• Korean Journal of Radiology
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• v.25 no.2
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• pp.179-188
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• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• The Journal of the Korean life insurance medical association
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• v.2 no.1
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• pp.135-142
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• 1985

For the past 10 years, the socioeconomic status of our country was markedly improved. Accordingly, our foodintake patterns and other alt parts are preparing to blance with developed countries. Especially, be westernizing or improving our foodintake patterns, we intake much fat diet(animal food) while our physical activities decrease and alcohol consumtion's population, smoking population gradually increase. For such reasons, the population of obese tendency and cardiovascular diseases are increased. According to recent reports, among all death causes in our country, cardiovascular diseases(hypertension, hypertensive cardiovascular diseases, ischemic heart diseases) occupyd top rank, we know. I(the author) studied the inter-relation between serum cholesterol level which is the important factor of the cardiovascular diseases and essential hypertension liver diseases, hyperglycemia, some cardiac problems which are main decline causes in life insurance's medical assessment, and body weight distribution. Studied samples were selected on 4,313 cases(male; 1,791, female; 2,522) who were tested liver function test from June, 11th, 1980 to Dec., 31st, 1983 on our medical department's laboratory. I selected two groups in those cases: one group was serum cholesterol level 180mg/dl over(11% of whole LFT examed cases: No=502 cases), the other group was serum cholesterol level 120-160mg/dl(No= 502 cases). For convenience, the group of serum cholesterol level 180mg/dl over was "A" the other group was "B", I described. All examed persons of LFT were resident m Tae-Jon city in that time. On the result, 1) Decline rate is 10.5% on the "A" group, 5.9% on the "B" group. "A" group reveals 1.8 times higher than "B" group. 2) On decline causes, Essential hypertension is 4.0 times higher on the "A" group than "B", liver function's abnormalities are 2.0 times higher on "A" group than "B" and other diseases are same on "A" and "B". On the "A" group, essential hypertension is considerably higher than "B" group. 3) On the body weight distribution, the cases of 70kg(B.W.) over is 19.7% on "A", 10.6% on "B" group. Obese tendency is 1.8 folds higher on "A" group than "B" group. Studing the result, we find high serum cholesterol concentration is closely related with essential hypertension, obese tendency and liver function's abnormalities on the life insurance's medical examination part, also. On the future, we will more carefully consider the serum cholesterol concentration on our medical examnination and assessment of life insurance, I think.

• Journal of Radiation Protection and Research
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• v.31 no.2
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• pp.69-89
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• 2006

Biological mechanisms for ionizing radiation effects are different at low doses than at high doses. Radiation hormesis involves low-dose-induced protection and high-dose-induced harm. The protective component is associated with a reduction in the incidence of cancer below the spontaneous frequency, brought about by activation of defensive and repair processes. The Linear No-Threshold (LNT) hypothesis advocated by the International Commission on Radiological Protection (ICRP) and the Biological Effects of ionizing Radiation (BEIR) Report VII for cancer risk estimations Ignores hormesis and the presence of a threshold. Cancer incidences significantly less than expected have been found in a large number of epidemiological studies including, airline flight personnel, inhabitants of high radiation backgrounds, shipyard workers, nuclear site workers in scores of locations throughout the world, nuclear power utility workers, plutonium workers, military nuclear test site Participants, Japanese A-bomb survivors, residents contaminated by major nuclear accidents, residents of Taiwan living in $^{60}Co$ contaminated buildings, fluoroscopy and mammography patients, radium dial painters, and those exposed to indoor radon. Significantly increased cancer was not found at doses <200 $mSv^*$. Evidence for radiation hormesis was seen in both sexes for acute or chronic exposures, low or high LET radiations, external whole- or partial body exposures, and for internal radionuclides. The ubiquitous nature of the Healthy Worker Effect (HWE)-like responses in cellular, animal and epidemiological studies negates the HWE as an explanation for radiation hormesis. The LNT hypothesis is wrong and does not represent the true nature of the dose-response relationship, since low doses or dose-rates commonly result in thresholds and reduce cancer incidences below the spontaneous rate. Radiation protection organizations should seriously consider the cost and health implications of radiation hormesis.

• The Korean Journal of Nuclear Medicine
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• v.30 no.4
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• pp.507-515
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• 1996

Background : Potassium channel opener (K-opener) opens ATP-sensitive K'-channel located at cell membrane and induces potassium efflux from cytosol, resulting in intracellular hyperpolarization. Newly synthesized K-opener is currently examined for pharmacologic potency by means of rubidium release test from smooth muscle strip pre-incubated with Rb-86. Since in-vivo behavior of thallium is similar to that of rubidium, we hypothesized that K-opener can alter T1-201 kinetics in vivo. Purpose : This study was prepared to investigate the effects of pinacidil (one of potent K-openers) on the T1-201 uptake and clearance in cultured myocyte, and in-vivo biodistribution in mice. Methods : Spontaneous contracting myocytes were prepared to imitate in-vivo condition from 20 hearts of 3-5 days old Sprague-Dawley rat and cultured for 3-5 days before use ($5{\times}10^5$ cells/ml). Pinacidil was dissolved in 10% DMSO solution at a final concentration of 100nM or l0uM and was co-incubated with T1-201 in HBSS buffer for 20-min to evaluate its effect on cellular T1-uptake, or challenged to cell preparation pre-incubated with T1-201 for washout study. Two, 40 or $100{\mu}g$ of pinacidil was injected intravenously into ICR mice at 10 min after $5{\mu}Ci$ T1-201 injection, and organ uptake and whole body retention rate were measured at different time points. Results : Co-incubation of pinacidil with T1-201 resulted in a decrease in T1-201 uptake into cultured myocyte by 1.6 to 2.5 times, depending on pinacidil concentration and activity of T1-201 used. Pinacidil enhanced T1-201 washout by 1.6-3.1 times from myocyte preparations pre-incubated with T1-201. Pinacidil treatment appears to be resulted in mild decreases in blood and liver activity in normal mice, in contrast, renal and cardiac uptake were mildly decreased in a dose dependent manner. Whole body retention ratios of T1-201 were lower at 24 hour after injection with $100{\mu}g$ of pinacidil than control. Conclusion : These results suggest that treatment with K-opener may affect the interpretation of T1-201 myocardial images, due to decreasing thallium accumulation and enhancing washout from myocardium.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.1
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• pp.22-27
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• 2004

In the present study, the protective effects of Artemisia capillaris (AC) on the DNA damage induced by $^{60}$ Co ${\gamma}$-rays were evaluated using alkaline single-cell gel electrophoresis (SCGE, comet assay) in the mouse peripheral lymphocytes and micronuclei (MN) formation test in the Chinese hamster ovary (CHO) cells. We also investigated the effect of AC on 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the mouse liver and thymus exposed to ${\gamma}$-ray, The tail moment and the frequency of MN, which were markers of DNA damage in the SCGE and MN formation test, were decreased in the groups treated with AC extract before exposure to 200 cGy of ${\gamma}$-ray. We also observed its activities, lowering 8-OHdG level, an index of oxidative DNA damage, in the groups treated with AC extract before whole body ${\gamma}$-irradiation (800 cGy). It is plausible that scavenging of free radicals by AC may have played an important role in providing the protection against the radiation-induced damage to the DNA. These results indicated that AC protects the DNA damage induced by ${\gamma}$-rays and might be a useful radioprotector, especially since it is a relatively nontoxic product.

• Korean Journal of Hazardous Materials
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• v.2 no.1
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• pp.18-26
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• 2014

We analyzed the demand of competent authorities requiring adequate technical information for initial investigation of chemical accidents. Reflecting technical reports on chemical accident response by environmental agencies in the U.S. and Canada, we presented information on environmental diffusion and toxic effects available for the first chemical accident response. Hydrogen fluoride may have the risk potential to corrode metals and cause serious burns and eye damages. In case of inhalation or intake, it could have severe health effects. The substance itself is inflammable, but once heated, it decomposes producing corrosive and toxic fume. In case of contact with water, it can produce toxic, corrosive, flammable or explosive gases and its solution, a strong acid, may react fiercely with a base. In case of hydrogen fluoride leak, the preventive measures are to decrease steam generation in exposed sites, prevent the transfer of vapor cloud and promptly respond using inflammable substances including calcium carbonate, sodium bicarbonate, ground limestone, dried soil, dry sand, vermiculite, fly ash and powder cement. The method for fire fighting is to suppress fire with manless hose stanchions or monitor nozzles by wearing the whole body protective clothing equipped with over-pressure self-contained breathing apparatus from distance. In case of transport accident accompanied with fire, evacuation distance is 1,600m radius. In cae of fire, fire suppression needs to be performed using dry chemicals, CO₂, water spray, water fog, and alcohol-resistance foam, etc. The major symptoms by exposure route are dyspnoea, bronchitis, chemical pneumonia and pulmonary edema for respiration, skin laceration, dermatitis, burn, frostbite and erythema for eyes, and nausea, diarrhea, stomachache, and tissue destruction for digestive organs. In atmosphere, its persistency is low, and its bioaccumulation in aquatic organism is also low.

• Applied Biological Chemistry
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• v.21 no.3
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• pp.150-184
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• 1978

Nutritional characteristics and physio-chemical properties of mycelial growth and fruitbody formation of oyster mushroom(Pleurotus ostreatus)in synthetic media, the curtural condition for the commerical production in the rice straw and poplar sawdust media, and the changes of the chemical components of the media and mushroom during the cultivation were investigated. The results can be summarized as follows: 1. Among the carbon sources mannitol and sucrose gave rapid mycelial growth and rapid formation of fruit-body with higher yield, while lactose and rhamnose gave no mycelial growth. Also, citric acid, succinic acid, ethyl alcohol and glycerol gave poor fruit-body formation, and acetic acid, formic acid, fumaric acid, n-butyl alcohol, n-propyl alcohol and iso-butyl alcohol inhibited mycelial growth. 2. Among the nitrogen sources peptone gave rapid mycelial growth and rapid formation of fruit-body with higher yield, while D,L-alanine, asparatic acid, glycine and serine gave very poor fruit-body formation, and nitrite nitrogens, L-tryptophan and L-tyrosine inhibited mycelial growth. Inorganic nitrogens and amino acids added to peptone were effective for fruit-body growth, and thus addition of ammonium sulfate, ammonium tartarate, D,L-alanine and L-leucine resulted in about 10% increase fruit-body yield. L-asparic acid about 15%, L-arginine about 20%, L-glutamic acid, and L-lysine about 25%. 3. At C/N ratio of 15.23 fruit-body formation was fast, but the yield decreased, and at C/N ratio of 11.42 fruit-body formation was slow, but the yield increased. Also, at the same C/N ratio the higher the concentration of mannitol and petone, the higher yield was produced. Thus, from the view point of both yield of fruit-body and time required for fruiting the optimum C/N ratio would be 30. 46. 4. Thiamine, potassium dihydrogen phosphate and magnecium sulfate at the concentration of $50{\mu}g%$. 0.2% and 0.02-0.03%, respectively, gave excellent mycelial and fruit-body growth. Among the micronutrients ferrous sulfate, zinc sulfate and manganese sulfate showed synergetic growth promoting effect but lack of manganese resulted in a little reduction in mycelial and fruit-body growth. The optimum concentrati on of each these nutrients was 0.02mg%. 5. Cytosine and indole acetic acid at 0.2-1mg% and 0.01mg%, respectively, increased amount of mycelia, but had no effect on yield of fruit-body. The other purine and pyrimidine bases and plant hormones also had no effect on mycelial and fruit-belly yield. 6. Illumination inhibited mycelial growth, but illumination during the latter part of vegetative growth induced primordia formation. The optimum light intensity and exposure time was 100 to 500 lux and 6-12 hours per day, respectively. Higher intensity of light was injurous, and in darkness only vegetative growth without primordia formation was continued. 7. The optimum temperature for mycelial growth was $25^{\circ}C$ and for fruit-body formation 10 to $15^{\circi}C$. The optimum pH range was from 5.0 to 6.5. The most excellent fry it-body formation were produced from the mycelium grown for 7 to 10 days. The lesser the volume of media, the more rapid the formation of fruit-body; and the lower the yield of fruit-body; and the more the volume of media, the slower the formation of fruit-body, and the higher the yield of fruit-body. The primordia formation was inhibited by $CO_2$. 8. The optimum moisture content for mycelial growth was over 70% in the bottle media of rice straw and poplar sawdust. 10% addition of rice bran to the media exhibited excellent mycelial growth and fruit-body formation, and the addition of calciumcarbonate alone was effective, but the addition of calcium carbonate was ineffective in the presence of rice bran. 9. In the cultivation experiments the total yield of mushroom from the rice straw media was $14.99kg/m^2$, and from the sawdust media $6.52kg/m^2$, 90% of which was produced from the first and second cropping period. The total yield from the rice straw media was about 2.3 times as high as that from the sawdust media. 10. Among the chemical components of the media little change was observed in the content of ash on the dry weight basis, and organic matter content decreased as the cultivation progressed. Moisture content, which was about 79% at the time of spawning, decreased a little during the period of mycelial propagation, after which no change was observed. 11. During the period from spawning to the fourth cropping about 16.7% of the dry matter, about 19.3% of organic matter, and about 40% of nitrogen were lost from the rice straw media; about 7.5% of dry mallet, about 7.6% of organic matter, and about 20% of nitrogen were lost from the sawdust media. For the production of 1kg of mushroom about 232g of organic matter and about 7.0g of nitrogen were consumed from the rice straw media; about 235g of organic matter and about 6.8g of nitrogen were consumed from the sawdust media, 1㎏ of mushroom from either of media contains 82.4 and 82.3g of organic matter and 5.6 and 5.4g of nitrogen, respectively. 12. Total nitrogen content of the two media decreased gradually as the cultivation progressed, and total loss of insoluble nitrogen was greater than that of soluble nitrogen. Content of amino nitrogen continued to increase up to the third cropping time, after which it decreased. 13. In the rice straw media 28.0 and 13.8% of the total pentosan and ${\alpha}$-cellulose, respectively, lost during the whole cultivation period was lost during the period of mycelial growth; in the sawdust media 24.1 and 11.9% of the total pentosan and ${\alpha}$-cellulose, respectively, was lost during the period of mycelial growth. Lignin content in the media began to decrease slightly from the second cropping time, while the content of reduced sugar, trehalose and mannitol continued to increase. C/N ratio of the rice straw media decreased from 33.2 at spawining to 30.0 at ending; that of the sawdust media decreased from 61.3 to 60.0. 14. In both media phosphorus, potassium, manganese and zinc decreased, at magnesium, calcium and copper showed irregular changes, and iron had a tendency to be increased. 15. Enzyme activities are much higher in the rice straw media than in the sawdust media. CMC saccharifying and liquefying activity gradually increased from after mycelial propagation to the second cropping, after which it decreased in both media. Xylanase activity rapidly and greatly increased during the second cropping period rather than the first period. At the start of the third cropping period the activity decreased rapidly in the rice straw media, which was not observed in the sawdust media. Protease activity was highest after mycelial propagation, after which it gradually decreased. The pH of the rice straw media decreased from 6.3 at spawning to 5.0 after fourth cropping; that of the sawdust media decreased from 5.7 to 4.9. 16. The contents of all the components except crude fibre of the mushroom from the rice straw media were higher than those from the sawdust media. Little change was observed in the content of the components of mushroom cropped from the first to the third period, but slight decrease was noticed at the fourth cropping.

• Korean Journal of Poultry Science
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• v.35 no.2
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• pp.123-129
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• 2008

This study was conducted to investigate the effects of antibiotic and yeast supplemental high energy diet on growth performance, blood characteristics and carcass trait in broilers. Total of four hundred-eighty broilers were randomly allocated into three treatments with eight replications for five weeks. Dietary treatments included 1) CON (control; basal diet), 2) HED (high energy diet) and 3) YD (HED; yeast added to HED instead of virginiamycin, Sacchromyces cerevisiae, $15{\times}10^{10}$). During whole period, weight gain had high tendency in HED treatment. However, there were not significant among treatments (P>0.05). Feed intake was higher in YD treatment than others. However, there were not significant among each treatments (P>0.05). Feed/Gain ratio was significantly lower in HED treatment than others (P<0.05). In blood characteristics, RBC, WBC and lymphocyte were not significant (P>0.05) among treatments. Liver weigh, LW/BW ratio, leg meat weigh, LMW/BW ratio, breast meat weigh, BMW/BW ratio, abdominal fat weigh and AF/BW ratio were not significant (P>0.05). However, body weight was improved (P<0.05) in HED treatment. In conclusion, this experiment is shown that HED treatment affects Feed/Gain ratio and body weight at final period in broilers.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.535-563
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• 1993

New techniques for regenerating the destructed periodontal tissue have been studied for many years. Current acceptable methods of promoting periodontal regeneration alre basis of removal of diseased soft tissue, root treatment, guided tissue regeneration, graft materials, biological mediators. Platelet-derived growth factor (PDGF) is one of polypeptide growth factor. PDGF have been reported as a biological mediator which regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the possibility of using the PDGF as a regeneration promoting agent for furcation involvement defect. Eight adult mongrel dogs were used in this experiment. The dogs were anesthetized with Pentobarbital Sodium (25-30 mg/kg of body weight, Tokyo chemical Co., Japan) and conventional periodontal prophylaxis were performed with ultrasonic scaler. With intrasulcular and crestal incision, mucoperiosteal flap was elevated. Following decortication with 1/2 high speed round bur, degree III furcation defect was made on mandibular second(P2) and fourth(P4) premolar. For the basic treatment of root surface, fully saturated citric acid was applied on the exposed root surface for 3 minutes. On the right P4 20ug of human recombinant PDGF-BB dissolved in acetic acid was applied with polypropylene autopipette. On the left P2 and right P2 PDGF-BB was applied after insertion of ${\beta}-Tricalcium$ phosphate(TCP) and collagen (Collatape) respectively. Left mandibular P4 was used as control. Systemic antibiotics (Penicillin-G benzathine and penicillin-G procaine, 1 ml per 10-25 1bs body weight) were administrated intramuscular for 2 weeks after surgery. Irrigation with 0.1% Chlorhexidine Gluconate around operated sites was performed during the whole experimental period except one day immediate after surgery. Soft diets were fed through the whole experiment period. After 2, 4, 8, 12 weeks, the animals were sacrificed by perfusion technique. Tissue block was excised including the tooth and prepared for light microscope with H-E staining. At 2 weeks after surgery, therer were rapid osteogenesis phenomenon on the defected area of the PDGF only treated group and early trabeculation pattern was made with new osteoid tissue produced by activated osteoblast. Bone formation was almost completed to the fornix of furcation by 8 weeks after surgery. New cementum fromation was observed from 2 weeks after surgery, and the thickness was increased until 8 weeks with typical Sharpey’s fibers reembedded into new bone and cementum. In both PDGF-BB with TCP group and PDGF-BB with Collagen group, regeneration process including new bone and new cementum formation and the group especially in the early weeks. It might be thought that the migration of actively proliferating cells was prohibited by the graft materials. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• 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.