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  • Title/Summary/Keyword: 복합독성

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Effects of complex extracts having Drynariae Rhizoma on suppression of collagenolysis and bone resorption in mouse calvarial osteoblasts (골쇄보(骨碎補) 복합제제가 생쥐의 calvarial osteoblast에서 collagen 용해와 골재흡수에 미치는 영향)

  • Hong, Shi-Nae;Jeong, Ji-Cheon
    • The Journal of Dong Guk Oriental Medicine
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    • v.9
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    • pp.179-191
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    • 2000
  • Anti-bone resorption properties of the Korean herbal medicine, CEDR, which is comprised 5 herbs of [Drynariae Rhizoma, Loranthi Ramus, Cibotii Rhizoma, Amydae carapax, Psoraleae semen], were investigated. Mouse calvarial osteoblast cells were isolated and cultured. Mouse osteoblasts, which were stimulated by PTH, 1,25(OH)2D3, TNFα and IL-1 as bone resorption agents, showed increased collagenolysis by producing the active gelatinase. IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. The results of in vitro cytotoxicities showed that CEDR extracts have no any cytotoxicities in concentrations of 160μg/ml and furthermore there is no any cytotoxicity even in concentration of 120μg/ml on mouse calvarial bone cells. CEDR extracts had protective activity against PTH (5 units/ml, or IL1α (1 ng/ml) or TNFα or 1,25(OH)2D3 (20 ng/ml), IL1α and IL1βinduced collagenolysis in the mouse calvarial cells. Pretreatment of the CEDR extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore, the medicinal extracts were shown to have the protective effects against collagenolysis induced by IL1α and IL1β. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the CEDR extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resorption agents of PTH, 1,25(OH)2D3, TNFα, IL1β and IL1α with strong protective effect in pretreatment with the extracts. CEDR extracts were shown to have the inhibiting effects against IL1α and IL1βstimulated bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. These results indicated that the CEDR extracts are highly stable and applicable to clinical uses in osteoporosis.

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Cell Death Study in Embryonic Stem Cell-derived Neurons and Its Applications (배아줄기세포 유래 신경계세포에서의 세포사멸 연구와 그 응용)

  • Lee, Chul-Sang
    • Development and Reproduction
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    • v.12 no.1
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    • pp.1-8
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    • 2008
  • Specific protocols to increase the differentiation of neuronal cells from embryonic stem (ES) cells have been well established, such as retinoic acid induction and lineage selection of neuronal cells. For the neuropathological studies, ES-derived neurons (ES neurons) must show normal physiological characteristics related to cell death and survival and should be maintained in vitro for a sufficient time to show insults-specific cell death without spontaneous death. When mouse ES cells were plated onto astrocytes monolayer after retinoic acid induction, most ES cells differentiated into neuronal cells, which were confirmed by the presence of specific neuronal markers, and the cultures were viable for at least four weeks. When these cultures were examined for vulnerability to glutamate excitotoxicity, ES neurons were vulnerable to excitotoxic insults mediated by agonist-specific receptors. The vulnerability to excitotoxic death increased with developmental age of ES neurons in vitro. Specific receptors for Neurotrophin and GDNF family ligands were present in ES neurons. GDNF and NT-3 could modulate the survival and excitotoxic vulnerability of ES neurons. The vulnerability and resistance to toxic insults, which are essential requirements of model culture systems for neuropathological studies, make ES neurons to a useful model culture system. Especially ES cell are highly amenable to genetic modification unlikely to primary neuronal cells, which will give us a chance to answer more complicated neurophysiological questions. Recently there was an outstanding attempt to explore the cellular toxicity using human ES cells (Schrattenholz & Klemm, 2007) and it suggested that ES cells could be a new model system for neurophysiological studies soon and go further a large-scale screening system for pharmacological compounds in the future.

