• Title/Summary/Keyword: Animal disease model

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The effects of PEP-1-FK506BP on dry eye disease in a rat model

  • Kim, Dae Won;Lee, Sung Ho;Ku, Sae Kwang;Lee, Ji Eun;Cha, Hyun Ju;Youn, Jong Kyu;Kwon, Hyeok Yil;Park, Jong Hoon;Park, Eun Young;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.3
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    • pp.153-158
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    • 2015
  • As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

  • Kim, JiYoun;Lee, JaeHee;Shin, SoJung;Cho, AhRang;Heo, Yong
    • Toxicological Research
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    • v.34 no.1
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    • pp.7-12
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    • 2018
  • Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

Dental imaging characterization of micropigs

  • Lee, Hyeyeon;Choi, Mihyun;Chang, Jinhwa;Jung, Joohyun;Kim, Mieun;Lee, Namsoon;Kim, Junyoung;Choi, Mincheol
    • Korean Journal of Veterinary Research
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    • v.50 no.4
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    • pp.311-317
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    • 2010
  • Recently the micropig has been developed as human disease model. The dental and orofacial region of micropig is similar to that of humans, so it has been used for testing implant materials and techniques. The purpose of this study is on dental image at each age using radiography and computed tomography. Total twenty-two male micropigs, two or three animals of each 1, 3, 5, 7, 9, 12, 18 and 24 months old, were given radiographic examinations. After general anesthesia, extra- and intra-oral radiographic technique and computed tomographic scans were performed to assess the dental characterization of micropigs. The total deciduous dental formula comprised 28 teeth and was depicted as Di 3/3, Dc 1/1, Dp 3/3. The total permanent dental formula comprised 44 teeth and was depicted as I 3/3, C 1/1, P 4/4, M 3/3. Hypodontia of the first premolars was common in the micropig. The permanent teeth erupted from 3 to 24 month after birth. The sequence of eruption of the permanent teeth was M1, P1, I3, C, M2, I1 + P3 + P4, P2, I2, M3. Dental imaging enables visualization of the unerupted teeth and gives more information about the development of the teeth. The growth pattern of the teeth obtained through radiographic and computed tomographic examination provides basic data in the micropig as animal model for dental research.

The Inhibitory Effect of Premature Citrus unshiu Extract on Atopic Dermatitis In Vitro and In Vivo

  • Kang, Gyeoung-Jin;Han, Sang-Chul;Yi, Eun-Jou;Kang, Hee-Kyoung;Yoo, Eun-Sook
    • Toxicological Research
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    • v.27 no.3
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    • pp.173-180
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    • 2011
  • Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.

Cell Culture Models of Human Norovirus: the End of the Beginning? (인간노로바이러스의 세포배양 기술개발 : 새로운 시작?)

  • Nguyen, Minh Tue;Park, Mi-Kyung;Ha, Sangdo;Choi, In-Soo;Choi, Changsun;Myoung, Jinjong
    • Microbiology and Biotechnology Letters
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    • v.45 no.2
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    • pp.93-100
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    • 2017
  • Human norovirus (hNoV) infection accounts for the vast majority of virus-mediated gastroenteritis cases worldwide. It causes self-limiting acute illnesses in healthy individuals lasting for a few days, however, in immunocompromised patients, hNoV can establish chronic and potentially fatal infections. Since its discovery in 1968, much effort had been made to develop cell culture and animal infection models to no avail. Only recently, some promising breakthroughs in the development of in vitro infection models have been made. Here, we will contrast and compare those models and discuss what further needs to be done to develop a reliable and robust cell culture model.

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

  • Cho, Dong-Charn;Cheong, Jin-Hwan;Yang, Moon-Sul;Hwang, Se-Jin;Kim, Jae-Min;Kim, Choong-Hyun
    • Journal of Korean Neurosurgical Society
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    • v.49 no.2
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    • pp.83-91
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    • 2011
  • Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test Mechanical hyperalgesia was measured throughout the 28-day post -operative course via the von Frey test Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (lba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of lba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of lba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

Overexpression of HER-2/neu in Malignant Mammary Tumors: Translation of Clinicopathological Features from Dog to Human

  • Muhammadnejad, Ahad;Keyhani, Elahe;Mortazavi, Pejman;Behjati, Farkhondeh;Haghdoost, Iraj Sohrabi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6415-6421
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    • 2012
  • Background: Canine mammary gland tumors (CMGTs) are the most common tumor found in bitches. Changes in HER-2/neu genes in human breast cancer (HBC) lead to decrease in disease-free survival (DFS) and overall survival rate (OSR). Previous studies have demonstrated that the biological behavior of malignant mammary gland tumors (MMGTs) is similar to that of HBC. The present study aimed at evaluating the relationship between overexpression of HER-2/neu and clinicopathological features in MMGTs to represent a model of prognostic factors for HBC. Materials and Method: The clinicopathological data of 35 MMGTs were obtained. Immunohistochemical staining with HER-2, Ki-67 and CD34 markers was conducted with sections from paraffin-embedded blocks. According to standard protocols, histological type, grade, margin status, lymphovascular invasion (LVI), HER-2/neu score, proliferation rate and microvessel density (MVD) of tumors were determined and the association of HER-2/neu overexpression with these parameters was assessed statistically. Results: The IHC results showed that 12 (34.3%) cases were HER-2/neu positive. Statistical analyses indicated a significant relationship between HER-2 positivity and tumor grade (p=0.043), which also was demonstrated with cancer stage (p=0.035), tumor margin involvement (p=0.016), proliferation index (p=0.001) and MVD (p=0.001); however, there was no statistical relationship between LVI and tumor size. Overexpression of the HER-2/neu gene in MMGTs results in similar biological behavior as that of HBC; as a result, these tumors have can be considered to have important similarities in clinicopathological characteristics. Conclusions: MMGTs can be regarded as an HBC animal model. Further studies in this field would result in new treatments that could be beneficial for both dogs and humans.

