• Journal of Pharmaceutical Investigation
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• 제17권4호
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• pp.205-211
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• 1987

Renal dysfunction can have pronounced effects on the pharmacokinetic and pharmacodynamic characteristics of drugs. Because the exploration of these effects in patients may be limited by ethical and practical considerations, it often become necessary to perform studies on animals with experimental renal failure(ERF). ERF was produced in rats by the administration of uranyl nitrate, glycerol, salicylate, gentamicin and folate in this study. Changes in glomerular filtration rate(GFR) and renal secretion clearance of tetraethylammonium bromide$(CL^{scn}_{TEA})$, together with morphological changes of kidney cortex were evaluated and compared among ERF models. GFR(or glomeruli) and $CL^{scn}_{TEA}$(or renal tubules) were not damaged parallelly in some ERF model rats. Therefore, it seemed to be necessary to adjust dosage regimen of some basic drugs like TEA in renal dysfunction considering the functional changes of renal secretion in addition to glomerular filtration.

• Toxicological Research
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• 제30권3호
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• pp.141-148
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• 2014

Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.

• 한국농공학회논문집
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• 제65권1호
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• pp.27-39
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• 2023

This study was to quantitatively evaluate periodic and maximum energy loads for broiler-standard design models by the Ministry of Agriculture, Food and Rural Affairs (2016). Building energy simulation method was used to compute heating and cooling loads of the designed broiler houses according to regional locations and insulation characteristics of wall and roof. It considered sensible and latent heat generation from broilers, dynamic operation of ventilation system according to environment variations. It was found that variation of periodic heating loads was relatively higher than that of periodic cooling loads according to thickness changes of wall and roof. Assuming that broiler was raised at every even-month, periodic heating and cooling loads were 6 and 18% lower, respectively than odd-month raising condition. When recommendation rules of insulation characteristics (wall and roof thickness) by the Ministry of Land, Infrastructure and Transport was adopted, periodic heating load of Jeju-si was 20.3% higher than national average values. Based on the BES computed periodic and maximum energy loads under the designed experimental condition, these results can contribute to reestablishing standard design of broiler houses, especially for insulation characteristics, and designing management strategies for efficient energy uses.

• Archives of Pharmacal Research
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• 제22권4호
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• pp.354-360
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• 1999

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034,$ 7-carboxymethyloxy-3^{l}, 4^{l},$ 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD : two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3~3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 gm/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.

• 대한화장품학회지
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• 제25권2호
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• pp.59-75
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• 1999

Skin is continuously exposed to external stimuli including ultraviolet radiation, which is a major cause of skin photoaging. According to recent discoveries, UVA with a lower energy but deep-penetrating properties, compared to UVB, is likely to play a major part in causing skin photoaging. The clinical and histochemical changes of photoaging are well characterized, but the biochemical mechanisms are poorly understood partly due to the lack of suitable experimental systems. In this work, three-dimensional, reconstituted skin culture models were prepared. After certain period of maturation, the equivalent models were shown to be similar in structure and biochemical characteristics to normal skin. Mature dermal and skin equivalent models were exposed to sub-lethal doses of UVA, and the effects of UVA relevant to dermal photoaging were monitored, including the production of elastin, collagen, collagenase(MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1). Interestingly, dermal and skin equivalents reacted differently to acute and chronic exposure to UVA. Elastin production was increased as soon as one week after commencing UVA irradiation by chronic exposure, although a single exposure failed to do so. This early response could be an important advantage of equivalent models in studying elastosis in photoaged skin. Collagenase activity was increased by acute UVA irradiation, but returned to control levels after repeated exposure. On the other hand, collagen biosynthesis, which was increased by a single exposure, decreased slightly during 5 weeks of prolonged UVA exposure. Collagenase has been thought to be responsible for collagen degeneration in dermal photoaging. However, according to the results obtained in this study, elevated collagenase activity is not likely to be responsible for the degeneration of collagen in dermal photoagig, while reduced production of collagen may be the main reason. It can be concluded that reconstituted skin culture models can serve as useful experimental tools for the study of skin photoaging. These culture models are relatively simple to construct, easy to handle, and are reproducible Moreover the changes of dermal photoaging can be observed within 1-4 weeks of exposure to ultraviolet light compared to 4 months to 2 years for human or animal studies. These models will be useful for biochemical and mechanistic studies in a large number of fields including dermatology, toxicology, and pharmacology.

• Asian Pacific Journal of Cancer Prevention
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• 제15권6호
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• pp.2405-2425
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• 2014

Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (${\leq}5Gy$) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury.

