• 제목/요약/키워드: Drug Dose

검색결과 1,564건 처리시간 0.031초

피부사상균 감염개에서 Ketoconazole 경구투여시의 간독성에 관한 연구 (Hepatotoxicity in treatment of canine dermatophytosis with ketoconazole)

  • 배성수;김철호;김태융;강정부
    • 대한수의학회지
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    • 제45권2호
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    • pp.255-261
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    • 2005
  • The purpose of this study is to compare hepatotoxicity of each treatment for dermatophytosis; one is the administration of the ketoconazole only and the other, ketoconazole with diphenyl-dimeththyl-dicarboxylate. Have chosen the range of 14-24 months of healthy dogs divided by two groups (group 1 and group 2) for the experiment of which test proved positive in dermatophytosis diagnosis and showed normal reaction in terms of physical examination, blood chemistry and especially of liver function. Group 1 was administrated ketoconazole orally at 10 mg/kg/day and of same dose of ketoconazole with diphenyl-dimethyl-dicarboxylate for group 2. After administering, we have tested two groups by blood collecting every one week in order to check the differences of hepatotoxicity state through AST, ALT and r-GTP, the barometers of liver function which lasted for 12 weeks. Moreover, tested Indocyanine Green (ICG), known as susceptible gauge of function of excretion before starting the experiment and tested ICG as well after 12 weeks. The experiment of result the value of group 1 in AST, ALT and r-GTP has been highly rised after administering ketoconazole for 10 weeks meanwhile, of group 2 has shown a steady state troughout the whole experiment. For ICG test, we injected 0.5 mg/kg of ICG into a vein for both groups and tested the retention rate at regular interval of 15, 30, 45 minutes. The results of retention rate in two groups were similar to before the drug administration. However, after 12 weeks the retention rate of group 1 has been delayed, on the other hand, retention rate of group 2 were a steady state. In conclusion, the administration of ketoconazole only for a long period of time induced hepatotoxicity where as, the administration of ketoconazole with diphenyl-dimethyl-dicarboxylate didn't induce hepatotoxicity. Therefore, when doctors prescribes for a dog with dermatophytosis should not administrate ketoconnazole itself but with diphenyl-dimethyl-dicarboxylate and one who has abnormal condition of liver function should not be prescribed ketoconazole treatment. If there is a case needed to prescribe ketoconazole treatment, the regular monitoring should be accompanied by at the same time.

담쟁이덩굴 추출물과 분획물의 항산화, 항당뇨 및 항염증 효과 (Antioxidant, Antidiabetic, and Anti-Inflammatory Effects of Extracts and Fractions from Parthenocissus tricuspidata Stems)

  • 조은경;최영주
    • 생명과학회지
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    • 제23권3호
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    • pp.399-405
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    • 2013
  • 본 연구에서는 담쟁이덩굴 추출물이 항산화, 항당뇨 및 항염증 효과에 미치는 영향을 조사하고자 수행하였다. 담쟁이덩굴 열수 및 에탄올 추출물의 총 페놀함량은 각각 61.5 mg TAE/g과 122.1 mg TAE/g으로 에탄올 추출물에서 훨씬 높게 나타났다. 에탄올 추출물과 부탄올 분획물의 DPPH 라디칼 소거활성은 1 mg/ml에서 95%와 92%의 radical 소거능을 나타내어 positive control로 사용한 비타민 C와 유사한 항산화력을 보였다. SOD 활성은 에탄올 추출물과 부탄올 분획물 1 mg/ml 농도에서 91%, 97%로 높은 활성을 나타내었다. DPPH radical 소거능과 SOD 활성을 측정한 결과 항산화 활성은 모두 농도 의존적으로 증가하였으며 특히 열수추출물과 비교할 때 에탄올 추출물과 부탄올 분획물에서 높은 항산화 효과를 보였다. 담쟁이덩굴 추출물의 ${\alpha}$-glucosidase 활성억제 효과는 에탄올 추출물과 핵산 및 부탄올 분획층에서 높은 항당뇨 효과를 나타내었다. 이러한 결과는 지금까지 항당뇨 약물로 사용된 것보다도 높은 것으로 나타났다. LPS에 의하여 유도된 NO 합성은 1 mg/ml 농도의 담쟁이추출물을 처리함으로써 NO 합성이 약 40%로 감소하였다. 이러한 결과들은 담쟁이 추출물의 우수한 항산화, 항당뇨, 항염 효과를 시사하고 있으며 특히, 천연 항당뇨 기능성 소재로서 담쟁이 추출물의 활용 가능성이 높을 것으로 사료된다.

