• Title/Summary/Keyword: preclinical test

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ASSESSMENT OF LOCAL LYMPH NODE ASSAY AS AN ALTERNATIVE METHOD FOR SKIN SENSITIZATION POTENTIAL

  • Hwang, In-Chang;Kim, Hyung-Soo;Dong, Mi-Sook;Park, Jae-Hyun;Lee, Jong-Kwon;Oh, Hye-Young;Park, Young-In
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.194-194
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    • 2001
  • Preclinical test methods for allergenic potential chemicals has been widely used to assess human risks and has been developed. Recently, the murine local lymph node assay (LLNA) has been proposed as a prospective method to identify contact allergens and to replace conventional the guinea pig maximization test (GPMT). The objective of this study was to establish LLNA and to evaluate allergenicity of chemicals by LLNA. (omitted)

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Genotoxicity Studies of STB-HO-BM, a Germanium Complex (게르마늄 복합물인 STB-HO-BM에 대한 유전독성에 관한 연구)

  • Song Si-Whan;Jung Winston;Hong Dong-Ho
    • Toxicological Research
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    • v.22 no.2
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    • pp.145-151
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    • 2006
  • We have investigated the genotoxicity of STB-HO-BM using in vitro and in vivo system such as Ames reverse mutation test, chromosomal aberration test and micronucleus test. in Ames reverse mutation test, STB-HO-BM treatment at the dose range up to 5,000 ug/plate did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA102, TA1535, TA 1537 and in Escherichia coli WP2 uvrA with and without metabolic activation. Any significant aberration wasn't observed in chinese hamster lung (CHL) fibroblast cells treated with STB-HO-BM at the concentration of 12.5, 2.5, 5 mg/ml both in the absense and presence of metabolic activation system. In mouse micrnucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice orally administered with STB-HO-BM at the doses of 0.5, 1.0, 2.0 g/kg. These results indicate that STB-HO-BM has no mutagenic potential under the condition in this study.

In Vivo Spinal Distribution of Cy5.5 Fluorescent Dye after Injection via the Lateral Ventricle and Cisterna Magna in Rat Model

  • Lee, Kee-Hang;Nam, Hyun;Won, Jeong-Seob;Hwang, Ji-Yoon;Jang, Hye Won;Lee, Sun-Ho;Joo, Kyeung Min
    • Journal of Korean Neurosurgical Society
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    • v.61 no.4
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    • pp.434-440
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    • 2018
  • Objective : The purpose of this study was to find an optimal delivery route for clinical trials of intrathecal cell therapy for spinal cord injury in preclinical stage. Methods : We compared in vivo distribution of Cy5.5 fluorescent dye in the spinal cord region at various time points utilizing in vivo optical imaging techniques, which was injected into the lateral ventricle (LV) or cisterna magna (CM) of rats. Results : Although CM locates nearer to the spinal cord than the LV, significantly higher signal of Cy5.5 was detected in the thoracic and lumbar spinal cord region at all time points tested when Cy5.5 was injected into the LV. In the LV injection Cy5.5 signal in the thoracic and lumbar spinal cord was observed within 12 hours after injection, which was maintained until 72 hours after injection. In contrast, Cy5.5 signal was concentrated at the injection site in the CM injection at all time points. Conclusion : These data suggested that the LV might be suitable for preclinical injection route of therapeutics targeting the spinal cord to test their treatment efficacy and biosafety for spinal cord diseases in small animal models.

Preclinical Evidence and Underlying Mechanisms of Polygonum multiflorum and Its Chemical Constituents Against Cognitive Impairments and Alzheimer's Disease

