• Journal of the Korean Society of Radiology
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• v.15 no.5
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• pp.643-647
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• 2021

The purpose of this study was to access the possibility and ideal model for corrosive-induced tissue hyperplasia in the rat esophagus. Twenty rat were divided into two group: a healthy group, corrosive group. corrosive burn in esophagus were produced using 30% NaOH on the distal esophagus. After surgical procedure, behavioral and weight changes were monitored on a weekly. At 3 weeks after surgical procedure, fluoroscopic esophagogram was performed and then all rats sacrificed for histological analysis by administering inhalable pure carbon dioxide. Technical surgery for corrosive stricture were 100%. A total of 2 rats died in corrosive group from a corrosive burn related to dysphagia within 14 days. The esophageal stenosis ratio was significantly higher in the corrosive group than in the healthy group (40.1 ± 9.2 % and 1.4 ± 7.2%, respectively; p = 0.001). The tissue hyperplasia ratio was also significantly higher in the Corrosive group (62.5 ± 9% and 22.08 ± 6%, respectively; p = 0.001). Infusion of 30% NaOH may suggest alternative option to evaluation tool for preclinical study in a rat corrosive model.

• Journal of the Korean Society of Radiology
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• v.16 no.5
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• pp.559-565
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• 2022

In this study, we intend to develop a granulation tissue formation model. As a pilot experiment, a contrast agent was injected into the pylorus in 3 rats, the normal pylorus lumen size was confirmed, and a stent was placed. Stent migration was confirmed in to the duodenum within 1 week. In this experiment, stent was sutured and fixed to induce granulation tissue formation after gastrostomy under a fluoroscopic guidance. Twenty rats were divided into Healthy Group / Gastrostomy Group. After anesthesia of the Gastrostomy Group, an abdominal incision was performed, and gastrostomy was performed under a fluoroscopic guidance, and a stent was placed into the pylorus. In order to prevent stent migration due to peristalsis, suture between the pylorus and the proximal end of the stent was performed. Postoperative behavior and weight changes were monitored daily. Four weeks after surgery, gastrointestinal fluoroscopy imaging was performed and rats were sacrifices. To evaluate the degree of granulation formation, the stent was sectioned transversely. Gastrostomy group was statistically significantly higher than Healthy Group in granulation area ratio (all p<.001). In conclusion, it is considered that the level of tissue overgrowth formation for preclinical evaluation of the pylorus stricture model through gastrostomy is appropriate as a research evaluation tool.

• Journal of Life Science
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• v.32 no.8
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• pp.611-621
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• 2022

Dimethyl sulfoxide (DMSO) is commonly used as control or vehicle solvent in preclinical research of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) due to its ability to dissolve lipophilic compounds and cross the blood brain barrier. However, the biochemical effects of DMSO on the outcomes of preclinical research are often overlooked. In the present study, we investigated whether the long-term oral administration of 5% DMSO affects the neurological, functional, and histological disease phenotype of the copper/zinc superoxide dismutase glycine 93 to alanine mutation (SOD1-G93A) mouse model of amyotrophic lateral sclerosis. SOD1-G93A transgenic mice showed shortened survival time and reduced motor function. We found that administration with DMSO led to increased mean survival time, reduced neurological scores, and improved motor performance tested using the rotarod and grip strength tests. On the other hand, DMSO treatment did not attenuate motor neuron loss in the spinal cord and denervation of neuromuscular junctions in the skeletal muscle. These results suggest that DMSO administration could improve the quality of life of the SOD1-G93A mouse model of ALS without affecting motor neuron denervation. In conclusion, the use of DMSO as control or vehicle solvent in preclinical research may affect the behavioral outcomes in the SOD1-G93A mouse model. The effect of the vehicle should be thoroughly considered when interpreting therapeutic efficacy of candidate drugs in preclinical research.

• Journal of the Korean Society of Radiology
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• v.6 no.2
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• pp.93-98
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• 2012

Micro-computed tomography (microCT) is an important tool for preclinical vascular imaging, with micron-level resolution. This non-destructive means of imaging allows for rapid collection of 2D and 3D reconstructions to visualize specimens prior to destructive analysis such as pathological analysis. Objectives. The aim of this study was to suggest a method for ex vivo, postmortem examination of stented arterial segments with microCT. And ex vivo evaluation of stents such as bare metal or drug eluting stents on in-stent restenosis (ISR) in rabbit model was performed. The bare metal stent (BMS) and drug eluting stent (DES, paclitaxel) were implanted in the left or right iliac arteries alternatively in eight New Zealand white rabbits. After 4 weeks of post-implantation, the part of iliac arteries surrounding the stent were removed carefully and processed for microCT. Prior to microCT analysis, a contrast medium was loaded to lumen of stents. All samples were subjected to an X-ray source operating at 50 kV and 200 ${\mu}A$ by using a 3D isotropic resolution. The region of interest was traced and measured by CTAN analytical software. Objects being exposed to radiation had different Hounsfield unit each other with values of approximately 1.2 at stent area, 0.12 ~ 0.17 at a contrast medium and 0 ~ 0.06 at outer area of stent. Based on above, further analyses were performed. As a result, the difference of lengths and volumes between expanded stents, which may relate to injury score in pathological analysis, was not different significantly. Moreover, ISR area of BMS was 1.6 times higher than that of DES, indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. And ISR area of BMS was higher ($1.52{\pm}0.48mm^2$) than that of DES ($0.94{\pm}0.42mm^2$), indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. Though it was not statistically significant, it showed that the extent of neointema of mid-region of stents was relatively higher than that of anterior and posterior region in parts of BMS as showing cross-sectional 2-D image. suggest that microCT can be utilized as an accessorial tool for pathological analysis.

