• Title/Summary/Keyword: Models, animal

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Effects of fibrin-binding oligopeptide on osteopromotion in rabbit calvarial defects

  • Lee, Ju-A;Ku, Young;Rhyu, In-Chul;Chung, Chong-Pyoung;Park, Yoon-Jeong
    • Journal of Periodontal and Implant Science
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    • v.40 no.5
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    • pp.211-219
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    • 2010
  • Purpose: Fibronectin (FN) has been shown to stimulate bone regeneration in animal models. The aim of this study was to evaluate the capacity of bovine bone mineral coated with synthetic oligopeptides to enhance bone regeneration in rabbit calvarial defects. Methods: Oligopeptides including fibrin-binding sequences of FN repeats were synthesized on the basis of primary and tertiary human plasma FN structures. Peptide coated and uncoated bone minerals were implanted into 10 mm calvarial defects in New Zealand white rabbits, and the animals were sacrificed at 4 or 8 weeks after surgery. After specimens were prepared, histologic examination and histomorphometric analysis were performed. Results: At 4 weeks after surgery, the uncoated groups showed a limited amount of osteoid formation at the periphery of the defect and the oligopeptide coated groups showed more osteoid formation and new bone formation in the center of the defect as well as at the periphery. At 8 weeks, both sites showed increased new bone formation. However, the difference between the two sites had reduced. Conclusions: Fibrin-binding synthetic oligopeptide derived from FN on deproteinized bovine bone enhanced new bone formation in rabbit calvarial defects at the early healing stage. This result suggests that these oligopeptides can be beneficial in reconstructing oral and maxillofacial deformities or in regenerating osseous bone defects.

In vitro test using chorioallantoic membrance vascular assay to assess the irritancy potential of surfactants (CAMVA(Choriollantoic Membrane Vascular Assay)를 이용한 계면활성제의 자극 평가에 관한 연구)

  • Go, Jae-Suk;An, Su-Seon;Park, Jong-Ho
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.21 no.1
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    • pp.67-83
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    • 1995
  • Skin irritations accompany the series of complex, physical and chemical changes. Alternative methods which reflect the biological phenomenon more sensitively are necessary for the purpose of reducing the animal tests and improving the accuracy and reliability. Chorioallantoic membrane (CAM) vascular assay is a in vitro method which utilizes the chorioallantoic membrane of hen's fertilized egg of about 10 days old. Test substances are placed directly onto the surface of the CAM and 1 hour later the CAM vasculature is subjectively evaluated to determine with a chemically related-injurious reponse including the appearance of haemorrage, congestion, coagulation, and so on. In this research, using the various surfactants, the correlations of CAMVA with in vivo models (intradermal safety test and human primary irritation test) were investigated. And CAMVA closely correlated to intradermal safety test (r=0.89) and human primary irritation test (r=0.90). From the result, it seems that CAMVA can also be used as a method for predicting the skin irritaions.

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Reovirus and Tumor Oncolysis

  • Kim, Man-Bok;Chung, Young-Hwa;Johnston, Randal N.
    • Journal of Microbiology
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    • v.45 no.3
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    • pp.187-192
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    • 2007
  • REOviruses (Respiratory Enteric Orphan viruses) are ubiquitous, non-enveloped viruses containing 10 segments of double-stranded RNA (dsRNA) as their genome. They are common isolates of the respiratory and gastrointestinal tract of humans but are not associated with severe disease and are therefore considered relatively benign. An intriguing characteristic of reovirus is its innate oncolytic potential, which is linked to the transformed state of the cell. When immortalized cells are transfected in vitro with activated oncogenes such as Ras, Sos, v-erbB, or c-myc, they became susceptible to reovirus infection and subsequent cellular lysis, indicating that oncogene signaling pathways are exploited by reovirus. This observation has led to the use of the virus in clinical trials as an anti-cancer agent against oncogenic tumors. In addition to the exploitation of oncogene signaling, reovirus may further utilize host immune responses to enhance its antitumor activity in vivo due to its innate interferon induction ability. Reovirus is, however, not entirely benign to immunocompromised animal models. Reovirus causes so-called "black feet syndrome" in immunodeficient mice and can also harm neonatal animals. Because cancer patients often undergo immunosuppression due to heavy chemo/radiation-treatments or advanced tumor progression, this pathogenic response may be a hurdle in virus-based anticancer therapies. However, a genetically attenuated reovirus variant derived from persistent reovirus infection of cells in vitro is able to exert potent anti-tumor activity with significantly reduced viral pathogenesis in immunocompromised animals. Importantly, in this instance the attenuated, reovirus maintains its oncolytic potential while significantly reducing viral pathogenesis in vivo.

