• Title/Summary/Keyword: Mast

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Agarwood Inhibits Histamine Release from Rat Mast Cells and Reduces Scratching Behavior in Mice -Effect of Agarwood on Histamine Release and Scratching Behavior-

  • Inoue, Eiji;Shimizu, Yasuharu;Masui, Ryo;Tsubonoya, Tomoe;Hayakawa, Tomomi;Sudoh, Keiichi
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.239-245
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    • 2016
  • Objectives: This study was conducted to clarify the effects of agarwood on histamine release from mast cells in rats and on the scratching behaviors in mice. Methods: Histamine release from rat mast cells induced by compound 48/80 or concanavalin A (Con A) and compound 48/80-induced scratching behavior in mice were examined to investigate the effects of agarwood. The hyaluronidase activity and the 3',5'-cyclic adenosine monophosphate (cAMP) levels in mast cells were examined to investigate the mechanisms for the inhibition of histamine release. The correlation between the inhibitory effects of agarwood on histamine release and the content of its typical ingredients, a 2-(2-phenylethyl)chromone derivatives, was analyzed using thin-layer chromatography. Results: Agarwood showed an inhibitory effect on mast-cell histamine release induced by compound 48/80 or Con A without any effect on hyaluronidase activity; this effect involves an increase in the cAMP levels in mast cells. Oral administration of agarwood showed an inhibitory effect on compound 48/80-induced scratching behavior in mice. The inhibitory effects of agarwood on histamine release were quite different, depending on the area where the agarwood was produced, its quality, and its market price. No correlation was found between the inhibitory effects of agarwood on histamine release and the typical ingredients of agarwood, which are 2-(2-phenylethyl)chromone derivatives. Conclusion: These results show that agarwood inhibits histamine release from mast cells partially through an increase in the cAMP levels in cells. We suggest that some active ingredients of agarwood must be effective on oral intake and that agarwood can be used to treat patients with a number of conditions, including urticaria, atopic dermatitis, and bronchial asthma, in which an increase in histamine release occurs. Differences in the pharmacological effects of this crude drug among markets may provide important information for the quality control of this herbal medicine.

An Anti-Cancer Drug Candidate CYC116 Suppresses Type I Hypersensitive Immune Responses through the Inhibition of Fyn Kinase in Mast Cells

  • Park, Young Hwan;Kim, Hyun Woo;Kim, Hyuk Soon;Nam, Seung Taek;Lee, Dajeong;Lee, Min Bum;Min, Keun Young;Koo, Jimo;Kim, Su Jeong;Kim, Young Mi;Kim, Hyung Sik;Choi, Wahn Soo
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.311-317
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    • 2019
  • Mast cells are the most prominent effector cells of Type 1 hypersensitivity immune responses. CYC116 [4-(2-amino-4-methyl-1,3-thiazol-5-yl)-N-[4-(morpholin-4-yl)phenyl] pyrimidin-2-amine] is under development to be used as an anti-cancer drug, but the inhibitory effects of CYC116 on the activation of mast cells and related allergy diseases have not reported as of yet. In this study, we demonstrated, for the first time, that CYC116 inhibited the degranulation of mast cells by antigen stimulation ($IC_{50}$, ${\sim}1.42{\mu}M$). CYC116 also inhibited the secretion of pro-inflammatory cytokines including TNF-${\alpha}$ ($IC_{50}$, ${\sim}1.10{\mu}M$), and IL-6 ($IC_{50}$, ${\sim}1.24{\mu}M$). CYC116 inhibited the mast cell-mediated allergic responses, passive cutaneous anaphylaxis (ED50, ~22.5 mg/kg), and passive systemic anaphylaxis in a dose-dependent manner in laboratory experiments performed on mice. Specifically, CYC116 inhibited the activity of Fyn in mast cells and inhibited the activation of Syk and Syk-dependent signaling proteins including LAT, $PLC{\gamma}$, Akt, and MAP kinases. Our results suggest that CYC116 could be used as an alternative therapeutic medication for mast cell-mediated allergic disorders, such as atopic dermatitis and allergic rhinitis.

Comparison of Intradermal Skin Test and Multiple Allergen Simultaneous Test Results in Canine Atopic Dermatitis

