• Title/Summary/Keyword: Models, animal

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Ginsenoside (20S)Rg3 Ameliorates Synaptic and Memory Deficits in an Animal Model of Alzheimer's Disease

  • Kim, Tae-Wan
    • 한국약용작물학회:학술대회논문집
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    • 2011.09a
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    • pp.31-45
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    • 2011
  • The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

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Development of a Chronic Skin Wound Defect: A Swine Model (돼지를 이용한 만성피부결손상처의 모델)

  • Sohn, Hyung Bin;Son, Dae Gu;Kim, Jun Hyung;Han, Ki Hwan;Ryoo, Nam Hee;Kwon, Sun Young
    • Archives of Plastic Surgery
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    • v.33 no.5
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    • pp.606-611
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    • 2006
  • Purpose: Animal models of a chronic wound are yet to be fully developed, and animal studies on this subject has yet to take place. The purpose of this study is to create the foundation for research on chronic wound healing based on a swine model, the most similar to that of a human. Methods: Three female 2-3 month old 'yolkshires' were used. Total of eight full thickness skin defects, $6{\times}3cm$ sized, were created on the back of each pigs. Three groups were created for comparison; Group I (n=4) was left as they were after full skin thickness excision, while the excised tissues of Group II (n=3) were turned inside out and sutured so that the epidermis would come in contact with the fascia. Group III (n=3) were excised full skin thickness in depth and silicone blocks were implanted in them. Dressing was not practised so that the wounds would be vulnerable to infection. Results: In Group III, the skin contraction rate was the least among the three groups for each three weeks of observation respectively. Also during the three weeks, bacteral colonization was at the highest among the comparison. On the third week, inflammatory cells were still active, but the generations of epidermis and collagen synthesis were detected minimally. Conclusion: The Group III was relatively the most similar model of chronic wounds. and modification of the silicone blocks, could provide us with a very effective chronic skin wound model similar to human.

Effect of Parthenogenetic Mouse Embryonic Stem Cell (PmES) in the Mouse Model of Huntington′s Disease

  • 이창현;김용식;이영재;김은영;길광수;정길생;박세필;임진호
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.80-80
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    • 2003
  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.

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Practical Use of DNA Polymorphisms in the Avian Immunoglobulin Light Chain Constant Domain for Species-specific PCR (조류의 종 특이 구별을 위한 항체 유전자의 이용)

  • Choi, J.W.;Kang, S.J.;Park, M.S.;Kim, J.-K.;Han, J.Y.
    • Journal of Animal Science and Technology
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    • v.50 no.1
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    • pp.9-18
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    • 2008
  • Species-specific polymorphisms in chicken, pheasant, turkey, and quail were identified by cloning and sequencing of the immunoglobulin constant domain (IgLC). A set of species-specific primers were then designed on the basis of polymorphisms in the IgLC between species, as well as two additional sets of primers for the cytochrome b and tapasin genes, for the purpose of species identification. Together, the primers successfully distinguished specific species from chicken by species-specific PCR. This simple but unambiguous method may be used to screen avian inter-species germline chimeras, which are valuable models for the conservation of endangered species.

Forage Intake and Nutrient Requirements of Fallow Weaner Deer in Southern Australia

  • Ru, Y.J.;Fischer, M.;Glatz, P.C.;Wyatt, S.;Swanson, K.;Falkenberg, S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.5
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    • pp.685-692
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    • 2003
  • Information on nutrient requirements and forage intake of fallow weaner deer is required for the development of feeding strategies during the year. An experiment was conducted in which 60 fallow weaner deer (grazing on medic and ryegrass based pastures) were supplemented with a concentrated diet at three levels. The diet contained 2% minerals, 30% lupin and 68% barley grain. Twelve deer from each treatment were dosed with commercial alkane capsules in May, June, July, September and October to predict nutrient intake. The relationships between body weight gain and intake of metabolisable energy and crude protein were established using a general linear models analysis. Dry matter intake from pastures ranged from 0.137 kg to 0.304 kg in May and June and increased to 1.2 kg in October. Nutrient intake from pastures was strongly influenced by amount of supplementary feed and gender. Digestible energy intake from pastures was 1.3, 3.8 and 6.1 MJ/day higher for males than females in July, August and October, respectively. The protein and energy intake was strongly correlated with body weight gain. The energy requirement for maintenance were 7.3, 8.2, 10.2, 10.2 and 10.7 MJ DE/day and the DE required for each kg body weight gain were 19, 18, 29, 34 and 49 MJ in May, June, August and October, respectively. The protein requirement for maintenance was 12.2, 12.6, 15.0, 11.4 and $8.5g/W^{0.75}$ in May, June, July, August and October, respectively. The nutrient requirement defined from this study can be used to assist farmers to explore the possible pasture and stock management practices under southern Australian conditions. However, further research is required to develop rapid and cheap methods for estimating dry matter intake, nutritive value of pastures and to quantify the potential growth rate of fallow deer in southern Australia.

Cancer Cell Targeting with Mouse TERT-Specific Group I Intron of Tetrahymena thermophila

  • Ban, Gu-Yee;Song, Min-Sun;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.1070-1076
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    • 2009
  • Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

Biodegradable Screws Containing Bone Morphogenetic Protein-2 in an Osteoporotic Rat Model

  • Jin, Eun-Sun;Kim, Ji Yeon;Lee, Bora;Min, JoongKee;Jeon, Sang Ryong;Choi, Kyoung Hyo;Jeong, Je Hoon
    • Journal of Korean Neurosurgical Society
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    • v.61 no.5
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    • pp.559-567
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    • 2018
  • Objective : The aim of this study was to evaluate the effect for biodegradable screws containing bone morphogenetic protein-2 (BMP-2) in an osteoporotic rat model. Methods : Twenty-four female Wistar rat (250-300 g, 12 weeks of age) were randomized into four groups. Three groups underwent bilateral ovariectomy (OVX). Biodegradable screws with or without BMP-2 were inserted in the proximal tibia in two implantation groups. The extracted proximal metaphysis of the tibiae were scanned by exo-vivo micro-computed tomography. Evaluated parameters included bone mineral density (BMD), trabecular bone volume (BV/TV), trabecular number, trabecular thickness, and trabecular separation (Tb.Sp). The tibia samples were pathologically evaluated by staining with by Hematoxylin and Eosin, and trichrome. Results : Trabecular formation near screw insertion site was evident only in rats receiving BMP-2 screws. BMD and BV/TV significantly differed between controls and the OVX and OVX with screw groups. However, there were no significant differences between control and OVX with screw BMP groups. Tb.Sp significantly differed between control and OVX and OVX with screw groups (p<0.05), and between the OVX and OVX with screw BMP group (p<0.05), with no statistically significant difference between control and OVX with screw BMP groups. Over the 12 weeks after surgery, bone lamellae in direct contact with the screw developed more extensive and thicker trabecular bone around the implant in the OVX with screw BMP group compared to the OVX with screw group. Conclusion : Biodegradable screws containing BMP-2 improve nearby bone conditions and enhance ostoeintegration between the implant and the osteoporotic bone.

Effect of Allium sativum on cytochrome P450 and possible drug interactions

  • Janil, Ashutosh;Mehta, Anita A
    • Advances in Traditional Medicine
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    • v.6 no.4
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    • pp.274-285
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    • 2006
  • Allium sativum (Family Amaryllidaceae or Liliaceae) is used worldwide for various clinical uses like hypertension, cholesterol lowering effect, antiplatelets and fibrinolytic activity etc. Due to these common house hold uses of Allium sativum, as a herbal supplements, and failure of patients to inform their physician of the over-the-counter supplements they consume leads to drugnutrient interactions with components in herbal supplements. Today these types of interactions between a herbal supplement and clinically prescribed drugs are an increasing concern. In vitro studies indicated that garlic constituents modulated various CYP (cytochrome P450) enzymes. CYP 3A4 is abundantly present in human liver and small intestine and contributes to the metabolism of more than 50% of commonly used drugs including nifedipine, cyclosporine, erythromycin, midazolam, alprazolam, and triazolam. Extracts from fresh and aged garlic inhibited CYP 3A4 in human liver microsomes. The in vivo effects of garlic constituents are found to be species depended and the dosing regimen of garlic constituents appeared to influence the modulation of various CYP isoforms. Studies have indicated that the inhibition of various CYPs by organosulfur compounds from garlic was related to their structure also. Studies using in vitro, in vivo, animal and human models have indicated that various garlic constituents can be the substrates, inhibitors and or inducers of various CYP enzymes. The modulation of CYP enzyme activity and expression are dependent on the type and chemical structure of garlic constituents, dose regime, animal species and tissue, and source of garlic thus this review throws light on the possible herb drug interaction with the use of garlic.

