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Studies on the Safety of Artemisiae Capillaris Herba - With the Perinatal and Lactational Reproductive Toxicity - (인진의 안정성에 대한 연구 - 주산$\cdot$수유기 생식 독성을 중심으로 -)

  • Wang Wu-Hao;Park Jae-Hyun
    • The Journal of Korean Medicine
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    • v.26 no.2 s.62
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    • pp.32-51
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    • 2005
  • Objectives: To study the effect of Artemisiae Capillaris Herba extracts, that have been used as oriental medicine to treat liver disease, on the perinatal and lactational n;)productive toxicity of SD rats when administered by oral lavage. Methods: Female SD rats were dosed from 6 days of gestation to 3 weeks postpartum. This was conducted in accordance with the recommendations of the KFDA Guidelines for Detection of Toxicity to Reproduction for Medicinal Products. Results: No Artemisiae Capillaris Herba extracts treatment-related changes in clinical signs, mortalities, implantation number, dead fetus number, loss rate of fetus, number of live young, survival rate of fetus, sex ratio of live young, external anomalies, pregnancy periods, viability index, lactational index, survival rate of litters at 4 days after birth or delivery index were demonstrated in any dosed levels in this study. However, the body weight and gains, food consumption and absolute organ weights of brain, adrenal glands, liver, spleen, kidney, ovaries and heart were significantly increased in 2000 or 1000mg/kg-dosing groups and the relative organ Weights of adrenal glands were significantly increased in 2,000mg/kg-dosing groups. Therefore, it was concluded that this increase was natural according to growth. Also, no changes of gross findings, clinical signs, mortalities, body weight and gains, physical development results, necropsy findings, organ weight, faculty test, open filed test and water-filled simple T-maze test, copulation, fertility, pregnancy indices, body weight and gains during gestation periods, necropsy findings, corpora lutea number, implantation number, implantation rate, dead fetus number, post-implantation loss rate, live young, post-implantation survival rate, sex ratio of live young, external anomalies and individual body weights of live young were demonstrated in any dosed levels in this study. Conclusions: It is considered that the NOAEL (No-Observed-Adverse-Effect Level) for perinatal and lactational reproductive toxicity of Artemisiae Capillaris Herba extracts was up to 2000mg/kg/day because no changes of other perinatal and lactational reproductive indices were demonstrated.

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Single Oral Dose Toxicity Study of Water Extracts of Picrorrhiza Rhizoma In ICR Mice

  • Lee Hyeung-Sik;Lee Ik-Gu;Ku Sae-Kwang
    • Toxicological Research
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    • v.22 no.2
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    • pp.117-126
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    • 2006
  • This study was conducted to obtain the acute information of the oral dose toxicity of lyophilized water extract of Picrorrhiza Rhizoma (PR) - dried underground stem of Picrorrhiza kurroa, having various pharmacological effects, in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$), approximate lethal dose and target organs, test article was administered once by oral gavage to male and female ICR mice at 2000, 1000, 500 and 250 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing with organ weight and histopathology of 12 types of principle organs. As the results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for hair loss, a significantly (p<0.05) increase of body weight gains in 2000mg/kg of PR extracts-dosing male group and some sporadic gross findings. In addition, no meaningful changes on the organ weight and histopathology of 12 types of principle organs were detected in the present study except for significantly (p<0.05) but dose independent changes on thymus, spleen and popliteal lymph nodes weights, and some sporadic accidental histopathological findings. The results obtained in this study suggest that the PR extract is non-toxic in mice and is therefore likely to be safe for clinical use. The $LD_{50}$ and approximate lethal dose of PR extracts in both female and male mice were considered as over 2000 mg/kg.

