• Title/Summary/Keyword: Toxicity Test

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A Study on the Effect and Mechanism of Gamikyejakjimogawusul-tang Herbal Acupuncture on Induced Rheumatoid Arthritis model of DBA/1 mice (계작지모가우슬탕(桂芍知母加牛膝湯) 약침이 류마티스 관절염 생쥐에 미치는 영향)

  • Jung, Soon Hyun;Cho, Chong kwan;Kim, So Yun;Kim, Young Il
    • Journal of Haehwa Medicine
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    • v.24 no.2
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    • pp.35-57
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    • 2016
  • Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.

Efficacy and Toxicity of Anti-VEGF Agents in Patients with Castration-Resistant Prostate Cancer: a Meta-analysis of Prospective Clinical Studies

  • Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8177-8182
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    • 2014
  • Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline ${\geq}50%$) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy.

Guideline of Improvement and Evaluation of Prescribing Errors in Colorectal Chemotherapy (대장암 항암 화학요법의 처방 오류 평가 및 개선안 제시)

  • Lim, Hyun-Soo;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.2
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    • pp.158-166
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    • 2013
  • Background: Colorectal cancer shows a significant increase in South Korea due to westernization of diet, lack of dietary fiber, drinking and smoking, irregular defecation. There are surgery, chemotherapy, radiation therapy in treatment of colorectal cancer. There may be a medication errors in the process of chemotherapy because of its high toxicity, narrow therapeutic index and the health status of cancer patients. Consequently medication errors can cause increasing the risk of death, prolonging hospital stay and increasing the cost. Among medication errors on medication use process, prescribing errors are of particular concern due to higher risk of serious consequences. It is important for pharmacist to prevent the prescribing errors before reaching patient. Therefore we analyzed the prescriptions of colorectal cancer, classified prescribing errors, suggested guideline to reduce prescribing errors and verified the importance of pharmacist's role in prevention of medication errors activity. Methods: We collected the numbers of prescriptions of colorectal cancer(n=2,373) through anti cancer management program and EMR and analyzed the errors of prescriptions by categories from Oct 1st 2011 to Sep 30th 2012 at Chungbuk National University Hospital. We reviewed the prescriptions as follows - patients' characteristics, the result of test, previous prescriptions, characteristics of antineoplastic agents and patients' allergy, drug sensitivity, adverse events. Prescriptions are classified into inpatient and outpatient and analyzed the errors of prescriptions by categories (dosage form, dose, input, diluents, regimen, product). Results: Total prescription number of inpatient and outpatient of colorectal cancer was 1,193 and 1,180 and that of errors was 107(9%) and 22(1.9%), respectively. In case of errors of categories, the number of errors of dosage form is 69 and 8, errors of dose is 15 and 5, errors of input is 9 and 9 in inpatient and outpatient prescriptions, respectively. Errors of diluents is 8, errors of regimen is 3, errors of product is 3 in only inpatient prescriptions. In case of errors of categories by inpatient department, the number of errors of dosage form is 34 and 35, errors of dose is 7 and 8, errors of input is 6 and 3, errors of diluents is 4 and 4, errors of regimen is 2 and 1, errors of product is 2 and 1 in SG and HO, respectively. In case of outpatient department, the number of errors of dosage form is 8 in HO, errors of dose is 5 in HO, errors of input is 5 and 4 in SG and HO, respectively. Conclusions: The rate of errors of inpatient is higher than that of outpatient. Junior doctors are engaged in prescriptions of inpatient and pharmacist need to pay attention to review all prescriptions. If prescribing errors are discovered, pharmacist should contact the prescriber and correct the errors without delay. The guideline to reduce prescribing errors might be upgrading software of anti cancer management program, education for physicians as well as pharmacists and calling prescriber's attention to preventing recurrence of errors.

