• Title/Summary/Keyword: Daily Dose

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Single Oral Dose Toxicity Test and Four Weeks Repeated Oral Dose Determination Test of Crude Antifungal Compounds Produced by Bacillus subtilis SN7 in Rats (Bacillus subtilis SN7이 생성한 조항균 물질의 단회 경구투여 독성 시험 및 4주 반복 경구투여 용량 결정 시험)

  • Chang, Hae-Choon;Koh, Sang-Bum;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.27 no.3
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    • pp.437-449
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    • 2016
  • To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.

Single and Four-Week Oral Toxicity Studies of Difructose Dianhydrides (DFA IV) in Sprague-Dawley Rats (Difructose Dianhydrides (DFA IV)의 랫드를 이용한 단회 및 4주간 반복 경구투여 독성시험)

  • Lee Chang-Woo;Lee Myong-Lyoll;Kim Hwan-Mook;Yoon Won-Kee;Kim Seung-Hwan;Son Hwa-Young;Kim Hyoung-Chin
    • Toxicological Research
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    • v.20 no.3
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    • pp.263-272
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    • 2004
  • This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

Intraperitoneal Paclitaxel Combined with S-1 Plus Oxaliplatin for Advanced Gastric Cancer with Peritoneal Metastasis: a Phase I Study

  • Kim, Dong-Wook;Seo, Won Jun;Youn, Sang Il;Jee, Ye Seob;Jang, You-Jin;Kim, Jong-Han
    • Journal of Gastric Cancer
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    • v.21 no.4
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    • pp.418-425
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    • 2021
  • Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m2/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m2 on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m2, and the dose escalation was set in units of 20 mg/m2 up to 80 mg/m2. Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m2. Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m2, when combined with a systemic SOX regimen.

Antihypertensive Effect of Wild Mountain Ginseng Cultured Root Extract in Spontaneously Hypertensive Rats (Spontaneously Hypertensive Rats에 있어서 산삼배양근 추출물의 항고혈압 효과)

  • Yang, Deok-Chun;In, Jun-Gyo;Lee, Bum-Soo;Han, Seung-Ho;Kim, Eun-Jeong;Kim, Kil-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.6
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    • pp.1482-1486
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    • 2008
  • The antihypertensive effects of the Wild Mountain Ginseng Cultured Root Extract (WMGCE) were investigated in spontaneously hypertensive rats (SHR). Daily oral administration of the WMGCE (100 and 200 mg/kg) exhibited a significant decrease in blood pressure in SHR rats during for 8 weeks. The systolic blood pressure was dose- and time-dependently decreased significantly from the second weeks (p < 0.05) to the end of WMGCE treatment in SHR. The WMGCE decreased the plasma levels of sodium, potassium, chlorides, urea and osmolarity in SHR rats but no statistically significant change was observed. Furthermore, no significant changes were noted on heart weight, heart rate and diameter of aorta after WMGCE treatment in SHR. Our results suggest that daily oral administration of WMGCE at the dose of 100 and 200 mg/kg for 8 weeks exhibited antihypertensive activities.

A Phase n Study on UFT Therapy for Head and Neck Squamous Cell Carcinoma (두경부 편평세포암종에 대한 UFT 투여 후 항종양효과에 관한 제2상 임상 연구)

  • Choi Jong-Ouck;Choi Geon;Jung Kwang-Yoon
    • Korean Journal of Head & Neck Oncology
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    • v.10 no.1
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    • pp.74-79
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    • 1994
  • A Phase II study of UFT which is a mixture of Tegafur and Uracil was conducted in two institutions during past two years. Ninty-four patients of head and neck squamous cell carcinoma entered this trial, of which sixty-eight were evaluated. Among those, thirty-six cases were previously untreated and thirty-two cases were recurrent UFT was administrated orally at a daily dose of $400mg/m^2$ for eight weeks. The results were as following: 1) Overall response was 30.88%, but for 38.36% for 36 cases of the untreated cases, 21.88% for 32 cases of recurrent cases. 2) UFT was more effective in early stage and well differentiated squamous cell carcinoma and UFT tended to reduce the tumor size maximally at fourth or fifth week 3) There was no serious side effects except mild gastrointestinal disturbances such as nausea and vomiting, which were recovered immediately after stop or reducing a daily dose. Therefore, UFT therapy is clinically effective for head and neck squamous cell carcinoma and also may be useful for combination or palliative chemotherapy because of mild side effects.