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Concurrent Chemoradiotherapy in Locally Advanced Carcinoma of The Uterine Cervix : A Phase I/II Prospective Study (국소적으로 진행된 자궁경부암의 방사선치료와 복합 항암화학요법의 동시치료 결과)

  • Kang One Chul;Choi Eun Kyung;Chung Weon Kuu;Kim Jong Hoon;Chang Hyesook;Kim Yong Man;Kim Young Tak;Nam Joo Hyun;Mok Jung-Eun;Lee Moo-Song
    • Radiation Oncology Journal
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    • v.16 no.3
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    • pp.311-323
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    • 1998
  • Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/m2/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/m2/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52% and 64%, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58% and 36%, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71% and 40%, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9% (19/68) : local failure in 5.9% (4/68), distant metastasis in 10.3% (7/68) and both in 11.8% (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78% (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

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Phase II Study of Concurrent Chemotherapy with Etoposide and Cisplatin (EP) and Radiation Therapy for Unresectable Stage III Non-small Cell Lung Cancer (수술이 불가능한 제 III기 비소세포폐암에서 Cisplatin 및 Etoposide(EP)의 화학요법과 방사선요법의 병행요법(2상 임상연구))

  • Hur, Nam-Hyun;Lee, Choon-Taek;Kim, Jae-Hag;Jang, Jae-Jin;Nam, Seung-Mo;Park, Yeon-Hee;Ryoo, Baek-Yeol;Kim, Tae-You;Im, Young-Hyuck;Kang, Yoon-Koo;Kim, Mi-Sook;Yoo, Seong-Yul;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.776-784
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    • 1997
  • Background : Various combinations of treatment modalities have been reported in stage III non-small cell lung cancer (NSCLC). however, the standard treatment modality has not established yet. Recently, the efficacy of concurrent chemotherapy and radiation therapy has been reported in locally advanced lung cancer. We evaluate the response rate, toxicity, and survival of concurrent chemotherapy with etoposide and cisplatin(EP) and radiation therapy for unresectable stage III NSCLC. Method : Between October 1995 and December 1996, 32 patients with histologically proven unresectable stage III NSCLC without malignant pleural effusion were entered into this study. Twenty-nine patients were eligible for the response, survival, and toxicity analysis. Induction was two cycles of chemotherapy with etoposide and cisplatin plus concurrent chest RT to 4500cGy. Resection was attempted if the clinical response offered surgical resectability. Boost radiation therapy upto 5940cGy and one cycle of EP were performed if the disease were stable or responsive but still unresectable. Results : Of 29 eligible patients, 22(75.9%) showed partial response(PR). The progression free interval was 6.3months(range 1.1 to 19.5months). Surgical resection was performed in one patient. The median survival was 12.1months and one-year survival rate was 50.6%. The major toxicity was leukopenia( grade 3, 46%). Thrombocytopenia over grade 3 was found in 11%. Radiation pneumonitis occurred in 13 patients(46%). Conclusion : Concurrent chemotherapy(EP) plus radiotherapy was effective and tolerable in the treatment of unresectable stage III NSCLC.

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Phase II Study of Gemcitabine and Vinorelbine as a Combination Chemotherapy for the Second-Line Treatment of Nonsmall Cell Lung Carcinoma (비소세포 폐암 환자의 2차 치료로서 Gemcitabine과 Vinorelbine의 병합 요법의 효과)

