• Title/Summary/Keyword: repeated dose

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Modulatory Effect of Four Azulene Derivatives from the Fruiting Bodies of Lactarius hatsudake on Interferon-$\gamma$ Production (젖버섯아재비 자실체로부터 분리한 Azulene계 화합물이 Interferon-$\gamma$ 생성에 미치는 영향)

  • Xu, Guang Hua;Kim, Jae-Wha;Li, Gao;Yoo, Ick-Dong
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.36 no.2
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    • pp.151-156
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    • 2010
  • Investigation of secondary bioactive metabolites from the fruiting bodies of Lactarius hatsudake led to the isolation of four azulene derivatives by means of repeated column chromatography and preparative HPLC, and they were identified as 1-formyl-4-methyl-7-isopropyl azulene (1), lactaroviolin (2), 4-methyl-7-isopropyl-azulene-1-carboxylic acid (3), and 1-formyl-4-methyl-7-(1-hydroxy-1-methylethyl) azulene (4) by their physico-chemical properties and spectroscopic analysis. The isolated compounds were evaluated for the effects on modulation of cytokines in natural killer cell line (NK92 cells). Compounds 1 and 4 strongly inhibited IFN-$\gamma$ production in a dose-dependent manner, corresponding to 101.3 % and 92.7 % inhibition at 400 ${\mu}M$, and 11.9 % and 24.1 % at 100 ${\mu}M$, respectively, whereas compounds 2 and 3 showed weak inhibitory effect on INF-$\gamma$ production, corresponding to 45.9 % and 18.0 % inhibition at 400 ${\mu}M$.

Effectiveness of the Respiratory Gating System for Stereotectic Radiosurgery of Lung Cancer (Lung Cancer의 Stereotactic Radiosurgery시 Respiratory Gating system의 유용성에 대한 연구)

  • Song Heung Kwon;Kim Min Su;Yang Oh Nam;Park Cheol Su;Kwon Kyung Tae;Kim Jeong Man
    • 대한방사선치료학회:학술대회논문집
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    • 2005.06a
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    • pp.13-17
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    • 2005
  • Introduction : For stereotactic radiosurgery (SRS) of a tumor in the region whose movement due to respiration is significant, like Lung lower lobe, the gated therapy, which delivers radiation dose to the selected respiratory phases when tumor motion is small, was peformed using the Respiratory gating system and its clinical effectiveness was evaluated. Methode and Materials : For two SRS patients with a tumor in Lung lower lobe, a marker block (infrared reflector) was attached on the abdomen. While patient' respiratory cycle was monitored with Real-time Position Management (RPM, Varian, USA), 4D CT was performed (10 phases per a cycle). Phases in which tumor motion did not change rapidly were decided as treatment phases. The treatment volume was contoured on the CT images for selected treatment phases using maximum intensity projection (MIP) method. In order to verify setup reproducibility and positional variation, 4D CT was repeated. Result : Gross tumor volume (GTV) showed maximum movement in superior-inferior direction. For patient $\#$1, motion of GTV was reduced to 2.6 mm in treatment phases ($30\%\~60\%$), while that was 9.4 mm in full phases ($0\%\~90\%$) and for patient $\#$2, it was reduced to 2.3 mm in treatment phases ($30\%\~70\%$), while it was 11.7 mm in full phases ($0\%\~90\%$). When comparing two sets of CT images, setup errors in all the directions were within 3 mm. Conclusion : Since tumor motion was reduced less than 5 mm, the Respiratory gating system for SRS of Lung lower lobe is useful.

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A Study on GHS Classification of 3-Methylpentane by Subacute Inhalation Toxicity (아급성흡입독성시험을 이용한 3-Methylpentane의 GHS 분류·표시)

  • Chung, Yong Hyun;Han, Jeong Hee;Shin, Seo Ho
    • Journal of the Korean Institute of Gas
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    • v.21 no.1
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    • pp.6-17
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    • 2017
  • Objectives : The purpose of this study was to obtain information regarding Globally Harmonized System(GHS) classification and health hazards that may result from a 4 weeks inhalation exposure of 3-Methylpentane in Sprague-Dawley rats. Methods : The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 412(Subacute Inhalation Toxicity). The Rats were divided into 4 groups(5 male and 5 female rats in each group) and exposed to 0 ppm, 284 ppm, 1,135 ppm, 4,540 ppm 3-Methylpentane in each exposure chamber for 6 h/day, 5 days/week, for 4 weeks. After two weeks, the test animals were autopsied and carried out blood test and biochemical tests and histopathological examination. We used PRISTIMA (Toxicology data management system) to confirm the system and to have confidence of the raw data. Results : No death and particular clinical presentation including weight change and change of feed rate was observed. Relationship between dose, gender and response was also not significantly changed in hematologic examination, biochemical examination of blood and blood coagulation time. The histopathologic lesions caused by the test substance did not appear. Conclusions : NOAEL(No Observable Adverse Effect Level) of 3-Methylpentane is more than 4,540 ppm in male group and female group and the Ministry of Employment and Labor Guidance Announcement No. 2013-37(criteria for the classification marks and Safety of Chemicals) Specific target organ toxicity(repeated exposure) was determined with a substance that is not the separator material.