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Effects of Physalis peruviana L on Toxicity and Lung Cancer Induction by Nicotine Derived Nitrosamine Ketone in Rats

  • El-Meghawry El-Kenawy, Ayman;Elshama, Said Said;Osman, Hosam-Eldin Hussein
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.5863-5868
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    • 2015
  • Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

Development of Prototype Quality Assurance Procedure for Blood Irradiator Using Glass Dosimeter Jig (유리선량계 지그를 이용한 혈액조사기의 정도관리 절차 초안 개발)

  • Jeong, Dong-Hyeok;Kang, Yeong-Rok;Moon, Young-Min;Kim, Hyo-Jin;Kwak, Dong-Won;Kim, Jeung-Kee;Lee, Man-Woo
    • Progress in Medical Physics
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    • v.23 no.2
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    • pp.123-126
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    • 2012
  • For the purpose of quality assurance (QA) of the blood irradiator, QA programs for daily, monthly, and yearly were developed. For daily tests, simple items for basically operating the machine are recommended. For monthly and yearly tests, the measurement of dose to assure the dose delivery system are performed by a dosimetry devices (Glass dosimeter jig) developed in this study. The QA program is practical for clinical environment.

In Vivo Antitumor Efficacy of Cw252053, A Folate-based Thymidylate Synthase Inhibitor

  • Oh, Se-Woong;Ha, Jong-Ryul;Baek, Du-Jong
    • Archives of Pharmacal Research
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    • v.24 no.4
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    • pp.323-326
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    • 2001
  • Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

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Effect of DHEA administration during dexamethasone treatment on mass of hindlimb muscles of rat (Dexamethasone 치료기간 중의 DHEA 투여가 쥐의 뒷다리근 질량에 미치는 영향)

  • Choe, Myoung-Ae;Shin, Gi-Soo;Lee, Eun-Ju;An, Gyeong-Ju
    • Journal of Korean Biological Nursing Science
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    • v.3 no.1
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    • pp.63-74
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    • 2001
  • The purpose of this study was to determine the effect of DHEA with dexamethasone on body weight and wet weight and relative weight of atrophied hindlimb muscles induced by dexamethasone treatment. $200{\sim}225g$ Wistar rats were divided into control(C), dexamethasone(D), dexamethasone and DHEA(DDH) groups. Dexamethasone was injected daily at a dose of 5mg/kg. DHEA was administered daily at a dose of 5mg/kg by oral ingestion during 7days. The data were analyzed by Kruskal-Wallis test and Mann-Whitney U test using the SPSSWIN 9.0 program. Body weight and muscle weight of plantaris and gastrocnemius of dexamethasone group decreased significantly compared with that of control group. Muscle weight of plantaris of DDH group increased significantly compared with dexamethasone group. Body weight of DDH group decreased significantly compared to control group, but relative weight of plantaris and gastrocnemius of DDH group increased significantly compared to control group. Based on these results, it can be suggested that DHEA administration during dexamethasone treatment can be suggested that DHEA administration during dexamethasone treatment can increase weight of atrophied plantaris muscle induced by dexamethasone treatment.

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Colchicine Derivatives Allows Prolonged Survival of Cardiac Allograft in the Rat (백서에서의 동종이형의 심장이식후 Colchicine 변형 물질 투여군의 장기 변존)

  • Kim Young-Hak;Lee Hyung-Chang;Chung Won-Sang;Kang Jung-Ho;Kim Hyuck;Chon Sun-Ho;Shin Sung-Ho
    • Journal of Chest Surgery
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    • v.38 no.9 s.254
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    • pp.595-600
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    • 2005
  • Background: Colchicine with its immunosupressive properties has been used with benefcial effects in autoimmune disease, such as Gout, etc. Whether colchicine, by virtue of the above property, could attenuate the process of cardiac allograft rejection in the rats is investigated in this report. Material and Method: We compared the untreated group (Control, n=6), Cyclosporin A group (10 mg/kg, daily, n=20), and Colchicine derivative group (Colchicine 40 ${\mu}g$/kg, n=20) of cardiac allografts in the rats. Result: In the untreated control group (n=6), all of 6 rats showed rejection within 3 weeks after cardiac allograft. In the cyclosporin A group (n=20), cyclosporin A (10 mg daily oral dose) was administered at a 10 mg daily oral dose and promoted long-term survival (over 100 days). The cyclosporin A group had one mortality at the 18th post-operative day due to infection. Furthermore, in the Colchicine derivatives group (n=20) with a daily IP (Intra Peritoneum) dose (40 ug/kg/day), we observed long-term survival.(> 100 days), except for one rat that died of an anesthetic problem (respiratory failure) at the 9th post-operative day. Conclusion: Experiments have also been performed to evaluate whether the effect of colchicine derivatives allowed prolonged survival of cardiac allografts compared with the cyclosporin A administration group in the rats.