• 한방재활의학과학회지
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• 제30권1호
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• pp.79-93
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• 2020

Objectives While sciatic neuropathy is one of the common symptoms which have the lifetime incidence of 13~40%, still there is no consensus about the standardized and the most effective conservative treatment. In addition, the importance of systematic review and meta-analysis of preclinical are growing as they could suggest possible effective treatment strategy for future studies. Therefore, we conducted systematic review and meta-analysis to estimate analgesic effect of acupuncture on sciatica in rat models. Methods Systematic search was conducted for all controlled comparative preclinical trials which assessed analgesic effect of acupuncture in sciatica rat models. Database of PubMed, EMBASE, Web of Science, CNKI and 6 Korean databases were used. The primary outcome was pain, which is evaluated by stimulus behavior tests in rat models. We assessed the methodological quality with Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool. RevMan 5.3 was used for meta-analysis and subgroup analysis was conducted according to treatment site, acupuncture point, treatment period and frequency used in electroacupuncture. Results 14 studies were finally included following our inclusion criteria. The data from meta-analysis indicated that the acupuncture significantly improved the result values of behavior tests for pain evaluation, compared to no-treatment control group in animal models (standardized mean difference=4.43, 95% confidence interval 3.16 to 5.69, Z=6.84, p<0.00001; χ²=68.02, p<0.00001; I²=82%). The results of subgroup analysis indicate that acupuncture treatment of unilateral site, distal acupoints, longer treatment period and applying 2/100 Hz frequency in electroacupuncture could be more effective. Conclusions Systematic review and meta-analysis of animal studies are getting important for the future clinical studies and the improvement of heatlh care. Therefore the results of the study would provide evidence and better design for the forthcoming studies.

• 한국임상수의학회지
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• 제27권5호
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• pp.533-539
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• 2010

최근 줄기세포를 이용한 재생의학분야의 세포치료 연구가 활발히 진행되고 있으나 상대적으로 복잡한 구조를 갖는 신장에서는 난치성 질환인 급성신부전에 대한 줄기세포 치료의 효과는 아직도 논란의 여지가 많다. 이는 연구자마다 다양한 동물모델을 사용하는 것이 한 원인으로 지적되고 있다. 본 연구에서는 줄기세포의 치료효과 분석을 위한 최적의 동물모델 조건을 확립하고자 한다. 쥐를 사용하여 세 종류의 급성신장손상모델을 다음과 같이 다양한 농도와 조건에서 분석하였다: glycerol (대조군, 8 ml/kg, 10 ml/kg), cisplatin (대조군, 5 mg/kg, 10 mg/kg)과 허혈/재관류 (대조군, 35 분 허혈, 45 분 허혈). 줄기세포의 재생능력 평가를 위한 모델의 적합성 정도를 신장손상과 회복의 형태적, 기능적 패턴과 생존률 분석을 통하여 실시하였다. 독성모델인 glycerol과 cisplatin은 각각 10 ml/kg과 7.5 mg/kg 농도에서, 그리고 허혈모델은 45 분 모델에서 대조군 및 다른 비교모델에 비해 장기간의 관찰 기간 동안 신기능의 유의적 차이를 보였다. 또한 45 분 허혈 모델에서 50%의 사망률을 보인 것을 제외하고는 모든 군에서 관찰기간 동안 100% 생존율을 보였다. 조직소견에서 허혈과 glycerol 모델에서는 2일째, cisplatin 모델에서는 5일째 각각 유의적인 조직변화가 관찰되었다. 따라서, 관찰기간 동안 급격한 생존율 감소 없이 안전하고, 조직학적 평가와 신기능에서 대조군과 유의적인 차이를 보이는 cisplatin 7.5 mg/kg, glycerol 10 ml/kg, 35 분 허혈 모델이 치료효과를 평가하기에 적합한 모델로 사료되며, 줄기세포의 세포치료효과 분석에 적합한 급성신장손상 모델로 추천된다.

• 한국치위생학회지
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• 제7권4호
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• pp.595-609
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• 2007