Vaccinium uliginosum L. Improves Amyloid β Protein-Induced Learning and Memory Impairment in Alzheimer's Disease in Mice

  • Choi, Yoon-Hee;Kwon, Hyuck-Se;Shin, Se-Gye;Chung, Cha-Kwon
    • Preventive Nutrition and Food Science
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    • v.19 no.4
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    • pp.343-347
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    • 2014
  • The present study investigated the effects of Vaccinium uliginosum L. (bilberry) on the learning and memory impairments induced by amyloid-${\beta}$ protein ($A{\beta}P$) 1-42. ICR Swiss mice were divided into 4 groups: the control ($A{\beta}40$-1A), control with 5% bilberry group ($A{\beta}40$-1B), amyloid ${\beta}$ protein 1-42 treated group ($A{\beta}1$-42A), and $A{\beta}1$-42 with 5% bilberry group ($A{\beta}1$-42B). The control was treated with amyloid ${\beta}$-protein 40-1 for placebo effect, and Alzheimer's disease (AD) group was treated with amyloid ${\beta}$-protein 1-42. Amyloid ${\beta}$-protein 1-42 was intracerebroventricular (ICV) micro injected into the hippocampus in 35% acetonitrile and 0.1% trifluoroacetic acid. Although bilberry added groups tended to decrease the finding time of hidden platform, no statistical significance was found. On the other hand, escape latencies of $A{\beta}P$ injected mice were extended compared to that of $A{\beta}40$-1. In the Probe test, bilberry added $A{\beta}1$-42B group showed a significant (P<0.05) increase of probe crossing frequency compared to $A{\beta}1$-42A. Administration of amyloid protein ($A{\beta}1$-42) decreased working memory compared to $A{\beta}40$-1 control group. In passive avoidance test, bilberry significantly (P<0.05) increased the time of staying in the lighted area compared to AD control. The results suggest that bilberry may help to improve memory and learning capability in chemically induced Alzheimer's disease in experimental animal models.

Frequency Dependent Electroacupuncture Modulates the Visceromotor Responses to Colonic Distension in TNBS-Induced Colonic Inflammatory Rats (흰쥐의 급성 대장염에 대한 주파수에 따른 전침 효과 연구)

  • Choi, Yun-Young;Yang, Seung-Bum;Ahn, Sung-Hun;Sohn, In-Chu;Kim, Jae-Hyo
    • Korean Journal of Oriental Medicine
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    • v.17 no.3
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    • pp.105-114
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    • 2011
  • Objectives : The transient inflammation has been demonstrated to alter visceral motor response (VMR) and acute mucosal inflammation may precede the manifestation of visceral hyperalgesia in animal models. The purpose of our study is to compare effects of the different frequencies applied electroacupuncture (EA) on acupoints in acute colitis induced by trinitrobenzenesulphonic acid (TNBS). Methods : In Male Sprague-Dawley rats, weighing 250~400g, a single colorectal administration of TNBS (5mg/kg) was made and electrode for electromyography (EMG) recording were stitched into the external oblique musculature. EA of either ST25 or ST36 were applied and stimulation parameter was modulated as follows: 2, 10, or 100 Hz with intensity of 2 mA and 1 ms pulse duration for 30 min. The balloon was inserted intra-anally and VMR to colorectal distension (CRD) was quantified with an EMG recording system. Results : The VMR increased significantly 3 days after TNBS intra-rectal colonic injection in rats. Both 2 Hz and 10 Hz EA on ST36 suppressed VMR to CRD in the acute colitis model but not 100 Hz. Only 10 Hz EA on ST25 suppressed VMR to CRD in the acute colitis. Conclusions : These data show that 10 Hz EA potently inhibits hypersensitivity of colorectum after TNBS induced colitis.