Development of bio-fusion materials with skin penetrating property derived from Aurelia aurita (경피 침투율이 높은 보름달 물해파리 유래 바이오 융합 소재 개발)

  • Kim, Hyoung Sik;Seo, Hyo Hyun;Lee, Seo-Hui;Lim, Hyun Jung;Shin, Jeong Won;Kim, Seop Ri;Moh, Sang Hyun;Kim, Kwang-Hwan
    • Journal of the Korea Convergence Society
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    • v.8 no.1
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    • pp.35-42
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    • 2017
  • Previously, we reported LVH peptiede derived from Aurelia aurita as cosmecetuticals with anti-winkle activity. In this study, we synthesized pal-LVH using palmitic acid to enhance skin permeability of LVH and examined the effects as cosmeceuticals of pal-LVH. To evaluate these effects, we performed cell toxicity, wound healing, and patch test for skin irritation with LVH and pal-LVH and compared these results for their effects. As a result. pal-LVH was not showed in cytotoxicity and allergenic effect like as LVH. Besides, pal-LVH had almost same excellent anti-ageing properties in high concentration and anti-winkle effect in low concentrationwas as LVH. These results suggested synthesis of palimitic acid and LVH did not affect any functions as cosmeceuticals with increasing skin permeability. Therefore, pal-LVH can be adaptable as new cosmecetuticals with anti-winkle and anti-ageing materials and applied in the development of medicine through various convergence study.

Effects of Galgeunhaegitang-gamibang Administration along with Samhwangseze-gamibang on Atopic Dermatitis of NC/Nga Mice (갈근해기탕가미방(葛根解肌湯加味方)과 삼황세제가미방(三黃洗劑加味方) 병용이 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Hwang, Chi-Hwan;Yun, Chae-Sung;Song, Seung-Hyeon;Weon, Young-Ho;Hwang, Chung-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.21 no.2
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    • pp.1-18
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    • 2008
  • Objectives: Galgeunhaegitang-gamibang(GH) and Samhwangseze-gamibang(SG) has been known that they are helpful for treatment of atopic dermititis clinically, but there is no report about the effect of GH and SG. So, author aimed to investigate the effects of GH and SG on atopic dermititis of NC/Nga mice. Methods : NC/Nga mice were divide into three group : normal, control, and experimental group. Atopic dermatitis was induced in the control and experimental group by spreading DNCB. Then GH was orally administered three times in a week for 8 weeks to the experimental group and SG was spreaded two times in a day for 8 weeks to the experimental group, while the control group was given normal saline. We observed changes of clinical skin severity score, serum IgE, IL-4, IL-4, IL-5, IL-6, IgM, IgGl, $IFN-{\gamma}$ and so on. We used one-way ANOVA test statistically(p<0.01). Results : Clinical skin severities of experiment group in 13 and 16weeks were significantly decreased by 48% and 55% compared to the control group. Serum IgE, IL-4, IL-5, IL-6, IgM, IgGl levels of experimental group were singnificantly decreased compared to the control group. Serum $IFN-{\gamma}$ level of the experimental group was significantly increased against control group. mRNA expression levels of IL-4, IL-5, IL-6 and CCR3 in the skin tissues of experimental group were significantly decreased compared to the control group. In contrary, $IFN-{\gamma}$y mRNA expression level were increased compared to the control group. Histological observation of the ear and skin tissues showed that the extents of inflammation and infiltrated immune cells in the epidermis and dermis of experimental group were highly deminished compared to the control group. Judging from that $IL-1{\beta}$, $TNF-{\alpha}$, IL-6 expression of gene, the effects of inflammatory cytokine revelation were significantly decreased compared to the control group. In the model inducing COX-2 activity in RAW 264.7 cell, COX-2 activity was significantly inhibited depending on the density of GH compared to the control serum. According to cell multiplication, examination of cell toxicity showed that GH is safe at the density of 10, 50, 100mg/l and even 1000mg/l. Conclusion : Accordin to the above results, it is considered that GH and SG is effective treatment for the atopic dermatitis.