  • Jihyun Cha;Ji Hwan Yun;Ji Hye Choi;Jae Ho Lee;Byung Tae Choi;Hwa Kyoung Shin
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.70-81
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    • 2024
  • Objectives: Cognitive impairments, ranging from mild to severe, adversely affect daily functioning, quality of life, and work capacity. Despite significant efforts in the past decade, more than 200 promising drug candidates have failed in clinical trials. Herbal remedies are gaining interest as potential treatments for dementia due to their long history and safety, making them valuable for drug development. This review aimed to examine the mechanisms behind the effect of Polygonum multiflorum on cognitive function. Methods: This study focused primarily on the effects of Polygonum multiflorum and its chemical constituents on cognitive behavioral outcomes including the Morris water maze, the passive avoidance test, and the Y maze, as well as pathogenic targets of cognitive impairment and Alzheimer's disease (AD) like amyloid deposition, amyloid precursor protein, tau hyperphosphorylation, and cognitive decline. Additionally, a thorough evaluation of the mechanisms behind Polygonum multiflorum's impact on cognitive function was conducted. We reviewed the most recent data from preclinical research done on experimental models, particularly looking at Polygonum multiflorum's effects on cognitive decline and AD. Results: According to recent research, Poligonum multiflorum and its bioactive components, stilbene, and emodin, influence cognitive behavioral results and regulate the pathological target of cognitive impairment and AD. Their mechanisms of action include reducing oxidative and mitochondrial damage, regulating neuroinflammation, halting apoptosis, and promoting increased neurogenesis and synaptogenesis. Conclusion: This review serves as a comprehensive compilation of current experiments on AD and other cognitive impairment models related to the therapeutic effects of Polygonum multiflorum. We believe that these findings can serve as a basis for future clinical trials and have potential applications in the treatment of human neurological disorders.

Use of in vitro assays for evaluating physiological functionality of foods: General consideration

  • Chun Hyang Sook
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2003.11a
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    • pp.74-77
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    • 2003
  • A new health paradigm may be evolving that would place emphasis on the positive aspects of diet, identifying components that are physiologically active and that contribute to the prevention of disease onset. It has been increasingly difficult to evaluate the impact of new bioactive materials and food products on the well being of society. Thus, testing systems for both health function and toxicity have become very elaborate, complex, and interrelated, making their interpretation difficult and open to controversy. To select the proper starting materials, to screen the appropriate health functionality and to determine the efficacy of product, a reliable, reproducible, sensitive and predictive assay is required. Particularly, in uitro assay is the first stage in preclinical test on physiologically active materials and have many advantages in terms of time, cost and convenience. However, several factors as well as some limitations should be considered in this assay system. This presentation, therefore, will address the use of in uitro assays for evaluating physiological functionality of foods coupled with general consideration.

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Metabolomic approach for evaluating drug response

  • Jung, Byung-Hwa
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.11-15
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    • 2007
  • Metabolomics is an emerging technology which makes it possible to evaluate change of biological system in response to the physiological, environmental alterations. It has advantages in the simplicity and sensitivity to analyze metabolites since the researcher can use cutting edge instrument, such as mass spectrometry and simple sample preparation method compared to genomics or proteomics. Nowadays this technology has been tried in pharmaceutical area to investigate toxicity and efficacy of drug candidates and drugs in preclinical test. The metabolomic applications on the pharmaceutics for early prediction on toxicity and efficacy are described in this presentation. The multivariate analysis to get metabolic fingerprinting and its relations with the physiological changes are investigated with several drugs. Feasibility of metabolomic application for pharmaceutical area would be suggested from those researches.

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The biomechanical and biological effect of supercooling on cortical bone allograft

  • MuYoung Kim ;Hun-Young Yoon
    • Journal of Veterinary Science
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    • v.24 no.6
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    • pp.79.1-79.16
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    • 2023
  • Background: The need for a storage method capable of preserving the intrinsic properties of bones without using toxic substances has always been raised. Supercooling is a relatively recently introduced preservation method that meets this need. Supercooling refers to the phenomenon of liquid in which the temperature drops below its freezing point without solidifying or crystallizing. Objectives: The purpose of this study was to identify the preservation efficiency and applicability of the supercooling technique as a cortical bone allograft storage modality. Methods: The biomechanical effects of various storage methods, including deep freezing, cryopreservation, lyophilization, glycerol preservation, and supercooling, were evaluated with the three-point banding test, axial compression test, and electron microscopy. Additionally, cortical bone allografts were applied to the radial bone defect in New Zealand White rabbits to determine the biological effects. The degree of bone union was assessed with postoperative clinical signs, radiography, micro-computed tomography, and biomechanical analysis. Results: The biomechanical properties of cortical bone grafts preserved using glycerol and supercooling method were found to be comparable to those of normal bone while also significantly stronger than deep-frozen, cryopreserved, and lyophilized bone grafts. Preclinical research performed in rabbit radial defect models revealed that supercooled and glycerol-preserved bone allografts exhibited significantly better bone union than other groups. Conclusions: Considering the biomechanical and biological superiority, the supercooling technique could be one of the optimal preservation methods for cortical bone allografts. This study will form the basis for a novel application of supercooling as a bone material preservation technique.

