• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.2
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• pp.55-62
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• 2020

A 22-month-old girl who had taken iron supplements due to iron deficiency anemia, presented bloody mucoid stool for one month. She had a bruise at the right periorbital area due to minor trauma and hepatosplenomegaly. Laboratory studies showed anemia, thrombocytopenia, elevated alkaline phosphatase (ALP), hypophosphatemia, decreased haptoglobin, hypocomplementemia, negative direct/indirect Coomb's test, normal vitamin D3 level and high PTHi. Wrist x-ray showed no signs of rickets. The abdominal ultrasound showed only accessory spleen. Tandem mass spectrometry was normal. During follow up, bloody stool regressed after seven days of withdrawal of iron supplement and cow milk, and the total CO2 level had been within 15-20 mEq/L with normal anion gap. NGS (next generation sequencing) panel test for evaluation of renal tubular acidosis showed negative results. After low dose steroid and vitamin D supplements under the impression of hypocomplementemic vasculitis, thrombocytopenia, C3/C4, decreased haptoglobin, and elevated ALP level became normal. At 57 months of age, laboratory findings showed elevated liver enzyme, ALP and gamma-glutamyl transferase again. And liver cirrhosis with splenomegaly and diffuse renal disease were reported with abdomen CT scan. Liver biopsy reported macro- and micronodular cirrhosis. Urine organic acid profile showed elevated succinylacetone level. Whole exome sequencing revealed novel compound heterozygous mutations (NM_00137.2:c.107T>C, NM_00137, 2:c.614T>C) in FAH gene and confirmed by Sanger sequencing. Consequently, the patient was diagnosed as chronic hereditary tyrosinemia type I. She started low phenylalanine/tyrosine diet and nitisinone treatment. Our case had presented symptoms very slowly, which is the first case of chronic tyrosinemia type I in South Korea.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.36 no.6
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• pp.576-585
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• 1991

General procedures of seed preparation as conventional guide had been established in China before most of Korean literature documented them. ‘Chwijongbeob’ (method of seed select) was to select good quality of seeds and to discard the rest. In ‘Seonjongbeob’ (method of seed grading) although China employed only ‘Sooseonbeob’ (method of seed select with water), but seeds were selected in order of selection of seeds by winds, selection of seeds by sieve and selection of seed with water in Korea. As compared with the recent techniques, those methods were perfect techniques for selection of good quality seeds of rice, except for method of seed selection by salt water was developed. The method for measurement of seed moisture, and for measurement of melted snow, spoiled urine and extracted juice by boiling water with the bone of livestock were originated from ancient China. The farming books in Korea were more or less followed the above methods. However, these techniques were complicated and impractical interms of validity and rationality. Also, it is judged that these tchniques are more appropriate in dry areas and alkaline soil of China rather than in Korean conditions. The plowing is a work to begin farming, and is operated for air ventilation between atmosphere and earth. Also, this techniques was adopted in the farming books from the early to the late Chosun dynasty without changes. Fields were deep-plowed in the first, in fall (or in spring) and for cultivation, and were shallow -plowed in the second, in spring (or in summer) and in intertillage. The former was for water reserve and land preparation, and the later was for weed control with intertillage. However, plowing in fall which was different from fallowing in dry areas, was recommended in Korea (Jikseol). but was not practiced in Sejongsilrok. This was changed with time, and plowing for cultivation in Korea was interrelated with use of green manure crops, method of plowing of upseting plough, method of manure practice and sometimes dry plowing. In addition, until the 15th century method of using a kind of plowing-tool made of log as farm tools was created to support reclamation for enlargement of farm land in mountaineous and coastal areas. For desolate farm lands by many internal and external disturbances, one tried to recover yield ability by increasing labor productivity from the 17th or 18th century. To do this, ‘Banjongbeob’ (culture method by upset plowing weed control) and ‘Hwanubeob’(culture method by firing weed control) which were cultural methods of ancient China were readapoted but the results were not clearly informed. Also, the reality of those was reexamined in the end of the Chosun dynasty.