The purpose of this study was to classify the courses of the dental-hygiene curricula into several categories by field, to incorporate the subjects in the same category into an integrated course, and to suggest how to ensure the successful phase-in application of integrative education according to Ronald M. Harden's 11-stage integrative ladder model. The findings of the study were as follows: 1. When the existing curricula were analyzed, it's found that many credits were provided to the courses in the area of basic dentistry that offered both theory and practice. In particular, the subjects tested by the national examination were offered by every college. In the field of public oral health, the largest number of credits was allocated to theory of oral prophylaxis and practice courses. In clinical area, clinical practice, in the area of dental office management, dental insurance course was given the largest credit. There were 31 to 61 major subjects in the colleges, which indicated that the major subjects were segmented in detail. 2. It seemed necessary to incorporate the subjects in the field of basic dentistry into oral biology, and theory of oral prophylaxis/practice, preventive dentistry/practice, preclinical stage, emergency treatment and introduction to dental hygiene should be integrated in to clinical dental hygiene. The courses in clinical area should be combined into clinical dentistry, and in the field of medical management, dental insurance, hospital management and medical relation law should be incorporated into management of dental clinic. 3. In the 11-stage integrative ladder, the subjects in the same field could perfectly be incorporated as the stages advanced. Each of the subjects was less emphasized, and communication and joint plans among teachers who were respectively in charge of the courses were increasingly considered important. Specifically, there should be a consensus among the teachers in regard to the outline of teaching programs, order of education. objects and objectives of programs and what and how to evaluate.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2000년도 The 7th International Symposium
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• pp.116-122
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• 2000

The molecular modification of antiepileptic drugs and direct synthesis of new drugs with the predetermined antiepileptic properties are perspective. New neurochemical attacking to solve the problem including prevention and inhibition of seizures seems to be related to ginsenosides and ginseng polypeptides. The main study based on the severity of febrile convulsions of rat pups has been done from the earlier investigations of antiepileptical action of ginsenosides between KGTRI and MSU (Chepurnov, Park et al., 1995) with different kinds of experimental models of epilepsy. From the cultured cell line DAN25 of ginseng root, the extracts of ginsenosides made in "BIOKHIMMASH" were studied by the project of preclinical anticonvulsant screening (Stables, Kupferberg, 1997). The inhibition of severity of convulsions, decrease of seizures threshold, decrease of audiogenic seizures in rats of different strains and normalization of cerebral blood flow (measured by hydrogen test) were demonstrated in rats after i.c.v., intraperitoneally and orally administration, respectively. The antiepileptical effects by the combination of compounds from ginseng; were compared with the iuluence of Rg1, Rb1, Rc and with the well known antiepileptical drugs such as carbamazepine, valproic acid. The base for the research is obtained by using the WAG/Rij strain (Luijtelaar, Coenen, Kuznetcova), an excellent genetic model for human generalized absence epilepsy. The improving action of gensinosides was effectively demonstrated on the model of electrical kindling of amygdala of WAG/Rij rats with genetically determined absences, and the influences of ginsenosides on the slow wave discharges have also been being investigated. The different characteristics of a kindling process exerted in the sex-different region of the amygdala and demonstrated that the level of sex steroids and content of neurosteroids in amygdaloid tissue can modify the development of seizures. The chemical structures of ginsenosides not only have some principal differences from well-known antiepileptical drugs but the Plant Pharmacology gives us unique possibility to develop new class of antiepileptic drugs and to improve its biological activity.

• Molecules and Cells
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• 제46권9호
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• pp.558-572
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• 2023

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

• Journal of Chest Surgery
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• 제47권4호
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• pp.333-343
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• 2014

Background: A preclinical study was conducted for evaluating a valved conduit manufactured with a glutaraldehyde (GA)-fixed bovine pericardium treated using an anticalcification protocol. Methods: Bovine pericardia were decellularized, fixed with GA in an organic solvent, and detoxified. We prepared a valved conduit using these bovine pericardia and a specially designed mold. The valved conduit was placed under in vitro circulation by using a mock circulation model, and the durability under mechanical stress was evaluated for 2 months. The valved conduit was implanted into the right ventricular outflow tract of a goat, and the hemodynamic, radiologic, histopathologic, and biochemical results were obtained for 6 months after the implantation. Results: The in vitro mock circulation demonstrated that valve motion was good and that the valved conduit had good gross and microscopic findings. The evaluation of echocardiography and cardiac catheterization demonstrated the good hemodynamic status and function of the pulmonary xenograft valve 6 months after the implantation. According to specimen radiography and a histopathologic examination, the durability of the xenografts was well preserved without calcification at 6 months after the implantation. The calcium and inorganic phosphorus concentrations of the explanted xenografts were low at 6 months after the implantation. Conclusion: This study demonstrated that our synergistic employment of multiple anticalcification therapies has promising safety and efficacy in the future clinical study.

