• 대한한방내과학회지
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• 제24권2호
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• pp.190-202
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• 2003

Object : The effect of Banhabakchulchunma-tang extracts on the hepatic, splenic and cardiac toxicity induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. Methods : The changes of body weight, clinical signs, necropsy findings and organ weights of liver, spleen and heart were observed with blood GOT and GPT levels. Results : 1. Decrease of body weight and The degrees of anorexia, ataxia and dehydration after Doxorubicin treatment were dose-dependently inhibited by Banhabakchulchunma-tang extracts. 2. Increase of absolute and relative liver and heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of liver congestion necrotic spot and the degrees of heart congestion enlargement were dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. It is also demonstrated that elevated serum GOT and GPT levels in doxorubicin treatment group were significantly decreased in Banhabakchulchunma-tang extracts dosing groups. 3. Decrease of absolute and relative spleen weight observed in doxorubicin treatment group were dose-dependently inhibited by Banhabakchulchunma-tang extracts. In addition, the degrees of splenic atrophy were significantly and dose-dependently decreased after Banhabakchulchunma-tang extracts dosing groups compared to that of doxorubicin treatment group. Conclusion : the toxicity of doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of liver, spleen and heart, elevation of serum GOT and GPT levels) was inhibited and/or prevented by Banhabakchulchunma-tang extracts. According to these results, it is considered that Banhabakchulchunma-tang has some preventive effect against to doxorubicin induced toxicity.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.300-306
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• 1999

To study the antigenicity of BR92021(Vi polysaccharide typhoid vaccine), active systemic ana-phylaxis and passive cutaneous anaphylaxis were tested in guinea pigs. The groups were as follows: group I(low dose, 30 $\mu\textrm{l}$/kg), group II(high dose, 300 $\mu\textrm{l}$/kg), group III(300 $\mu\textrm{l}$/kg plus complete Freund's adjuvant), group IV(positive control, ovalbumin plus complete Freund's adjuvant) and group V(saline-treated control). Male Hartley guinea pigs at 7 weeks of age were sensitized subcutaneously with the test article or saline three times per week for three weeks(j.e., total 9 times). For groups III and IV, animals were sensitized subcutaneously with either the test article or ovalbumin plus complete Freund's adjuvant once per three week for 6 weeks(i.e., total 3 times). Twelve days after the last sensitization, the blood was collected from the sensitized animals for the passive cutaneous anaphylaxis test. In addition, the sensitized animals were subjected to the active systemic anaphylaxis test on fourteen days after the last sensitization by an intravenous challenge with either the test article or ovalbumin. In group I, mild(1/5) or moderate(4/5) symptoms of anaphylactic shock were observed. In group II, no sign(1/5), moderate(3/5) and severe(1/5) symptoms were observed. In group III, four animals of revealed moderate signs and one of 5 showed no signs of anaphylactic shock. In group IV, all 5 animals showed severe signs of shock. In group V, one of 5 revealed moderate and four of 5 showed no signs. The necropsy findings related to the active systemic anaphylaxis were observed in most animals of groups I to V In the passive cutaneous anaphylaxis test, the antiserum was diluted 10- to 5120- fold and was injected intradermally on the clipped back of recipient animals, followed by an intravenous challenge with either the test article or ovalbumin. No animals in groups I, II, III and V showed the positive reaction, whereas all animals in group IV, the positive control, showed the positive reaction at the dilution range of x1280 to x5120. Our results indicate that the test article, BR92021, may have weak antigenic potential in male guinea pigs.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.127-137
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• 1996

