• Toxicological Research
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• 제8권2호
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• pp.217-233
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• 1992

This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

• Toxicological Research
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• 제8권2호
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• pp.235-253
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• 1992

A subacute toxicity study of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) was carried out to obtain information on its toxicological profiles, and to determine the maximum tolerated dose in beagle dogs. Four groups of beagle dogs (2M and 2F per group, 0,0.5,1.0,2.0mg/kg/day)were given 15 i.v. injections of SKI 2053R. In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group was treated with cisplatin(0.7mg/kg/day)according to the same treatment schedule. The dosing schedule was divided into 3 courses of 5 consecutive days with 23-day dose-free intervals between each course. After completion of the treatments, remaining dogs were necropsied under established guidelines. Three of four dogs in the high dose group and one of four dogs in the middle dose group treated with SKI 2053R died of hypovolemic shock secondary to hemorrhagic and ulcerative enterocolitis. No toxicity-related mortality occurred in the low dose group of SKI 2053R. No survivor was observed in the group of cisplatin. Clinical signs including vomiting, diarrhea, anorexia and loss body weight were apparent in dogs given either cisplatin or high and middle doses of SKI 2053R. Severe thrombocytopenia and leukocytopenia were observed in the high dose group of SKI 2053R and cisplatin-treatment group, while toxicities as bone marrow suppression were reversible. The significant elevation of serum ALP values in group of SKI 2053R(2.0 mg/kg/day and 1.0mg/kg/day) and cisplatin(0.7mg/kg/day)was observed. Slight proteinuria waa observed in high and middle dose level groups of SKI 2053R. In histopathological examinations, pathological alterations of liver, kidney and spleen were noted dose-dependantly in dogs treated with SKI 2053R, and there was no overt sign of toxicity in low dose group of SKI 2053R. Compared to SKI 2053R, more severe durg-related toxicities occurred in dogs treated with cisplatin. It waw estimated that maximum tolerated dose of SKI 2053R in this treatment schedule was 0.5~0.7mg/kg/day. In conclusion, overall toxic potential of SKI 2053R was approximately 3 times lower than that of cisplatin with respect of lethality.

• 대한핵의학회지
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• 제27권1호
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• pp.88-97
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• 1993

Anterior abdominal scintigraphy after intravenous injection of $^{99m}Tc$-human serum albumin ($^{99m}Tc$-HSA 20 mCi) was done in 16 patients with connective tissue diseases and 15 healthy control patients. Patients with proteinuria or hepatopathy were excluded. 1) 7 (44%) patients among 16 connective tissue disease patients without the apparent evidence of external protein loss showed abnormal intestinal accumulation of albumin. 6 patients with positive albumin scintigraphy showed bypoalbuminemia. 2) There was no false positive scintigraphic finding in control group. 3) The serum albumin level in connective tissue disease patients ($3.1{\pm}0.6 g/dl$, n=16) was lower than control patients ($3.9{\pm}0.3 g/dl$, n=15) (p<0.0001). 4) The serum albumin level was lower in connective tissue disease patients with positive $^{99m}Tc$-HSA scan ($2.8{\pm}0.6 g/dl$, n=7) than the connective tissue disease patients with negative scan ($3.3{\pm}0.3 g/dl$, n=9) (p<0.05). 5) The hemoglobin level in connective tissue disease patients with positive nan ($10.6{\pm}2.91 g/dl$) was lower than that of the control group ($13.6{\pm}1.5 g/dl$) (p<0.05). Mypoalbuminemia is frequently involved in chronic connective tissue diseases. Protein losing enteropathy (PLE) is also responsible for the majority of the bypoalbuminemia in these patients. But it has been ignored because the conventional method for the diagnosis of PLE was difficult to perform. $^{99m}Tc$-HSA scan also must be validated by more extended study and comparison with the quantitative study such as stool ${\alpha}-1$ antitrypsin measurement. There must be a reevaluation of PLE in various diseases especially in connective tissue diseases with easy, fast, economical, and non-invasive method.

• 한국임상수의학회지
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• 제17권2호
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• pp.443-449
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• 2000

