1.Increased expression of galectin-9 in experimental autoimmune encephalomyelitis
Jinhee CHO ; So Jin BING ; Areum KIM ; Hak Sun YU ; Yoon Kyu LIM ; Taekyun SHIN ; Jonghee CHOI ; Youngheun JEE
Korean Journal of Veterinary Research 2014;54(4):209-218
Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), reflects pathophysiologic steps in MS such as the influence of T cells and antibodies reactive to the myelin sheath, and the cytotoxic effect of cytokines. Galectin-9 (Gal-9) is a member of animal lectins that plays an essential role in various biological functions. The expression of Gal-9 is significantly enhanced in MS lesions; however, its role in autoimmune disease has not been fully elucidated. To identify the role of Gal-9 in EAE, we measured changes in mRNA and protein expression of Gal-9 as EAE progressed. Expression increased with disease progression, with a sharp rise occurring at its peak. Gal-9 immunoreactivity was mainly expressed in astrocytes and microglia of the central nervous system (CNS) and macrophages of spleen. Flow cytometric analysis revealed that Gal-9+CD11b+ cells were dramatically increased in the spleen at the peak of disease. Increased expression of tumor necrosis factor (TNF)-R1 and p-Jun N-terminal kinase (JNK) was observed in the CNS of EAE mice, suggesting that TNF-R1 and p-JNK might be key regulators contributing to the expression of Gal-9 during EAE. These results suggest that identification of the relationship between Gal-9 and EAE progression is critical for better understanding Gal-9 biology in autoimmune disease.
Animals
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Antibodies
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Astrocytes
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Autoimmune Diseases
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Biology
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Central Nervous System
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Cytokines
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Disease Progression
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Encephalomyelitis, Autoimmune, Experimental
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Humans
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Lectins
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Macrophages
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Mice
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Microglia
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Models, Animal
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Multiple Sclerosis
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Myelin Sheath
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Phosphotransferases
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RNA, Messenger
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Spleen
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T-Lymphocytes
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Tumor Necrosis Factor-alpha
2.Chemoprevention of Mammary, Cervix and Nervous system Carcinogenesis in Animals using Cultured Panax ginseng Drugs and Preliminary Clinical Trials in Patients with Precancerous Lesions of the Esophagus and Endometrium.
Vladimir G BESPALOV ; Valeriy A ALEXANDROV ; Andrey Y LIMARENKO ; Boris O VOYTENKOV ; Valeriy B OKULOV ; Mels K KABULOV ; Alexander P PERESUNKO ; Larisa I SLEPYAN ; Viktor V DAVYDOV
Journal of Korean Medical Science 2001;16(Suppl):S42-S53
The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.
Adenocarcinoma/chemically induced/prevention & control
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Adult
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Animal
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Antineoplastic Agents, Phytogenic/*therapeutic use
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Cells, Cultured
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Cervix Neoplasms/chemically induced/prevention & control
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Clinical Trials
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Cytotoxicity Tests, Immunologic
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Disease Models, Animal
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Endometrial Neoplasms/pathology/prevention & control
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Endometrium/pathology
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Esophageal Neoplasms/pathology/prevention & control
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Esophagus/pathology
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Estradiol/blood
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Female
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Fibroadenoma/chemically induced/prevention & control
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Human
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Macrophages, Peritoneal/cytology/immunology
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Male
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Mammary Neoplasms, Experimental/chemically induced/prevention & control
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Mice
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Mice, Inbred C57BL
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Neoplasms, Experimental/chemically induced/*prevention & control
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Nervous System Neoplasms/chemically induced/prevention & control
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Panax/*metabolism
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Precancerous Conditions/pathology/*prevention & control
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Rats
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Tissue Culture
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Uterine Neoplasms/chemically induced/prevention & control
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Vaginal Neoplasms/chemically induced/prevention & control
3.Erythropoietin and autoimmune neuroinflammation: lessons from experimental autoimmune encephalomyelitis and experimental autoimmune neuritis.
