• Title/Summary/Keyword: 치료 저항성

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Evaluation of the Bioequivalence of Simvastatin 20mg Tablets in Healthy Volunteers (조코 정에 대한 엘바스타 정의 생물학적 동등성 평가)

  • Yun, Hwi-yeol;Kang, Wonku;Kwon, Kwang-il
    • Korean Journal of Clinical Pharmacy
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    • v.15 no.1
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    • pp.41-45
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    • 2005
  • 심바스타틴은 cholesterol 생합성 과정에서 속도 조절 효소인 HMG-CoA reductase의 강력한 상경적 길항약으로서 고지혈증 치료에 널리 쓰이는 약물이다. 심바스타틴 제제인 MSD 사의 조코 20 mg정을 대조약으로 하여 시험약인 유영 제약의 엘바스타 20mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 2정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 심바스타틴의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도곡선 하 면적 ($AUC_{12hr}$)과 최고 혈중 농도($C_{max}$)를 사용하였다. 12시간 까지의 혈중 농도 곡선 하 면적의 기하 평균은 $17.30ng{\cdot}ml/hr$(시험약)과 $17.35ng{\cdot}ml/hr$(대조약)으로 나타났다. 최고 혈중 농도의 경우 각 각 5.08 ng/ml(시험약)과 5.20 ng/ml(대조약)으로 관찰 되었다. $AUC_{12hr}$의 경우 로그변환한 평균치 차의 $90{\%}$ 신뢰구간이 log0.8510 - log1.1694이었고, $C_{max}$의 경우 log0.8176 - log1.1649로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 엘바스타 정 20mg은 대조약 조코정 20 mg에 대하여 생물학적 동등한 것으로 판정되었다.트리머 전기비저항 탐사를 수행하였다. 이를 통해 하저에 케이블을 설치하는 방식에 비해 매우 신속하고 경제적으로 하저에 분포하는 이상대의 분포범위와 발달방향을 규명할 수 있었다.대에 대해 가장 효과적이다. 모델과 현장 적용 결과들을 통해 GRM SSM 방법을 이용하여 불규칙한 굴절면을 가진 지층들에 대해 좀 더 신뢰할 수 있는 정밀한 탄성파 속도를 산출할 수 있음을 보여주고 있다.별한 주의를 기울여야 한다.EX>$\alpha/\beta$=10인 경우 $62.0\~121.9\;Gy_{10}$ (중앙값: $93.0\;Gy_{10}$)의 분포를, ${\alpha/\beta}=3$인 경우 $93.6\~187.3\;Gy_3$ (중앙값=$137.6\;Gy_3$ )의 분포를 보였다. MD-BED $Gy_3$는 직장합병증 발생과의 관계는 통계적으로 유의하였고, 방광합병증과는 유의하지 않았다. 직장합병증과의 연관성은 MD-BED $Gy_3$보다 개별 환자의 직장전벽 총 선량 BED값인 R-BED $Gy_3$가 훨씬 더 높았다. 요도카테터 풍선의 후방지점이 대변하는 방광의 총 선량 BED값인 V-BED $Gy_3$도 방광합병증과 경향성 테스트에서 통계적 유의성을 보였다. 하지만, 어떠한 방사선선량도 골반제어율과 의미 있는 상관관계를 보이지 않았다. 본 기관에서 주치의의 선호도에 따라 강내근접치료가 외부방사선치료의 중간에 시행되는 형태인 샌드위치기법과 외부방사선치료 후반부에 시행되는 순차적 기법으로 구분하였을 때, 두 방식간 치료성적 및 합병증의 차이는 없었다. 총 치료기간에 대한 분석에서는 치료기간이 길어질수록 재발 위험이 커지는 경향을 보였으나, 나이 및 병기, 종양의 크기, MD-BED $Gy_{10}$

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Betulinic Acid Induces Apoptosis in Humam Mucoepidermoid Carcinoma Cells Through Regulating Specificity Protein 1 and Its Downstream Molecule, Survivin

  • Lee, Jung-Eun;Jung, Ji-Youn;Yoo, Hyun-Ju;Cho, Sung-Dae
    • Journal of Food Hygiene and Safety
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    • v.28 no.3
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    • pp.202-206
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    • 2013
  • High-grade mucoepidermoid carcinomas (MECs) have difficulty in cure and 5-year survival rate is quiet low. Therefore, we need new therapeutic agents and molecular targets. Betulinic acid (BA) is one of the materials which is easily found in the world and shows tumor-suppress effects in various tumor types. In addition, many kinds of normal tissues have a resistance to BA treatment. In this study, we investigated the anti-proliferative activity of BA and its molecular targets in MC-3 human MEC cells using western blot analysis and DAPI staining. BA inhibited cell viability and induced apoptosis in MC-3 cells. It affected Specificity protein 1 (Sp1) and its downstream molecule, survivin whereas it did not affect myeloid cell leukemia-1 (Mcl-1). Therefore, we suggest that BA can be a potential anti-cancer drug candidate regulating Sp 1 and survivin to exert apoptotic cell death.