A Study on Reaction Rate of Solid SCR for NOx Reduction of Exhaust Emissions in Diesel Engine (디젤엔진 배출가스 질소산화물 저감을 위한 Solid SCR의 반응률에 관한 연구)

  • Lee, Hoyeol;Yoon, Cheon Seog;Kim, Hongsuk
    • Transactions of the Korean Society of Automotive Engineers
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    • v.21 no.6
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    • pp.183-194
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    • 2013
  • Liquid urea based SCR has been used in the market to reduce NOx in the exhaust emission of the diesel engine vehicle. This system has several problems at low temperature, which are freezing below $-12^{\circ}C$, solid deposit formation in the exhaust, and difficulties in dosing system at exhaust temperature below $200^{\circ}C$. Also, it is required complicated exhaust packaging equipment and mixer due to supply uniform ammonia concentration. In order to solve these issues, solid urea, ammonium carbonate, and ammonium carbamate are selected as ammonia sources for the application of solid SCR. In this paper, basic research on reaction rate of three ammonia-transporting materials was performed. TGA (Thermogravimetric Analysis) and DTA (Differential Thermal Analysis) tests for these materials are carried out for various heating conditions. From the results, chemical kinetic parameters such as activation energy and frequency factor are obtained from the Arrhenius plot. Additionally, from test results of DSC (Differential Scanning Calorimeter) for these materials, chemical kinetic parameters using the Kissinger method are calculated. Activation energies of solid SCR from this experiment are compared with proper data of literature study, then obtained data of this experiment are used for the design of reactor and dosing system for candidate vehicle.

Experimental Investigation on DeNOx Performance according to the Urea-SCR System Control at Various Operating Conditions for Diesel Engines (디젤엔진의 운전조건 변화 및 Urea-SCR 시스템 제어에 따른 DeNOx 성능에 대한 실험적 연구)

  • Han, Jung-Won;Gong, Ho-Jeong;Hwang, In-Goo;Myung, Cha-Lee;Park, Sim-Soo
    • Transactions of the Korean Society of Automotive Engineers
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    • v.18 no.6
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    • pp.76-83
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    • 2010
  • Recently, as the current and future emission regulations go stringent, the research of NOx reduction has become a subject of increasing interest and attention in diesel engine. Selective Catalytic Reduction (SCR) is one of the effective technology to reduce NOx emission from diesel engine. Especially, Urea-SCR that uses urea as a reductant is becoming increasingly popular as a cost effective way of reducing NOx emissions from heavy duty vehicles. In this research, we designed urea injector and DCU (Dosing Control Unit) specially developed for controlling the Urea-SCR process onboard vehicles. As passenger and commercial diesel engine experiment, we grasped characteristics of NOx emission and SCR catalyst temperature level in advance. As a result, highest NOx emission level was shown in condition of low engine speed and high load. On the other hand, SCR catalyst temperature was highest at high engine speed and load. On the basis of these result, we conducted the NOx reduction test at steady engine operating conditions using the urea injector and DCU. It was shown that 74% NOx conversion efficiency on the average and 97% NOx conversion efficiency was obtained at high SCR catalyst temperature.

The Safety and Pharmacokinetics of Cyanidin-3-Glucoside after 2-Week Administration of Black Bean Seed Coat Extract in Healthy Subjects

  • Jeon, Sang-Il;Han, Seung-Hoon;Lee, Jong-Tae;Hong, Tae-Gon;Yim, Dong-Seok
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.249-253
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    • 2012
  • We analyzed the pharmacokinetics of C3G on data from twelve subjects, after 2-week multiple dosing of black bean (Phaseolus vulgaris, Cheongjakong-3-ho) seed coat extract, using the mixed effect analysis method (NONMEM, Ver. 6.2), as well as the conventional non-compartmental method. We also examined the safety and tolerability. The PK analysis used plasma concentrations of the C3G on day 1 and 14. There was no observed accumulation of C3G after 2-week multiple dosing of black bean seed coat extract. The typical point estimates of PK were CL (clearance)=3,420 l/h, V (volume)=7,280 L, Ka (absorption constant)=9.94 $h^{-1}$, ALAG (lag time)=0.217 h. The black bean seed coat extract was well tolerated and there were no serious adverse events. In this study, we confirmed that a significant amount of C3G was absorbed in human after given the black bean seed coat extract.

