• Title/Summary/Keyword: In-vivo Test.

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The Effect of Dansamtongmek-tang and Dansamsengmek-san on Hyperlipidemia and Brain & Cell Damage by Hypoxia (단삼통맥탕(丹蔘通脈湯)과 단삼생맥산(丹蔘生脈散)이 고지혈증 및 Hypoxia로 유발된 뇌손상과 세포손상에 미치는 영향)

  • Kim, Yong-Jin;Yu, Byeong-Chan;Kim, Yoon-Sik;Seol, In-Chan
    • The Journal of Korean Medicine
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    • v.27 no.3 s.67
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    • pp.107-131
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    • 2006
  • Background and Aims: Dansamtongmek-tang (DSTMT) and Dansamsengmek-san (DSSMS) have been used for many years as therapeutic agents for the acute stage of cerebrovascular disease, hypertension and hyperlipidemia in Oriental medicine, but the effects of DSTMT and DSSMS on hyperlipidemia and safety for cell damage are not yet well-known. This study was done to investigate the effects of DSTMT and DSSMS on hyperlipidemia. Methods: In vivo test: after administering DSTMT and DSSMS to SHR and ICR occurred hyperlipidemia for 3 weeks, we analyzed body weight, cholesterol levels. TG, HDL-chol, LDL-chol, LDH in plasma, brain, liver and kidney tissue, and DNA by RT-PCR. In vitro test: after administering DSTMT and DSSMS to human hepatocellular carcinoma in hypoxia, we observed cell cohesion by light microscope, analyzed the inflow of Ca2+ by confocal laser scanning microscope and DNA by RT-PCR. Results: DSTMT significantly decreased the levels of triglyceride and increased the levels of HDL-cholesterol in SHR, and significantly decreased the levels of LDL-cholesterol and body weight and increased the levels of HDL-cholesterol in ICR. DSSMS significantly decreased body weight, total cholesterol levels, LDL-cholesterol, LDH and cardiac risk factor (CRE) in SHR and significantly decreased the levels of total cholesterol, triglyceride, LDL-cholesterol, LDH and CRF in ICR. DSTMT had an effect on protecting cells from damage by inhibiting production of p53 mRNA, and in DSSMS, by inhibiting production of p53 mRNA and p21 mRNA after hypoxia. DSTMT effectively blocked off Ca2+ at low density, but DSSMS effectively blocked off Ca2+ at high density. Both DSTMT and DSSMS had an effect on inhibiting lipid metabolism by blocking off production of apo B mRNA. Conclusions: These results suggest that DSTMT and DSSMS might be usefully applied for treatment of hyperlipidemia and suppression of brain damage.

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Effect of YGF251 on Secretion Of IGF-1 in Human Blood (YGF251 투여에 의한 인체내 혈중의 IGF-1 분비량 변화 효과)

  • 김재수;박준홍;조한성;박점석;홍억기
    • KSBB Journal
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    • v.17 no.4
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    • pp.403-408
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    • 2002
  • For stimulating the in vivo secretion of IGF-1 (insulin-like growth factor-1) which is well known to promote the various physiological actions in human body, the natural herbal extract, YGF251 (young growth factor 251), was developed and evaluated for its effect as IGF-1 secretagogue in this study. The clinical study was peformed as double blind test, and 31 adult female and male volunteers between the age of 40 and 70 were investigated for their changes of concentration of IGF-1 , insulin level, weight, blood pressure, and liver and kidney functions. As the result of paired sample test on the change of the concentration of IGF-1, in YGF251 treated group, it was 245.6 ng/mL before dosing. The concentration of IGF-1 was increased to 269.3 ng/mL after a month and to 275.6 ng/mL after two months, and both were statistically significant (p〈0.05). While in control group, the concentration of IGF-1 was 280.0 ng/mL before dosing, but decreased to 239.2 ng/mL after a month and to 230.2 ng/mL after two months, and both were also statistically significant (p〈0.05). In YGF251 treated group, the concentration of insulin in blood increased about 2 times after a month dosing as an average level, but in control group, it showed a decrease of 36% compared with before dosing. And there were little changes regarding to the measured weight and blood pressure. Various measured data in order to observe the alteration in liver and kidney functions by the administration of YGF251 showed a little change within measuring error range.