  • Lee, EunJoo;Ha, EunSil;Park, SangHoon;Hur, GyuYoung;Jung, KiHwan;Jeong, HyeCheol;Lee, SungYong;Kim, JeHyeong;Lee, SangYeub;Sin, Chol;Shim, JaeJeong;In, KwangHo;Kang, KyungHo;Yoo, SeHwa
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.5
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    • pp.510-516
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    • 2005
  • Backgroud : Lung cancer is the leading cause of cancer deaths in Korea and the number of lung cancer deaths is increasing. The higher response rates, decreased toxicity and improved performance status of the first-line treatments have resulted in an increased number of patients becoming candidates for second-line therapy. Several new antineoplastic agents, including gemcitabine, docetaxel and paclitaxel, have recently demonstrated second-line activity. This phase II study evaluated the efficacy and toxicity of gemcitabine and vinorelbine as combination chemotherapy for Korean patients with NSCLC as a second-line treatment. Methods : Sixty response-evaluable patients were enrolled from December 2000 to July 2003. We conducted a phase II study of a combination gemcitabine and vinorelbine chemotherapy for patients with histologically confirmed NSCLC that was stage IIIB and IV disease at the time of diagnosis, and the disease had progressed onward or the patients had relapsed after first-line platinum-based chemotherapy. They were treated with intravenous gemcitabine 1000mg/m2 and intravenous vinorelbine 25mg/m2 on days 1 and 8. This chemotherapy regimen was repeated every 3 weeks. Results : A total of 215 cycles of treatment were given and the mean number of cycles was 3.6 cycles. All the patients were evaluable for the toxicity profile. The response rate was 10% according to the WHO criteria. The median progression free survival was 3.8 months and the median survival time was 10.1 months. The 1-year survival rate was 32.9%. Grade III and IV neutropenia were seen in 20 (33.3%) and 7 (11.7%) patients, respectively. Conclusion : The combination of gemcitabine and vinorelbine is active and well tolerated as a second-line therapy for patients with advanced nonsmall cell lung carcinoma.

Effect of Mulberry (Morus alba L.) Extract on Blood Flow Improvement (오디 추출물(Morus alba L.)의 혈행개선 효과)

  • Park, Youn-Sil;Kang, Seong-Sun;Choi, Hyoung-Ja;Yang, Sung-Jun;Shon, Ho-Hyeong;Seo, Hyeong-Ho;Jeong, Jong-Moon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.4
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    • pp.498-506
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    • 2014
  • The objective of this study was to investigate the beneficial effects of mulberry extract (MBE) on blood flow improvement. The SC50 value for the DPPH radical scavenging activity of MBE was 89.36±5.46μg/mL. Analysis of the cellular toxicity of MBE on RAW 264.7 and HepG2 cells showed no toxicity under a concentration of 2,500 μg/mL. We found that MBE inhibited the enzyme activity of cyclooxygenase (COX)-2 as well as oxidation of human LDL. Western blotting analysis showed that MBE inhibited protein expression of COX-2 and 5-lipoxygenase in RAW 264.7 cells. In addition, MBE inhibited protein expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, MBE reduced the serum levels of total cholesterol and C-reactive protein in a concentration-dependent manner. These results both in vitro and in vivo suggest that MBE can be employed for the improvement of blood flow.

Composition Ratio Analysis of Transesterification Products of Olive Oil by Using Thin Layer Chromatography and Their Applicability to Cosmetics (올리브 오일의 에스터 교환반응 생성물의 TLC를 이용한 조성비 분석 및 화장품에의 응용가능성 평가)

  • Park, So Hyun;Shin, Hyuk Soo;Kim, A Rang;Jeong, Hyo Jin;Xuan, Song Hua;Hong, In Kee;Lee, Dae Bong;Park, Soo Nam
    • Applied Chemistry for Engineering
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    • v.29 no.3
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    • pp.342-349
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    • 2018
  • In this study, the physicochemical properties, emulsifying capacity, moisture content and cytotoxicity of the composite material produced by transesterification reactions of the olive oil (olive oil esters) were investigated for cosmetic applications. Olive oil esters with short (S) and long (L) reaction times were studied. From the TLC-image analysis, composition ratios of the olive oil esters S were found to be 5.2, 24.1, 46.4, and 21.9% for mono-, di-, tri-glyceride, and fatty acid ethyl ester, respectively. Those of the olive oil esters L were 4.1, 24.7, 40.6, and 28.8% for mono-, di-, tri-glyceride, and fatty acid ethyl ester, respectively. The iodine value, acid value, saponification value, unsaponified matter, refractive index, and specific gravity were determined and purity tests were also carried out and normalized to establish standards and testing methods for using olive oil esters in cosmetics. To evaluate their emulsifying capacities, the O/W emulsion was prepared without surfactants and the formation of the emulsified particles were confirmed. After 5 days of applying the olive oil esters to human skin, the skin moisture retention was improved by 13.1% from the initial state. For the evaluation of toxicity on human skin cells, the olive oil esters showed 90% or more of the cell viability at 0.2200μg/mL. These results suggested that olive oil esters can be applied as natural/non-toxic ingredients to cosmetics industries.

