• 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.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.17 no.6
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• pp.511-522
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• 1984

The Nagdong is one of the biggest rivers in Korea, which is very important water source not only for tap water of Pusan city but also for the industrial water. Therefore, authors tried to check the water quality year by year. In this experiment one hundred and twenty water samples collected from August 1983 to July 1984 were analyzed bacteriologically and physiologically. Fifteen sampling stations were established between near Samrangjin and estuary of the river. To evaluate the water quality, temperature, pH, chloride ion, salinity, chemical oxygen demand (COD), electrical conductivity, nutrients, total coliform, fecal coliform, fecal streptococcus, viable cell count and bacterial flora were observed. The variation of water temperature was ranged $-1.5{\sim}29.0^{\circ}C$ (Mean value $13.9{\sim}16.5^{\circ}C$), it in spring was higher as $10{\sim}15^{\circ}C$ about $10^{\circ}C$ than in winter and it in autumm was very stabilized as about $20^{\circ}C$ at each station. The pH variation of the samples was ranged $6.68{\sim}9.15$. The range of concentration of chloride ion and salinity varied $7.4{\sim}l,020.5$ mg/l and $1.05{\sim}33.0\%0$, respectively. Especially, salinity of the 3rd water war was the higher than others as $25.76{\sim}31.58\%0$. COD was ranged $1.45{\sim}14.94$ mg/l and the lower part of the Nagdong River was heavily contaminated by domesitc sewage and waste water from the adjacent factor area. The range of electrical conductivity was $1.360{\times}10^2{\sim}5.650{\times}10^4{\mu}{\mho}/cm$ and that was by far higher the estuary than the upper. Concentration of nutrients were $0.008{\sim}0.040$ mg/l (Mean value $0.019{\sim}0.068$ mg/l) for $NO_2-N,\;0.038{\sim}5.253$ mg/l ($0.351{\sim}2.347$ mg/l) for $NO_3-N,\;0.100{\sim}2.685$ mg/l($0.117{\sim}1.380$ mg/l) for $NH_4-N,\;0.003{\sim}0.084$ mg/l($0.014{\sim}0.065$ mg/l) for $PO_4-P$ and $0.154{\sim}6.123$ mg/l ($1.165{\sim}3.972$ mg/l) for $SiO_2-Si$, respectively. Usually nutrients contents of the water in the upper part(included station 1 to 5) were higher than those of the estuarine area. The bacterial density of the samples ranged 7.3 to 460,000/100 ml for total coliforms, 3.6 to 460,000/100 ml for fecal coliform, $0{\sim}46,000/100ml$ for fecal streptococcus and $<30{\sim}1.2{\times}10^5/ml$ for viable cell count. Composition of coliform was $28\%$ Escherichia coli group, $18\%$ Citrobacter freundii group, $31\%$ Enterobacter aerogenes group and $22\%$ others. Predominant species among the 659 strains isolated from the samples were Pseudomonas spp. ($42\%$), Flavobacterium spp. ($20\%$) and Moraxella spp. ($12\%$).

• Journal of Korean Society of Forest Science
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• v.19 no.1
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• pp.1-23
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• 1973