A three-year-old male jindo with generalized skin lesions (including seborrhea, hyperk- eratosis, alopecia, papules, and ecchymoses), pruritus lymph node enlargement, and fever was brought to Veterinary Teaching Hospital, College of Veterinary Medicine, Chungbuk National Uni- versity. There were no laboratory findings for parasites and fungi in the hair and skin But, the com- plete blood counts (CBC) showed leukocytosis and severe cosinophilia, It was suspected to be an inflammatory and allergic dermatitis. Thus, prednisoIone (0.5 mg/kg PO, BID for 1 week) and ampi- cillin (10 mg/kg PO, BID for 1 week given. One week later, pruritus and ecchymoses were reduced. These treatments were repeated for 7 day again. Three months later, the dog was presented again due to the relapse and exacerbation of the clinical signs. The signs were as follows; severe pru- ritus, vesicobullous skin lesions, anorexia, emaciation, lameness, and welling of carpal joints that showed inflammatory skin lesion and draining of synovia-like fluid. The values of WBC counts were returned to normal ranges. In contrast, eosinophilia was still observed. Coombs test for patient RBC and serum were negative. Hypoalbuminemia (2.5g/dl) was shown by serum chemistry. The uri- nalysis revealed and presence of leukocytes. Luxation finding of right radial carpal joint by polyarthritis was shown in radiography of affected joints.Lupus eryhematosus(LE) cells also appeared in peripheral blood and synovial fluid of affected joints. Definitely, antinuclear antibody (ANA) of patient serum using feline peripheral blood mononuclear cells was detected by all immu- nofluorescence. Based on these findings such as sedum ANA-Positive. major signs (skin disease, non- erosive polyarthritis with soft tissue swelling. and proteinuria), minor signs (fever), and LE cell-pos- itive, a diagnosis of systemic lupus crythematosus (SLE) was mad\ulcorner in this dog. The dog with SLE was administered with Pre(2.0 mg/kg PO, BID for first 4 week and then QOD) to inhibit the production of autoantibodies and with ampicillin (10 mg/kg PO, BID for first 4 weeks and then QOD) to prevent the secondary infection. The condition of this dog was monitored every 2 weeks by physical examinations, radiography, CBC, serum chemistry and urinalyais. At 8th week of treat- ment, the state of SLE evaluated by physical examinations and laboratory findings was markedly improved except for proteinura.

• 한국임상수의학회지
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• 제28권3호
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• pp.314-317
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• 2011

체중이 4.3 kg인 중성화된 16세의 암컷 말티즈견이 약 2주 동안 누런색의 비강과 구강 분비물, 식욕부진과 기면 증상으로 내원하였다. 신체검사에서 구강내 왼쪽 혀 밑 부위에 약 $3{\times}3$ cm 크기의 궤양성 종괴, 심한 치은치주염, 구취, 중등도의 치석, 발열과 아래턱의 연조직 부종을 관찰하였다. 방사선 사진상에서 위턱과 아래턱의 앞 부위에서 골융해 소견을 볼 수 있었다. 총혈액검사와 혈액화학검사에서 혈소판수치, $NH_3$, AST와 ALP의 증가를 관찰할 수 있었으며, 요검사에서 혈뇨와 단백뇨가 나타났다. 조직검사결과 구강 편평 세포암으로 진단되었다. 축주의 거부로 외과적 처치는 실시하지 않았으며, 약물요법으로 carboplatin 주사와 piroxicam 구강내 투여를 병용하였다. 처음 약물투여 후 5일에 지속적인 구토 증상이 나타났으며, 이에 piroxicam을 meloxicam으로 대체하였으며 구토증상은 소실되었다. Meloxicam의 종양에 대한 치료효과에 대한 보고는 흔하지 않지만, 위장관계에 대한 부작용 발생은 piroxicam에 비해 낮음을 알 수 있었다. 이환견은 총 3회의 carboplatin 주사를 실시하였으나, 세 번째 주사 투여 후 5일에 심한 기면증상, 구토와 혈변 증상으로 내원하였고, 검사결과 심한 신기능부전 소견을 보였으며, 축주의 요구에 의해 안락사하였다.

• 농촌의학ㆍ지역보건
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• 제17권1호
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• pp.5-16
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• 1992

The maternal and child health is a basis of national health, and indicates the level of social welfare and health of the country, because it is related with community welfare status, general cultural conditions, and medical and health sciences. This is a study carried out to identify the present practices of maternal and child health care programs implemented by the private clinics located in Guns(counties ; rural area) in Kyungsangnam Province and to propose alternatives to improve their current programs through a self-administrative questionnaire. The subjects were 90 private physicians who operated their own clinics since 1990 and were general practitioners, Obstertrician/Gynecologists or pediatricians: This survey was conducted by mail from 15 January to 25 February 1992. The response rate was 94.4 percent. 1) The major manpower for MCH programs of the studied clinics was physicians and nurseaids. 70.3% of physicians were general practitioners, 81.1% of nursing manpower were nurseaids. 31.1% of the studied clinics employed lab-technicians. 89.2% of them had MCH room whatever the size and the setting, and 84.4% of Ob/Gyn clinics installed laboratory equipments. 2) 55.4% and 63.5% of the studied clinics provided 151 or above consulting services and curative services of MCH per physician a month respectively and 33.8% and 25.7% of them provided 10 or less consulting services and curative services per physician a month. 91.9% of lab-technicians had 10 or less laboratory tests per technician a month. 3) There was a difference between Ob/Gyn and pediatric clinics in terms of services delivered : for example, 80% of Ob/Gyn clinics provided pre- and post- natal care services, while 84.6% of pediatric clinics provided vaccinations for children. It was also found that only a few of general practitioners involved pre-and post- natal care services. 4) There were no clinics which had opened regular health education session but 24.3% of them had opened the sessions irregularly. Ob/Gyn clinics put emphasis on maternity and pediatric clinics did on child health, but general practitioners touched with both maternal and child health. 21.6% of the studied clinics had some kind of educational materials for MCH programs. Most of the materials were pamphlets or small booklets. 5) Proteinuria/glucosuria, blood pressure and blood type were tested in 48.6~69% of the studied clinics ; tests for blood sugar and hepatitis B were provided in 39.2~41.9% of them, most of them were done in Ob/Gyn clinics. 6) 41.9% of physicians, 29.7% of nurses and 45.9% of nurses-aids wanted to receive on-job-training for MCH programs.