Mechanisms of Motility Change on Trinitrobenzenesulfonic Acid-Induced Colonic Inflammation in Mice

  • Cheon, Gab Jin;Cui, Yuan;Yeon, Dong-Soo;Kwon, Seong-Chun;Park, Byong-Gon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.6
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    • pp.437-446
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    • 2012
  • Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by recurrent episodes of colonic inflammation and tissue degeneration in human or animal models. The contractile force generated by the smooth muscle is significantly attenuated, resulting in altered motility leading to diarrhea or constipation in IBD. The aim of this study is to clarify the altered contractility of circular and longitudinal smooth muscle layers in proximal colon of trinitrobenzen sulfonic acid (TNBS)-induced colitis mouse. Colitis was induced by direct injection of TNBS (120 mg/kg, 50% ethanol) in proximal colon of ICR mouse using a 30 G needle anesthetized with ketamin (50 mg/kg), whereas animals in the control group were injected of 50% ethanol alone. In TNBS-induced colitis, the wall of the proximal colon is diffusely thickened with loss of haustration, and showed mucosal and mucular edema with inflammatory infiltration. The colonic inflammation is significantly induced the reduction of colonic contractile activity including spontaneous contractile activity, depolarization-induced contractility, and muscarinic acetylcholine receptor-mediated contractile response in circular muscle layer compared to the longitudinal muscle layer. The inward rectification of currents, especially, important to $Ca^{2+}$ and $Na^+$ influx-induced depolarization and contraction, was markedly reduced in the TNBS-induced colitis compared to the control. The muscarinic acetylcholine-mediated contractile responses were significantly attenuated in the circular and longitudinal smooth muscle strips induced by the reduction of membrane expression of canonical transient receptor potential (TRPC) channel isoforms from the proximal colon of the TNBS-induced colitis mouse than the control.

Application of the Total Artificial Heart as an Implantable Biventricular Assist Device by Left Thoracotomy in an Ovine Model (양에서 좌측 개흉술 하에 완전인공심장의 체내이식형 양심실 보조장치로 사용에 관한 연구)

  • 원태희;민병구;김원곤
    • Journal of Chest Surgery
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    • v.34 no.4
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    • pp.296-304
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    • 2001
  • 배경: 이번 연구의 목적은 체내이식형 양심실 보조장치의 개발을 위한 안전하고 간편한 동물실험 모델을 확립하는 것이며 이동작동형 완전 인공심장의 양심실 보조장치로의 사용 가능성을 알아보는 것이다. 대상 및 방법: 7마리의 Corridale 양을 대상으로 실험하였다. 5번째 늑간극을 통하여 좌측 개흉술을 시행하고 좌측 유출로 캐뉼라는 하행 대동맥에 Dacron graft을 사용하여 연결하였고 유입로 캐뉼라는 좌심방에 삽입하였다. 우측 유출로 캐뉼라는 하행 대동맥과 같은 방법으로 주폐동맥에 연결하였으며 유입로 캐뉼라는 혜동맥을 하방으로 젖혀 우심방이를 노출시킨 다음 우심방이에 삽입하였다. 4마리에 있어서는 양심실 보조장치를 전복막강(preperitoneal space)에 위치시켰으며 2마리에 촤측흉강 내에, 1마리에서는 외부에 위치시켰다. aPTT는 수술전 aPTT의 2∼2.5배로 맞추어 주었다 결과: 수술중 또는 수술직후 사망한 경우는 없었으며 7마리 모두 인공호흡기 이탈이 가능하였고 스스로 기립하고 음식물 섭취도 가능하였다. 1마리는 술후 2일째 혈전 색전증 및 인공호흡기 작동 잘못으로 사망하였으며 2마리의 겨우는 술후 2일째 각각 양심실 보조장치의 작동 잘못 및 호흡부전으로 사망하였고, 3마리의 경우는 술후 4일째 혈전색전증으로 인한 급성신부전 및 호흡부전 등으로 사망하였다. 1마리에 있어서는 28일간 생존하였으며 양심실 보조장치의 구동 장치에 연결된 라인의 마로로 인해 양심실 보조장치의 작동이 정지되었으나 바로 양심실 보조장치를 제거하고 살릴 수 있었다. 모든 경우에 있는 캐뉼라를 삽입하고 양심실 보조장치를 작동시키는데 큰 어려움이 없었다. 7마리 중 4마리에서 혈전이 발견되었으며 특히 판막을 연결한 부위에 혈전생성이 많았다. 그러나 캐뉼라에는 혈전생성이 없었다. 결론: 양에 있어서 좌측 개흉술 및 전복막강 공간에 양심실 보조장치를 위치시키는 이번 동물실험 모델은 체내 이식형 양심실 보조장치 개발을 위한 좋은 동물실험 모델이라고 생각된다. 또한 디동 작동기형 완전 인공심장의 혈전생성을 억제할수 있는 방법들의 연구개발이 지속된다면 장기간의 체내 이식형 양심실 보조장치로 사용할 수 있을 것으로 생각된다.