This study was performed to investigate the toxicity of DA-125 in beagle dogs, an anthracycline antitumor antibiotic. The dogs were administered DA-125 i.v. at 0.0023, 0.0375, 0.15 and 0.6 mg/kg/day, 6 days/week for 26 weeks. At 0.6 mg/kg, all male and female dogs were either sacrificed moribundly or dead during the 26-week treatment. The dogs revealed inactivity, salivation, dark bloody discharge, swelling of the subcutaneous injection site, abscess, and ulceration in the abdominal wall and legs. At 0.15 mg/kg, anorexia, salivation, and swelling of the injection site were observed. The food consumption was decreased with a statistical significance at 6 and 12 weeks treatment in males of 7.6 mg/kg. At 0.0375, 0.15 and 0.6 mg/kg, body weights were decreased significantly in a dose-related fashion after 17 weeks treatment. Total white blood cell counts for male dogs at 0.6 mg/kg were lower than those of control dogs after 13 weeks treatment, which appeared mainly due to decreased neutrophils. At 0.15 mg/kg, testicular atrophy was found in all males by gross pathology and the testicular weights were significantly decreased when compared to those of control males. Microscopically, the testis showed moderate atrophy of the seminiferous tubules and marked decrease in number of spermatozoa in the epididymal tubules. At 0.6 mg/kg, petechia or echymotic hemorrhage was observed in gastrointestinal tract, heart, lungs, and other organs at the necropsy, Marked atrophy of thymus were observed in both males and females. In addition, severe testicular atrophy was noted in all males. Microscopically, gastrointestinal tract showed hemorrhage, epithelial denudation, hypermucus secretion, and atrophy of intestinal villi. Seminiferous tubules of the atrophic testis were lined with Sertoli cells only and devoid of germ cells. Severe oligospermia or aspermia was present in the epididymal tubules. Bone marrow showed marked depletion of hemopoietic cells. In addition, marked atrophy was found in the lymphoid tissue of gastrointestinal tract, various Iymph nodes, and thymus. Injection sites showed marked inflammatory response with necrosis, necrotizing vasculitis, thrombus formation, and ulceration in the skin. According to the present results, no observed effect level appeared to be 0.0375 mg/kg. At 0.15 mg/kg, testis was a target organ, while at 0.6 mg/kg hemopoietic tissue, gastrointestinal tract, and testis were considered to be target organs. At 0.6 mg/kg the test compound seems to inflict a damage on the blood vessels causing hemorrhage in the various organs and tissues.

• Parasites, Hosts and Diseases
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• 제36권1호
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• pp.23-32
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• 1998

마우스 백혈병 바이러스인 LP-BM5 MuLV를 감염시켜 면역결핍 상태 (Murine AIDS: MfdDS)로 유도한 C57BL/6 마우스에 10 종류의 가시아메바 분리주를 감염시켜 가시아메바 분리 주별 병원성을 평가하였다. LP-BM5 MuLV에 감염된 C57BL/6 마우스는 MfdDS 모델의 특징적 소견인 비장 종대와 임파절 종대를 나타내었고, 가시아메바의 배양 온도에 따른 MAIDS 모델 마 우스의 치사율의 유의적 차이는 없었으나. 분리주에 따른 MAIDS 마우스의 치사율은 상당한 차이 가 있었다. 아메바성 육아종성 뇌염 환자의 뇌에서 분리한 A. henlvioc-3A주가 가장 높은 치사 율을 나타내었고. 조직 배양 중 분리된 A. culbensonih-1주가 2번째로 높은 치사율을 나타내었 다. 국내 토양에서 분리한 A. ccstellanii KA/S2주와 A.polvphagaga KAS3주는 매우 낮은 치사율 을 보였다. 가시아메바를 비강 내 접종으로 감염시킨 마우스는 정맥 내 주사로 감염시킨 마우스에 비해 만성적 경과를 보였다. 사망한 마우스의 폐와 뇌의 육안적 병리 소견은 일관된 성적을 나타 내지는 않았고. 마우스 개체마다 다양하였다 병리 조직학적 소견으로는 뇌 조직에서보다 폐 조직 에서 더 심한 염증과 괴사를 보였으나. OC-3A주로 감염시켜 사망한 마우스의 뇌조직에서는 심한 염증반응과 가시아메바 영양형을 관찰할 수 있었다. 가시아메바 분리주마다 병원성이 다른 것으로 미루어 보아 가시아메바의 병원성은 유전적 요인에 의해 결정될 것으로 생각되며 추후 가시아메바 병원성 결정인자에 대한 연구가 필요하다고 사료된다.

