• Biomolecules & Therapeutics
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• 제28권5호
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• 한국정보전자통신기술학회논문지
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• 제15권6호
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• pp.477-484
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• 2022

본 연구는 집속형초음파자극시스템의 카트리지부를 시료로 사용하여 의료기기 안전성 평가 기준인 GLP(Good Laboratory Practice)에 관한 시험 중 동물실험을 통한 피부 자극 시험 및 피부 감작성시험을 진행하였다. New Zealand White Rabbit 암컷 6마리를 이용하여 IACUC 승인 후 시험을 진행하였으며, 실험기간 동안 사망한 개체 수는 없었으며, 실험동물에서 어떤 이상 증상도 관찰되지 않았다. 극성, 비극성 자극 지수는 모두 '0.0'으로 나타났다. 또한, 피부감작성 평가의 경우 IACUC 승인을 통한 기니피그 30마리를 통하여 대조군 및 실험군으로 나누어 시험검체 및 공시험액을 별도의 희석 없이 용출액 자체를 사용하여 모든 유도 및 유발단계를 적용하였다. 실험결과대조동물의 피부반응 등급은 0등급이었으며, 시험동물의 피부반응에서 1등급 이상을 나타내는 동물은 없었다. 두 시험 결과에서 피부의 이상 증상은 발견되지 않았으며, 인체에 적용하여 환자를 치료할 경우 시험에 사용된 시험재료로부터 피부의 이상 증상이 생기는 질환 등은 나타나지 않는지에 관하여 안정성을 알아 보고자 하였다.

• 인지과학
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• 제31권3호
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• pp.55-76
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• 2020

사회성은 인간 삶의 고유 영역이자 종합적인 능력으로서 중요한 가치를 지닌다. 일반 통념상 사회성 부족이 게임 이용의 대표적인 문제점으로 지적되는 가운데, 본 문헌 고찰에서는 비디오 게임 중 온라인 비디오 게임을 대상으로 사회적 역량과의 관계를 살펴본 연구들을 분석했다. 해당 분야에는 현재 온라인 게임 안의 관계가 실제 관계를 대체하거나 보완하여 사회성 발달을 저해할 것이라는 견해와 온라인 비디오 게임이 직접적으로 사회성에 악영향을 미치지 않으며 오히려 사회적 학습의 공간을 제공함으로써 유익한 결과를 낼 수 있다는 주장이 팽팽하게 맞서고 있다. 또한 온라인 게임 이용과 심리특성 및 사회적 역량을 측정한 대규모 설문 조사에서도 게임 이용과 사회성 저하 간의 뚜렷한 관계성이 관찰되지 않았다. 이에 본 문헌 고찰 연구를 통해 온라인 게임 플레이가 사회성 저하를 초래한다는 고정관념에서 벗어날 것과 관련 연구의 타당성을 높이기 위한 노력이 필요함을 제안한다.

• 대한약리학회지
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• 제30권2호
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• pp.205-215
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• 1994

It is well known that chronic stimulation with CCK gives rise to growth of exocrine pancreas and to increased content of enzyme proteins in pancreas. However, littls Is known about changes of the secretory function of exocrine pancreas which has been chronically stimulated with CCK, especially about the responsiveness to secretagogues such as CCK, caerulein and carbachol. The present study was performed to investigate the effect of camostat on secretory profiles and the responsiveness to secretagogues of exocrine pancreas by observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8) and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for 4 or 10 days. The results summarized as follows : 1) The maximal effective concentration of CCK-8 in amylase release in the camostat treated group was greater than control group, but that of carbachol was not different between groups. 2) Analysis of the stimulated amylase release as the percentage of the maximal response revealed that camostat treatment caused right-shift of the dose-response curve of CCK-8. Camostat did not cause significant changes in the dose-response curve of carbachol. 3) There were considerable increases in the amylase release in the camostat-treated group, compared to the control when acini were stimulated with CCK-8 $10^{-9}\;M$ and carbaochol $10^{-6}\;M$, and higher concentrations. 4) There was a reverse correlation between the tissue content and the maximal release(percent of the total content) of amylase. These results suggest that chronic exposure of exocrine pancreas to increased endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to secretagogues, especially at higher concentrations of CCK and carbachol.

• 동의생리병리학회지
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• 제21권5호
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• pp.1285-1290
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• 2007

The present study aims to identify and characterize genes that cause differen genes between non-responders and responders to electroacupuncture (EA) on mechanical allodynia following peripheral nerve injury. Under sodium pentobarbital anesthesia, animals were subjected to unilateral transection of the superior caudal trunk at the level between S1 and S2 spinal nerves. EA stimulation (2Hz, 0.3 ms, 0.2-0.3 mA) was delivered to Zusanli (ST36) for 30 min 2 weeks after the surgery. The degree of mechanical allodynia was assessed quantitatively by touching the tail with von Frey hair (2.0 g) at 10 min intervals. The rats, which showed an EA-induced decrease of response frequencies under 10 %, were classified as non-responders and those displaying an EA-induced decrease of response frequencies 20 % or more were classified as responders. Results from oligonucleotide microarray, to which cDNAs from the spinal dorsal horn (DH) were applied, showed that hemoglobin beta chain complex and chondroitin sulfate proteoglycan-5 decreased and limbic system-associated membrane protein increased in the non-responder group, whereas calcium-independent alpha-Iatrotoxin receptor homolog-3 increased in the responder group. These results suggest that The functional abnormality of molecules regulating cell adhesion, intracellular signal transduction and cell differentiation in the spinal DH may be involved in the anti-allodynic effect of EA.