• 한국임상수의학회지
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• 제24권2호
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• pp.82-87
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• 2007

태국에서 생산된 Pedigree사의 개 사료를 1개월 이상 섭취한 5마리의 개가 식욕절폐, 쇠약, 구토, 다음다뇨 증상을 보였으며 증상이 심한 개는 혈액성 설사와 저체온증을 보였다. 특징적인 임상병리학적 소견으로 BUN과 creatinine이 높았으며 일부의 개에서는 GGT, 무기인과 lipase가 높았으나 CBC는 특이적인 임상병리학적 소견이 없었다. 요분석에서는 혈뇨, 저비중뇨, 단백뇨와 calcium oxalate와 유사한 결정이 관찰되었다. 증상이 심한 두 마리는 폐사하였으며 나머지의 개는 사료의 변경과 보조요법에 의하여 점차 회복되었다. 전형적인 병리학적 소견은 신장에서 관찰되어 신장의 위축, 일부 사구체의 모세혈관 충혈, 세뇨관의 미만성 변성과 이영양성 석회화, 세뇨관의 괴사와 재생, 세뇨관 내강 내에 황갈색 판상 형광성 물질 또는 파편이 관찰되었다. 섭취한 사료와 동일한 개봉하지 않은 사료 내의 ochratoxin A와 citrinin의 농도를 분석한 결과 각각 372.8ppb와 8.3ppb가 검출되었다. 병력, 임상증상, 임상병리소견, 병리학적 소견 및 사료 내의 곰팡이독소의 분석을 통하여 ochratoxin A와 citrinin의 중독에 의한 신부전으로 최종진단을 내렸다.

• 동의생리학회지
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• 제14권2호통권20호
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• pp.189-198
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• 1999

Aminoglycosides, including gentamicin, have been used as antibiotics for the various infections by gram-negative bacteria. However, there are some restrictions for using these drugs. Gentamicin, a typical aminoglycoside, has the side effect of nephrotoxicity, including polyuria, glycosuria, proteinuria, glomerulonephritis, and uremia. The aims of this study were to examine the prevention or reduction effects of Jinmootang on the gentamicin-induced nephrotoxicity and to investigate the possible mechanisms on the effect of Jinmootang. The subcutaneous injections of 60mg of gentamicin per kg of boby weight to Sprague-Dawley rats for 8 days induced typical symptoms of nephrotoxicity by aminoglycosides. 0.6ml of water extract Jinmootang (100ml/chup) was orally treated in the experimental animal. 24-hour urine was collected with the metabolic cage and plasma was sampled from the abdominal aorta. The plasma concentration of sodium was significantly decreased by the treatment of gentamicin but it was not-significantly changed by the treatment of Jinmootang to the animal. The concentration of potassium was greatly decreased in the gentamicin-treated animals. However. it was returned to the normal level in the Jinmootang-treated animals. The concentrations of creatinine and urea were increased by gentamicin treatment. But, Jinmootang reduced these concentrations. Nevertheless, the osmolalities of plasma in both group were not different from each other. Even though the plasma concentration of aldosterone was not significantly changed, the mean value was increased by the gentamicin intoxication. The concentration of aldosterone was decreased by the treatment of Jinmootang. The reduction of aldosterone level in plasma could be a factor to improve the hypokalemia. The fractional excretion of potassium was much higher than normal by the treatment of gentamicin and it was decreased by 50% in the Jinmootang-treated rats. Therefore, the reabsorption of potassium was significantly increased by the treatment of Jinmootang, even though the filtered load of potassium in the experimental group was much highter than control. Even though the concentration of plasma aldosterone was decreased by the treatment of Jinmootang, the fractional excretion of sodium was not increased, slightly lower. These data suggested that Na reabsorption was increased in the proximal tubule by Jinmootang. The filtered load of glucose in the Jinmootang-treated group was greater than in control. Nevertheless, the fractional excretion of glucose in the experimental group was not different from that in control. These results indicate that glucose reabsorption was increase in the proximal tubule by Jinmootang treatment. The results of this study suggest that Jinmootang could improve the some nephrotoxic symptoms induced by gentramicin treatment. Hypokalemia, the reduced glomerular filtration rate, and dysfunctions of renal proximal tubule and distal nephron were significantly recovered to normal level. The increase of glomerular filtration rate by Jinmootang might contribute to eliminate the waste product, including creatinine and urea, and/or gentamicin through the kidney.

