• Title/Summary/Keyword: Preclinical

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I. Primary cultured hepatocytes as a key in vitro model to improve preclinical drug development (간세포 배양-약물대사를 위한 모델 연구)

  • 이경태
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.135-140
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    • 1994
  • Over past decades, numerous in vitro model has been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as : 1. the characterization of main biotransformation reactions. 2. the identification of phase I and phase II isozymes involved in such reactions 3. the evaluation of interspecies differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles 4. the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions 5. the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obstained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers.

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The effect of ginsenosides on depression in preclinical studies: A systematic review and meta-analysis

  • Kim, Yunna;Cho, Seung-Hun
    • Journal of Ginseng Research
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    • v.45 no.3
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    • pp.420-432
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    • 2021
  • Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics

  • Mathew, Ryan K.;Rutka, James T.
    • Journal of Korean Neurosurgical Society
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    • v.61 no.3
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    • pp.343-351
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    • 2018
  • Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

Hippocampus and Schizophrenia (해마와 정신분열병)

  • Chung, Young Chul
    • Korean Journal of Biological Psychiatry
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    • v.10 no.1
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    • pp.20-44
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    • 2003
  • Schizophrenics suffer not only psychotic symptoms but also cognitive deficits such as an attentional difficulty, memory impairment, poor abstraction, etc. These cognitive abnormalities have been reported to be significantly related to the social and occupational outcome in schizophrenia. Thus, it is important to explore the cause and pathophysiology for the cognitive abnormalities in patients with schizophrenia. In this regard, hippocampus is one of the most promising brain areas to search for the clue because it is closely involved in memory related function. In fact, during the past several decades, there have been extensive studies supporting hippocampal abnormalities as a cause of schizophrenia in both clinical and preclinical field. In this review, basic anatomical knowledge about hippocampus and major findings of preclinical and clinical studies which investigated the correlation between schizophrenia and hippocampus were highlighted. The contents are 1) anatomical structure of hippocampus, 2) neuronal pathway and receptor distribution in hippocampus, 3) function of hippocampus, 4) hippocampal animal model for schizophrenia, 5) hippocampus-related studies on antipsychotic drugs, and 6) clinical studies in hippocampus in patients with schizophrenia.

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The Potential of Renal Progenitor Cells in Kidney Diseases: Preclinical Findings

  • Jo, Jeong Hyun;Kim, Ki Hoon;Kim, Tae Min
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.2
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    • pp.70-74
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    • 2019
  • The kidney is a highly complex organ, and acute or chronic renal diseases can occur with various complications such as diabetes and hypertension. So far, no target specific treatment is available in acute or chronic renal failure, necessitating the development of alternative therapeutic strategy. Recent experimental findings suggest that the renal function and structure can be restored after being treated with various sources of stem/progenitor cells. In this review, we discuss up-to-date findings of the potential of renal progenitor/stem cells in alleviating renal injuries with a focus on preclinical studies. We also review cellular mechanisms underlying the therapeutic function of these cells.

Preclinicnl Trial of Radiation Synovectomy with Ho-166 (Ho-166 활액막절제술의 임상시험)

  • Lee, Jong-Doo
    • 대한핵의학회:학술대회논문집
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    • 1999.05a
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    • pp.200-204
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    • 1999
  • Rheumatoid arthritis (RA) is o chronic inflammatory disease of joints with proliferation of synovial epithelial tissue. Therapeutic approach of the RA consists of pharmacological and surgical interventions. Synovectomy is indicated in patients with progressive inflammatory signs and symptoms intractable to medical treatment including local intracavitary steroid injection. Recently, local injection of radionuclides which emit high energy beta rays are labeled with chemical compounds such as $^{90}Y,\;^{165}Dy-ferric$ hydroxide macroaggregate and have been introduced as an alternative therapeutic modality to surgical synovectomy. Holmium-166 is one of beta emitter and Ho-166-chitosan complex was developed for radiation synovectomy. Preclinical trial is on-going at our hospital using Ho-166-chitosan. The procedure and methods of preclinical trial are discussed.

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