The Formulation and Bioavailability of Oral Sustained Release Sulindac Delivery System (설린닥의 경구용 지속성 제제설계 및 생체이용율)

  • Rhee, Gye-Ju;Park, Sun-Hee;Whang, Sung-Joo
    • YAKHAK HOEJI
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    • v.41 no.1
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    • pp.60-73
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    • 1997
  • In order to design a 24 hr sustained release preparation of sulindac for oral administration, fast release pellet (FR), slow release pellet (SR) and two combined formulation (1 : 1 and 1 : 2) were prepared. The pharmacokinetic effect of such preparations has been evaluated using rabbits as a suitable in vivo model, and tested in man. Dose determination was carried out using curve fitting according to RSTPJP II program. In bioavailability test using rabbit, AUCs of sulindac in a few designed formulations were similar to each other. $C_{max}$- of RF and SR were 1.8 times and 1.2 times higher, respectively, compared to that of combined formulation (FR:SR=1:1). While plasma concentration of FR and SR decreased rapidly, that of combined formulation (FR:SR 1:1) lasted at the level close to $C_{max}$ for 24 hrs. Plasma concentration of sulfide form from the combined pellet(FR:SR=1:1) lasted for 24 hrs, and its AUC value was 1.4-fold, 2.7-fold. and 1.2-fold greater than FR pellet, SR pellet and combined pellet (FR:SR 1 : 2). Thus, the combined pellet of 1:1 ratio was found to be the most effective for oral sustained release formulation. Bioavailability test in human showed that AUC of sulfide from TSRP (1 : 1) was approximately 1.5 times greater than total AUC of Immbaron$^{\circledR}$ administered twice in a day. While $T_{max}$ of sulfide from lmmbaron$^{\circledR}$ was 4.33 +/- 1.37 hr (lst administration) and 3.33 ${pm}$ 0.82 hr (2nd administration), respectively, that of sulfide from TSRP increased to 7.17 ${pm}$ 2.86 hr. Plasma concentration of sulfide from TSRP was sustained at more, than 1.0 ${\mu}g{\cdot}$hr/ml until 24 hrs after one dose administration. In addition, TSRP may decrease local adverse reaction in the stomach, since plasma concentration of sulfide from the combined pellet was low within 2hrs in the stomach. In conclusion, it is suggested that TSRP formulation may be effective for oral 24 hr sustained release formulation of sulindac dosing 300 ~ 350mg once a day.

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Evaluating the Micronucleus Induction Potential for the Genotoxicity Assay Using the Human Skin Model, KeraSkinTM (인공피부모델 KeraSkinTM을 이용한 유전독성 평가)

  • Lee, Su-Hyon;Jung, Haeng-Sun;Kim, Seol-Yeong;Kim, Hye Soo;Lim, Kyung-Min;Chung, Young-Shin;Choe, Tae-Boo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.3
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    • pp.211-216
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    • 2016
  • Micronucleus test is genotoxicity assay for detection of micronuclei in the cytoplasm of interphase cells. The reduction and replacement of in vivo toxicity testing on animals require the development of in vitro models to predict the genotoxicity or other tests for cosmetic products. In this study, we evaluated a genotoxicity assay for topically applied chemicals using a three-dimensional human reconstructed skin model, KeraSkin$^{TM}$. Two genotoxins, mitomycin C (MMC) and methyl methanesulfonate (MMS), induced significant dose-related increases in cytotoxicity and micronuclei induction in the skin model. In contrast, two non-genotoxins, 4-nitrophenol (4-NP) and trichloroethylene (TCE), induced cytotoxicity but not micronucleus formation. In conclusion, micronucleus test using human skin model may be useful for predicting in vitro genotoxic potentials of cosmetic products.