Development of cell models for high-throughput screening system of Charcot-Marie-Tooth disease type 1

  • Choi, Yu-Ri;Jung, Sung-Chul;Shin, Jinhee;Yoo, So Young;Lee, Ji-Su;Joo, Jaesoon;Lee, Jinho;Hong, Young Bin;Choi, Byung-Ok
    • Journal of Genetic Medicine
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    • 제12권1호
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    • pp.25-30
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    • 2015
  • Purpose: Charcot-Marie-Tooth disease (CMT) is a peripheral neuropathy mainly divided into CMT type 1 (CMT1) and CMT2 according to the phenotype and genotype. Although molecular pathologies for each genetic causative have not been revealed in CMT2, the correlation between cell death and accumulation of misfolded proteins in the endoplasmic reticulum (ER) of Schwann cells is well documented in CMT1. Establishment of in vitro models of ER stress-mediated Schwann cell death might be useful in developing drug-screening systems for the treatment of CMT1. Materials and Methods: To develop high-throughput screening (HTS) systems for CMT1, we generated cell models using transient expression of mutant proteins and chemical induction. Results: Overexpression of wild type and mutant peripheral myelin protein 22 (PMP22) induced ER stress. Similar results were obtained from mutant myelin protein zero (MPZ) proteins. Protein localization revealed that expressed mutant PMP22 and MPZ proteins accumulated in the ER of Schwann cells. Overexpression of wild type and L16P mutant PMP22 also reduced cell viability, implying protein accumulation-mediated ER stress causes cell death. To develop more stable screening systems, we mimicked the ER stress-mediated cell death in Schwann cells using ER stress inducing chemicals. Thapsigargin treatment caused cell death via ER stress in a dose dependent manner, which was measured by expression of ER stress markers. Conclusion: We have developed genetically and chemically induced ER stress models using Schwann cells. Application of these models to HTS systems might facilitate the elucidation of molecular pathology and development of therapeutic options for CMT1.

랫드를 이용한 황기의 지상부 추출물에 대한 90일 반복경구투여 독성시험 (A 90 Day Repeated Dose-Oral Toxicity Study of Extracts from Astragalus membranaceus-Aboveground Parts in Rats)

  • 박영철;이지선;김동윤;손혜영;이정우;최유순;김광기;유창연;정일민;임무혁;이경재;최리나;심훈섭;임정대
    • 한국약용작물학회지
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    • 제21권6호
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    • pp.474-485
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    • 2013
  • Pharmacological studies and clinical practices have indicated that Radix Astragali, a dried root of Astragalus membranaceus possesses a lot of biological activities, including antioxidant, hepatoprotective, anti-diabetic, tonic, diuretic, antimicrobial, antiviral, and immunological activities. These biological activities approved by the modern pharmacological studies are mainly due to the constituents of Astragalus membranaceus including polysaccharides, saponins, flavonoids, amino acids, and trace elements. In resent, the main constituents in the root part showing a lot of biological activities has been isolated also from the aboveground parts such as leaves and sprouts in our laboratory. However, the safety evaluation for the aboveground parts of Astragalus membranaceus should be checked before expanding their application as one of food. In the study, a 90-day rat oral gavage study has been conducted with the extracts from Astragalus membranaceus-above-ground parts at doses of 1000, 3000, and 5000mg/kg/day. The following endpoints were evaluated: clinical observations, body weight, gross and microscopic pathology, clinical chemistry, and hematology. Based on the analysis of these endpoints, it was estimated that NOEL (no observed effect level) for male rats and NOAEL (no observed adverse effect level) for female rats are 5000mg/kg/day of the water-extracts from Astragalus membranaceus-aboveground parts.