• Tuberculosis and Respiratory Diseases
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• v.44 no.1
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• pp.25-43
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• 1997

Introduction : The outcome and incidence of acute respiratory distress syndrome (ARDS) could be variable related to the varied definitions used for ARDS by researchers. The purpose of the national survey was to define the risk factors of ARDS and investigate the prognostic indicies related to mortality of ARDS in Korea according to the definition of ARDS determined by the American-European Concensus Conference on 1992 year. Methods : A Multicenter registry of 48 University or University-affliated hospital and 18 general hospital s equipped with more than 400 patient's beds conducted over 13 months of patients with acute respiratory distress syndrome using the same registry protocol. Results : 1. In the 12 months of the registry, 167 patients were enrolled at the 24 hospitals. 2. The mean age was 56.5 years (${\pm}17.2$ years) and there was a 1.9:1 ratio of males to females. 3. Sepsis was the most common risk factors (78.1%), followed by aspiration (16.6%), trauma (11.6%), and shock (8.5%). 4 The overall mortality rate was 71.9%. The mean duration was 11 days (${\pm}13.1$ days) from the diagnosis of ARDS to the death. Respiratory insufficiency appeared to be a major cause in 43.7% of the deaths followed by sepsis (36.1%), heart failure (7.6%) and hepatic failure (6.7%). 5. There were no significant differences in mortality based on sex or age. No significant difference in mortality in infectious versus noninfectious causes of ARDS was found. 6. There were significant differences in the pulse rate, platelet numbers, serum albumin and glucose levels, the amounts of 24 hour urine, arterial pH, $Pa0_2$, $PaCO_2$, $Sa0_2$, alveolar-arterial oxygen differences, $PaO_2/FIO_2$, and PEEP/$FI0_2$ between the survivors and the deaths on study days 1 through 6 of the first week after enrollment. 7. The survivors had significantly less organ failure and lower APACHE III scores at the time of diagnosis of ARDS (P<0.05). 8. The numbers of organ failure (odd ratio 1.95, 95% confidence intervals:1.05-3.61, P=0.03) and the score of APACHE III (odd ratio 1.59, 95% confidence interval:1.01-2.50, P=0.04) appeared to be independent risk factors of the mortality in the patients with ARDS. Conclusions : The mortality was 71.9% of total 167 patients in this investigation using the definition of American-European Consensus Conference on 1992 year, and the respiratory insufficiency was the leading cause of the death. In addition, the numbers of organ failure and the score of APACHE III at the time of diagnosis of ARDS appeared to be independent risk factors of the mortality in the patients with ARDS.

• Journal of Nutrition and Health
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• v.6 no.1
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• pp.1-9
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• 1973