• The Korean Journal of Pain
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• 제4권2호
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• pp.152-156
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• 1991

경부 신경근병이 의심되는 31예의 환자에 경막외강 스테로이드 주입으로 치료하여 다음과 같은 결과를 얻었다. 1) 총 31예중 10예에서는 1회만을 주입하였다. 2) 최소한 1주일 간격으로 2회이상 주입한 21예중 15예에서 증상의 호전을 보였고 6예에서는 효과가 없었다. 3) 총 88회 주업중 2회의 지주막 천자외에는 합병증이 없었다. 이상의 결과로 보아 cervical radiculopathy가 의심되는 환자는 수술적 치료를 적용하기 전에 다른 종류의 대중적 치료와 더불어 경막외 스테로이드률 주입하는 것이 안전하고 효과적인 것으로 사료된다.

• Natural Product Sciences
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• 제10권6호
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• pp.284-288
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• 2004

We have recently reported that red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng (Panax ginseng C. A. Meyer), showed immunomodulatory antitumor activities, mainly mediated by nitric oxide (NO) production by macrophage. In this study, we examined the effect of RGAP on anticancer activity using lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC tumor cells transplanted into mice as well as antimetastatic activity using B16-F10 melanoma. When RGAP (300 mg/kg) were treated to mice implanted with one of the three kinds of tumor cells, the tumor weight significantly decreased compared with control mice. Tumor inhibition ratios of RGAP (300 mg/kg) in mice transplanted with lung carcinoma 3LL, sarcoma 180 and adenocarcinoma JC cells were 26.8%, 29.3% and 31.6%, respectively. Hundred mg/kg of RGAP did not cause a significant decrease in tumor weight compared with control group. When RGAP was administered i.p. with the dose of 100 and 300 mg/kg in B16-F10 melanoma-bearing mice, lung metastasis were reduced significantly in mice. Corrected phagocytic index was also remarkably increased by RGAP. These results suggest that stimulation of phagocytic activity of macrophages may be a mechanism for in vivo anticancer and antimetastasis activities of RGAP.

• 대한한의학회지
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• 제24권4호
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• pp.120-126
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• 2003

Object : This study was done to evaluate the inhibitory effect of Samul-tang (Siwu-tang) on collagen production by cultured murine hepatic non-parenchymal cells. Methods : Hepatic non-parenchymal cells were cultured from normal Sprague-Dawley rats and established in a primary cell culture on uncoated plastic culture plates. The Samul-tang (Siwu-tang) was treated into the cell culture media for 72 hours and the cells were harvested for analysis. Analyses were done on cell proliferation, [3H]thymidine incorporation assay and procollagen type IC-peptide. Results : The cultured cells resembled fibroblasts in shape and produced procollagen which is consistent to fibrogenesis in vivo. Proliferation of the non-parenchymal cells was inhibited slightly and the [3H]thymidine incorporation assay showed a dose-dependent decrease by Samul-tang (Siwu-tang) treatment. Production of procollagen type I C-peptide was decreased by low-concentration treatment of the Samul-tang (Siwu-tang), but increased by high-concentration treatment. Conclusion : It seemed that the cells were responding to the Samul-tang (Siwu-tang) in low-concentration, thus producing less collagen. However, when the drug was administered with high enough concentration to cause excessive stimulation of cells, it seemed that the activated cells might overly produce procollagen, the precursor of collagen, thus aggravating fibrosis of the liver. So, it is considered that the proper concentration of Samul-tang (Siwu-tang) is important when treating patients with liver cirrhosis based on the patients' status.

• The Korean Journal of Pain
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• 제14권2호
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• pp.193-198
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• 2001

Background: Anterior atlantoaxial subluxation (AAS) is a frequent phenomenon in rheumatoid arthritis (RA). AAS compresses the C2 ganglion or nerve and is a cause of posterior neck pain or occipital headache. Methods: We selected RA patients that had developed posterior neck pain or occipital headache caused by AAS. AAS was diagnosed by an increase of ADI (atlantodental interval). A distance of 3 mm or more was considered significant. Patients with vertical subluxation or symptoms suggestive of myelopathy were excluded. Before C2 RF ganglionotomy, we proceeded with a C2 ganglion block or greater occipital nerve block used by local anesthetics. For C2 RF ganglionotomy, the patient was placed in the supine position on a fluoroscopic table. A 100 mm, 4 mm active tip electrode was chosen. Following sensory stimulation at 0.2 to 0.6 V, the lesion was performed at a temperature of $60^{\circ}C$ to $65^{\circ}C$ for 60 sec. We followed up the patient after 6 months later. Results: All cases were female and the average duration of RA was 8.5 years. The duration of posterior neck pain or occipital headache was 1-8 months. The average ADI was 4.2 mm and the McGregor index was 3.3 mm on the average. In all cases, the score on the 4 point Likert scale was 4 (pain free) during the follow-up period. Conclusions: We found that the occipital headache or posterior neck pain caused by AAS in rheumatoid arthritis patients was alleviated over a short term follow up. C2 RF ganglionotomy is suggested as an effective palliative treatment for AAS in RA patients.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.125-130
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• 1999

저자들은 최근 25세 여자 환자로 뚜렷한 가족력이 없으면서 3-4세경부터 발생한 근육의 강직현상과 현저한 근비대소견이 있는 환자를 경험하였다. 임상적으로 타진성 근긴장증을 보이고 전기생리적 검사로 새끼손가락 외향근에서의 운동과 반복신경자극에서 복합근육활동전위의 감소를 보였으며, 이두박근의 근생검 소견상 용적이 증가된 근섬유와 중심핵화현상이 관찰되었다. 환자는 mexiletin 경구 투여후 근육의 강직현상이 다소 호전되었다. 이에 문헌고찰과 함께 Becker형 선천성 근긴장증 1례를 보고하는 바이다.