Toxicity Studies of DA-l25, an Anthracycline Antitumor Antibiotic : Intravenous Repeated Doses for 26 Weeks in Beagle Dogs (Anthracycline계 항암성 항생물질 DA-125의 Beagle dog에 대한 26주 반복정맥투여독성시험)

  • 차신우;박종일;정태천;신호철;하창수;김형진;양중익;한상섭;노정구
    • Biomolecules & Therapeutics
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    • v.4 no.2
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    • pp.127-137
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    • 1996
  • This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

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Cyclofarnesane sesquiterpene glucoside from the whole plant of Loranthus tanakae and its cytotoxicity ('꼬리겨우살이'(Loranthus tanakae) 전초로부터 cyclofarnesane sesquiterpene glucoside의 분리 동정 및 세포독성)

  • Joo, Sun-Woo;Kim, Hyoung-Geun;Oh, Eun-Ji;Ko, Jung-Hwan;Lee, Yeong-Geun;Kang, Se-Chan;Lee, Dae Young;Baek, Nam-In
    • Journal of Applied Biological Chemistry
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    • v.62 no.1
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    • pp.7-10
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    • 2019
  • The whole plants of Loranthus tanakae were repeatedly extracted with 80% aqueous MeOH and the concentrate was partitioned into ethyl acetate (EtOAc), n-butyl alcohol (n-BuOH) and $H_2O$ fractions. The repeated silica gel ($SiO_2$), octadecyl $SiO_2$ (ODS), and Sephadex LH-20 column chromatographies for the n-BuOH fraction led to isolation of a cyclofarnesane sesquiterpene glucoside. The chemical structure including stereo structure was determined to be a (1'R,3'S,5'R,8'S,2E,4E)-dihydrophaseic acid $3^{\prime}-O-{\beta}-{\text\tiny{D}}$-glucopyranoside on the basis of spectroscopic analyses. This compound was isolated for the first time from L. tanakae in this study. Compound 1 showed a moderate dose-dependent cytotoxicity against human Caucasian gastric adenocarcinoma cells and human hepatocyte cari-noma cells cell lines at higher than $50{\mu}g/mL$.

Phenolic compounds from the flowers of Cosmos bipinnatus and their anti-atopic activity (코스모스(Cosmos bipinnatus) 꽃으로부터 phenolic 화합물의 분리 동정과 항아토피 효과)

  • Jeon, Hyeong-Ju;Kim, Hyoung-Geun
    • Journal of Applied Biological Chemistry
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    • v.65 no.3
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    • pp.215-219
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    • 2022
  • The flowers of Cosmos bipinnatus were extracted with solvent made with methanol:water (4:1) and the concentrates were partitioned into ethyl acetate (EtOAc), n-butanol (n-BuOH), and water (H2O) fractions. The octadecyl silica gel (ODS) and silica gel (SiO2) column chromatographies were repeated for the EtOAc fraction to isolated of two phenolic compounds. The chemical structure of the isolated compounds were identified as benzyl O-β-ᴅ-glucopyranoside (1), and 2-phenylethyl O-β-ᴅ-glucopyranoside (2) through spectroscopic datas such as nuclear magnetic resornance, infrarad spectroscopy, and mass spectroscopy. These two compounds were first isolated from C. bipinnatus flowers through this study. To evaluate the anti-atopic activity of the two isolated compounds using a HaCaT cell line induced by ultraviolet light, several experiments were conducted and neither both compounds showed toxicity in the concentration range of 1 to 1,000 ㎍/mL. In the results of anti-atopic activity through Thymus and activation regualted chemokine (TARC) assay, both compounds showed dose-dependent TARC inhibitory activity. In particular, compound 1 showed significant activity even in a low concentration range of 10 ㎍/mL, and in different concentration ranges. Also compound 1 showed higher inhibitory activity than other compound, confirming that the anti-atopic activity was the most excellent. Based on these results, it is considered that it can be used as a functional cosmetic material.

4-F-PCP, a Novel PCP Analog Ameliorates the Depressive-Like Behavior of Chronic Social Defeat Stress Mice via NMDA Receptor Antagonism

  • Darlene Mae D., Ortiz;Mikyung, Kim;Hyun Jun, Lee;Chrislean Jun, Botanas;Raly James Perez, Custodio;Leandro, Val Sayson;Nicole, Bon Campomayor;Chaeyeon, Lee;Yong Sup, Lee;Jae Hoon, Cheong;Hee Jin, Kim
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.227-239
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    • 2023
  • Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.