Mechanisms of Hela Cell Apoptosis Induced by Abnormal Savda Munziq Total Phenolics Combined with Chemotherapeutic Agents

  • Zhang, Yun-Xia;Abliz, Guzalnur;Ye, Wei-Jun;Mutalipu, Zuohelaguli;Li, Xiao-Wen;Wang, Hai-Qin;Buranjiang, Gulimire;Upur, Halmurat
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.743-747
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    • 2014
  • Objective: To investigate the effects of abnormal Savda Munziq (ASMq) total phenolics combined with cisplatin and docetaxel on the Hela cell growth. Methods: In vivo cultured Hela cells were treated with cisplatin, docetaxel, total phenolics, cisplatin+total phenolics or docetaxel+total phenolics. MTT was performed to assess inhibition of cell proliferation, flow cytometry to detect apoptosis, and semi-quantitative RT-PCR to test for survivin and Bcl-2 expression. Results: The total phenolics, cisplatin and docetaxel had significant inhibitory and apoptosis-promoting effects on Hela cells (P<0.05), with the early apoptotic rates of $12.8{\pm}0.70%$, $18.9{\pm}3.79%$ and $15.8{\pm}3.8%$; the total phenolics, cisplatin and docetaxel significantly decreased the expression of Bcl-2 and survivin (all P<0.01), especially when used in combination. Conclusion: ASMq total phenolics, combined with cisplatin and docetaxel, could promote the apoptosis of Hela cells possibly through reducing the expression of Bcl-2 and survivin.

Development of Real-time Closed-loop Neurostimulation System for Epileptic Seizure Suppression (뇌전증 경련 억제를 위한 실시간 폐루프 신경 자극 시스템 설계)

  • Kim, Sowon;Kim, Sunhee;Lee, Yena;Hwang, Seoyoung;Kang, Taekyeong;Jun, Sang Beom;Lee, Hyang Woon;Lee, Seungjun
    • Journal of Biomedical Engineering Research
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    • v.36 no.4
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    • pp.95-102
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    • 2015
  • Epilepsy is a chronic neurological disease which produces repeated seizures. Over 30% of epileptic patients cannot be treated with anti-epileptic drugs, and surgical resection may cause loss of brain functions. Seizure suppression by electrical stimulation is currently being investigated as a new treatment method as clinical evidence has shown that electrical stimulation to brain could suppress seizure activity. In this paper, design of a real-time closed-loop neurostimulation system for epileptic seizure suppression is presented. The system records neural signals, detects seizures and delivers electrical stimulation. The system consists of a 6-channel electrode, front-end amplifiers, a data acquisition board by National Instruments, and a neurostimulator and Generic Osorio-Frei algorithm was applied for seizure detection. The algorithm was verified through simulation using electroencephalogram data, and the operation of whole system was verified through simulation and in- vivo test.

Induction of Phase II Enzyme Activity by Artemisia asiatica Nakai Aqua-acupuncture Solution (애엽(艾葉) 약침액(藥鍼液)에 의한 Phase II 효소 활성 유도)

  • Yoon Sung-Mook;Cho Kyoung-Hee;Shon Yun-Hee;Nam Kyung-Soo;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.18 no.1
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    • pp.1-9
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    • 2001
  • Artemisia asiatica Nakai aqua-acupuncture solution (ANAS) was administered once daily for 10 days before the tumor implantation ($1{\times}10^6\;cells$). Body weight, spleen weight and the number of ascitic tumor cells were measured at 6 days after tumor implantation. The change of body weight and the survival rate of mice were observed for 21 days. It was used three biomarkers (quinone reductase, glutathione, glutathione S-transferase) to test chemopreventive potentials of ANAS. ANAS exerted antitumor activity by inhibiting the growth of Ehrlich ascites tumor cells in vivo. Mice given Ehrlich cells and ANAS at $CV_{12}$ and $BL_{18}$ had 57.1% to 49.2% survival after 21 days. Quinone reductase activity and glutathione levels were increased with ANAS. However, glutathione S-transferase level was 1.1-fold with ANAS. These results suggest that ANAS has chemopreventive potential by inducing QR activity and increasing GSH level.