• 생명과학회지
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• 제26권2호
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• pp.204-211
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• 2016

본 실험에서는 유산균발효 독활의 마우스 단회 경구 투여 독성 자료를 얻기 위해 식품의약품안전청 고시 제 2013-121 “의약품 등의 독성시험 기준”에 의거하여, 설치류 투여 한계 용량인 2,000 mg/kg을 최고 투여군을 설정하고 공비 2로 1,000 및 500 mg/kg 투여군을 중간 및 저용량 투여군으로 설정하여 실험을 실시하였으며, 그 결과는 독활 열수 추출물 2,000 mg/kg 암수 투여군 및 암수 매체 대조군과 비교 평가 하였다. 본 실험의 결과, 설치류 투여한계 용량인 2,000 mg/kg 투여군까지, 유산균발효 독활 열수 추출물 투여와 관련된 사망례, 임상증상, 체중, 장기중량, 육안부검 및 조직병리학적 소견이 인정되지 않았다. 따라서 유산균발효 독활 열수 추출물의 마우스에 대한 단회 경구 투여 반수 치사량 및 개략적 치사량은 암수 각각 2,000 mg/kg이상으로 산출되었으며, 특정 임상증상 및 표적 장기 역시 없는 것으로 판단되어, 유산균발효 독활은 매우 안전한 물질로 판단된다. 또한 독활 열수 추출물 2,000 mg/kg 투여와 관련된 사망례, 임상 증상, 체중, 장기중량, 육안 및 조직병리학적 변화 역시 인정되지 않았다. 이러한 결과는 독활의 활용도를 증대시키는 기초 자료가 될 것으로 사료된다.

• 생명과학회지
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• 제22권3호
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• pp.340-346
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• 2012

가금류 제품에서 항생제의 잔류와 내성균의 출현으로 인해 항생제 대체물질에 대한 연구가 활발히 진행되고 있으며, 특히 생균제와 활성촉진제 또는 이들을 조합한 신바이오틱의 사용이 권장되고 있다. 본 연구는 새로운 생균제 CS61 배양액의 사료첨가 급여가 육계의 성장 및 사료효율에 미치는 영향과 안전성을 평가하여 항생제를 대체할 수 있는 사료첨가제로서의 개발가능성을 알아보기 위해 수행하였다. CS61 배양액은 0, 0.1 및 1%의 용량으로 28일간 사료에 혼합하여 육계에게 급여하였다. 시험결과, 시험물질 처치군에서 부검 시의 체중과 일당증체량이 대조군에 비해 용량의존적으로 증가하였다. CS61 배양액의 사료 내 첨가는 대조군 동물에 비해 사료효율도 개선하는 것으로 나타났다. 반면, 일반증상과 사망률, 부검소견, 혈액학치 및 혈청생화학치에서는 시험물질의 처치와 관련된 독성소견이 관찰되지 않았다. RAW 264.7 세포를 이용한 일산화질소 시험에서 정제된 CS61 펩타이드는 lipopolysaccharide에 유도된 일산화질소 생성을 용량의존적으로 억제하였다. 본 시험결과는 육계에 CS61 배양액의 사료첨가 급여는 항염증효과를 통해 성장과 사료효율을 개선할 수 있음을 보여주며, 사료첨가제로서 CS61 배양액의 유용성과 개발가능성을 시사해 주고 있다.

• 생태와환경
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• 제40권3호
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• pp.370-378
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• 2007

본 연구는 갑천의 지류인 반석천에서 도시화에 따른 서식지 교란과 수질오염의 영향에 따른 생태계 건강성 평가를 위해 2005년 7월부터 2006년 4월까지 어류를 이용한 해부학적 건강도 평가 모델지수(HAI),생태계 건강도 평가 지수(IBI)및 물리적 서식지 평가 모델(QHEI)을 이용하여 총체적 건강도를 평가하였다. 상기 모델의 시간적, 공간적인 분석을 위해 상류로부터 하류까지 총 6개 지점을 선정하여 3회 조사하였다. 생태계 건강도 평가결과 평균 24(악화${\sim}$보통상태)로 나타났고, 물리적 서식지 건강도는 평균 116(보통${\sim}$양호상태)으로 나타났다. 생태계 건강도와 물리적 서식지 건강도의 상관분석 결과 물리적 서식지 건강도는 생태계 건강도에 영향을 주는 것으로 사료되었고, 특히 서식처의 비율$(M_1)$, 유량/유속의 다양성 $(M_3)$, 여울의 빈도$(M_7)$와 높은 상관관계를 보였다. 해부학적 건강도 평가 결과 대조군은 0(최적상태)으로 나타난 반면, 처리군(T1, T2)은 각각 5 (양호상태), 50 (악화상태)로 나타났으며, 생태계 건강도가 높은 지점에서 개체건강도 역시 최적상태로 나타났다. 본 연구 결과 생태계 건강도 평가(IBI), 물리적 서식지 평가(QHEI) 및 해부학적 개체 건강도 평가(HAI)를 통한 평가 기법은 하천 생태계의 총체적 건강도 평가를 위한 좋은 모델인 것으로 사료된다.