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Differentiation of Human Mesenchymal Stem Cells towards Neuronal Lineage: Clinical Trials in Nervous System Disorders

  • Hernandez, Rosa;Jimenez-Luna, Cristina;Perales-Adan, Jesus;Perazzoli, Gloria;Melguizo, Consolacion;Prados, Jose
    • Biomolecules & Therapeutics
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    • v.28 no.1
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    • pp.34-44
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    • 2020
  • Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.

The Association between Mast Cell Distribution and Acupoint Specificity: A Comprehensive Review (경혈에서의 비만세포 분포특성에 대한 연구 고찰)

  • Ji, JeongYeon;Bae, Sun-Jeong;Oh, Ju-Young;Jung, Hyuk-Sang;Park, Hi-Joon
    • Korean Journal of Acupuncture
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    • v.37 no.3
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    • pp.145-158
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    • 2020
  • Objectives : Mast cells, the multifunctional immune cells which can be activated by various stimulations, have been in the limelight recently at the fields of acupuncture research. This study aimed to investigate the association between the distribution of mast cell and acupoint specificity. We focused on the characteristics of mast cell distribution of acupoints in normal, pathologically sensitized, and acupoint-stimulated state. Methods : Literature searches were performed on PubMed and EMBASE for dates ranging to February 2019, by using terms "acupuncture", "moxibustion", "acupoint", "mast cell". Finally, 18 papers were collected by inclusion and exclusion criteria. To assess the quality of included studies, modified SYRCLE's risk of bias tool for animal studies was used. Results : Overall, the studies showed that the number of the mast cells was higher in acupoints than non-acupoints. After pathological sensitization, increasing tendency towards the mast cell number was reported in acupoints. The increase of mast cells was also observed after acupuncture or moxibustion. However, when the acupoint stimulation was repeated for several days in pathological models, the results did not show consistent tendency. In quality assessments, most of the studies showed unclear risk of bias. Conclusions : The studies showed a consistent trend about the association with mast cell distribution and acupoint specificity. However, we could not certainly affirm the relationship due to insufficient qualities of included studies. Not only the distribution but also the functions should be considered in further researches to identify the relationship between mast cells and acupuncture effect.

The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD

  • Kim, You-Sun;Hong, Goohyeon;Kim, Doh Hyung;Kim, Young Min;Kim, Yoon-Keun;Oh, Yeon-Mok;Jee, Young-Koo
    • Experimental and Molecular Medicine
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    • v.50 no.11
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    • pp.9.1-9.10
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    • 2018
  • Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.