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Development of Polymeric Coating Material for Effective Drug-eluting Stent (효율적인 약물 방출 스텐트 제조를 위한 고분자 코팅물질 개발)

  • Park, Tae-Hyun;Jo, Eun-Ae;Na, Kun
    • Polymer(Korea)
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    • v.35 no.5
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    • pp.483-487
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    • 2011
  • For the preparation of effective non-vascular drug eluting stent (DES), pullulan acetate (PA) was investigated as a coating material for polytetrafluorethylene (PTFE)-covered stent. PA was coated on PTFE-covered stent (PTFE-stent) by dip coating technique, and then its surface morphology, drug release behavior and cellular toxicity were tested. Field emission-scanning electron microscopy (FE-SEM) result indicated that its surface was smoother after PA coating without any cracking. The sustained release behavior of paclitaxel from PA-coated PTFE membrane was observed for 80 days. Also, the biological stability of paclitaxel in the membrane was confirmed by annexin V binding assays. Furthermore, the antitumor activity was demonstrated by an in vivo test against CT-26 murine colorectal tumors. From the results, we concluded that PA was expected as a useful coating material to design an effective non-vascular DES.

The influence of sodium hypochlorite concentration on the fibrin structure of human blood clots and transforming growth factor-beta 1 release: an ex vivo study

  • Anisha Mishra ;Velmurugan Natanasabapathy;Nandini Suresh
    • Restorative Dentistry and Endodontics
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    • v.47 no.4
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    • pp.42.1-42.11
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    • 2022
  • Objective: This study investigated the effects of various concentrations of sodium hypochlorite (NaOCl) on human whole-blood clotting kinetics, the structure of the blood clots formed, and transforming growth factor (TGF)-β1 release. Materials and Methods: Human whole blood was collected from 5 healthy volunteers and divided into 4 groups: CG (control, 0.5 mL of blood), BN0.5 (0.5 mL of blood with 0.5 mL of 0.5% NaOCl), BN3 (0.5 mL of blood with 0.5 mL of 3% NaOCl), and BN5.25 (0.5 mL of blood with 0.5 mL of 5.25% NaOCl). The effects of NaOCl on clotting kinetics, structure of fibrin and cells, and release of TGF-β1 were assessed using thromboelastography (TEG), scanning electron microscopy (SEM), and enzyme-linked immunosobent assay, respectively. Statistical analysis was conducted using the Kruskal Wallis and Mann-Whitney U tests, followed by the post hoc Dunn test. A p value < 0.05 indicated statistical significance. Results: The blood samples in BN0.5 and BN3 did not clot, whereas the TEG of BN5.25 showed altered clot formation. Samples from the CG and BN3 groups could only be processed with SEM, which showed that the latter lacked fibrin formation and branching of fibers, as well as clumping of red blood cells with surface roughening and distortion. TGF-β1 release was significantly highest in BN3 when all groups were compared to CG (p < 0.05). Conclusions: Each concentration of NaOCl affected the release of TGF-β1 from blood clots and altered the clotting mechanism of blood by affecting clotting kinetics and cell structure.

Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

  • Da Silva, Aleksandro S.;Fanfa, Vinicius R.;Otto, Mateus A.;Gressler, Lucas T.;Tavares, Kaio C.S.;Lazarotto, Cicera R.;Tonin, Alexandre A.;Miletti, Luiz C.;Duarte, Marta M.M.F.;Monteiro, Silvia G.
    • Parasites, Hosts and Diseases
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    • v.49 no.4
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    • pp.427-430
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    • 2011
  • The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2(D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of $40.9{\pm}0.3$ (C), $20{\pm}9.0$ (D) and $35.6{\pm}9.3$ (E) days compared to the control group (B) which was $4.3{\pm}0.5$ days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas.