 2019Google Scholar,7Raney S.G. Franz T.J. Lehman P.A. et al.Pharmacokinetics-based approaches for bioequivalence evaluation of topical dermatological drug products.Clin Pharmacokinet. 2015; 54: 1095-1106Crossref PubMed Scopus (53) Google Scholar The relationship between the results in this ex vivo study and clinical efficacy, as well as the applicability to other OTC moisturizer formulations, requires further investigation.