Taekyun SHIN ; Meejung AHN ; Changjong MOON ; Seungjoon KIM
Anatomy & Cell Biology 2012;45(4):215-220
Erythropoietin (EPO) is known to have numerous biological functions. While its primary function is during haematopoiesis, recent studies have shown that EPO plays important role in cytoprotection, immunomodulation, and antiapoptosis. These secondary functions of EPO are integral to tissue protection following hypoxic injury, ischemia-reperfusion injury, and spinal cord injury in the central nervous system. This review focuses on experimental evidence documenting the neuroprotective effects of EPO in organ-specific autoimmune nervous system disorders such as experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN). In addition, the immunomodulatory role of EPO in the pathogenesis of EAE and EAN animal models of human multiple sclerosis and Guillain-Barre syndrome, respectively, will be discussed.
Autoimmune Diseases
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Central Nervous System
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Cytoprotection
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Encephalomyelitis
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Encephalomyelitis, Autoimmune, Experimental
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Erythropoietin
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Guillain-Barre Syndrome
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Hematopoiesis
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Humans
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Immunomodulation
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Models, Animal
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Multiple Sclerosis
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Nervous System Diseases
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Neuritis, Autoimmune, Experimental
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Neuroprotective Agents
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Reperfusion Injury
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Spinal Cord Injuries
4.Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases.
Hong Kyung LEE ; Sang Hee LIM ; In Sung CHUNG ; Yunsoo PARK ; Mi Jeong PARK ; Ju Young KIM ; Yong Guk KIM ; Jin Tae HONG ; Youngsoo KIM ; Sang Bae HAN
Immune Network 2014;14(2):81-88
Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-beta, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.
Adipose Tissue
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Arthritis, Rheumatoid
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Autoimmune Diseases*
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B-Lymphocytes
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Bone Marrow
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Crohn Disease
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Dendritic Cells
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Dinoprostone
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Encephalomyelitis, Autoimmune, Experimental
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Heme Oxygenase-1
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Humans
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Intercellular Signaling Peptides and Proteins
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Interleukin-10
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Leukocytes
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Lupus Erythematosus, Systemic
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Mesenchymal Stromal Cells*
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Models, Animal*
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Nitric Oxide
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Placenta
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Stem Cells
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T-Lymphocytes
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T-Lymphocytes, Regulatory
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Umbilical Cord
5.A study of experimental autoimmune encephalomyelitis in dogs as a disease model for canine necrotizing encephalitis
Jong Hyun MOON ; Hae Won JUNG ; Hee Chun LEE ; Joon Hyeok JEON ; Na Hyun KIM ; Jung Hyang SUR ; Jeongim HA ; Dong In JUNG
Journal of Veterinary Science 2015;16(2):203-211
In the present study, the use of dogs with experimental autoimmune encephalomyelitis (EAE) as a disease model for necrotizing encephalitis (NE) was assessed. Twelve healthy dogs were included in this study. Canine forebrain tissues (8 g), including white and grey matter, were homogenized with 4 mL of phosphate-buffered saline for 5 min in an ice bath. The suspension was emulsified with the same volume of Freund's complete adjuvant containing 1 mg/mL of killed Mycobacterium tuberculosis H37Ra. Under sedation, each dog was injected subcutaneously with canine brain homogenate at four sites: two in the inguinal and two in the axillary regions. A second injection (booster) was administered to all the dogs using the same procedure 7 days after the first injection. Clinical assessment, magnetic resonance imaging, cerebrospinal fluid analyses, necropsies, and histopathological and immunohistochemical examinations were performed for the dogs with EAE. Out of the 12 animals, seven (58%) developed clinically manifest EAE at various times after immunization. Characteristics of canine EAE models were very similar to canine NE, suggesting that canine EAE can be a disease model for NE in dogs.