Pulmonary Toxicity Following High-Dose Chemotherapy With Peripheral Blood Stem Cell Transplantation (고용량 항암화학요법 후에 발생한 폐손상)

  • Lee, Sun-Min;Park, Kwang-Joo;Oh, Yoon-Jung;Cheong, Seong-Cheoll;Hwang, Sung-Chul;Lee, Yi-Hyung;Kim, Hyun-Soo;Lim, Ho-Yeong;Kim, Hugh-Chul;Yim, Hyun-Ee;Hahn, Myung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.1
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    • pp.77-89
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    • 1999
  • Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/m2 and that of cyclophosphsmide was 6,000 mg/m2. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

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Growth Inhibition of Rats Fed Raw or Heated Korean Beans and the Effect of Methionine or Protein Supplementation (한국산 생두류 및 익힌두류를 섭취한 흰쥐의 성장저해와 Methionine 및 단백질 첨가의 영향)

  • Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.18 no.2
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    • pp.126-138
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    • 1985
  • A study was made on the effect of anti-nutritional factors found in some Korean beans : soybean, red bead, mung bean and kidney bean. Two animal experiments were conducted to investigate the nutritional value of the beans. The first experiment, in which the diet contained 15% protein from raw beans, compared the intensity of inhibition caused by methionine deficiency or a total amino acid deficiency. In the second experiment, the conditions were the same as in experiment I, except that heated beans were substituted for raw beans. Severe growth inhibition and high mortality was found in the raw kidney bean and red bean groups than in the soybean and mung bean groups. As no effect on the growth inhibition of raw bean groups was shown by methionine and protein supplementation, the inhibition could be ascribed mainly to the low feed intake and the low protein digestibility caused by toxic factors. Pancreatic enlargement was obserbed in all the raw bean groups. A increase in body weight, a decrease in mortality and a decrease in the weight pancreases were found in the heated bean groups. But the digestility of the diet and of the protein and the PER by heating did not increase as markedly as weight, except in the heated red bean groups. Even with heat treatment, the whole inhibitory action could not be eliminated.

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Comparative Chemical Compositions of Four Kinds of Tochukaso (동충하초 품종별 영양성분 비교)

  • Oh, Se-Wook;Kim, Sun-Hee;Song, Hyo-Nam;Han, Dae-Seok
    • Korean Journal of Food Science and Technology
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    • v.35 no.1
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    • pp.15-22
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    • 2003
  • Nutritional compositions of three Tochukaso species (Paecilomyces tenuipes hosted by Larva and pupa, Cordyceps militaris, C. sinensis) were compared. Fruiting body and host fractions were separately analyzed. Fruiting body fraction of P. tenuipes (36.6%) hosted by larva was higher than that hosted by pupa (10.2%), an indication that the quality of the former is superior to the latter. Carbohydrate content of C. sinensis (39.6%) was 2.57 times higher than those of others, probably due to the presence of polysaccharides. Protein and crude lipid contents of C. sinensis and C. militaris were 25.8 and 10.3%, and 75.1 and 3.9%, respectively. C. sinensis showed the lowest Ca content and 3075 times higher Fe content among the samples tested. Vitamin A content of C. militaris was 308.9 IU/100g, two fold higher than those of the other species. Saturated fatty acid content was the highest in P. tenuipes (pupa, 27.7%), whereas unsaturated fatty acid was the highest in P. tenuipes (larva, 83.3%). Aspartic acid, glutamic acid, and glycine were abundant in all species. Cordycepin content of C. militaris was 2050 times higher than those of the other species.