• Journal of Korean Medicine for Obesity Research
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• v.17 no.1
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• pp.37-45
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• 2017

Recently the global epidemic problem of obesity has stimulated intense interest in the study of physiological mechanisms using animal models as a way to gain crucial data required for translation to human studies. Panax ginseng has been reported to have anti-obesity or antidiabetic effects in many animal studies; however, there have been few studies investigating human obesity. Herein, we will assess and examine the evidence supporting the anti-obesity effect of Panax ginseng in animal models with respect to anthropometric and metabolic outcomes. We will include controlled, comparative studies assessing the effect of Panax ginseng in preclinical studies of obesity. Panax ginseng will be administered during or following the induction of experimental obesity. The primary outcome measure will be anthropometric assessment and the secondary outcome measures will include adipose tissue weight, total amount of food consumed and metabolic parameters. We will search MEDLINE, Embase, PubMed, Web of Science, and Scopus without language, publication date, or other restrictions. Ethical approval will not be necessary as the data collected in this study will not be individual patient data, consequently there will be no concerns about violations of privacy. After finishing the whole procedure, the results will be disseminated by publication in a peer-reviewed journal or presented at a relevant conference. This protocol has been registered on the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) website (http://www.camarades.info).

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.27-30
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• 1994

잠재적으로 항감염 약제로 사용될 가능성이 있는 약제들의 초기 연구과정에서 주된 관심사는 이들이 미생물(세균, 바이러스, 기타 기생충)에 대한 작용들이 있는가 하는 점이다. 이러한 작용들이 실험적으로 충분히 연구가 된 후에야 실험동물에서 그 효과를 연구한다. 항 바이러스 제제의 경우에는 세포배양을 통한 연구가 그 약제의 독성과 효용성을 나타내는데 필수적인 것이 된다. 여러 종류의 동물을 이용한 생체실험에서 약제의 일반적인 흡수와 배설, 분포 등에 관한 정보와 약제 자체와 동물 내에서의 대사적 변화에 대한 정보가 제공된다. 여러 가지 미생물로 감염을 시킨 적합한 동물과 여러 가지 용량으로 치료하는 실험을 통하여 약제의 항 감염 능력이 알려지게 된다. 동물에서의 생체실험과 실험관내에서 실험을 하고 나서야 사람에서의 연구가 이루어지게 된다. 소위 전임상시험에서 대표적 병원성 미생물에 대한 생물학적효과, 약리학적 효과와 독성 그리고 동물실험모델에서의 가능한 효과가 결정된 후에 임상시험에 들어가기 마련이다. 항균제의 임상시험에는 각각의 감염질환에 대한 진단 및 치료기준을 반영하는 것이 기본이다. 새로운 항균제의 임상시험에서는 안전성과 효과가 반드시 밝혀져야 한다. 1상에서는 인체에서의 약리효과, 안전성이 주목적이며, 2상과 3상은 겹쳐지는 점도 있으나 하나 또는 그 이상의 적응증에 대한 항균제의 효과와 단기간의 부작용은 2상에서 관찰하여야하며, 다수의 환자에서 제안된 적응질환의 무작위임상시험과 다수에서의 안전성도 3상에서 관찰하여야 한다. 4상에서는 이상에서의 자료로 시판된 후에도 계속해서 감시하는 것으로 지속적으로 안전성을 관찰하는 것이다. 이러한 기본사항외에도 소아, 임산부, 고령자등에서의 임상시험도 넓은 의미에서 포함되어야 할 것이며 또한 질적인 면에서 조절하는 Quality Assurance도 중요하다.양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.5주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 모든 처리군들이 대조군에 비하여 높게 발현되는. 것이 관찰되었으나 시험개시후 26주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 대조군에 비하여 차이가 거의 없었다. 따라서 랫드에서 화학적으로 유도한 간암발생 과정에서 NK 세포활성이 현저하게 억제되는 것으로 생각되며, c-myc 종양단백의 발현은 시험개시후 15주에 그 발현이 확실한 것으로 사료되어 진다.에 영향을 주는 성분이 있음을 제시하였다.1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.바와 같이 MCl에서 작은 Dv 값을 갖는데, 이것은 CdCl$_{4}$$^{2-}$ 착이온을 형성하거나 ZnCl$_{4}$$^{2-}$ , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서던지 NH$_{4}$$^{+}$의 경우 Dv값이 제일 작았다. 바. 본 연구의 목적중의 하나인 인체유

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.