I. Subject of the Study: Studies on the economical nutrition supplement of cereal foods for the improvement in our notional eating habits. II. Purpose and Importance of the Study: 1. Our nation is confronted with the situation that the rice, a principal food, short of some essential amino acids, lysine and threonine, leads to imbalanced meals insufficient in the nutrient of protein, to bring many difficulties in the elevation of our national physique. 2. The shortage of even the rice imperfect in the nutrient of protein makes the import of lots of foreign rice inevitable. It is considered that the protein supplement and decrease in the consumption amount, of rice, is a serious key to the solution of our food difficulty, and then a way of the proetin supplement of rice through the addition of essential amino acid is to be rarely applied in the view of the our present finance and situation. 3. In the present experiment, therefore, it aims to the suggestion of an aspect of the improvement in our national eating habits guiding in the nutrition elevation which our nation can afford economically through the development of first, a way of the protein supplement by the mixture of cereals producted plentifully in our country, and second, a way of the decrease in the consumption amount and the improvement in the nutrition of rice through the substitution of the other cereals for rice. III. Contents of Scope of the Study: 1. Objects of the study: Objects of the study are the following three items; a) The nutrition supplement of rice through the mixture of cereals. Our nation makes mainly rice as a principal food, but practically many kinds of cereal are produced in our country. They contain different levels and qualities of each nutrient and they are different from one another in the kinds of essential amino acid consisting protein. For that reason, the mutual complement efficeincy of insufficient nutrients is observed through the mixture of cereals. b) The nutrition supplement of rice through the addition of superior protein sources to rice, a principal food. The development of rice as superior foods in the sense of nutrition is conducted through the risement in protein quality by the addition of protein sources in good quality, for example, fish flour (anchovy flour), egg powder, milk powder, and so on, and through the supplement of vitamins and minerals. c) The decrease in the consumption amount of rice through the substitution of the other cereals for rice, as a principal food. The compensation for the short amount of rice is made by the reduction in the consumption of rice through the discovery of a way of substitution of the other cereals for rice, as a principal food and of the settlement of problems in nutrition and finance subsequent to this. 2. Contents of the study: a) An ideal mixture-ratio of cereals is established for rats by feeding mixed foods(rice-barely or rice-wheat) containing 5%, 15%, 25%, 35% and 45% level of either barely or wheat. b) The nutritive value is determined in the whole subsititution of other foods for rice, and then, a way of the complement of over and under nutrients is devised. c) The ideal combination is investigated for rats through feeding mixed foods of main food, rice and supplement foods of protein sources, soy bean, fish flour, egg powder and milk Powder. d) According to results from the above three experiments, the concise functional test for men and the examination of economical property are made. 3. Scope of the study: a) The observation of the effect of each diet on the growth rate for rats. The growth rate of rats was observed for 15 groups of mixed foods of a main food, rice, and wheat flour, barley powder or soy bean powder, respectively, and 12 groups of wheat flour diets supplemented with $1{\sim}3%$ milk powder, and rice or wheat flour diets supplemented with 5% of milk powder, egg powder, fish flour or soy bean powder, respectively. b) The determination of food consumption. The food consumption was determined at weekly intervals for 27 kinds of diet described in a) item. c) The determination of food efficiency rate. The food efficiency rate for each diet was determined by calculation from the gained body weight and the food consumption amount at the same intervals described in b) item. d) The determination of protein efficiency rate. The protein efficiency rate for each diet was determined by calculation form gained body weight and the protein amount of the food consumption amount at the same intervals described c) item. e) The determination of the body component. The hematocrite and hemoglobin levels in the blood, total nitrogen in the serum, blood sugar, and lipids and glycogen in the liver were determined. f) The observation of nitrogen balance. As a means of the observation of nitrogen balance, the total nitrogen in the urine was determined. g) The analysis of economical property. The economical property was analyzed as the gained body weight to the amount equivalent to one won through the conversion of the food consumption amount into money. h) The functional test for men. The concise functional test for men was made in order to establish if the best diet for experimental animals can be applied to men. IV. Results of the Study: The national food product plan, nationwide nutritive enlightment and the improvement activities in our country eating habits, especially, mixed and powder food problems are to be significantly referred, and the following results must be applied. a) In the mixed foods of cereals, the mixed food of the rice-barley containing $5{\sim}15%$ level of barley is best in terms of nutrition. b) The addition of superior protein sources, egg, Bilk, soy bean, or fish, respectively to either rice or wheat flour makes a great risement in the nutritive value. c) The animal protein is more effective in the elevation of nutritive value of cereals. d) Rice takes the most nutritive operation and has the highest preference, among rice, wheat flour and barley. e) Wheat flour is more economical than rice in evaluation of the gained body weight to the regular money, and the addition of fish or soy bean is more economical than that of any other supplement food. But the above results are true of the range of nutrition and economical property. f) The study on the nutrition composition and barley will lead to the improvement in our national eating habits as mixed food of the rice-barley containing $5{\sim}15%$ level of barley is more nutritive. g) This study on the nutrition only for the growing animal can not be considered as a perfect and entire evaluation. Consequently, the perfect data for our national nutrition can be obtained from the experiment similar to this for the much longer period examining, in details, the growth rate, change of physical strength, mental and bodily change, average life span, and resistance ability to infectious diseases.