Animals
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Brain/pathology
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Disease Models, Animal
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Dog Diseases/immunology
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Dogs
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Encephalitis/immunology
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Encephalitis/veterinary
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Encephalomyelitis, Autoimmune, Experimental/immunology
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Encephalomyelitis, Autoimmune, Experimental/veterinary
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Female
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Fluorescent Antibody Technique/veterinary
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Immunization/veterinary
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Immunohistochemistry/veterinary
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Magnetic Resonance Imaging/veterinary
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Male
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Necrosis/immunology
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Necrosis/veterinary
6.Micro-computed tomography evaluation and pathological analyses of female rats with collagen-induced arthritis
Journal of Veterinary Science 2015;16(2):165-171
Imaging techniques have been introduced to assess the efficacy and toxicity of developing pharmaceuticals. The purpose of this study was to perform a comprehensive characterization of collagen-induced arthritis (CIA) in rats using micro-computed tomography (micro-CT) and to compare the results with data from conventional pathological examination. Arthritis was induced by collagen in 24 female Wistar rats. Micro-CT and pathological analyses were performed to assess arthritis progression. Micro-CT analysis showed marked joint destruction occurring in a time-dependent manner following collagen administration. Bone volume was significantly decreased in the tibia at weeks 3 and 4 compared to week 0 (p < 0.05 and p < 0.01, respectively). Additionally, percent bone volume was significantly reduced in the tibia at week 4 compared to week 0 (p < 0.05). In contrast, bone surface/bone volume and trabecular separation were significantly increased in the tibia of the animals at week 4 compared to week 0 (p < 0.05). Severe joint destruction with extensive inflammation, erosion of cartilage and bone, and infiltration of inflammatory cells were observed in the knee joints of the collagen-treated rats. Taken together, micro-CT made it possible to quantify CIA lesions and should be performed with pathological examination in rats.
Animals
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Arthritis, Experimental/chemically induced
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Arthritis, Experimental/diagnosis
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Disease Models, Animal
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Female
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Pathology, Clinical
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Random Allocation
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Rats
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Rats, Wistar
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X-Ray Microtomography
7.Therapeutic Approaches for Inhibition of Protein Aggregation in Huntington's Disease.
Experimental Neurobiology 2014;23(1):36-44
Huntington's disease (HD) is a late-onset and progressive neurodegenerative disorder that is caused by aggregation of mutant huntingtin protein which contains expanded-polyglutamine. The molecular chaperones modulate the aggregation in early stage and known for the most potent protector of neurodegeneration in animal models of HD. Over the past decades, a number of studies have demonstrated molecular chaperones alleviate the pathogenic symptoms by polyQ-mediated toxicity. Moreover, chaperone-inducible drugs and anti-aggregation drugs have beneficial effects on symptoms of disease. Here, we focus on the function of molecular chaperone in animal models of HD, and review the recent therapeutic approaches to modulate expression and turn-over of molecular chaperone and to develop anti-aggregation drugs.
Huntington Disease*
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Models, Animal
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Molecular Chaperones
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Neurodegenerative Diseases
8.An experimental model of ischemia in rabbit hindlimb.
Ju Hee HONG ; Yong Whee BAHK ; Jun Suk SUH ; Byung Kook KWAK ; Hyung Jin SHIM ; Jin Soo KIM ; Ho Sung KIM ; Young Ho MOON ; Sung Jin KIM ; Jin Wook CHUNG ; Jae Hyung PARK
Journal of Korean Medical Science 2001;16(5):630-635
This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia.
Angiography
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Animal
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Blood Pressure
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*Disease Models, Animal
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Hindlimb/*blood supply
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Ischemia/*physiopathology/radiography
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Male
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Rabbits
9.Experimental Atherosclerosis in Pigs.
Yonsei Medical Journal 1987;28(1):1-5
No abstract available.
Animal
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Arteries/pathology
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Arteriosclerosis/pathology*
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Diet, Atherogenic
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Disease Models, Animal
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Support, U.S. Gov't, P.H.S.
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Swine
10.Animal Models of Neurodegenerative Diseases.
Brain & Neurorehabilitation 2011;4(1):30-34
Animal models of human diseases are essentially required to investigate the pathophysiological mechanisms of the diseases, and to test potential therapies for the clinics. However, neurodegenerative diseases including Parkinson's disease (PD) are particularly difficult to model or to recapitulate the features because most of them have multifactorial etiologies and chronically progressive symptoms, although Huntington's disease (HD) has an identified etiology such as an excessive expansion of CAG repeats. In this review, PD and HD which were typical neurodegenerative diseases were studied. The animals of PD were roughly classified into a neurotoxic model and a genetic model, and those of HD were divided into excitotoxic, transgenic, knock-in, and knock-out models. Insights obtained from these animal models of neurodegenerative diseases will guide us toward the understanding of the disease mechanisms, the design of new therapeutic strategies, and finally translation into the clinics.
Animals
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Humans
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Huntington Disease
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Models, Animal
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Models, Genetic
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Neurodegenerative Diseases
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Parkinson Disease