• Childhood Kidney Diseases
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• 제17권2호
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• pp.149-153
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• 2013

응고성 미세혈관병증은 빠른 진단이 예후에 중요한 인자이나, 현재의 진단 기준에 따라서는 thrombotic thrombocytopenic purpura, haemolytic uremic syndrome 외의 비전형적인 응고성 미세혈관병증의 진단이 늦어짐에 따라 나쁜 예후를 초래하게 되는 경우가 많다고 보고되어 있다. 본 저자들은 시행한 혈액 검사상 용혈의 증거가 없는 빈혈, 혈소판 감소증 그리고 급성 신부전을 보인 소아 환아에서 신조직 검사를 통해 비특이적 응고성 미세혈관병증을 진단받은 1증례를 보고하고자 한다. 14세 여자 환아는 3주간 지속된 발열, 구역과 전신 부종을 주소로 본원으로 전원되었다. 내원하여 시행한 혈액 검사상 빈혈과 혈소판 감소증을 보였으나, 용혈의 증거는 없었으며, 혈정 크레아티닌이 증가되어 있었다. 내원 이후 급성 신부전과 발열은 지속적으로 진행되었으며, 소변 검사상 단백뇨가 발생하였다. 환아는 내원 40일경 신고혈압과 동반된 전신 경련이 5분간 있어 뇌 자기 공명 영상을 촬영하였으며, 가역성 후백질 뇌병증 증후군의 양상을 보여 항 경련제 투여를 시작하였다. 이후 지속되는 혈소판 감소증 및 발열은 고용량 스테로이드 치료를 진행한 후 호전되었으나, 급성 신부전 및 단백뇨가 지속되어 신장 조직 검사를 진행하였으며, 검사 결과상 혈전성 미세혈관병증의 소견을 보였다. 이와 같이 조직검사상에서는 응고성 미세혈관병증을 보이나 전형적인 응고성 미세혈관병증의 혈액학적인 진단 기준이 충족되지 않는 비특이적 형태의 응고성 혈관병증의 효과적인 진단을 위하여 보체 기전이나 ADAMTS 13와 같은 유전자 범위의 보다 활발한 연구를 통한 효과적인 진단 기준의 마련이 되어야 할 것으로 보인다.

• Childhood Kidney Diseases
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• 제17권2호
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• pp.79-85
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• 2013

목적: 단백뇨 질환의 실험모델인 puromycin aminonucleoside (PAN)에서 관찰할 수 있는 족세포의 병리학적 이상에 있어서 P-cadherin의 변화를 생체 외 족세포 배양실험을 통하여 알아보고자 하였다. 방법: PAN에 의한 족세포의 P-cadherin의 변화를 생체 외 배양실험을 통해 알아보고자 백서 사구체 상피세포(GEpC)를 배양하여 다양한 농도의 PAN을 투여하여 confocal 현미경을 통하여 P-cadherin의 분포를 관찰하였고, Western blotting 과 RT-PCR을 사용하여 P-cadherin 발현의 변화를 관찰하였다. 결과: 외곽세포질에 분포하는 P-cadherin은 단일세포 혹은 응집환경에서 PAN의 농도가 올라갈수록 내부로 응집되는 현상를 볼 수 있었다. Western 분석에서, P-cadherin 단백양은 PAN에 농도-의존적으로, 특히, 고농도인 50 mg/mL에서 24시간과 48시간이 노출 조건에서 각각 21.9% (P< 0.05)와 31.9% (P<0.01)의 의미 있는 감소소견을 보였다. RT-PCR에서도 48시간에서 50 mg/mL PAN을 첨가한 조건에서 23.5%의 의미 있는 감소를 보였다(P<0.05). 결론: PAN은 족세포에서 P-cadherin을 세포막으로부터 내부로의 응집을 유발하고, P-cadherin mRNA의 발현 감소와 단백수준에서 양의 감소를 초래함으로서, 단백뇨의 발생에 기여할 것이라 사료된다.