• Journal of Chest Surgery
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• 제51권2호
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• pp.114-121
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• 2018

Background: Unfractionated heparin is commonly used for anticoagulation in extracorporeal membrane oxygenation (ECMO). Several studies have shown that nafamostat mesilate (NM) has comparable clinical outcomes to unfractionated heparin. This study compared anticoagulation with NM and heparin in a large-animal model. Methods: Beagle dogs (n=8; weight, 6.5-9 kg) were placed on venovenous ECMO. Blood samples were taken every hour and the following parameters were compared: hemoglobin level, activated partial thromboplastin time (aPTT), thromboelastography (TEG) data, platelet function, and inflammatory cytokine levels. Results: In both groups, the aPTT was longer than the baseline value. Although the aPTT in the NM group was shorter than in the heparin group, the TEG parameters were similar between the 2 groups. Hemoglobin levels decreased in both groups, but the decrease was less with NM than with heparin (p=0.049). Interleukin $(IL)-1{\beta}$ levels significantly decreased in the NM group (p=0.01), but there was no difference in the levels of tumor necrosis factor alpha or IL-10 between the 2 groups. Conclusion: NM showed a similar anticoagulant effect to that of unfractionated heparin, with fewer bleeding complications. NM also had anti-inflammatory properties during ECMO. Based on this preclinical study, NM may be a good alternative candidate for anticoagulation in ECMO.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.207-243
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• 2016

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments, as well as repetitive and restrictive behaviors. The phenotypic heterogeneity of ASD has made it overwhelmingly difficult to determine the exact etiology and pathophysiology underlying the core symptoms, which are often accompanied by comorbidities such as hyperactivity, seizures, and sensorimotor abnormalities. To our benefit, the advent of animal models has allowed us to assess and test diverse risk factors of ASD, both genetic and environmental, and measure their contribution to the manifestation of autistic symptoms. At a broader scale, rodent models have helped consolidate molecular pathways and unify the neurophysiological mechanisms underlying each one of the various etiologies. This approach will potentially enable the stratification of ASD into clinical, molecular, and neurophenotypic subgroups, further proving their translational utility. It is henceforth paramount to establish a common ground of mechanistic theories from complementing results in preclinical research. In this review, we cluster the ASD animal models into lesion and genetic models and further classify them based on the corresponding environmental, epigenetic and genetic factors. Finally, we summarize the symptoms and neuropathological highlights for each model and make critical comparisons that elucidate their clinical and neurobiological relevance.

• Radiation Oncology Journal
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• 제8권2호
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• pp.151-154
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• 1990

영남대학교 의과대학 치료방사선과학교실에서는 코발트-60원격치료기를 이용하여 80마리의 ICR 백서를 대상으로 서로다른 세가지 선량율로 600 cGy 단일조사를 시행한뒤 9주일동안 체중 및 말초혈액소견의 변화를 추적조사한 결과 다음과 같은 성적을 얻었다. 1. 체중변화는 선량율에 상관없이 조사 1주일부터 감소하여 6-7주일부터 치료전의 체중까지 회복 되었다. 2. 혈색소의 변화는 전 추적조사기간에 걸쳐 변화가 없었다. 3. 말초 혈액내의 백혈구의 총수는 조사 1주일부터 3주일까지 형태학적 구분이 안되는 수개의 세포만이 인지되었고 4주일부터 호중구의 회복이 임파구에 비해서 현저하였으며 8-9주일부터 조사전의 상태로 완전 회복되었다. 이상의 결과를 토대로 보다 다양한 실험을 거친후 저선량율 전신조사의 가장 큰 단점인 장시간의 조사로 인한 기계의 무리와 환자 위치고정의 해결을 위하여 분당 선량율을 15 cGy까지 올릴 수 있으리라 기대된다.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.107-115
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• 2017

Over the last decade, physiologically based pharmacokinetics (PBPK) application has been extended significantly not only to predicting preclinical/human PK but also to evaluating the drug-drug interaction (DDI) liability at the drug discovery or development stage. Herein, we describe a case study to illustrate the use of PBPK approach in predicting human PK as well as DDI using in silico, in vivo and in vitro derived parameters. This case was composed of five steps such as: simulation, verification, understanding of parameter sensitivity, optimization of the parameter and final evaluation. Caffeine and ciprofloxacin were used as tool compounds to demonstrate the "fit for purpose" application of PBPK modeling and simulation for this study. Compared to caffeine, the PBPK modeling for ciprofloxacin was challenging due to several factors including solubility, permeability, clearance and tissue distribution etc. Therefore, intensive parameter sensitivity analysis (PSA) was conducted to optimize the PBPK model for ciprofloxacin. Overall, the increase in $C_{max}$ of caffeine by ciprofloxacin was not significant. However, the increase in AUC was observed and was proportional to the administered dose of ciprofloxacin. The predicted DDI and PK results were comparable to observed clinical data published in the literatures. This approach would be helpful in identifying potential key factors that could lead to significant impact on PBPK modeling and simulation for challenging compounds.