비단벌레(Crysochroa fulgidissima) 에탄올추출물의 NO 증강 및 염증인자억제활성 (NO and Cytokine Production due to Crysochroa fulgidissima)

  • 안미영;김순자;정혜경;서윤정;박해철;이영보;김미애
    • 한국응용곤충학회지
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    • 제50권3호
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    • pp.227-233
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    • 2011
  • 비단벌레(C. fulgidissima)는 동아시아에서 중풍을 치료하는 약으로 한국에서는 살충, 지양제로서 사용한 기록이 있다. 본 연구는 비단벌레의 에탄올 추출물의 내피세포에서의 산화질소(NO) 증강효과와 내피성 산화질소 합성효소(eNOS)의 양적 증가를 조사하였다. 그 결과 비단벌레 에탄올 추출물은 양성대조약물 sodium nitroprusside에 비해 65.9%의 NO 증강 효과를 가지는 것을 확인하였다. 또한 eNOS에 대해서도 농도 의존적으로 증가시킴을 확인하였다. 염증성부착인자인 ICAM-1과 VCAM-1 수치와 염증매개인자 프로스타글란딘 $E_2$를 조사하여 비단벌레 에탄올 추출물의 염증억제 기전을 조사한 결과, HUVEC 세포에서 농도 의존적으로 염증매개인자와 염증성부착인자의 감소를 확인하였다. 아울러 혈관성 내피성장인자(VEGF)의 낮은 수치를 HUVEC 세포에서 관찰할 수 있었다. 에탄올 추출물을 HPLC로 부분정제 후 GC-MS와 MALDI-TOF 분석을 통하여 일부 칸다리딘 성분 함유함을 확인하였다

Latex of Ficus carica L. Induces Apoptosis Through Caspase and Bcl-2 Family in FaDu Human Hypopharynx Squamous Carcinoma Cells

  • Shin, Bo Su;Lee, Seul Ah;Moon, Sung Min;Han, Seul Hee;Hwang, Eun Ju;Kim, Su-Gwan;Kim, Do Kyung;Kim, Jin-Soo;Park, Bo-Ram;Kim, Chun Sung
    • International Journal of Oral Biology
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    • 제42권4호
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    • pp.183-190
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    • 2017
  • Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

직접 대면 방식과 병행한 전화를 이용한 복약상담이 제 2형 당뇨병 환자의 치료성과에 미치는 영향 (The Effects of Follow-up Telephone Calls Combined with Face-to-face Meetings on Clinical and Humanistic Outcomes in Patients with Type 2 Diabetes Mellitus)

  • 곽은정;신현정;천부순
    • 약학회지
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    • 제59권6호
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    • pp.270-277
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    • 2015
  • There is a lack of evidence on the impact of pharmacist interventions in diabetes care in South Korea. The aim of this study was to investigate the effects of pharmacist counseling on clinical and humanistic outcomes in patients with type 2 diabetes. An uncontrolled before-and-after study was conducted at the outpatient diabetes clinic in a teaching hospital in Gyeongnam, South Korea between January 2 and November 30, 2014. A total of 37 patients were enrolled. During the study periods, the participants and pharmacists met every 2 weeks via follow-up telephone calls in addition to face-to-face meetings upon returning for care visit. At each meeting, a structured patient counseling was performed and the average duration of each meeting was 15~30 minutes. The participants were requested to record daily self-care activities. At the end of this study, patients' satisfaction on pharmacist care was evaluated using the questionnaire developed by us. Compared to baseline, significant reductions (mean${\pm}$standard deviation, p<0.05) in HbA1c were observed at each follow-up period: $-0.32{\pm}0.72%$ from baseline to 3 months; $-0.52{\pm}0.76%$ from baseline to 6 months; $-0.72{\pm}0.76%$ from baseline to 9 months. Over the same follow-up period, the proportions of patients achieving target HbA1c (defined as HbA1c<6.5%) were 3.1%, 10.3%, and 20%, respectively. The proportions of patients who never missed a dose during the same follow-up period were 43.8%, 31.0%, and 20.0%, respectively. The results from the patient satisfaction survey indicated that pharmacist counseling improved patients' knowledge about diabetes and possible drug interactions. Especially, the information on a healthy diet and lifestyle was the most satisfying. To conclude, follow-up telephone calls combined with face-to-face meetings improved clinical and humanistic outcomes in patients with type 2 diabetes mellitus.