The Effect of Systemic Hypertension on the Pediatric Brain (중추신경계에 미치는 소아 고혈압의 영향)

  • Hur, Yun-Jung
    • Childhood Kidney Diseases
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    • v.15 no.1
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    • pp.22-28
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    • 2011
  • Hypertension is one of the most common chronic diseases in childhood and adolescence. Untreated hypertension adversely affects many organs including heart, brain, kidney and peripheral arteries. We reviewed the complication of central nervous system caused by pediatric hypertension. Cerebral blood flows are maintained constantly in response to changes in blood pressure by cerebral autoregulation. Severe hypertension which destructs cerebral autoregulation results in acute hypertensive encephalopathy syndrome, ischemic or hemorrhagic stroke. Chronic pediatric hypertension induces learning disability and cognitive defect which are subclinical symptom prior to brain damage caused by severe hypertension. We should consider the effect of hypertension on pediatric brain because appropriate antihypertensive drugs could prevent these complications.

Treatment of Vasodilatory Shock after Cardiac Surgery : Low Dose Arginine Vasopressin Therapy - Three cases report - (개심술후 발생한 Vasodilatory Shock의 치료 : Arginine Vasopressin의 소량투여요법 - 3례 보고 -)

  • 이교준;김해균;정은규;김도형;강두영;이응석
    • Journal of Chest Surgery
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    • v.35 no.3
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    • pp.227-230
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    • 2002
  • The vasodilatory shock after cardiopulmonary bypass is defined as the condition involving severe and persistent form of hypotension, tachycardia, normal or increased cardiac output and decreased systemic vascular resistance. Because of the unsuccessful response to infusion of fluids or catecholamine vasopressors, a sustained systemic shock state occurs and results in a high morbidity and mortality. We successfully treated this syndrome of 3 patients after open heart surgery with low dose of arginine vasopressin(AVP). Therefore, we report these cases with a review of related articles.

Effects of Sodium Butyrate, a Histone Deacetylase Inhibitor, on TRAIL-mediated Apoptosis in Human Bladder Cancer Cells (인체 방광암세포에서 histone deacetylase 억제제인 sodium butyrate이 TRAIL에 의한 apoptosis 유도에 미치는 영향)

  • Han, Min-Ho;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.4
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    • pp.431-438
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    • 2016
  • The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is considered a promising anticancer agent due to its unique ability to induce cancer cell death having only negligible effects on normal cells. However, many cancer cells tend to be resistant to TRAIL. In this study, we investigated the effects and molecular mechanisms of sodium butyrate (SB), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in 5637 human bladder cancer cells. Our results indicated that co-treatment with SB and TRAIL significantly increased the apoptosis induction, compared with treatment with either agent alone. Co-treatment with SB and TRAIL effectively increased the cell-surface expression of death receptor (DR) 5, but not DR4, which was associated with the inhibition of cellular Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme (FLICE) inhibitory protein (c-FLIP). Furthermore, the activation of caspases (caspase-3, -8 and -9) and degradation of poly(ADP-ribose) were markedly increased in 5637 cells co-treated with SB and TRAIL; however, the synergistic effect was perfectly attenuated by caspase inhibitors. We also found that combined treatment with SB and TRAIL effectively induced the expression of pro-apoptotic Bax, cytosolic cytochrome c and cleave Bid to truncated Bid (tBid), along with down-regulation of anti-apoptotic Bcl-xL expression. These results collectively suggest that a combined regimen of SB plus TRAIL may offer an effective therapeutic strategy for safely and selectively treating TRAIL-resistant bladder cancer cells.

Roles of Local Estrogen and Progesterone Mediated Receptors in the Regulation of Endometrial Inflammation (자궁내막 염증에 대한 지엽적 에스트로겐 및 프로게스테론 매개 수용체의 역할)

  • Gyesik Min
    • Journal of Life Science
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    • v.33 no.1
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    • pp.102-113
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    • 2023
  • This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.

Dose Distribution and Design of Dynamic Wedge Filter for 3D Conformal Radiotherapy (방사선 입체조형치료를 위한 동적쐐기여과판의 고안과 조직내 선량분포 특성)

