• Title/Summary/Keyword: Cutaneous Stimulation

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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.

Effects of Low-power Laser and TDP on the Cutaneous Wound Healing (피부상처 치유에 대한 저에너지레이저와 특정전자파의 효과)

  • Ahn So-Youn;Park Sang-Ock
    • The Journal of Korean Physical Therapy
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    • v.9 no.1
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    • pp.1-18
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    • 1997
  • The purpose of this study is to investigate the effects of the low power Helium Neon-Infra Red(HeNe-IR) laser and the special electromagnetic therapeutic apparatus stimulation, which is usually designated as TDP by using the initial of Tending Diancibo Pu which is the Chinese inscribed with English, on wound healing in rat. The seventy-five Sprague-Dawley adult female and male rats were assigned to the experimental and control groups. Each rat was anesthetized with pentobarbital sodium, and three full-thickness incisions with 12mm length wert made on the back of the half cf the rats and three deep second degree burns were made on the back of the remainder of the rats. From 34 hours after being injured, the rats of the experimental laser group were irradiated with the 157mW electric power HeNe-IR laser for 2 minutes every day and the rats of the experimental TDP group were stimulated with TDP irradiation with the 4km spot distance for 20 minutes every day during the 17 days. The rats were sacrificed and the wound parts of its were incised on the first day, 4th day, 7th day, 10th day and 17th day respectively after the beginning of wound treatment with laser and TDP irradiation. The incised wound parts were processed appropriately for the light microscopic and electron microscopic examination. The length of incised wound was measured with microcaliper before the wound part was incised. There was a significant decrease in the length of the incised wound of the experimental laser and TDP group, compared with that of control group at 4th day, 7th day and 10th day(p<0.01) after surgery. Through the histological examination of the wound site, the more rapid epithelialization and collagen formation in experimental groups were showed, compared with control group. The histological results were analyzed and summarized as the follows; The epidermis begins to be regenerated and the granulation tissue begins to be changed to the mature pattern in the H-E stained incised skin of the laser and TDP treatment group on the 4th day. The epidermis shows the complete regeneration and the granulation tissue in the dermis in mostly to be matured in the laser and TDP treatment group on the 7th day, compared with control group. The chronic inflammatory cells are oberved and the necrosis of the collagen fibers are partially observed in control group on the 10th day. The dermis of the laser and TOP treatment group reveals relatively compactly arranged collgen bundles with the mature collagen fibers on the 10th day. The epidermis and dennis of the laser and TDP group are repaired normally and the hair follicles are well regenerated on the 17th day. The mild edema and the granulation tissue is observed in the dermis of the control groups and the delayed treatment process is observed on the 17th day. The Most of proliferated collagen fibrils are found to be compact and regular in electron micrograph of burn skin of the laser treatment group on the 10th day hut the interstitial eadema and some inflammatory cells are found in the control group. The above results suggest that through the visual and histological examination the epithelized epithelium and the proliferation of the collagen liters in the dermis occur very effectively with the low power laser treatment and the TDP treatment in the incised wound healing and the burn wound healing.

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Toxicity of lectin extracted from Korean mistletoe (Viscum album coloratum) in piglets and its effects on the immunogenicity of Aujeszky's disease virus vaccines (한국산 겨우살이(Viscum album coloratum)로부터 추출된 lectin의 돼지에 대한 독성 및 오제스키병 백신의 면역원성에 미치는 영향)

  • Yeo, Sang-Geon
    • Korean Journal of Veterinary Research
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    • v.46 no.3
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    • pp.225-234
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    • 2006
  • In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.