A Comparison of Peripheral Doses Scattered from a Physical Wedge and an Enhanced Dynamic Wedge (금속쐐기와 기능강화동적쐐기의 조사야 주변부 선량 비교)

  • Park, Jong-Min;Kim, Hee-Jung;Min, Je-Soon;Lee, Je-Hee;Park, Charn-Il;Ye, Sung-Joon
    • Progress in Medical Physics
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    • v.18 no.3
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    • pp.107-117
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    • 2007
  • In order to evaluate the radio-protective advantage of an enhanced dynamic wedge (EDW) over a physical wedge (PW), we measured peripheral doses scattered from both types of wedges using a 2D array of ion-chambers. A 2D array of ion-chambers was used for this purpose. In order to confirm the accuracy of the device we first compared measured profiles of open fields with the profiles calculated by our commissioned treatment planning system. Then, we measured peripheral doses for the wedge angles of $15^{\circ},\;30^{\circ},\;45^{\circ},\;and\;60^{\circ}$ at source to surface distances (SSD) of 80 cm and 90 cm. The measured points were located at 0.5 cm depth from 1 cm to 5 cm outside of the field edge. In addition, the measurements were repeated by using thermoluminescence dosimeters (TLD). The peripheral doses of EDW were (1.4% to 11.9%) lower than those of PW (2.5% to 12.4%). At 15 MV energy, the average peripheral doses of both wedges were 2.9% higher than those at 6MV energy. At a small SSD (80 cm vs. 90 cm), peripheral dose differences were more recognizable. The average peripheral doses to the heel direction were 0.9% lower than those to the toe direction. The results from the TLD measurements confirmed these findings with similar tendency. Dynamic wedges can reduce unnecessary scattered doses to normal tissues outside of the field edge in many clinical situations. Such an advantage is more profound in the treatment of steeper wedge angles, and shorter SSD.

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Clinical Efficacy of Combination Chemotherapy with Ifosfamide Cisplatin, and Etoposide(ICE) in Advanced Non-Small Cell Lung Cancer (진행성 비소세포 폐암 환자에서 Ifosfamide, Cisplatin Etoposide(ICE) 복합화학요법의 효과)

  • Lee, Gu;Kim, Byung Duk;Kang, Hee Jung;Lee, Sang Won;Oh, Hyun A;Bae, Sung Hwa;Lee, Jae Lyun;Lee, Kyung Hee;Hyun, Myung Soo;Shin, Kyeong Cheol;Jung, Jin Hong;Lee, Kwan Ho;Ryu, Hun Mo
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.4
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    • pp.309-316
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    • 2002
  • Background: To evaluate the efficacy and toxicity of combination chemotherapy using ifosfamide, cisplatin, and etoposide in patients with advanced non-small cell lung cancer(NSCLC). Materials and methods: Thirty-three patients with inoperable NSCLC(stage IIIb+IV) who had measurable diseases, and had not been treated with chemotherapeutic drugs, were enrolled in this study(from March 1995 to December 1996). The patients received ifosfamide($1500mg/m^2/day$, a full drop with Mesna on days 1-5), Cisplatin ($80mg/m^2/day$ infusion with a hydration on day 2), and Etoposide ($100mg/m^2/day$ infusion for 2 hours on days 1-3). The treatment was repeated every 4 weeks. Results: Ten patients showed a partial responses (30.3%). The overall survival time of the responders was longer than that of the non-responders (median 55 vs 22 weeks, p=0.01). The toxicities of this treatment were tolerable. Grade 3 or 4 leukopenia was observed in 21%. There was 1 death related to febrile neutropenia. The non-hematologic toxicity was mild. The relative dose intensity given to the patients was 0.86 ifosfamide, 0.87 cisplatin, and 0.89 etoposide, showing an average dose intensity of 0.87. Conclusions: A combination regimen of ifosfamide, cisplatin, and etoposide is effective and tolerable for treating advanced non-small cell lung cancer.

Toxicity Study of Detoxication Sulphur at 3 Months Post-treatment in Rats (제독유황에 대한 3개월간 랫드에서 반복경구투여 독성에 관한 연구)

  • Lee, Jin-Seok;Kwon, Jung-Ki;Han, Sang-Hyeon;An, In-Jung;Kim, So-Jung;Lee, Seung-Ho;Park, Young-Seok;Park, Byung-Kwon;Kim, Byeong-Soo;Kim, Sang-Ki;Kim, Il-Ho;Choi, Chang-Sun;Jung, Ji-Youn
    • Journal of Food Hygiene and Safety
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    • v.25 no.3
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    • pp.263-268
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    • 2010
  • This study was demonstrate a repeated oral dose toxicity of detoxication sulphur in 8-weeks-old female Sprague-Dawley (SD) rats. The rats were treated with dose of 0.2%, 1%, 5% detoxication sulphur and 1% sulphur of feed consumption administered for 13 weeks. To evaluate the safety of detoxication sulfur, we examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. As a result, no significant differences in body weight, feed intake, hematological examination and histopathological between control and detoxication sulphur treatment group were found. Serum biochemical results were not shown significant differences in 0.2% and 1% the treated groups compared with control group. But glucose level were decrease, also ALT and ALP level were increase in 5% treated group. All of these results indicate that 1% detoxication sulphur of feed consumption may be safety in SD rat.