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      Antifungal Effects of Bee Venom Components on Trichophyton rubrum: A Novel Approach of Bee Venom Study for Possible Emerging Antifungal Agent

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          Abstract

          Background

          Bee venom (BV) has been widely investigated for potential medical uses. Recent inadvertent uses of BV based products have shown to mitigate signs of fungal infections. However, the component mediating the antifungal effect has not been identified.

          Objective

          This investigation compares bee venom in its whole and partial forms to evaluate the possible component responsible for the antifungal effect.

          Methods

          Forty-eight plates inoculated with Trichophyton rubrum were allocated into four groups. The groups were treated with raw BV (RBV), melittin, apamin and BV based mist (BBM) respectively and each group was further allocated accordingly to three different concentrations. The areas were measured every other day for 14 days to evaluate the kinetic changes of the colonies.

          Results

          The interactions of ratio differences over interval were confirmed in groups treated with RBV and BBM. In RBV, the level of differences were achieved in groups treated with 10 mg/100 µl ( p=0.026) and 40 mg/100 µl ( p=0.000). The mean difference of ratio in groups treated with RBV was evident in day 3 and day 5. The groups that were treated with melittin or apamin did not show any significant interaction. In BBM groups, the significant levels of ratio differences over time intervals were achieved in groups treated with 200 µl/100 µl ( p=0.000) and 300 µl/100 µl ( p=0.030).

          Conclusion

          The the bee venom in its whole form delivered a significant level of inhibition and we concluded that the venom in separated forms are not effective. Moreover, BV based products may exert as potential antifungal therapeutics.

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          Most cited references19

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          Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses.

          Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.
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            Epitope-specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro.

            Bee venom phospholipase A2 (PLA) is the major allergen in bee sting allergy. It displays three peptide and a glycopeptide T cell epitopes, which are recognized by both allergic and non-allergic bee venom sensitized subjects. In this study PLA- and PLA epitope-specific T cell and cytokine responses in PBMC of bee sting allergic patients were investigated before and after 2 mo of rush immunotherapy with whole bee venom. After successful immunotherapy, PLA and T cell epitope peptide-specific T cell proliferation was suppressed. In addition the PLA- and peptide-induced secretion of type 2 (IL-4, IL-5, and IL-13), as well as type 1 (IL-2 and IFN-gamma) cytokines were abolished, whereas tetanus toxoid-induced cytokine production and proliferation remained unchanged. By culturing PBMC with Ag in the presence of IL-2 or IL-15 the specifically tolerized T cell response could be restored with respect to specific proliferation and secretion of the type 1 T cell cytokines, IL-2 and IFN-gamma. In contrast, IL-4, IL-5, and IL-13 remained suppressed. Treatment of tolerized T cells with IL-4 only partially restored proliferation and induced formation of distinct type 2 cytokine pattern. In spite of the allergen-specific tolerance in T cells, in vitro produced anti-PLA IgE and IgG4 Ab and their corresponding serum levels slightly increased during immunotherapy, while the PLA-specific IgE/IgG4 ratio changed in favor of IgG4. These findings indicate that bee venom immunotherapy induces a state of peripheral tolerance in allergen-specific T cells, but not in specific B cells. The state of T cell tolerance and cytokine pattern can be in vitro modulated by the cytokines IL-2, IL-4, and IL-15, suggesting the importance of microenvironmental cytokines leading to success or failure in immunotherapy.
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              Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae).

              Turmeric oil and curcumin, isolated from Curcuma longa L., were studied against fifteen isolates of dermatophytes, four isolates of pathogenic molds and six isolates of yeasts. The inhibitory activity of turmeric oil was tested in Trichophyton-induced dermatophytosis in guinea pigs. The results showed that all 15 isolates of dermatophytes could be inhibited by turmeric oil at dilutions of 1:40-1:320. None of the isolates of dermatophytes were inhibited by curcumin. The other four isolates of pathogenic fungi were inhibited by turmeric oil at dilutions of 1:40-1:80 but none were inhibited by curcumin. All six isolates of yeasts tested proved to be insensitive to both turmeric oil and curcumin. In the experimental animals, turmeric oil (dilution 1:80) was applied by dermal application on the 7th day following dermatophytosis induction with Trichophyton rubrum. An improvement in lesions was observed in 2-5 days and the lesions disappeared 6-7 days after the application of turmeric oil.
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                Author and article information

                Journal
                Ann Dermatol
                Ann Dermatol
                AD
                Annals of Dermatology
                The Korean Dermatological Association; The Korean Society for Investigative Dermatology
                1013-9087
                2005-3894
                April 2018
                21 February 2018
                : 30
                : 2
                : 202-210
                Affiliations
                Department of Dermatology, Catholic University of Daegu School of Medicine, Daegu, Korea.
                [1 ]Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Korea.
                Author notes
                Corresponding author: Kwan Kyu Park, Department of Pathology, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea. Tel: 82-53-650-4161, Fax: 82-53-650-4891, g9563009@ 123456cu.ac.kr
                Article
                10.5021/ad.2018.30.2.202
                5839892
                79e420ab-a008-469d-9b7d-25c185ad60ee
                Copyright © 2018 The Korean Dermatological Association and The Korean Society for Investigative Dermatology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 June 2017
                : 18 October 2017
                : 25 October 2017
                Funding
                Funded by: Rural Development Administration, CrossRef http://dx.doi.org/10.13039/501100003627;
                Award ID: PJ01132501
                Categories
                Original Article

                Dermatology
                antifungal agents,apamin,bee venoms,melitten,trichophyton
                Dermatology
                antifungal agents, apamin, bee venoms, melitten, trichophyton

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