Effect of Chamomile German Oil Application of IgG1 and IgE 1 to Atopic Dermatitis in NC/Nga Mice Model (Chamomile German 오일도포가 아토피성 피부염을 가진 NC/Nga 생쥐모델의 혈청 IgE와 IgG1양 변동에 미치는 영향)

  • Shin, Gil-Ran;Kim, Yang-Weon
    • Korean Journal of Human Ecology
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    • v.18 no.2
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    • pp.501-507
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    • 2009
  • Atopic dermatitis is one of the most common skin disease in children and a characteristic chronically recurrent form of dermatitis with a hereditary tendency, affecting infants and may extend to the childhood or th the adult age. Environmental factors, stress, and foodstuffs such as milk, egg may cause atopic dermatitis. Nc/Nga mice were used as an animal model for human atopic dermatitis. The divided by 4group such as normal group, BMAC group, FK506 group, MR group for this study raised in conventional conditions. To investigate effect of Chamomile German on atopic dermatitis in NC/Nga mice, the serum IgE and IgG1 level were measured while the severity degree of the skin lesion was examined by the naked eyes of two volunteers who were unaware of the treatment status. The results were the followings. 1. The score on the severity degree of skin dermatitis in FK 506 and MR group was lower than that in control group. 2. The serum IgE level in control group was higher 25% than that in normal group. 3. The serum level of IgE in FK506 and MR group compares to control group was decreased. 4. The serum IgG1 level was decreased more than 3.5 times in FK506 compared to control group while MR group had significantly less the serum IgG1 than control group. From the above results, treatment of Chamomile German oil had the effect on atopic dermatitis in NC/Nga mice. If scientific researches on aroma oil are performed in various way, aroma oil will be used to cure skin dermatitis as a alternative therapy in the future.

Alcohol Induced Hepatic Fibrosis in Pig

  • Lee, Chang-Woo;Lee, Cha-Soo;Jeong, Won-Il;Do, Sun-Hee;Noh, Dong-Hyung;Jeong, Kyu-Shik
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2002.11a
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    • pp.146-146
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    • 2002
  • Hepatic disease has been noted and reported for involvement various detrimental factors. Among many detrimental injury factors, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study is to develop animal model for hepatic fibrosis in pig with ethanol, and to search new anti-fibrogenic agent. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with ceramic water only, ceramic water + liquid diet containing 20% ethanol and normal tap water + containing 20% ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, comparing to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate necrosis were evident in the tap water + ethanol fed group 3. However, ceramic water intake group 1 showed normal. Moreover, in group 3, little fatty changes and mild necrosis were observed. Collagen fibers were detected in the spaces of surrounding periportal and interlobular areas in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts was markedly reduced in the group 2 of ceramic water + ethanol. In immunohistochemistry, myofibroblasts were detected in the ethanol and tap water treated group 3. No or a few myofibroblasts were observed in groups 1 and 2. CYP 2E1 was rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP 2E1 in the area of pericentral, while CYP 2E1 was significantly activated in group 3 fed tap and ethanol. Taken together above, alcohol fibrosis model in pig was established. Furthermore, ceramic water had an inhibitory and protecting ability for alcohol-induced hepatic damages.

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Experimental development of caprine enterotoxaemia with Clostridium perfringens type D whole culture in natural host and its treatments

  • Islam, Kbms;Rahman, Md Sidiqur;Ershaduzzaman, Md.;Taimur, Mjfa;Song, Hee-Jong
    • Korean Journal of Veterinary Service
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    • v.30 no.2
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    • pp.219-231
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    • 2007
  • The effects of intraduodenal administration of Clostridium perfringens type D whole culture in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species and the eventual evaluation of treatment with different drug preparations was also carried out. A total of 28 conventionally reared healthy unvaccinated black bangle goat kids of 6-12 months of age were dosed intraduodenally with whole cultures of C peliringens type D. Four kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. The clinical signs developed within 12 hours of post inoculation that were similar to those observed in naturally occurring cases. Among the clinical signs, diarrhea was most common (96.43%) followed by dyspnea (53.57%) and central nervous system (CNS) signs (25.0%). The most striking postmortem findings consisted of necrotizing pseudomembranous colitis (100.0%), lung edema (69.23%) and fluid filled intestines (61.53%). The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease. Beside this, treatment trial with different drug preparations showed penicillin combined with antitoxin was most effective (100.0%), followed by combination of oxytetracyclin with antitoxin, and combined preparation of antitoxin and sulfur drugs both showed 75% recovery rate. On the other hand, treatment with antitoxin, penicillin and oxytetracycline singly could protect goat enterotoxaemia only 25.0%, 50.0% and 50.0%, respectively. Thus in the present study, it eas observed that antisera in combination of antibiotics gave better recovery rate than the antitoxin or antibiotics alone.