Towards a Global Understanding and Standardisation of Education and Training in Microsurgery

  • Leung, Clement Chi Ming;Ghanem, Ali M.;Tos, Pierluigi;Ionac, Mihai;Froschauer, Stefan;Myers, Simon R.
    • Archives of Plastic Surgery
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    • v.40 no.4
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    • pp.304-311
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    • 2013
  • With an increasing emphasis on microsurgery skill acquisition through simulated training, the need has been identified for standardised training programmes in microsurgery. We have reviewed microsurgery training courses available across the six continents of the World. Data was collected of relevant published output from PubMed, MEDLINE (Ovid), and EMBASE (Ovid) searches, and from information available on the Internet of up to six established microsurgery course from each of the six continents of the World. Fellowships and courses that concentrate on flap harvesting rather than microsurgical techniques were excluded. We identified 27 centres offering 39 courses. Total course length ranged from 20 hours to 1,950 hours. Student-to-teacher ratios ranged from 2:1 to 8:1. Only two-thirds of courses offered in-vivo animal models. Instructions in microvascular end-to-end and end-to-side anastomoses were common, but peripheral nerve repair or free groin flap transfer were not consistently offered. Methods of assessment ranged from no formal assessment, where an instructor monitored and gave instant feedback, through immediate assessment of patency and critique on quality of repair, to delayed re-assessment of patency after a 12 to 24 hours period. Globally, training in microsurgery is heterogeneous, with variations primarily due to resource and regulation of animal experimentation. Despite some merit to diversity in curricula, there should be a global minimum standard for microsurgery training.

The Effects of Probiotics-Fermented Magnolia Denudata in Ovalbumin Induced Allergic Rhinitis Animal Model (알레르기 비염 동물 모델에서 유산균 발효 신이(辛夷)의 효과)

  • Song, Min-Kyung;Hong, Seung-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.26 no.1
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    • pp.35-49
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    • 2013
  • Objectives : We aimed to determine therapeutic effects of probiotics-fermented Magnolia denudata(MD) in the allergic rhinitis model mice. Methods : Polyphenol production, DPPH radical scavenging activity and NO inhibition of fermented MD by different bacterial strains were evaluated to select the one that is most suitable for fermentation. Thirty C57BL/6 mice were divided randomly into 5 groups as follows: normal group, ovalbumin(OVA)-treated plus water fed(CON group), OVA-treated plus unfermented MD fed(UMD group), OVA-treated plus fermented autoclaved MD fed(A-FMD group) and OVA-treated plus fermented unautoclaved MD fed(FMD group). After 9 weeks, we observed changes in the blood cell count, OVA-specific IgE level, nasal rubbing, nasal mucosal tissue and body weight. Results : Extract of MD fermented by Bifidobacterium breve(BB) for 48 hours showed the highest anti-oxidant activity and anti-inflammatory activity out of all the other bacterial strains. The number of eosinophil count in A-FMD, FMD group and platelet count in FMD group showed statistically significant decrease(p<0.05). OVA-specific IgE level decreased in all 3 experimental groups, significantly in UMD and A-FMD group. Nasal symptoms were attenuated in all 3 experimental groups, statistically significant in A-FMD and FMD group (p<0.05). Histologically, infiltration of eosinophils into the nasal mucosa decreased in all 3 experimental groups, especially marked decrease in FMD group. Conclusions : According to the above results, it is considered that probiotics-fermented Magnolia denudata has inhibitory effects on the allergic rhinitis animal models.