• Journal of Veterinary Clinics
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• v.34 no.6
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• pp.441-444
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• 2017

A 15-year-old spayed female Miniature Schnauzer was presented for unilateral foreleg lameness and pain. On physical examination, left elbow joint swelling and stiffness were identified. On a computed tomography (CT) scan, a periosteal reaction of the left humerus from the distal metaphysis to the epiphysis and cortical destruction of the medial condyle was observed. Based on blood tests, histopathology, and immunohistochemistry, it was concluded as a skeletal histiocytic sarcoma. Since the patient's pain was not controlled despite application of a fentanyl patch, a left forelimb amputation was decided upon as part of the palliative therapy. Metronomic chemotherapy with toceranib phosphate and pamidronate was initiated. Toceranib was administered for 3 months without the development of any adverse effects except mild neutropenia. However, 3 months after initiating treatment, the toceranib was discontinued due to moderate gastrointestinal disturbances. Over the next 2 months, a left mandibular bone mass and cortical bone destruction in the bilateral tibia and tarsal joint were identified on CT. The patient became unwilling to eat and was noted to have severe skeletal pain. The anorexia and lethargy were progressively worsening and the owner decided to euthanize the patient. A necropsy was performed and the patient was definitively diagnosed with disseminated histiocytic sarcoma based on histopathologic and immunohistochemical analyses. This report describes a Miniature Schnauzer dog with DHS managed with surgical removal and metronomic chemotherapy with toceranib that survived with an improved quality of life for 7 months.

• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.309-316
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• 2006

This is a case report on the occurrence of caprine arthritis-encephalitis (CAE) disease among dairy goats in a local farm located in Yeongdong-gun, Chungbuk. Previously, it was reported that the farm experienced intermittent deaths numbering 15 of the 97 goats raised for 5 months. Most of the goats less than 6 months of age were suffering from ataxia and posterior paresis, body tremor and abnormal head posterior. Affected animals frequently had stunted growth and had a rough coat. Goats more than 6 months of age were affected with an insidious, chronic arthritis characterized by articular swelling ('big knee') of the carpal, hock, and stifle joints. Necropsy revealed severely swollen mesenteric lymph nodes, under- flow of 2-3ml synovial fluid in the articular space and fibrous proliferation of synovial membrane. Histopathological examination showed perivascular accumulations of mononuclear inflammatory cells in the white matter of the brain, proliferative synovitis characterized by villous hypertrophy, synovial cell hyperplasia and infiltration by mononuclear inflammatory cells. Pulmonary lesions consists of patchy interstitial pneumonia with hyperplasia of lymphoid tissues and an extensive mononuclear inflammatory cell infiltration into the alveolar septa. Confirmation by nested PCR involves amplification of a 296 bp (lst PCR) and 184 bp (2nd PCR) fragments corresponding to the gag region of the CAE virus. This is the first time CAE has been reported in a local farm in Korea and emphasizes the importances of developing preventive measures against CAE.

• Korean Journal of Veterinary Service
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• v.40 no.4
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• pp.281-285
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• 2017

Six to seven-month-old 10 beef calves in 140-head beef cattle farm in Gimpo-si, Gyeonggi-do were suffered from ataxia and astasia. Two of them were submitted to Animal and Plant Quarantine Agency for diagnosis in July 9, 2015. At necropsy, the radius and tibia of both calves showed irregular thickening and hemorrhage of the physis in addition to hemorrhage and disruption of trabeculae in metaphysis. Histopathologically the physis showed irregular tongues of cartilage remaining the metaphysis. Disorganization, hemorrhage and fibrosis were observed in metaphyseal and epiphyseal bones. The serum 25-hydroxyvitamin $D_3$ ($D_3$) and calcium levels were lower than normal range. In addition, the serum $D_3$ levels in the other 9 calves of the same farm were lower than normal levels. Based on the pathological examination and serum chemistry measurements, we diagnosed this case as rickets caused by vitamin D deficiency in calves.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.35 no.1
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• pp.1-12
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• 2013

Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.993-1002
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• 2009

The object of this study was to evaluate the single dose toxicity of Taeumjowui-tang(TUJWT), a polyherbal formula have been traditionally used as prevention or treatment agent for obesity, in male and female mice. Aqueous extracts of TUJWT (Yield = 10.5%) was administered to female and male ICR mice as an oral dose of 2000, 1000 and 500 mg/kg (body wt.) according to the recommendation of KFDA Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy, organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for diarrhea restricted in TUJWT 2000 mg/kg treated one male mouse at 1 day after administration, and increases of popliteal lymph node weights in all TUJWT administered groups. In addition, no TUJWT-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for increases of the frequency of hypertrophy and hyperplasia of lymphoid cells in the popliteal lymph nodes in all TUJWT treatment groups with some sporadic accidental findings. These increases of popliteal lymph node weights with hypertrophy and hyperplasia of lymphoid cells were considered that related to the immune modulate effect of TUJWT not toxicological signs. The results obtained in this study suggest that the TUJWT does not cause any toxicological signs. The 50% lethal dose and approximate lethal dose of TUJWT aqueous extracts in both female and male mice were considered as over 2000 mg/kg.

• Toxicological Research
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• v.20 no.3
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• pp.273-280
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• 2004

The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.

• Toxicological Research
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• v.28 no.1
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• pp.11-18
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• 2012

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, $LD_{50}$ (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

• Korean Journal of Ecology and Environment
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• v.40 no.4
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• pp.560-568
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• 2007

The objectives of this study were to analyze ecological effects on effluents from the Sagok Stream (Chonnam province) as an abandoned mine drainage through necropsy-based health assessments and fish exposure tests, and to conduct In situ field pilot tests for restoration of stream water. Also, we analyzed water quality including general parameters and heavy metals. The tests were performed three times on April 2005, April 2006, and April 2007. Also, we constructed a reactor facility in the outflowing point of the abandoned mine for the remediation of AMD wastewater. In lab test, death rates in all three treatments were ${\geq}50%$ in the experiments. Necropsybased fish tissue assessments using the Health Assessment Index (HAI), indicated that the most frequently damaged tissue was liver (average: 20.8). Values of Health Assessment Index were lower in the control than any other treatments of T1, T2, and T3 and three treatments showed a distinct toxicity impacts by the AMD. In situ lethal test, concentration of Fe, Al and Zn decreased particularly by 85%, 99% and 94%, respectively through the disposal facility. Values of pH, ranged from 3.1 to 7.0, increased by 2.3 fold (mean=5.1) along with the reduction of metal contents. All fishes in P1 cage died 100% on 3 days later after the experimental setting, while all fishes in the P6 died 100% on 9 days later. Overall, these results evidently provide a key methodology for pilot test using the disposal facility and also clarify the toxicity of AMD once again, so this approach used in the pilot facilities here may reduce the acidic and toxic effects in the abandoned mining drainage.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.943-950
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• 2003

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1 ,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.

• Archives of Pharmacal Research
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• v.26 no.11
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• pp.917-924
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• 2003

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development ($IC_{25}=3.37{\times}10^{-5}$mg/mL) less than 17$\beta$-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3${\pm}4.2% and 138.5{\pm}$10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.