• Advances in Traditional Medicine
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• 제6권3호
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• pp.221-231
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• 2006

The aim of the present study is to investigate central nervous system (CNS) activity of the methanol extracts of leaves of Caesalpinia bonducella (MECB) and stem bark of Bauhinia racemosa (MEBR) (Caesalpinaceae) in Swiss albino mice and Wistar albino rats. General behavior, exploratory behavior, muscle relaxant activity and phenobarbitone sodium-induced sleeping time were studied. The results revealed that the methanol extracts of leaves of Caesalpinia bonducella at 100 - 200 mg/kg and stem bark of Bauhinia racemosa 100 - 200 mg/kg caused a significant reduction in the spontaneous activity (general behavioral profile), remarkable decrease in exploratory behavioral pattern (Y-maze and head dip test), a reduction in muscle relaxant activity (rotarod and traction tests), and also significantly potentiated phenobarbitone sodium-induced sleeping time. The results suggest that MECB and MEBR exhibit CNS depressant activity in tested animal models.

• Laboraroty Animal Research
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• 제34권4호
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• pp.166-175
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• 2018

Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line ($Rag-2^{-/-}$) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. $Rag-2^{-/-}$ mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in $Rag-2^{-/-}$ mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in $Rag-2^{-/-}$ mice. These findings indicate that our $Rag-2^{-/-}$ mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

• Journal of Chest Surgery
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• 제32권12호
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• pp.1065-1077
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• 1999

Background : Ventricular assist devices(VADs) are being used for patients in postcvardiotomy cardiogenic shock status bridge to cardiac transplant settings and in post-myocardial infarction cardiogenic shock. The VAD which was developed at the Deparment of medical engineering in Dankook University College of Medicine was a pneumatically driven device and can maintain pulsatile flow. The goal of this study is to develop animal experimental models using the VAD and to clarify the reliability and hemodynamic property adequacy of end organ perfusion durability and severity of thrombotic-hemolytic tendency of the device. Material and Method : The pneumatic VAD was applied to 8 adult female lambs, We examined some hemodynamic parameters such as arterial blood pressure pulmonary capillary wedge pressure(pcwp) pulmonary artery pressure(PAP) left atrial pressure hour urine output cardiac index VAD flow EKG to determine the reliability of the VAD and hemodynamic compatibility of the experimental animals within 24 hours of experiment. We also observed the end organ perfusion durability of the VAD and thrombotic-hemolytic property of the VAD after 24 hours of VAD insertion. Result: We could monitor all hemodynamic parameters including pcwp PAP cardiac index EKG, adn hour urine as true clinical settings. We observed that the reliability of the VAD was excellent and the hemodynamic property of the experimental animal and end organ perfusion were adequate within 24 hours of experiment. In four lambs surviving 24 hours after insertion the reliability of the VAD and end organ perfusion were excellent and no thrombotic-hemolytic tendency was noted. However after 15 days of experiment the diaphragm of the VAD was torn and it was recommende that the durability of the VAD should be extended. Conclusion : e conclude that the pneumatic VAD developed at Dankook University Biomedical Engineering has good hemodynamic property and low thromboembolic tendency and presents adequate end organ perfusion but we noted that the durability of the device should be expanded further. It will be possible to do more reliable experiment in the future according to the animal experimental method developed in this study especially with the heart failure models.

• Asian-Australasian Journal of Animal Sciences
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• 제24권12호
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• pp.1651-1659
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• 2011

This study was conducted to detect quantitative trait loci (QTL) for thirteen growth and meat quality traits in pigs by combing QTL experimental populations. Two F2 reference populations that were sired by Korea native pig (KNP) and dammed by Landrace (LN) or Yorkshire (YK) were generated to construct linkage maps using 123 genetic markers (mostly microsatellites) and to perform QTL analysis on porcine chromosomes (SSCs) 1, 2, 3, 6, 7, 8, 9, 11, 13, 14, and 15. A set of line-cross models was applied to detect QTL, and a series of lack-of-fit tests between the models was used to characterize inheritance mode of QTL. A total of 23, 11 and 19 QTL were detected at 5% chromosome-wise level for the data sets of KNP${\times}$LN, KNP${\times}$YK cross and joint sets of the two cross populations, respectively. With the joint data, two Mendelian expressed QTL for live weight and cooking loss were detected on SSC3 and SSC15 at 1% chromosome-wise level, respectively. Another Mendelian expressed QTL was detected for CIE a on SSC7 at 5% genome-wise level. Our results suggest that QTL analysis by combining data from two QTL populations increase power for QTL detection, which could provide more accurate genetic information in subsequent marker-assisted selection.