• 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 Microbiology and Biotechnology
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• 제28권12호
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• pp.2133-2140
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• 2018

Norovirus is the most common cause of acute gastroenteritis. Its pathogenesis is poorly understood owing to the difficulty of establishing viral infection in animal models. Here, post-weaning gnotobiotic pigs were infected with human norovirus genogroup II genotype 4 (HuNoV GII.4) to investigate the pathogenesis and replication of the virus. Three groups of four pigs were infected with $1{\times}10^5$, $1{\times}10^6$, or $1{\times}10^7$ genomic equivalent (GE) copies of HuNoV GII.4. Four pigs were used as negative controls. Blood and rectal swab samples were collected after viral infection, and gross legions were examined after necropsy. Diarrhea was induced in 25% and 75% of pigs infected with $1{\times}10^6$ and $1{\times}10^7$ GE copies, respectively. Viral shedding was detected in 50%, 75%, and 50% of pigs infected with $1{\times}10^5$, $1{\times}10^6$, and $1{\times}10^7$ GE copies, respectively. Viremia was detected in 25% of pigs infected with either $1{\times}10^6$ or $1{\times}10^7$ GE copies. When gross lesions of gastroenteritis were investigated, the ileum walls of the infected pigs were thinner than those of the controls. Villi atrophy and inflammatory cell infiltration were identified in the ileum of each infected pig. Viral capsid was identified in the jejunum, ileum, colon, spleen, and mesenteric lymph node. Virus replication was newly verified in the spleen and mesenteric lymph nodes by detection of negative-sense viral RNA. In conclusion, HuNoV GII.4 could induce acute gastroenteritis and replicate in the extra-intestinal lymphoid tissues in post-weaning gnotobiotic pigs. Therefore, such pigs would be a suitable animal model for studying the pathogenesis and replication of HuNoV.

• 한국동물위생학회지
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• 제42권1호
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• pp.39-42
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• 2019

Tetanus is an acute, often fatal, and infectious disease of all species of domestic animals caused by the neurotoxin of Clostridium tetani (C. tetani). This disease is usually known to develop after microbial contamination in the deep or penetrating wound sites. In February 2017, a farmer who was raising 76 cows injected foot and mouth disease vaccine to three or more cows with one syringe. Their clinical symptoms were observed 2 to 16 days after the vaccination. The initial symptoms were stiffness, rigidity of the neck and limbs, pricked ears, and prolapse of the third eyelid. Subsequently, there was recumbency with extension of the limbs, convulsions and opistotonus and the affected 20 cows were all died. Two dead cows were submitted to Animal and Plant Quarantine Agency for disease diagnosis. At necropsy, a focal edematous abscess of 15 to 20 cm in diameter was grossly observed in the subcutaneous and intramuscular tissue of scapular region and filled with a large amount of greenish pus. The feed was full in oral cavity and slightly observed in the trachea and lobes of lung. Histopathologically, focal granulomatous nodules with eosinophilic materials in the tissue were observed. In the lung, aspiration pneumonia and gram (+) bacteria were seen. The C. tetani was isolated in samples anaerobically cultured using reinforced clostridial medium and identified by PCR. To our knowledge, no previous outbreak of tetanus in cattle has affected such a high number of animals; neither has it been associated with misuse of the same syringe and needle to administer multiple individuals.