• 제목/요약/키워드: repeated toxicity

검색결과 333건 처리시간 0.022초

Repeated-Dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

  • Jang, Jongwon;Seo, Wookcheol;Chu, Hongmin;Park, Kyungtae;Kim, SunKyung;Park, Ju-Hun;Shin, Joon young;Choi, Dong ho;Kang, Hyung Won;Kim, Sungchul
    • Journal of Acupuncture Research
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    • 제37권2호
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    • pp.110-117
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    • 2020
  • Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene's test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD50 (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.

Ifosfamide and Doxorubicin Combination Chemotherapy for Recurrent Nasopharyngeal Carcinoma Patients

  • Dede, Didem Sener;Aksoy, Sercan;Cengiz, Mustafa;Gullu, Ibrahim;Altundag, Kadri
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.2225-2228
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    • 2012
  • Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Methods: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500 $mg/m^2$ days 1-3, mesna 2500 $mg/m^2$ days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS< 2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions. Results: Median age was 47 (min-max; 17-60). Twenty six (86.7 %) were male. Median cycles of chemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated. Conclusion: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy.

Histopathological Evaluation of Heart Toxicity of a Novel Selective PPAR-γ Agonists CKD-501 in db/db Mice

  • Yang, Hyun-Il;Kim, Woo Sik;Kim, Dal-Hyun;Kang, Jin Seok
    • Biomolecules & Therapeutics
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    • 제21권1호
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    • pp.84-88
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    • 2013
  • High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

Safety Evaluation of Kyungokgo-gamibang Administration Based on Hematological, Biochemical, Protein, and Lipid Profiles in Dogs

  • Song, Doo-won;Lee, Ga-won;Ro, Woong-bin;Kim, Heyong-seok;Kang, Hyun-min;Kim, Jong-won;Park, Soo-bin;Moon, Yang-seon;Na, Chang-su;Park, Hee-myung
    • 한국임상수의학회지
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    • 제38권1호
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    • pp.7-15
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    • 2021
  • Kyungokgo-gamibang, Kyungokgo with Iksuyongjingo and Sparassis crispa, is a traditional Korean medicine used for restorative effects. This study aimed to evaluate the safety of Kyungokgo-gamibang in healthy beagle dogs. In the single-dose oral toxicity study, three beagle dogs were orally administered 2,000, 1,000, and 500 mg/kg of Kyungokgo-gamibang and were observed for 14 days. In the repeated-dose oral toxicity study, nine healthy dogs were orally administered 0.2g/kg of Kyungokgo-gamibang (n = 3, low-dose group), 1 g/kg of Kyungokgo-gamibang (n = 3, high-dose group), or normal saline (n = 3, control group) twice a day for 8 weeks. The hematological, serum biochemical, urine, protein, and lipid profiles were evaluated to investigate the adverse effects of the Kyungokgo-gamibang. During the study period, the dogs demonstrated no clinical signs and the hematological, serum biochemical, urine, protein, and lipid analyses revealed unremarkable findings. The study results suggest that Kyungokgo-gamibang can be safely administered to dogs without any adverse effects.

Anti-Tuberculosis Activity of Pediococcus acidilactici Isolated from Young Radish Kimchi against Mycobacterium tuberculosis

  • Yoon, Youjin;Seo, Hoonhee;Kim, Sukyung;Lee, Youngkyoung;Rahim, MD Abdur;Lee, Saebim;Song, Ho-Yeon
    • Journal of Microbiology and Biotechnology
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    • 제31권12호
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    • pp.1632-1642
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    • 2021
  • Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.

