• Title/Summary/Keyword: Models, animal

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In vitro cytotoxic evaluation of some essential oils

  • P., Vijayan;Godavarthi, Ashok;Chandrashekhar, Raghu;Badami, Shrishilappa;SA, Dhanaraj;B., Suresh
    • Advances in Traditional Medicine
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    • v.3 no.4
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    • pp.187-190
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    • 2003
  • Seven essential oils were tested for in vitro cytotoxicity against the cancerous cell lines A-549, HEp-2 and DLA and normal BRL-3A, NRK-49F and Vero cell lines using standard MTT, SRB and dye exclusion techniques. The A-549 cell line was found to be the most susceptible to all the essential oils. The essential oils of A. nilagirica, A. calamus and O. sanctum were found to be the more active against these cells with mean $CTC_{50}$ values of 17.75, 19.00 and $24.37\;{\mu}g/ml$, respectively. The essential oil of Acorus calamus was found to be the most potent with low $CTC_{50}$ values against the cancerous and comparatively higher $CTC_{50}$ values against the normal cell lines. Artemisia pellens and Pelargonium graveolens oils also showed potent activity. These oils merit further investigation to identify the active principles and nature of the anti tumor activity in animal models.

Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet

  • Yin, Hu-Quan;Lee, Byung-Hoon
    • Toxicological Research
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    • v.24 no.2
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    • pp.113-117
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    • 2008
  • Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

DNA Vaccines against Infectious Diseases and Cancer

  • Han, Duk-Jae;Weiner, David B.;Sin, Jeong-Im
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.1-15
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    • 2010
  • Progress in the development of DNA vaccines and their delivery strategies has been made since their initial concept as a next generation vaccine. Since DNA vaccine includes non-infectious DNA parts of pathogens, it can't cause disease yet it closely mimic the natural process of infection and immune responses. Despite their early promising results of controlling infectious diseases and cancer in small animal models, DNA vaccines failed to display a level of immunogenicity required for combating these diseases in humans, possibly due to their lower protein expression levels. However, increasing evidence has shown that DNA vaccines are clinically well-tolerated and safe. Furthermore, one notable advantage of DNA vaccines includes convenient utilities of plasmid DNAs coding for antigens. For instance, any emerging pathogens could be prevented easily and timely by allowing the simple exchange of antigen-encoding genes. In this review, newly developed DNA vaccine strategies, including electroporation, which has emerged as a potent method for DNA delivery, targeting infectious diseases and cancer will be discussed with a focus on any on-going DNA vaccine trials or progress made pre-clinically and in clinics.

Neural Mechanism in Bronchial Asthma (기관지천식에서의 신경적 기전)

  • Choi, Byoung-Whui
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.2
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    • pp.73-86
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    • 1994
  • In addition to classic cholinergic and adrenergic pathways, the existence of a third division of autonomic control in the human airways has been proved. It is called a nonadrenergic noncholinergic(NANC) nervous system, and difficult to study in the absence of specific blockers. Neuropeptides are certainly suggested to be transmitters of this NANC nervous system. It is very frustrating to understand the pathophysiologic role of these peptides in the absence of any specific antagonists. However, further studies of neuropeptides might eventually lead to novel forms of treatment for bronchial asthma. Another study of the interaction between different components of the autonomic nervous system, either in ganglionic neurotransmission or by presynaptic modulation of neurotransmitters at the end-organ will elute neural control in airway disease, particularly in asthma. Studies of how autonomic control may be disordered in airway disease should lead to improvements in clinical management. Epithelial damage due to airway inflammation in asthma may induce bronchial hyperresponsiveness. Axon reflex mechanism is one of possible mechanisms in bronchial hyperresponsiveness. Epithelial damage may expose sensory nerve terminals and C-fiber nrve endings are stimulated by inflammatory mediators. Bi-directional communication between the nerves and mast cells may have important roles in allergic process. The psychological factors and conditioning of allergic reactions is suggested that mast cell activation might be partly regulated by the central nervous system via the peripheral nerves. Studies in animal models, in huamn airways in vitro and in patients with airway disease will uncover the interaction between allergic disease processes and psychologic factors or neural mechainsms.

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Improvement of Leptin Resistance (렙틴 저항성의 개선)

  • Kim, Yong Woon
    • Journal of Yeungnam Medical Science
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    • v.30 no.1
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    • pp.4-9
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    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

Dissemination of Advanced Mouse Resources and Technologies at RIKEN BioResource Center

  • Yoshiki, Atsushi
    • Interdisciplinary Bio Central
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    • v.2 no.4
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    • pp.15.1-15.5
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    • 2010
  • RIKEN BioResource Center (BRC) has collected, preserved, conducted quality control of, and distributed mouse resources since 2002 as the core facility of the National BioResource Project by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. Our mouse resources include over 5,000 strains such as humanized disease models, fluorescent reporters, and knockout mice. We have developed novel mouse strains such as tissue-specific Cre-drivers and optogenetic strains that are in high demand by the research community. We have removed all our specified pathogens from the deposited mice and used our quality control tests to examine their genetic modifications and backgrounds. RIKEN BRC is a founding member of the Federation of International Mouse Resources and the Asian Mouse Mutagenesis and Resource Association, and provides mouse resources to the one-stop International Mouse Strain Resource database. RIKEN BRC also participates in the International Gene Trap Consortium, having registered 713 gene-trap clones and their sequences in a public library, and is an advisory member of the CREATE (Coordination of resources for conditional expression of mutated mouse alleles) consortium which represents major European and international mouse database holders for the integration and dissemination of Cre-driver strains. RIKEN BRC provides training courses in the use of advanced technologies for the quality control and cryopreservation of mouse strains to promote the effective use of mouse resources worldwide.