  • Nam, Hyeyeon;Yun, Taesik;Koo, Yunhoi;Lee, Dohee;Chae, Yeon;Park, Jooyoung;Choi, Dongjoon;Kim, Hakhyun;Yang, Mhan-Pyo;Kang, Byeong-Teck
    • Journal of Veterinary Clinics
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    • v.38 no.3
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    • pp.120-126
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    • 2021
  • Intradermal skin test (IDST) is generally considered a useful tool in identifying causal allergens in canine atopic dermatitis. Currently, multiple allergen simultaneous test (MAST), an in vitro testing method for allergen-specific immunoglobulin E, is being used as an alternative method. However, there are no reports comparing the IDST and MAST results in the same dogs. This study compared the results of both tests to evaluate the agreement and correlation between them. The sensitivity, specificity, and accuracy of the MAST were 76.2%, 64%, and 66.7%, respectively. Moderate positive predicted value (PPV, 50-75%) or high sensitivity (80-100%) were identified for indoor allergens, such as cat epithelia, house dust, and house dust mites. In contrast, high negative predicted value (NPV, 93.3-100%) and specificity (60-100%) were observed for environmental allergens and fungi. Although the agreement between IDST and MAST for all allergens was fair (κ = 0.301), that for each allergen was poor (κ < 0.01), except for birch (κ = 0.158). Spearman's rank correlation analysis revealed a low correlation between the MAST and IDST results (ρ = 0.308, p = 0.001). As compared to the IDST results, the MAST results did not identify the causative allergens sufficiently. IDST may not be performed for environmental allergens and fungi with high NPV and specificity if the MAST result is negative, but it may have to be performed for indoor allergens with moderate PPV and high sensitivity when the MAST result is positive.

AT9283, 1-Cyclopropyl-3-(3-(5-(Morpholinomethyl)-1H-Benzo[d] Imidazole-2-yl)-1H-Pyrazol-4-yl) Urea, Inhibits Syk to Suppress Mast Cell-Mediated Allergic Response

  • Kim, Su Jeong;Choi, Min Yeong;Min, Keun Young;Jo, Min Geun;Kim, Jie Min;Kim, Hyung Sik;Kim, Young Mi
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.520-528
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    • 2022
  • Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC50, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC50, approx. 0.09 μM) and TNF-α (IC50, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

A Study on the Improvement of the Mast Design for Wind Detector (풍향풍속 검출기 마스트 설계 개선에 관한 연구)

  • Kim, Dong-Young;Park, Hae-Jin
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.22 no.5
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    • pp.98-107
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    • 2021
  • During the sea trial test for the aerovane in AOE-II, a malfunction occurred in the wind detector movement around 40 to 90° on the starboard side and around 270 to 320° on the port side. The purpose of this study was to analyze and improve the cause of the above phenomenon. The wind detector was covered with a mast structure and was not affected directly by the blowing wind, and a vortex air current was formed behind the mast structure, causing the motion malfunction. The above problem was solved by moving and installing the wind detector on the newly installed mast yard. After conducting vibration analysis and reviewing the effects of vibration, the wind detector was installed in the new mast yard and verified by a sea trial test. Since the improvement plan was slightly effective, the position of the wind detector moved away from the mast on the new mast yard and was re-verified through a sea trial test. The movement malfunction of the wind detector did not occur, confirming that it is an appropriate improvement plan.

Interplay of collagen and mast cells in periapical granulomas and periapical cysts: a comparative polarizing microscopic and immunohistochemical study

  • Deepty Bansal;Mala Kamboj;Anjali Narwal;Anju Devi;Nisha Marwah
    • Restorative Dentistry and Endodontics
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    • v.47 no.1
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    • pp.12.1-12.11
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    • 2022
  • Objectives: This pilot study aimed to establish the interrelationship between collagen and mast cells in periapical granulomas and periapical cysts. Materials and Methods: An observational cross-sectional study was conducted on the paraffin-embedded tissue sections of 68 specimens (34 periapical granulomas and 34 periapical cysts). The specimens were stained with picrosirius to observe collagen fiber birefringence and anti-tryptase antibody to evaluate the mast cell count immunohistochemically. The mean number and birefringence of collagen fibers, as well as the mean number of mast cells (total, granulated, and degranulated), and the mean inflammatory cell density were calculated. The data obtained were analyzed using the Kruskal Wallis test, Mann Whitney U test, and Spearman correlation test (p < 0.05). Results: The mean number of thick collagen fibers was higher in periapical cysts, while that of thin fibers was higher in granulomas (p = 0.00). Cysts emitted orange-yellow to red birefringence, whereas periapical granulomas had predominantly green fibers (p = 0.00). The mean inflammatory cell density was comparable in all groups (p = 0.129). The number of total, degranulated, and granulated mast cells exhibited significant results (p = 0.00) in both groups. Thick cyst fibers showed significant inverse correlations with inflammation and degranulated mast cells (p = 0.041, 0.04 respectively). Conclusions: Mast cells and inflammatory cells influenced the nature of collagen fiber formation and its birefringence. This finding may assist in the prediction of the nature, pathogenesis, and biological behavior of periapical lesions.