Reinfection by Opisthorchis Viverrini after Treatment with Praziquantel

  • Saengsawang, Phubet;Promthet, Supannee;Bradshaw, Peter
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.857-862
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    • 2016
  • Background: The prevalence of infection by the liver fluke, Opisthorchis viverrini (O. viverrini), has remained high in Northeast Thailand where it is a major risk factor for the eventual development of cholangiocarcinoma (CCA). The infection is acquired by the consumption of dishes containing unsafely prepared freshwater fish, a dietary tradition which has proved resistant to change. Since many people are aware that dosing with praziquantel (PZQ) is a successful treatment for an episode of the infection, there is a risk that, to avoid the long term consequences, they will engage in a cycle of infection, dosing and reinfection. Objectives: There is a dearth of studies of reinfection by O. viverrini, and the aims of this study were to assess re-infection rates in a typical province of Northeastern Thailand where O. viverrini infection is likely and to investigate factors associated with reinfection. Materials and Methods: A total of infected 607 villagers were treated with PZQ, and those found to be no longer infected were followed up at six-monthly intervals over 12 months. Results: At the end of this period data on 457 subjects were available for analysis using descriptive statistics and logistic regression, and 50 were found to have become reinfected, giving a cumulative reinfection rate of 10.9%. The results of a multiple logistic regression analysis showed that the only factor found to be associated with reinfection was past use of PZQ. Conclusions: Recommendations are made for future larger scale and better designed reinfection studies in the light of limitations of the current study. Further efforts are needed to discourage people from eating fish dishes likely to contain viable metacariae.

The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats

  • Safhi, Mohammed Mohsen;Anwer, Tarique;Khan, Gyas;Siddiqui, Rahimullah;Sivakumar, Sivagurunathan Moni;Alam, Mohammad Firoz
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.493-501
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    • 2018
  • The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

Hypolipemic Effect of 'Saengjinyanghyul-tang' water extracts in the Streptozotocin-induced Hyperlipemic SD Rat (생진양혈탕(生津養血湯) 물 추출물의 Streptozotocin 유발 고지혈증에 대한 효과)

  • Hur, Hyun;Kim, Dae-Jun;Byun, Joon-Seok;Choi, Bin-Hye
    • The Journal of Internal Korean Medicine
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    • v.27 no.2
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    • pp.444-458
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    • 2006
  • In the Present study, the therapeutic hypolipemic effect of water extract of Saengjinyanghyl-tang (SJYHT), a herbal extract mixture for treatment of diabetes in oriental medicine was tested in Streptozotocin-induced diabetic hyperlipemic SD rats. For detect the therapeutic effects, the test articles were once a day dosed for 28 days by gastric gavage at a dosage 1000, 500 and 250mg/kg from 25 days after STZ-dosing, and the changes on body weight and gains, serum LDL, HDL, Triglyceride and Total Cholesterol levels were observed In addition, the effects of test articles were compared to that of Simvastatin, a well known hypolipemic agents 10mg/kg-dosing group. Base on these results, although no meaningful effects were detected on the serum HDL levels, it is concluded that Saengjinyanghyul-tang water extracts have relatively good favorable effect treatment of STZ-induced diabetic hyperlipemia because they showed clear evidences inhibit the increase of serum LDL, Triglyceride and Total Cholesterol levels. Therefore, it is expected that Saengjinyanghyul-tang extract has favorable potency to development hypolipemic drugs. In addition, about 1000mg/kg of Saengjinyanghyul-tang extracts have similar effect compared to that of Simvastatin 10mg/kg. The effective dosage of Saengjinyanghyul-tang water extracts in the present study was considered as below 250mg/kg.

