• Title/Summary/Keyword: Dose-response

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Antinociceptive Efficacy of Korean Bee Venom in the Abdominal Pain of the Mouse (마우스 복통에 대한 한국산 봉독의 진통 효과)

  • Kim, Joong-Hyun;Lee, Hye-Yun;Kim, Myoung-Hwan;Han, Tae-Sung;Cho, Ki-Rae;Kim, Gon-Hyung;Choi, Seok-Hwa
    • Journal of Veterinary Clinics
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    • v.24 no.3
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    • pp.320-324
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    • 2007
  • This study was undertaken to assess the antinociceptive effect of Korean bee venom (BV) in mice. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee (Apis mellifera L.) to sting and release venom. After collection, whole BV was evaporated until dry using the BV collector. Experiments were performed on male ICR mice (weighing $30{\sim}35g$, 6 weeks old). Mice were divided into 4 groups, each comprising 8 mice. BV was diluted and amounts of 6 mg/kg body weight (BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a writhing test in mice. Intraperitoneal injection of acetic acid produced a tonic pain behavior, first observed at 3 to 9 min post-injection. This writhing response peaked at 20 min post-acetic acid injection, and then declined until it was undetectable at 60 min post-injection. The time elapse between the administration of acetic acid and the first observed pain behaviors indicated a dose-dependent suppressive effect. These results suggest that Korean BV may be used to achieve an antinociceptive effect for use in medical therapies.

A Study on the Development of a Health Risk Assessment Method for the Management of the Health Environment of Residents Living Around Areas Affected by Chemical Accidents (화학사고 주변 지역 거주자의 보건환경 관리를 위한 건강위해성 평가 방법 개발에 관한 연구)

  • Park, Sihyun;Park, Sejung;Park, Taehyun;Yoon, Danki;Jung, Jonghyeon;Gang, Sungkyu;Lee, Dongsoo;Seo, Youngrok;An, Yeonsoon;Lee, Cheolmin
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.28 no.1
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    • pp.1-17
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    • 2018
  • Objectives: This research is part of a study to be conducted over five years starting from 2017 by the Ministry of Environment on the development of technologies to evaluate the impact of chemical accidents on the human body. Methods: For this research, a five-stage specific study method was developed. Results: In brief, the developed health risk assessment method can be summarized as follows. First, a health risk assessment system was built based on the guidelines set forth by the USA NRC/NAS. Second, based on the disease manifestation theory, the health risk assessment method was divided into 1) a carcinogenic health risk assessment method focused on all carcinogens except non-genotoxic carcinogens and 2) a non-carcinogenic health risk assessment method focused on noncarcinogens including non-genotoxic carcinogens. Third, the detailed contents of the health risk assessment method were developed in four stages(hazard identification, dose-response assessment, exposure assessment, and risk determination) through theoretical consideration of the assessment of the level of health risk related to chemical exposure. Finally, a health risk assessment methodology, classified into stages to address acute, subacute/subchronic, and chronic conditions was developed after considering the physicochemical behavior of hazardous chemicals upon implementation of countermeasures after a chemical accident. Conclusions: A method to evaluate the health risks related to toxic chemicals generated by chemical accidents was developed. This study was performed with the purpose of developing a mathematical health risk assessment method to evaluate the health effects of exposure to hazardous chemicals upon implementation of emergency countermeasures after chemical accidents.

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products (천연물 항암제제 임상시험 평가지표 개발연구)

  • Namgung, Mi-Ae;Chang, Yoo-Sung;Jeong, Seung-Gi;Kim, Jin-Seung;Yoon, Sung-Woo;Jang, Ki-Young;Yoo, Hwa-Seung;Jung, Myeon-Woo;Lee, Sung-Ho;Kim, Sung-Hoon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1678-1727
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    • 2006
  • This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.