화학물질 우선순위 선정기법(CRS)을 활용한 허가대상 후보물질 선정 연구 (A Study on the Selection of Candidates for Substances Subject to Permission Using Chemicals Ranking and Scoring (CRS))

  • 김효동;박교식
    • 한국산업보건학회지
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    • 제32권3호
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    • pp.253-267
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    • 2022
  • Objectives: This study was performed to check whether the CRS (Chemical Ranking and Scoring) system is appropriate as a method to determine substances as candidates for substances subject to permission and to apply this system to the selection of candidates for substances subject to permission. Methods: A risk score was obtained by multiplying the hazard score and the exposure score and then ranking them. The hazard sub-indicators are carcinogenicity, germ cell mutagenicity, reproductive toxicity, specific target organ toxicity-repeated exposure, respiratory sensitization and endocrine disrupting chemicals. Exposure sub-indicators are persistence, bioaccumulation and emission volume. Sensitivity analysis was performed for missing values. Correlation analysis and multivariable linear regression analysis were performed among hazard, exposure and risk in order to confirm that CRS was an appropriate method. Results: As a result of the sensitivity analysis on missing values, it was confirmed that the effect on the risk ranking was not sensitive. Correlation and regression analysis confirmed that exposure had a greater effect on risk than hazard. Conclusions: The CRS system, which derives a risk score using a hazard and exposure score, is judged to be appropriate as a method for the selection of preliminary of candidates for substances subject to permission. Benzene, cadmium, nickel, and cobalt were selected as priority candidates for substances subject to permission.

천연염료 발효(天然染料 醱酵) 쪽으로 염색(染色)한 모발(毛髮)의 특성 연구(特性 硏究) (A Study on the Property of Hair Dyed with Fermented Indigo)

  • 김경선;이인숙;전동원;하병조
    • 패션비즈니스
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    • 제10권1호
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    • pp.120-131
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    • 2006
  • Recently, it has been reported that chemical hair coloring can cause allergic reactions, the toxicity issue of chemical hair color was issued. Therefore, there is an increasing interest in the hair coloration technique using non-toxic and bio-compatible hair color gotten from natural resource. In this study, the possibility using fermented Indigo as natural hair coloring agent was investigated. Bleached hair samples were dyed using Indigo, and the effect of dyeing frequency, the physical change after dyeing, color, surface and cross-section characteristics, and tensile property were also studied. In addition, the protection property of cationic detergent finishing on damaged hair samples were also studied. The following conclusions are made; 1. While bleached hair samples with low value showed the negligible effect of repeated dyeing, bleached hair samples with high value showed the good effect of repeated dyeing. 2. Hair sample dyed with Indigo showed a high light-fastness, however, tensile strength and elongation showed very low values (high damage on hair sample). 3. Cationic detergent finishing did not affect on the colorfastness because of decoloration after dyeing, however, it increased the smoothness of hair sample, and therefore, can use as protectant of damaged hair. 4. Hair scale was damaged after dyeing. It seemed that the alkali, potassium carbonate, increased pH of dyeing bath to 11, as a result, the hair was swollen, weaken, and dissolved on the prolonged dyeing time. Dyed hair sample became stiff and fine. 5. The color difference was 4.62 (a high fastness value) in the test of sunlight exposure, shampoo, cationic detergent finishing, and acid perspiration fastness.

Initial Risk Assessment of Disodium Disulphite in OECD High Production Volume Chemical Program

  • Sanghwan Song;Park, Yoonho;Park, Hye-Youn;Kwon, Min-Jeoung;Koo, Hyun-Ju;Jeon, Seong-Hwan;Na, Jin-Gyun;Park, Kwangsik
    • Toxicological Research
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    • 제18권1호
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    • pp.23-29
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    • 2002
  • Disodium disulphite, the HPV chemical, was assigned to Korea in order to implement OECD SIDS program in 1999. It was produced about 3,200 ton/year in 1998. This report evaluates the toxic potency of disodium disulphite based on the environmental and mammalian effects as well as human exposure. Oral $LD_{50}$ in rats is 1,540 mg/kg b.w. and effects was observed to the stomach, liver and the GI track that was filled with blood. For repeated dose toxicity, the predominant effect was the induction of stomach lesion due to local irritation. The no observed adverse effect lever for local (stomach irritation) was about 217 mg/kg bw/day. There is no evidence that disodium disulphite is genotoxic in vivo. No reproductive or developmental toxicty of disodium disulphite was observed for the period up to 2 yr and over three generation. In humans, urticaria and asthma with itching, edema, rhinitis, and nasal congestion were reported. Disodium disulphite is unlikely to induce respiratory sensitization but may enhance symptom of asthma in sensitive individuals. This chemical would be mainly transported to water compartment when released to environmental compartments since it is highly water soluble (470 g/l at 20). Low K oc (2.447) indicates disodium disulphite is so mobile in soil that it may not stay in the terrestrial compartment. The chemical has been tested in a limited number of aquatic species. hem acute toxicity test to fish, 96 hr-$LC_{50}$ was > 100 mg/1. For algae, 72 hr-$XC_{50}$ was 48.1 mg/1. For daphnid, the acute toxicity value of 48 hr-$EC_{50}$ was 88.76 mg/1, and chronic value of 21day-NOEC was > 10 mg/1. Therefore, PNEC of 0.1 mg/l for the aquatic organism was obtained from the chronic value of daphnid using the assessment factor of 100. Based on these data the disodium disulphite was recommended as low priority for further post-SIDS work in OECD.