Antigenicity of a Water Soluble Dimethyl Dimethoxy Biphenylate Derivative(DDB-S), a New Antihepatitis Agent (새로운 간염치료제인 수용성 DDB 유도체 (DDB-S)의 항원성 평가)

  • Han, Hyung-Mee;Kim, Jin-Ho;Choi, Kyoung-Baek;Kim, Hyung-Soo;Chung, Seung-Tae;Moon, Jeon-Ok;Lee, Chi-Ho;Kim, Joo-Il
    • Toxicological Research
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    • v.14 no.3
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    • pp.307-313
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    • 1998
  • Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.

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Colposcopy Requirement of Papanicolaou Smear after Atypical Squamous Cells of Undetermined Significance (ASC-US) by Follow-up Protocol in an Urban Gynaecology Clinic, a Retrospective Study in Thailand

  • Perksanusak, Thitichaya;Sananpanichkul, Panya;Chirdchim, Watcharin;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4977-4980
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    • 2015
  • Background: ASC-US cases are managed according to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guideline in which a human papillomavirus (HPV) test and repeat Pap smear are performed in the next 1 year. Colposcopy in cases of positive high risk HPV and persistent ASC-US or more in subsequent Pap smear is recommended. The HPV test is more expensive and still not currently a routine practice in Thailand. Objective: To identify the risk factors of persisted abnormal Pap smear and the colposcopic requirement rate in women with ASC-US. Materials and Methods: During 2008-2013, this study was conducted in Prapokklao Hospital, Chanthaburi, Thailand. Participants were women who attended gynaecology clinic for cervical cancer screening. Women who had cytological reports with ASC-US were recruited. During the study period, 503 cases were enrolled. Colposcopic requirement was defined as those who were detected with an ASC-US or more in subsequent Pap smears up to 1 year follow-up. Results: The colposcopic referral rate was 23.2 (85/365) percent at 12 months. Prevalence of cervical intraepithelial neoplasia (CIN) 2/3 was 3.3 (12/365) percent. Loss follow-up rate of subsequent Pap smear and colposcopic appointment were 27.4 (138/503) and 48.2 (41/85) percent, respectively. There was no invasive cancer. High risk factors for persisted abnormal Pap smears in subsequent test were premenopausal status, HIV infected patients and non-oral contraceptive pills (COC) users. Conclusions: Referral rate for colposcopy in women with ASC-US reports was rather high. Loss to follow-up rate was the major limitation. Immediate colposcopy should be offered for women who had high risk for silent CIN.

Anal Papanicolaou Smear in Women with Abnormal Cytology: a Thai Hospital Experience

  • Sananpanichkul, Panya;Pittyanont, Sirida;Yuthavisuthi, Prapap;Thawonwong, Nutchanok;Techapornroong, Malee;Bhamarapravatana, Kornkarn;Suwannarurk, Komsun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.1289-1293
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    • 2015
  • Background: Anal intraepithelial lesions (AIL) are likely to represent a precursor for anal cancer. Women infected with human immunodeficiency virus (HIV) may be at higher risk of anal cancer but a screening program for AIL still is not routinely recommended. We here studied the relationship of dysplastic cells from cervical and anal cytology in HIV-infected women. Materials and Methods: This prospective study was conducted in Prapokklao Hospital, Thailand during 2013-2014. Five hundred and ninety nine HIV-infected women were recruited. Participants who had cytological reports of equally or over "abnormal squamous/glandular cells of undetermined significance" (ASC-US) were classified as abnormal cervical or anal cytology. Descriptive statistics and logistic regression analysis were used to evaluate correlations between groups. Results: HIV-infected women with abnormal cervical cytology had 3.8 times more risk (adjusted odd ratio 3.846, 95% confidence interval 1.247-11.862, p-value. 019) for abnormal anal cytology. The major problem of the anal Pap test in this study was the inadequacy of the collected specimens for evaluation (34.4%, 206/599). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of cervical and anal Pap tests were 93.9/12.0, 87.3/96.9, 39.7/21.4, 99.4/94.1 and 88.1/91.4 percent, respectively. Conclusions: Abnormal cervical cytology in HIV-infected women indicates elevated risk for abnormal anal cytology. The sensitivity of the anal Pap test for detection of AIL 2/3 in HIV-infected women was quite low while specificity was excellent. Inadequacy of specimen collection for evaluation was a major limitation. Improvement of sample collection is recommended for future investigations.