The fabrication and evaluation of CdS sensor for diagnostic x-ray detector application (진단 X선 검출기 적용을 위한 CdS 센서 제작 및 성능 평가)

  • Park, Ji-Koon;Lee, Mi-Hyun;Choi, Young-Zoon;Jung, Bong-Zae;Choi, Il-Hong;Kang, Sang-Sik
    • Journal of the Korean Society of Radiology
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    • v.4 no.2
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    • pp.21-25
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    • 2010
  • Recently, various semiconductor compounds as radiation detection material have been researched for a diagnostic x-ray detector application. In this paper, we have fabricated the CdS detecton sensor that has good photosensitivity and high x-ray absorption efficiency among other semiconductor compounds, and evaluated the application feasibility by investigating the detection properties about energy range of diagnostic x-ray generator. We have fabricated the line voltage selector(LCV) for a signal acquisition and quantities of CdS sensor, and designed the voltage detection circuit and rectifying circuit. Also, we have used a relative relation algorithm according to x-ray exposure condition, and fabricated the interface board with DAC controller. Performance evaluation was investigated by data processing using ANOVA program from voltage profile characteristics according to resistive change obtained by a tube voltage, tube current, and exposure time that is a exposure condition of x-ray generator. From experimental results, an error rates were reduced according to increasing of a tube voltage and tube current, and a good properties of 6%(at 90 kVp) and 0.4%(at 320 mA) ere showed. and coefficient of determination was 0.98 with relative relation of 1:1. The error rate according to x-ray exposure time showed exponential reduction because of delayed response velocity of CdS material, and the error rate has 2.3% at 320 msec. Finally, the error rate according to x-ray dose is below 10%, and a high relative relation was showed with coefficient of determination of 0.9898.

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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Dasatinib Inhibits Lyn and Fyn Src-Family Kinases in Mast Cells to Suppress Type I Hypersensitivity in Mice

  • Lee, Dajeong;Park, Young Hwan;Lee, Ji Eon;Kim, Hyuk Soon;Min, Keun Young;Jo, Min Geun;Kim, Hyung Sik;Choi, Wahn Soo;Kim, Young Mi
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.456-464
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    • 2020
  • Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC50, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED50, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

The Effects of Rhus Extracts on The Cytotoxicity on Cancer Cells and E6 and E7 Oncogenes of Human Papillomavirus Type 16 (옻 추출물의 세포독성 및 자궁 경부암 바이러스 암 유발인자 E6 와 E7의 작용에 미치는 효과)

  • Cho, Young-Sik;Joung, Ok;Cho, Cheong-Weon;Lee, Kyung-Ae;Shim, Jung-Hyun;Kim, Kwang-Soo;Lee, Hong-Soo;Seung, Ki-Seung;Yoon, Do-Young
    • Korean Journal of Food Science and Technology
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    • v.32 no.6
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    • pp.1389-1395
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    • 2000
  • Cervical cancer has been one of the leading causes of female death from cancer worldwide with about 500,000 deaths per year. A strong association between certain human papillomaviruses (HPV types 16 and 18) and cervical cancer has been well known. An extract of natural products, Rhus, has been used to investigate whether this agent has the ability of inhibiting the oncogenes E6 and E7 of HPV type 16. This Rhus inhibited the proliferation of human cervical cancer cell lines (C-33A, SiHa, Caski) and HaCaT keratinocytes in a dose response manner. In vitro binding assay and ELISA showed that Rhus inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53. In addition, Rhus inhibited the in vitro binding of E7 and Rb which essential tumor suppressor for the control of cell cycle. The level of mRNA for E6 was also decreased by Rhus while that of E7 mRNA was not changed. Our data suggested that Rhus inhibited the oncogenecity of E6 and E7 of HPV 16 type, thus can be used as a putative anti-HPV agent for the treatment of cervical carcinomas by HPV.

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Association between vitamin D deficiency and anemia among Korean adolescent girls and young women (여자 청소년 및 젊은 여성의 비타민 D 결핍과 빈혈과의 연관성 분석)

  • Jang, Haeun;Park, Seonghee;Park, Kyong
    • Journal of Nutrition and Health
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    • v.52 no.6
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    • pp.552-558
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    • 2019
  • Purpose: Although vitamin D deficiency is common among Korean adolescent girls and young women, few studies have explored the potential health effects of vitamin D deficiency in this vulnerable population. This study examined the association between vitamin D deficiency and anemia in Korean adolescent girls and young women. Methods: The data from the Korea National Health and Nutrition Examination Survey 2008 ~ 2014 were used. A total of 3,643 girls and adult women aged 12 to 29 who provided all the information (including serum 25-hydroxy vitamin D, hemoglobin, and/or serum ferritin) needed for the analysis were included in the analysis. Demographic, lifestyle, and health data were obtained through survey questionnaires. Anemia and iron deficiency anemia were defined according to the World Health Organization cut-offs. Multivariable logistic regression, and restricted cubic spline regression were used in the analysis. Results: In fully adjusted logistic regression models, the vitamin D deficiency was significantly associated with higher prevalences of anemia (odds ratio (OR): 1.61, 95% confidence interval (CI): 1.04 ~ 2.49) and iron deficiency anemia (OR: 1.43, 95% CI: 1.01 ~ 2.03). In a cubic spline regression model, we observed a dose-response relationship between serum 25(OH)D concentration and anemia, and this linear relationship was also clearly observed between serum 25(OH)D concentration and iron deficiency anemia. Conclusion: Vitamin D deficiency may be associated with a higher prevalence of iron deficiency anemia and anemia in adolescent girls and young women. Alternatively, vitamin D deficiency may be a concurrent event for patients with anemia, which we cannot distinguish in this cross-sectional study. Further studies are needed to verify the causality in this population of low vitamin D levels.

Protective effects of Acanthopanax koreanum Kakai extract against carbon tetrachloride-induced liver injury in Sprague-Dawley rats (사염화탄소로 유도된 간 손상에 대한 섬오갈피 추출물의 보호 효과)

  • Yang, Yoon Kyoung;Wang, Lin;Kwon, Oran
    • Journal of Nutrition and Health
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    • v.47 no.2
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    • pp.106-112
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    • 2014
  • Purpose: This study was conducted in order to investigate the protective effects of ethanolic extract of Acanthopanax koreanum Nakai (AE) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups in order to receive the following experimental diets with intraperitoneal injection of $CCl_4$ (2.0 mL/kg body weight, 20% solution 0.65 mL) for eight weeks (n = 8 per group): $CCl_4$ control (CON), $CCl_4$ + AE 1% (AE1), $CCl_4$ + AE 3% (AE3), or $CCl_4$ + acanthoic acid 0.037%, which is equivalent to AE 3% (AA). Results: Highest serum ALT activity and albumin level were observed in the $CCL_4$ control group, but showed a significant decrease by either AE or AA supplementation in a dose-dependent manner (p = 0.0063 and 0.0076, respectively). Both hemotoxylin and eosin staining and Masson's staining indicated remarkable prevention of $CCl_4$-induced liver damage in the AE3 group. $TNF{\alpha}$ and IL-6 production were significantly lowered in the AE treated groups, but not in the AA group (p = 0.0016 and p = 0.0002, respectively). The effects of AE3 were greater than those of AA for inflammation and liver toxicity biomarkers. Conclusion: Taken together, the results suggested that ethanolic extract of Acanthopanax koreanum Nakai provided hepatoprotective effects, leading to the reduction of inflammatory response. In addition, the effect of AE was superior to that of single compound AA.

Effects of luteolin on chemical induced colon carcinogenesis in high fat diet-fed obese mouse (고지방식이를 급여한 비만 마우스에서 luteolin이 화학적으로 유도한 대장암 발생에 미치는 영향)

  • Park, Jeong-Eun;Kim, Eunjung
    • Journal of Nutrition and Health
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    • v.51 no.1
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    • pp.14-22
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    • 2018
  • Purpose: Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice. Methods: Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days. Results: Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma $TNF-{\alpha}$ and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT. Conclusion: Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.