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Quality Characteristics and Environmental Impact Assessment of Alkali-Activated Foamed Concrete (알카리활성 기포콘크리트의 품질특성 및 환경영향 평가)

  • Yang, Keun-Hyeok;Yoo, Sung-Won;Lee, Hyun-Ho;Kim, Sang-Chel
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.1 no.2
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    • pp.114-119
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    • 2013
  • The present study tested 5 concrete mixes to develop reliable mixing proportions for the sustainable alkali-activated(AA) foamed concrete as a thermal insulation material for the floor heating system of buildings. The AA binder used was composed of 73.5% ground granulated blast-furnace slag, 15% fly ash, 5% calcium hydroxide, and 6.5% sodium silicate. As a main variable, the unit binder content varied from $325kg/m^3$ to $425kg/m^3$ at a space of $25kg/m^3$. The test results revealed that AA foamed concrete has considerable potential for practical applications when the unit binder content is close to $375kg/m^3$, which achieves the minimum quality requirements specified in KS F 4039 and ensures economic efficiency. In addition, lifecycle assessment demonstrated the reduction in the environmental impact profiles of all specimens relative to typical ordinary portland cement foamed concrete as follows: 99% for photochemical oxidation potential, 87~89% for global warming potential, 78~82% for abiotic depletion, and 70~75% for both acidification potential and human toxicity.

A Case of Interstitial Pneumonitis developed by Interferon-${\alpha}$ Treatment for Chronic Hepatitis C (만성 C형 간염 환자에서 Interferon-${\alpha}$를 투여중 발생한 간질성 폐렴 1예)

  • Yoon, Jong Goo;Ahn, Joong Hyun;Ko, Seung Hyeon;Lee, Hyun Seoung;Kwon, Soon Seog;Kim, Young Kyoon;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.637-644
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    • 1996
  • Interstitial pneumonitis associated with interferon alpha therapy for chronic hepatitis C was first describe6 in 1994 by Kazoo et al In Japan. The mechanism of interstitial pneumonitis developed by interferon alpha was still unknown but immunologic, allergic of direct lung toxicity were suggested. We experienced a case of interstitial pneumonitis developed during interferon alpha therapy for chronic hepatitis C in a 52-year-old male patient. He was treated with 6 million units of interferon alpha intramuscularly 3 times per week for 4 weeks and noted progressive dyspnea and cough. These symptoms were subsided after 6 weeks' discontinuation of interferon alpha therapy. And so, he was retreated with 3 million units of interferon alpha 3 times per week for 8 weeks and felt dyspnea again. He was admitted to our hospital for further evaluation of progressive dyspnea. Arterial blood gas(ABG) values were $PaO_2$ 90.7 mmHg and $PaCO_2$ 31.9 mmHg, and antinuclear antibody(ANA) was negative. A chest X-ray film revealed diffuse reticulo-nodular shadows in bilateral lung fields, suggesting a diagnosis of interstitial pneumonitis. A marked increase in lymphocyte count and suppressor T cell were observed in bronchoalveolar lavage(BAL) fluid. Lymphocyte stimulation test with interferon alpha was positive. Interstitial pneumonitis was confirmed by transbronchial lung biopsy. After discontinuation of interferon alpha, we gave oral steroid in the condition that clinical symptoms were being improved gradually.

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Standardization Studies for the Oriental Mineral Medicine (광물성 약재(광물약)의 표준화에 관한 연구)

  • Kim, Seon-Ok;Park, Maeng-Eon
    • Economic and Environmental Geology
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    • v.48 no.3
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    • pp.187-197
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    • 2015
  • Oriental mineral medicines are single or mixture of more than one mineral species or rock/fossil which are used to treat disease. Mineral medicines remove harmful or useless substances to decrease toxicity and secondary effects, and cause the manufacture of medical compounds with increased efficacy. The extraction test is an accepted in vitro system to predict the bioaccessibility of major and minor elements from mineral medicine. It incorporates gastrointerstinal tract parameters representative of a human body that including stomach and small intestinal pH which are the same as digestion condition. The bioaccessibility of a mineral medicine is the fraction that is soluble in the gastrointestinal environment and is available for absorption. Reaction path modeling in the human body can predict digestion with gastric fluid as well as absorption in the small intestine, existence in body fluids and reaction progress of the exhaust process according to pH conditions in body. Also reaction path modeling can predict bioavailability, which is equal to existence rate in the body and the form and amount of a medicine in the body after intake. The study results from predicating the existence form mineral medicines in the body, and proving the effective ingredient using bioaccessibitily and human risk assessment, suggest these that should be necessary data for new medicine development.

Toxicity Test of Sucrose and Trehalose Prior to Cryopreservation in Immature Bovine Oocytes

  • Park, Sang-Hyoun;Yu, Il-Jeoung
    • Journal of Embryo Transfer
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    • v.23 no.4
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    • pp.263-267
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    • 2008
  • The purpose of this study was to determine toxic effect of sucrose and trehalose prior to cryopreservation on nuclear maturation and embryonic development in immature bovine oocytes. All cryoprotectant was prepared in tissue culture medium 199-HEPES (TCM 199-HEPES) with 10% fetal bovine serum (FBS). Immature oocytes were exposed to 1.2M ethylene glycol (EG) and 0.1M sucrose or 1.2M EG and 0.1M trehalose for 3 min and then were exposed to 3.2 M EG and 0.25 M sucrose or 3.2 M EG and 0.25 M trehalose for 1 min. Oocytes treated with cryoprotectants were exposed to 0.25 M sucrose or 0.25 M trehalose for 5 min and then 0.1 M sucrose or 0.1 M trehalose for 5 min. Depending on type of sugar added to cryopreservation solution, oocytes were allocated to sucrose group and trehalose group, respectively. Oocytes exposed to TCM 199-HEPES with 10% FBS were considered as control. Oocytes were cultured in TCM 199 supplemented with 10% FBS, 5 ng/ml epidermal growth factor, 0.01 IU/ml luteinizing hormone, and $1\;{\mu}g/ml$ estradiol for 24 h in $39^{\circ}C$, 5% $CO_2$. Nuclear maturation was assessed by staining oocytes with 1% aceto-orcein. Oocytes were fertilized in vitro and were cultured in TCM 199 supplemented with 10% FBS, 5 mM sodium pyruvate, and antibiotics in $39^{\circ}C$, 5% $CO_2$. The rates of cleavage and blastocyst, and cell number in blastocyst were assessed. Metaphase II rates were not different among experimental groups regardless of type of sugar. The cleavage rate of trehalose group (73.3%) was significantly higher (p<0.05) than those of sucrose group (62.8%) and control group (60.8%). The blastocyst rate was significantly higher in trehalose group (p<0.05). Mean cell number in blastocyst were not different among experimental groups, although cell number of blastocyst in trehalose group was significantly higher on day 7 (p<0.05). In conclusion, sucrose and trehalose were not toxic to immature bovine oocytes prior to cryopreservation. In particular, trehalose was more effective on embryonic development.

Antimutagenic and Cytotoxic Effects of Korean Wild Mushrooms Extracts (한국산 야생버섯 추출물의 항돌연변이원성 및 암세포 성장억제 효과)

  • Kim, Hyun-Jeong;Lee, In-Seon
    • Korean Journal of Food Science and Technology
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    • v.36 no.4
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    • pp.662-668
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    • 2004
  • Ames test revealed most methanol extracts of 13 Korean wild mushroom species have strong antimutagenic effects against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and benzo(a)pyrene[B(a)P]. Methanol extracts of Coriolus versicolor and Phaeolepiota aurea showed 74-94 and 83-88% antimutagenic effects against MNNG and B(a)P in Salmonella typhimurium TA100 strain, while 89 and 91% inhibitions were observed against B(a)P in TA98 strain, respectively. Most water extracts of wild mushrooms did not show antimutagenic activeiy on MNNG and B(a)P. Wild mushrooms extracts inhibited human colon carcinoma cells (HT29), human hepatoma cell (HepG2), and humann histiocytic lymphoma cell (U937) dose-dependently, with most methanol extracts exhibiting stronger effect than water extracts, Highest toxicity was observed against HT-29 cells in methanol extracts of Coriolus versicolor and Phaeolepiota aurea, showing 84% inhibition at 1 mg/mL, whereas C. versicolor water extract showed 53-65% inhibition against HepG2 and U937. These extracts did not show cytotoxic effects against human lymphocyte. Results revealed wild mushrooms have strong antimutagenic and in vitro cytotoxic effects.