• Toxicological Research
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• v.8 no.2
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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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• v.8 no.2
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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.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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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.

• Journal of Veterinary Clinics
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• v.17 no.2
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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.

• Journal of Veterinary Clinics
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• v.28 no.3
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• pp.314-317
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• 2011

A 16-year-old, spayed female, Maltese dog weighing 4.3 kg was presented with a 2-week history of yellowish nose-and oral-discharge, anorexia and lethargy. In physical examination, indefinite ulcerative mass about $3{\times}3$ cm in size in the left sublingual region, severe gingivoperiodontitis, halitosis, moderate dental calculus, fever and swelling of mandible soft tissue were noted. In radiographic view, periodontitis and bone lysis findings on the left rostral part of maxilla and mandible were observed. In complete blood count and blood chemistry test, thrombocytosis, increased levels of serum $NH_3$, AST and ALP were obtained. Urinalysis revealed hematuria and proteinuria. In histological examination, squamous cell carcinoma was diagnosed. No surgery was performed, but combined treatment with carboplatin and piroxicam was initiated. Five days after initiation of medication, because of insistent vomiting, piroxicam was substituted to meloxicam. Although the therapeutic efficacy of meloxicam could not be known; administration of meloxicam might be less potential to gastrointestinal side-effects than piroxicam. The dog totally received 3 times of carboplatin infusion. Five days after third infusion of carboplatin, the dog was hospitalized with severe lethargy, vomiting and bloody diarrhea. In examination, severe renal failure signs were noted, and the dog was euthanized.

• Journal of agricultural medicine and community health
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• v.17 no.1
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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.

• Journal of Veterinary Clinics
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• v.24 no.2
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• pp.82-87
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• 2007

Five dogs with renal failure were referred to the Veterinary Medical Teaching Hospital at Kangwon National University. These dogs had the common history of consumption of Pedigree dry dog food produced in Thailand plant for over 1 month. The dogs showed anorexia, emaciation, vomiting, and polydipsia/polyuria. And in one severely affected dog, bloody diarrhea and hypothermia were seen. The remarkable clinicopathological signs were high value of BUN and creatinine. In some dogs, GGT, phosphorus and lipase were increased. However, no significant changes of complete blood count were found. In urinalysis, hematuria, low specific gravity urine, proteinuria, and calcium oxalate-like crystals were observed. Two severely affected dogs were died. The remained dogs were recovered gradually after change of dog food and supportive therapy. Pathological findings were seen typically in kidneys. Renal atrophy, congestion of the glomerular capillary, and diffuse degeneration, necrosis, dystrophic calcification and regeneration in the tubular epithelium were seen. Yellowish brown fluorolucent laminated materials or particles were quite often found in the lumina of the necrotizing renal tubules of cortex and medulla. Proliferation of fibrous tissue in the interstitium was also seen. By the mycotoxin analysis of the Pedigree dry dog food, ochratoxin A (OTA) and citrinin were detected as much as the concentration of 372.8 ppb and 8.3 ppb, respectively. The final diagnosis of renal failure caused by OTA and citrinin toxicosis was made on the basis of history takings, clinical signs, clinicopathological and pathological findings, and analysis of mycotoxins.

• Journal of Oriental Physiology
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• v.14 no.2 s.20
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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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• v.17 no.2
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• pp.149-153
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• 2013

We report the case of a 14-year-old girl, diagnosed with atypical thrombotic microangiopathy (TMA). The patient presented with persistent fever, nausea, and newly developed peripheral edema. Her laboratory findings indicated chronic anemia with no evidence of hemolysis, thrombocytopenia, or elevated serum creatinine level. A few days after hospitalization, acute renal failure and fever worsened, and proteinuria developed. On day 40 of hospitalization, she experienced a generalized tonic seizure for 5 min, accompanied by renal hypertension. Brain magnetic resonance imaging revealed posterior reversible leukoencephalopathy syndrome. After steroid pulse therapy, a renal biopsy was performed because of delayed recovery from thrombocytopenia. The biopsy findings showed features of thrombotic microangiopathic hemolysis with fibrinoid change restricted. Current diagnostic criteria for TMA have focused on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, and diagnosis is based on the clinical presentation and etiology, with the consequence that idiopathic and atypical forms of TMA can be overlooked. Developing effective tools to diagnose TMA, such as studying levels of ADAMTS13 or testing for abnormalities in the complement system, will be the first step to improving patient outcomes.

• Childhood Kidney Diseases
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• v.17 no.2
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• pp.79-85
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• 2013

Purpose: To test whether the expression of P-cadherin, a component of slit diaphragms between podocyte foot processes, would be altered by puromycin aminonucleoside (PAN) in a cultured podocyte in vitro. Methods: Rat glomerular epithelial cells (GEpC) were cultured with various concentrations of PAN. The distribution of P-cadherin was examined with a confocal microscope. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the change in P-cadherin expression. Results: This study found that P-cadherin was concentrated in the inner and peripheral cytoplasm with high concentrations of PAN under immunofluorescence views. Western blotting of GEpC revealed that PAN induced a decrease of P-cadherin in dose- and time-dependent manners. A high dose ($50{\mu}g/mL$) of PAN decreased P-cadherin expression by 21.9% at 24 h (P <0.05) and 31.9% at 48 h (P <0.01) compared to those without PAN. In RT-PCR, high concentrations ($50{\mu}g/mL$) of PAN also decreased P-cadherin mRNA expression, similar to protein suppression, by 23.5% at 48 h (P <0.05). Conclusion: Podocytes exposed to PAN in vitro concentrated P-cadherin internally, and reduced P-cadherin mRNA and protein expression. This could explain the development of proteinuria in experimental PAN-induced nephropathy.