  • 추성실
    • Progress in Medical Physics
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    • v.9 no.2
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    • pp.77-88
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    • 1998
  • Wedge shaped isodoses are desired in a number of clinical situations. Hard wedge filters have provided nominal angled isodoses with dosimetric consequences of beam hardening, increased peripheral dosing, nonidealized gradients at deep depths along with the practical consequendes of filter handling and placement problems. Dynamic wedging uses a combination of a moving collimator and changing monitor dose to achieve angled isodoses. The segmented treatment tables(STT) that monitor unit setting by every distance of moving collimator, was induced by numerical formular. The characteristics of dynamic wedge by STT compared with real dosimetry. Methods and Materials : The accelerator CLINAC 2100C/D at Yonsei Cancer Center has two photon energies (6MV and 10MV), currently with dynamic wedge angles of 15$^{\circ}$, 30$^{\circ}$, 45$^{\circ}$ and 60$^{\circ}$. The segmented treatment tables(STT) that drive the collimator in concert with a changing monitor unit are unique for field sizes ranging from 4.0cm to 20.0cm in 0.5cm steps. Transmission wedge factors were measured for each STT with an standard ion chamber. Isodose profiles, isodose curves, percentage depth dose for dynamic wedge filters were measured with film dosimetry. Dynamic wedge angle by STT was well coincident with film dosimetry. Percent depth doses were found to be closer to open field but more shallow than hard wedge filter. The wedge transmission factor were decreased by increased the wedge angle and more higher than hard wedge filters. Dynamic wedging probided more consistent gradients across the field compared with hard wedge filters. Dynamic wedging has practical and dosimetric advantages over hard filters for rapid setup and keeping from table collisions. Dynamic wedge filters are positive replacement for hard filters and introduction of dynamic conformal radiotherapy and intensity modulation radiotherapy in a future.

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The effects of Allomyrina dichotoma larval extract on palmitate-induced insulin resistance in skeletal muscle cells (장수풍뎅이 유충 추출물이 고지방산 처리 골격근세포의 인슐린 저항성에 미치는 영향)

  • Kim, Kyong;Sim, Mi-Seong;Kwak, Min-Kyu;Jang, Se-Eun;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.462-475
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    • 2022
  • Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

The Effect of Robot Therapy on Upper Extremity Function in a Patient With Parkinson's Disease (로봇치료가 파킨슨병 환자의 상지 기능에 미치는 영향)

  • Lee, Inseon;Kim, Jongbae;Park, Ji-Hyuk;Park, Hae Yean
    • Therapeutic Science for Rehabilitation
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    • v.7 no.3
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    • pp.59-78
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    • 2018
  • Objective : The purpose of this study was to investigate the effect of robot-assisted therapy on upper extremity function. Methods : This study used a single-subject experimental A-B-A' design. Three Parkinson's disease patients took part. Each subject received a robot-assisted therapy intervention (45 min/session, 5 sessions/week for 4 weeks). Upper extremity movement was evaluated with the Reo Assessment tool in Reogo. The Jebsen-Taylor hand motor function test, Fugle-Mayer Assessment score, Box and Block Test, and Nine-hole pegboard test were assessed pre- and post-intervention. Results : After intervention, all subjects underwent 3D motion analysis of reaching function. There was overall improvement in resistance, smoothness, direction accuracy, path efficiency, initiation time, and time to moving target with robot-assisted therapy. Robot-assisted therapy may have a positive effect on upper extremity movement in Parkinson's disease. Conclusion : Robot-assisted therapy is considered an alternative in clinical occupational therapy to improve upper extremity function in Parkinson's disease.

The Effects of Water Extract of Polygonatum Odoratum (Mill) Druce on Insulin Resistance in 90% Pancreatectomized Rats (90% 췌장 절제 백서에서 둥굴레뿌리의 물추출물이 인슐린 저항성에 미치는 영향)

  • Park, Sun-Min;Ahn, Seung-Hee;Choi, Mi-Kyung;Choi, Soo-Ran;Choi, Soo-Bong
    • Korean Journal of Food Science and Technology
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    • v.33 no.5
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    • pp.619-625
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    • 2001
  • We determined whether the supplementation of Polygonatum Odoratum (Mill) Druce (POD) extract had a good effect on insulin resistance in peripheral tissues of 90% pancreatectomized (Px) and sham-operated (Sham) male Sprague Dawley rats. Px and Sham rats were divided into two groups; one group daily consumed 0.3 g of POD extracts per 1 ㎏ body weight for two months, and the other group had a placebo. All rats freely consumed a 40% fat diet. At the end of the experiment, a euglycemic hyperinsulinemic (EH) clamp was performed in a fasting, awake, and unstressed state to determine insulin resistance. At EH clamp, body weights were higher in Sham rats than Px rats, and serum glucose levels of baseline were affected by diabetic status and POD administration. Serum insulin concentrations were higher in Sham rats than Px rats, and POD administration decreased them in Sham rats compared to P. Glucose disposal rates in peripheral tissues increased with POD in both Px (n=10) and Sham (n=10) rats. But glycogen deposits in soleus muscle increased with POD administration in Px and Sham rats, and total glycogen synthase activity and fraction velocity were higher in POD groups. Triglyceride contents in quadriceps muscles decreased with POD in Px rats. In conclusions, POD improves insulin resistance by enhancing glucose utilization with increasing glycogen deposit and decreasing triglyceride contents in muscles.

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