세토카 가지 정유의 성분 분석 및 생리 활성 (Chemical Composition and Biological Activities of Essential Oil from 'Setoka' Branches)

  • 현주미;김정은;염현숙;송정민;김미량;이남호
    • 대한화장품학회지
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    • 제42권3호
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    • pp.227-233
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    • 2016
  • 본 연구에서는 세토카 가지 정유의 주요 성분을 분석하고 이들의 항균, 항염 및 세포독성 실험을 진행하였다. 세토카는 제주도에서 널리 재배되고 있는 감귤류의 품종이다. 세토카 나무의 가지는 간벌 작업으로 인해 대부분 폐기되고 있고, 이러한 폐자원의 활용은 최근 많은 관심을 받고 있다. 정유 성분은 세토카 가지의 에탄올 추출물을 호호바오일로 처리하여 얻었다. 세토카 정유의 주요 성분은 ethyl linoleate (64.1%), ethyl palmitate(16.5%), neophytadiene (11.1%) 및 ${\beta}$-citronellol (5.1%)임을 확인하였다. 이들의 항균활성을 확인하기 위하여 피부 관련 미생물에 대한 paper disc 확산법을 실시한 결과 Staphylococcus aureus 및 Propionibacterium acnes에서 좋은 항균활성을 보였다. 또한 항염활성을 확인하기 위해 lipopolysaccharide(LPS)로 염증이 유도된 대식세포에서 nitric oxide (NO) 생성량을 측정한 결과 세토카 정유 성분은 농도의존적으로 NO 생성을 저해하였다. WST-1 분석법을 이용하여 세포독성을 측정한 결과 RAW 264.7 macrophage 및 HaCaT 각질형성세포에서 세포생존율이 무처리 대조군과 비슷한 결과를 보였다. 이러한 결과를 바탕으로 세토카 가지 정유는 세포독성이 없으면서 염증억제 및 항균효과가 있음을 확인하였으며, 이를 응용한 화장품소재로써의 개발이 가능할 것으로 여겨진다.

Apoptotic Activity of Curcumin and EF-24 in HTB-41 Human Salivary Gland Epidermoid Carcinoma Cells

  • Kim, Ji-Won;Lee, Seul Ah;Go, Dae-San;Park, Byung-Sun;Kim, Su-Gwan;Yu, Sun-Kyoung;Oh, Ji-Su;Kim, Chun Sung;Kim, Jeongsun;Park, Jong-Tae;Kim, Do Kyung
    • International Journal of Oral Biology
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    • 제40권2호
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    • pp.63-69
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    • 2015
  • Curcumin (diferuloylmethane), a constituent of turmeric powder derived from the rhizome of Curcuma longa, has been shown to inhibit the growth of various types of cancer cells by regulating cell proliferation and apoptosis. However, a need exists to design more effective analogs because of curcumin's poor intestinal absorption. EF-24 (diphenyl difluoroketone), the monoketone analog of curcumin, has shown good efficacy in anticancer screens. However, the effects of curcumin and EF-24 on salivary gland epidermoid carcinoma cells are not clearly established. The main goal of this study was to investigate the effects of curcumin and EF-24 on cell growth and induction of apoptosis in human salivary gland epidermoid carcinoma cells. Our studies showed that curcumin and EF-24 inhibited the growth of HTB-41 cells in a dose- and time-dependent manner, and the potency of EF-24 was > 34-fold that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in HTB-41 cells, whereas the control HTB-41 cell nuclei retained their normal regular and oval shape. Curcumin and EF-24 promoted proteolytic cleavages of procaspase-3/-7/-9, resulting in an increase in the amount of cleaved caspase-3/-7/-9 in the HTB-41 cells. Caspase-3 and -7 activities were detected in viable HTB-41 cells treated with curcumin or EF-24. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptosis in HTB-41 human salivary gland epidermoid carcinoma cells, and that they may have potential properties as an anti-cancer drug therapy.

Regenerative effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) after sequestrectomy of medication-related osteonecrosis of the jaw (MRONJ)

  • Min, Song-Hee;Kang, No-Eul;Song, Seung-Il;Lee, Jeong-Keun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제46권3호
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    • pp.191-196
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    • 2020
  • Objectives: Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ. Materials and Methods: In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site. Results: This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann-Whitney U-test, P<0.05). Conclusion: Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.