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

  • Ali Osman, Kaya;Suleyman, Buyukberber;Metin, Ozkan;Necati, Alkis;Alper, Sevinc;Nuriye Yildirim, Ozdemir;Suleyman, Alici;Onur, Esbah;Veli, Berk;Celalettin, Camci;Arife, Ulas;Ugur, Coskun;Mustafa, Benekli
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권2호
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    • pp.463-467
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    • 2012
  • Purpose: To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. Patients and Methods: Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 $mg/m^2$ on days one and eight intravenously over 90 minutes, followed by docetaxel 75 $mg/m^2$ on day eight intravenously over one hour. Cycles were repeated every 3 weeks. Results: The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3 %) patients (2 CR, 11 PR) and stable disease in 21 (32.8 %). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1 %). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range;1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9 %). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5 %), mucositis (32.8 %), peripheral neuropathy (29.7%), and fatigue (26 %). There was no toxicity-related death. Conclusion: The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

Treatment outcome of hepatic re-irradiation in patients with hepatocellular carcinoma

  • Seol, Seung Won;Yu, Jeong Il;Park, Hee Chul;Lim, Do Hoon;Oh, Dongryul;Noh, Jae Myoung;Cho, Won Kyung;Paik, Seung Woon
    • Radiation Oncology Journal
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    • 제33권4호
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    • pp.276-283
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    • 2015
  • Purpose: We evaluated the efficacy and toxicity of repeated high dose 3-dimensional conformal radiation therapy (3D-CRT) for patients with unresectable hepatocellular carcinoma. Materials and Methods: Between 1998 and 2011, 45 patients received hepatic re-irradiation with high dose 3D-CRT in Samsung Medical Center. After excluding two ineligible patients, 43 patients were retrospectively reviewed. RT was delivered with palliative or salvage intent, and equivalent dose of 2 Gy fractions for ${\alpha}/{\beta}=10Gy$ ranged from $31.25Gy_{10}$ to $93.75Gy_{10}$ (median, $44Gy_{10}$). Tumor response and toxicity were evaluated based on the modified Response Evaluation Criteria in Solid Tumors criteria and the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0. Results: The median follow-up duration was 11.2 months (range, 4.1 to 58.3 months). An objective tumor response rate was 62.8%. The tumor response rates were 81.0% and 45.5% in patients receiving ${\geq}45Gy_{10}$ and $<45Gy_{10}$, respectively (p = 0.016). The median overall survival (OS) of all patients was 11.2 months. The OS was significantly affected by the Child-Pugh class as 14.2 months vs. 6.1 months (Child-Pugh A vs. B, p < 0.001), and modified Union for International Cancer Control (UICC) T stage as 15.6 months vs. 8.3 months (T1-3 vs. T4, p = 0.004), respectively. Grade III toxicities were developed in two patients, both of whom received ${\geq}50Gy_{10}$. Conclusion: Hepatic re-irradiation may be an effective and tolerable treatment for patients who are not eligible for further local treatment modalities, especially in patients with Child-Pugh A and T1-3.