• Childhood Kidney Diseases
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• v.5 no.2
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• pp.136-146
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• 2001

Purpose : One of the most difficult problems in the care of children with nephrotic syndrome remains the occurrence of relapses, despite initial response to steroids. Constantinescu reported that rapidity of initial response to steroid therapy could predict fewer relapses in the first year. So we evaluated the changes in serum lipid abnormalities in children with corticosensitive nephrotic syndrome before steroid treatment and the correlation between serum lipid levels and renal function, days to remission. Methods . We analyzed the Medical records of children who were managed by us between October 1994 and August 2000. In 33 patients with corticosensitive nephrotic syndrome, we evaluated the correlation between serum lipid levels and renal function [Creatinine clearance(Ccr)] and proteinuria before steroid treatment, and days to remission defined as the third day when the patient's urine becomes protein free. Results : There were 21 males and 12 females. Median age at presentation was 6.4 years (range: 1.8-17.3 years). Median days to remission were 15.4 days (range 4-42 days) on Prednisolone $60mg/m^2$ daily. The increased levels of triglyceride, total cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol/HDL cholesterol, Lipoprotein(a) were observed. But the level of HDL cholesterol was not increased. Serum albumin was decreased a]id proteinuria was increased before steroid treatment. But Ccr was not decreased. There were negative correlation between serum albumin and total cholesterol (r = -0.5157, P<0.005), LDL cholesterol (r = -0.5543, P<0.005), total cholesterol/HDL cholesterol (r = -0.4506, P<0.01), lipoprotein(a) (r = -0.4570, P<0.025), apolipoprotein B (r = -0.5297, P<0.025), apolipoprotein B/apolipoprotein Al (r = -0.5851, P<0.01), apolipoprotein B/HDL cholesterol (r = -0.4961, P<0.05) before steroid treatment. There was no correlation between proteinuria and serum lipid profiles. Also Ccr and serum lipid profiles were not correlated. There was positive correlation between days to remission and HDL cholesterol (r = +0.4511, P<0.05), apolipoprotein B (r = +0.5190, P<0.05), apolipoprotein B/HDL cholesterol (r = +0.7169, P<0.005). Conclusions : This results reveal that HDL cholesterol, apolipoprotein B and apolipoprotein B/HDL cholesterol can be used as a predictive factor in corticosensitive nephrotic syndrome. We could not determine the significant level of these lipids for insufficient patients number, but these level may predict future relapses of corticosensitive nephrotic syndrome patients and thus may allow to better management and treatment protocols. More data and long term follow up studies should be needed. (J Korean Soc Pediatr Nephrol 2001;5 : 136-46)

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.11-19
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• 1999

Purpose: MCNS is found in approximately $85\%$ of the idiopathic nephrotic syndrome in children and shows good prognosis with initial steroid therapy. MCNS most commonly appears between the ages of 2 and 10 yr. But the incidence and prognosis in adolescent MCNS are different from those found in young children; the prognosis and the response to therapy is unfavorable with increasing ages. So we compared the prevalence and the clinical manifestations of adolescent MCNS with that of childhood MCNS for management of adolescent MCNS. Methods: We conducted a retrospective study with a review of histopathologic findings and clinical manifestations of the 216 cases with MCNS which were divided into children group and adolescent group by their age of onset; under 12 years(childhood) and between 12-18 years(adolescent). Results: 1) The number of childhood idiopathic nephrotic syndrome was 245 cases, and that of adolescent idiopathic nephrotic syndrome was 55 cases. 188 cases($77\%$) showed MCNS, 30 cases($12\%$) FSGS, 4 cases($1.6\%$) MSPCN in childhood idiopathic nephrotic syndrome; 28 cases($51\%$) showed MCNS, 12 cases($22\%$) FSGS in adolescent idiopathic nephrotic syndrome. 2) The mean onset age was $7.53{\pm}5.5$ years, and the male to female ratio was 3.8:1 in childhood onset and 2.5:1 in adolescent onset with male predominance. 3) Hematuria was associated with $17\%$ of childhood onset and $39.3\%$ of adolescent onset disease(P=0.005). Hypertension appeared in $0.5\%\;and\;7\%$ in each group without significant difference between the groups. 4) 24 hour urine protein, SPI, albumin, BUN, cholesterol level showed no significant difference. 5) The response of childhood onset and adolescent onset MCNS to steroid therapy showed complete remission in $11.7\%\;&\;14.7\%$, infrequent relapsing in $29.2\%\;&\;28.5\%$, frequent relapsing in $23.9\%\;&\;14.7\%$, steroid dependent in $21.8\%\;&\;28.6\%$ each. Steroid resistant showed $13.3\%\;&\;14.7\%$ with no significance. 6) Immunosuppresant therapy was performed $57\%$ in childhood onset and $65\%$ in adolescent onset. 7) Mean number of relapse and duration from onset to first relapse showed no significance between two groups. Conclusion : Our results indicate that the incidence of hematuria, the rate of steroid dependent and frequent relapsing, and the recurrence rate were higher in adolescent MCNS; showed poorer steroid responsiveness and prognosis. Our data also point to the need for a more aggressive therapy to treat and make recommendations for the adolescent population as a whole.

• The Journal of Korean Medicine
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• v.15 no.2 s.28
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• pp.9-27
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• 1994

This study is to analyze of senile disease status and the social problem according to increased old ages, and then to find distributions of old man's diseases and health status efficiency of oriental-occidental contemporary health examination. And it is the first oriental-occidental contemporary health examination of old man performed by JeonJu Woosuk University Oriental Medicine Hospital and Woosuk-Clinic in nation. Methods The objects in this research are 641's old man of KimJe Gun's over 60's years performed medical examination at JeonJu Woosuk University Oriental- Mmedicine-Hospital and Woosuk-Clinic by oriental-occidental medical contemporary exam., from 1994, 24th June till 1994. 13th July. The 1st occident medical examination methods were consisted of chest x-ray check. blood and urine exam., measurement of blood pressure, visual power and audiometry. The Oriental medical examination methods were consisted of four diagnostics (望,聞,問,切), present illness. chief complaint, past history, families history, social history by question and SA Sang constitution test index. The results and conclusions The results and conclusions are the next: 1. In order of distribution. the athletic disease (75.8%),the digestive disease(43.4%), the circulatory disease(41.5%), the respiratory disease(22.3%), EENT disease(8.1%), the endocrinopathy(5.6%), and the genito-urinary disease(5.3%) are the results of the object about 641's old man, by the oriental-occidental medicine's contemporay exam. 2. Distribution of disease distiction are lumbago. gastritis and peptic ulcer. knee joint pain. heart disease. hypertension. chronic bronchitis. asthma. anemia. DM. Tbc. visual disturbance. CVA. etc in order. 3. Disease distribution according to age is almost high incident in 60-75years. Disease incidence is decreased except E.E.N.T disease in over 76years. 4. The relationships of disease and family history are: the 25.0% of CVA pts. has family history and the 11.6% of hypertension pts has family history. so they showed high relative family history. In addition the 5.6% of TBC pts. and the 2.6% of DM pts. have family history. 5. The relationships of disease and drinking are: Drinking proportion is the 36.4% in respiratory disease pts. the 34.7% in hypertension pts. the 33.3% in heart disease pts.. the 28.4% in digestive disease pts.. but because of no surveying drinking amount we can't know the absolut relationships of disease and drinking. 6. The relationships of Disease and smoking are: Smoking proportion is the 44.1% in respiratory disease pts.. the 38.0% in Heart disease pts.. the 29.8% in Hypertension pts.. but because of no surveying of smoking amount. we can't know the absolut relationships of disease and smoking. 7. Distribution of Sasang constitution is : Tae-eum-in 44.8%. So-yang-in 30.7%. So-eum-in 24.6%. Tae-yang-in 0.0%. And disease distribution of Sasang constitution distinction is ; Tae-eum-in has high incidence of circulation disease(50.0%) and respiratory disease(23.1%).So-yang-in has high incidence of athletics disease(77.7%) and EENT disease(12.2%), So-eum-in has high incidence of digestive disease(65.8%). 8. Distribution of abnormal result in occidental medical examination and oriental-occidental contemporal exam result is considerably different. This is the reason of needing oriental medicine exam, for characteristics of Senile. I think that the oriental-occidental contemporary examination in old man is much more effecient than only occident medical examination. This oriental-occidental contemporary examination has many defects because it is the first practice. To participate in the public health program efficiently. I think that we must improve lots of problems and present the model of the oriental-occidental contemporary examination and the project of oriental medicine's for public health.

• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.