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Effect of Glucose-diethyldithiocarbamate on Drug Metabolizing Enzymes in Rats (Glucose-diethyldithiocarbamate가 흰쥐의 약물 대사 효소에 미치는 영향 연구)

  • 최병기;신혜주
    • Biomolecules & Therapeutics
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    • v.8 no.4
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    • pp.299-304
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    • 2000
  • The modulation of cytochrome P450(P450) activities and glutathione S-transferase (GST) was investigated after i.p. administration of glucose-diethyldithiocarbamate (Glu-DDTC) to rats. P450 1 A2 and 2El activities were inhibited by 60% 4 hr after the administration of 200 mg Glu-DDTC/kg and those activities were recovered to original levels 24 hr after dosing. In contrast, GST activities were enhanced up to 24 hr after dosing. These results seem to be due to the bifunctional activity of Glu-DDTC. Glu-DDTC acts as an inhibitor of P450 enzymes as well as inducer of GST enzyme. Glu-DDTC inhibited PNP hydroxylation (P450 2El) and ethoxycoumarin O-deethylation (P450 1A2) in a dose-dependent manner up to 200 mg/kg wherease it did not affect testosterone 6$\beta$-hydroxylation (P450 3A) and pentoxyresorufin O-dealkylation (P450 2B) activities. Induction of GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzenen (DCNB) was dependent on the dose of Glu-DDTC and no species difference in the GST induction was seen between rat and mouse. Amoung GST subunits, Ya, Yb1 and partially Yb2 were induced by Glu-DDTC as conjugated by western blotting. The levels Yp, Yk and Yc subunits were not affected by Glu-DDTC treatment. Therefore the enhanced activity of GST toward CDNB and DCNB might be due to the induction of Ya, Ybl and partially Yb2 subunits. In conclusion, Glu-DDTC selectively inhibited P45O 1A2 and P450 2El activities whereas it enhanced Ya, Ybl subunits and partially Yb2 subunits of GST and the antimutagenic activity of this compound might be attributed from the modulation of these enzyme activities in animals.

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Evaluation of Pharmacist Intervention Program for Dosage Adjustment and IV-to-PO Conversion for $H_2$-Receptor Antagonist (신기능을 고려한 $H_2$-receptor antagonist의 용량, 용법 및 투여경로의 적절성 및 약사자문의 수용성)

  • Hwang, Bo Young;Oh, Jung Mi
    • Quality Improvement in Health Care
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    • v.9 no.2
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    • pp.230-240
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    • 2002
  • Background : The purpose of this study was to develop, implement and evaluate the pharmacist intervention program designed to identify and correctly adjust the dosage of $H_2$-receptor antagonists ($H_2RA$) in renally impaired patients and promote timely conversion of $H_2RA$ from IV to PO therapy. Methods : The study population consisted of renally impaired patients who received $H_2RA$ therapy from April 9 to May 8, 2001 at Hallym Medical Center. Each morning a specifically developed software program identified patients with serum creatinine (Scr) greater than 1.2 mg/dl or age greater than 65 years. The pharmacist, then screened the pharmacy profiles of the identified patients to determine if the patient was on $H_2RA$. For these patients on $H_2RA$ with renal impairement the creatinine clearance (CrCl) was calculated using Cockroft & Gault equation. The pharmacist determined the proper dosage for each identified patients based on the calculated CrCl and the oral dosage that would be appropriate for whom IV therapy was no longer indicated. Result : A total of 149 cases (101 patients) were monitored during the study period. The dosage was inappropriately prescribed for renal function in 61 of 149 cases (41%), and of those, pharmacist made recommendations for 58 cases of which 33 cases (57%) were accepted by the physicians. The administration route of H2RA was inappropriately used as IV in 22 of 53 cases (42%), and pharmacist made recommendations for those 22 cases of which 15 cases (68%) were accepted. Conclusion : Monitoring of patients with renal dysfunction by a pharmacist improved the dosing of $H_2RA$ and a dosing program of patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

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