Combustion Generated Fine Particles, Trace Metal Speciation, and Health Effects

  • Linak, William P.
    • Proceedings of the Korea Air Pollution Research Association Conference
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    • 2003.11a
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    • pp.195-195
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    • 2003
  • Combustion generated fine particles, defined as those with aerodynamic diameters less than 2.5 m, have come under increased regulatory scrutiny because of suspected links to adverse human health effects. Transition metals are of particular interest due to the results of a number of studies that have shown cardiopulmonary damage associated with exposure to these elements and their presence in coal, residual fuel oils, sewage sludge, and other combusted fuels and wastes. This lecture will review results from multi-di sciplinary studies being conducted at EPA and elsewhere examining the physical, chemical, and toxicological characteristics of combustion generated particles. The research describes how collaborative work between combustion engineers and health scientists can provide insight on how combustion processes affect particle properties and subsequent health effects as measured by a combination of in-vitro and in-vivo studies using a variety of animal models. The focus of this lecture is on the interdisciplinary approach required to address the problem. Difficulties are discussed. Engineering aspects involved in this approach are described in detail. Physical and chemical characterizations are performed using a variety of analytical approaches including new techniques of x-ray absorption fine structure (XAFS) spectroscopy and x-ray absorption near-edge structure (XANES) deconvolution of these spectra to gather metal speciation information.

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Glucosamine Inhibits Lipopolysaccharide-induced Inflammatory Responses in Human Periodontal Ligament Fibroblasts

  • Kim, Eun Dam;Park, Hyun-Jung;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.39 no.4
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    • pp.221-228
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    • 2014
  • Glucosamine is commonly taken by the elderly without prescription as a nutritional supplement to attenuate the progression or symptoms of osteoarthritis. Previous studies demonstrated that glucosamine shows anti-inflammatory effects in tissues such as blood vessels and the heart. However, there have been few reports about the effects of glucosamine on oral inflammatory diseases. Therefore, in this study, the effects of glucosamine on lipopolysaccharide (LPS)-induced inflammatory responses were investigated using human periodontal ligament fibroblasts (HPDLFs). HPDLFs were incubated in the presence and absence of glucosamine (10 mM) for 24 h, followed by treatment with E. coli LPS (100 ng/ml) or vehicle. Quantitative RT-PCR and ELISA results showed that LPS exposure significantly increased the levels of IL-6 and IL-8 mRNA and protein, while the effect was significantly suppressed by glucosamine treatment. Glucosamine did not attenuate, but slightly increased, the LPS-induced activation of mitogen activated kinases (ERK, p38, JNK). However, it suppressed the LPS-induced increase in the DNA binding affinity and transcriptional activity of NF-${\kappa}B$. These results suggest that glucosamine exerts anti-inflammatory effects on HPDLFs exposed to LPS via inhibition of NF-${\kappa}B$ activity, necessitating further studies using animal periodontitis models.

Prior Use of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Inhibitor, Simvastatin Fails to Improve Outcome after Experimental Intracerebral Hemorrhage

  • Jwa, Cheol-Su;Yi, Hyeong-Joong;Oh, Suck-Jun;Hwang, Se-Jin
    • Journal of Korean Neurosurgical Society
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    • v.50 no.5
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    • pp.403-408
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    • 2011
  • Objective : Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) $in$ $vivo$ suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH. Methods : Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured. Results : Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy. Conclusion : The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.

Pharmacological action and Toxicity of Angelica sinensis (당귀(Angelica sinensis)의 임상활용에 대한 효능 및 부작용연구)

  • Park, Yeong-Chul;Lee, Ji-Sun;Kim, Min-Hee;Kim, Dong-Yoon;Lee, Sun-Dong
    • Herbal Formula Science
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    • v.19 no.2
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    • pp.93-108
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    • 2011
  • Objectives : Angelica sinensis has been used extensively in Korean traditional medicine. Although thorough clinical trials are lacking, Various pharmacological actions for Angelica sinensis has been identified newly using animal models. In addition, it was reported that reactive intermediates, potentially causing toxic effects, was isolated from components in Angelica sinensis. In this article, it was purposed for explanation and introduction of new studies for Angelica sinensis. in terms of Pharmacological action and Toxicity. Methods : New studies for Angelica sinensis were reviewed and summarized in terms of pharmacological action and toxicity. Results and Conclusions : Angelica sinensis and its components including phthalide, phthalide dimers, polysaccharides, polyacetylenes, ligustilide와 butylidenephthalide as well as organic acid showed a variety of pharmacological actions on uterine, cardiovascular system and immune system. In addition, it was identified that three components of such as ligustilide, caffeic acid and safrole was biotransformed to reactive intermediates causing possibly toxicity.