An Experimental Study on the metabolism of 5-Hydroxytryptamine (5-Hydroxytryptamine 代謝에 관한 實驗的 硏究)

  • Hah, Jae Chung;Lee, Wuen Ho
    • The Korean Journal of Zoology
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    • v.16 no.1
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    • pp.13-23
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    • 1973
  • The changes in the quantitative distribution and in cytoplasmic granules of tongue mast cells and duodenal enterochromaffin cells in male albino rats were observed following oral administration of 40mg/kg body wt. isonicotinic acid hydraside (INH) and 20mg/kg body wt. pyridoxine. The results obtained are summarized as follows: 1. INH administered-rat showed a marked decrease in the number of mast cells, caused by leakage of cytoplasmic granules, while pyridoxine-rat showed increased the number of mast cells. 2. Similarly, INH-rat showed a marked decrease in the number of enterochromaffin cells. In the case of pyridoxine-rat, however, the number of enterochromaffin cells increased compared with that of the controls. 3. In view of the fact that a large dose of INH was harmful to the formation of mast cells and enterochromaffin cells. And considering that a moderate dose of pyridoxine stimulated the formation of the two kinds of cells and the amounts of cytoplasmic granules, it was concluded that pyridoxine might be concerned with the metabolism of secretory products, 5-Hydroxytryptamine.

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Characterization of the wind-induced response of a 356 m high guyed mast based on field measurements

  • Zhe Wang;Muguang Liu;Lei Qiao;Hongyan Luo;Chunsheng Zhang;Zhuangning Xie
    • Wind and Structures
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    • v.38 no.3
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    • pp.215-229
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    • 2024
  • Guyed mast structures exhibit characteristics such as high flexibility, low mass, small damping ratio, and large aspect ratio, leading to a complex wind-induced vibration response mechanism. This study analyzed the time- and frequency-domain characteristics of the wind-induced response of a guyed mast structure using measured acceleration response data obtained from the Shenzhen Meteorological Gradient Tower (SZMGT). Firstly, 734 sets of 1-hour acceleration samples measured from 0:00 October 1, 2021, to 0:00 November 1, 2021, were selected to study the vibration shapes of the mast and the characteristics of the generalized extreme value (GEV) distribution. Secondly, six sets of typical samples with different vibration intensities were further selected to explore the Gaussian property and modal parameter characteristics of the mast. Finally, the modal parameters of the SZMGT are identified and the identification results are verified by finite element analysis. The findings revealed that the guyed mast vibration shape exhibits remarkable diversity, which increases nonlinearly along the height in most cases and reaches a maximum at the top of the tower. Moreover, the GEV distribution characteristics of the 734 sets of samples are closer to the Weibull distribution. The probability distribution of the structural wind vibration response under strong wind is in good agreement with the Gaussian distribution. The structural response of the mast under wind loading exhibits multiple modes. As the structural response escalates, the first three orders of modal energy in the tower display a gradual increase in proportion.

Inhibitory effects of Polygoni cuspidati rhizoma on Mast Cell-Mediated Anaphylactic Reaction

  • Kang, Tae-Hee;Jeung, Eun-Suk;Choi, In-Young;Jeong, Hyun-Ja;Um, Jea-Young;Kim, Hyung-Min;Hong, Seung-Heon
    • Journal of Evidence-Based Herbal Medicine
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    • v.1 no.1
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    • pp.13-18
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    • 2008
  • Polygoni cuspidati Rhizoma (PCRH) has been used in treatment of menoxenia, skin burn, gallstone, hepatitis, hyperlipidaemia, favus athlete's foot, supperative dermatitis and inflammation. However, its effect in experimental models remains unknown. In this present study, the effect of PCRH for stability on mast cell was analyzed. Two g/kg PCRH inhibited the compound 48/80-induced anaphylaxis by 75%. In addition, PCRH inhibited the tumor necrosis factor-$\alpha$ and interleukin-8 secretion as compared with the phorbol 12-myristate 13-acetate plus calcium ionophore A23187 stimulated human mast cell line, HMC-1 cells. These results suggested PCRH may inhibit mast cell-mediated anaphylactic reaction.

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Inhibitory Effect of Lycopus lucidus on Mast Cell-Mediated Immediate-Type Allergic Reactions (택란의 비만세포 매개 즉시형 알레르기 반응의 억제 효과)

  • 김숙현;김대근;임종필;채병숙;신태용
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.405-410
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    • 2002
  • The effect of aqueous extract of Lycopus lucidus Turcz. (Labiatae)(LLAE) on mast cell-mediated immediate-type allergic reactions was investigated. LLAE (0.01 to 1 mg/g) dose-dependently inhibited systemic anaphylaxis induced by compound 48/80. LLAE (0.001 to 1 mg/g) also dose-dependently inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. When LLAE was pretreated at the same concentration with systemic anaphylaxis, serum histamine levels were reduced in a dose-dependent manner. LLAE (0.001 to 1 mg/mι) dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80. The level of cAMP in human mast cell line (HMC-1) cells, when LLAE (1 mg/mι) was added, significantly was increased, compared with that of normal control. These results provide evidences that LLAE may be beneficial in the treatment of allergic diseases.