The results of ground vegetation experiment conducted at completely denuded forestland in the mudstone region are summerized as follows: On the reaults of soiling quantity the effect of soiling was observed where depth of soiling over 10 cm was practiced, and a plot where treated with 15cm soiling and without fertilizer showed poor growth and it was even worser than the plot where soiling was practiced only 1 cm in thikness but applied adequate amount of fertilizers. The depth of slits between 30cm and 40cm showed no significant difference in the effect. A plot where covered with vegetation bag showed somewhat better results in seed loss and early growth but no differences observed in the fall result over the none covered plot. And then, it is recommendable to have soiling over 10cm in thikness with slit of 30cm and 30cm in depth and to apply 30 gram of fertilizer (22;22:11, 50 gram) per slit. On various soiling materials trial there were no striking differences in the effect of soiling between weathered granite soil, wheathered tuffs soil and weathered mudstone soil. In the treatment with various green materials, a plot treated with straw mat showed a significant difference at 1 percent. The results show that weathered mudstone soil is effective to use as soiling materials and straw mat treatment was better. On forest fertilization trial, in the mudstone region where red and black pine trees already existing at a rate of 2,000-3,000 trees per hectare had applied 110kg of compound fertilizers (9:12:3 and 22:22:11) per hectare basis in terms of plant nutrient. As a result, the difference in effect between the compound fertilizers was not found however the leaf color and leaf length of the fertilizer added plot showed darker and longer at 30 percent over the no fertilizer received plot. Compound fertilizers, 14:37:12 and 9:12:3 were applied to alder trees at a rate of 20 gram and 40 gram per tree in terms of plant nutrient and a remarkable growth accelerantion was observed where 40 grams of plant nutrient applied. The effect difference between the compound fertilizers was not found. On investigation of tree root elongation, forty years old red pine trees showed only 15cm tap root elongation through mudstone while black pine had 23 cm tap root elongation. The total length of supporting root elongtion of red and black pines showed 20 and 13 meters, respectively. The tap roots of Black locusts were not able to elongate through mudstone, however, the supporting roots tended to develop to the underneath of pine tree where some moisture content is available. Black locusts And grown on the residual soil of mudstone normally die between 8 to 10 years. The red pine trees show flat in tree shape while black pine had triangle in the shape. With the results it can be said that in an artificial reforestation in denuded forest land of the mudstone region the adequate slit and enough amount of fertiliizer application must be provided for the succesful performance of the program. On integrated experimental results of 1972. for the establishment of ground vegetation on the completely denuded forest land in mudstone region, soiling could be effectively practiced with weathered mudstone soil and it would not specially necessiate to have either weathered granite or tuffssoil for the soiling. And the soiling depth should be more than 10 cm in thickness. Among green materials used the straw mat proved to be the most effective reatment. Three major factors which enable to establish ground vegetation by the shortest period of time: A. Physical improvement of soil is necessary to breakdown of the horizontal cracks sushas Slit, contour line plot, seeding hole and etc., and soiling with weathered mudstone soil. B. Chemical improvement of soil: is needed sufficient amount of fertilizer application 300~400kg ha, $N+P_2O_5+K_2O$), and increased production of ground covering and expedite resolution of the vegetation (ground vegetation, fallen leaves and twigs). C. Complete establishment of the basic structure for the erosion control (Prevention of surface soil erosion)

• KOREAN JOURNAL OF CROP SCIENCE
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• v.3
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• pp.49-82
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• 1965

For the stable and high yields of low-land rice in Korea, the characteristics of rice plant for the vegetative and physiological responses, plant type formation, and yield components have been studied in order to obtain the fundamental data for the improvement of cultural practices, especially for the ideal fertilizer application. Furthermore the environmental conditions in Korea including temperatures, light, precipitation, and soil conditions have been compared in the broad sense with those in Japan, and the application of nitrogen, phosphorus, potassium, silicate and other micro-nutrients were described in relation to the characteristics of environmental conditions for the improvement of fertilizer application. 1. The average yield of polished-rice per 10 are in Korea is about 204 kg and this values are much less than those in Japan and Taiwan where they produce 77% to 13% more than in Korea. The rate of yield increase a year in Korea is 4.2 kg, but in Japan and Taiwan the rates of yield increase a year are 81 % and 62%, respectively. It was also found that the coefficient of variation of yield is 7.7% in Korea, 6.7% in Japan and 2.5% in Taiwan. This means that the stability of producing rice in Korea is very low when compared with those in Japan and Taiwan. 2. It was learned from the results obtained from the 'annual yield estimation experiment' that there are big differences in the respect of plant type formations between rice crops grown in Japan and Korea. The important differences found were as follows: (1) The numbers of spikelets per 3.3 square meters are 891 in Korea and 1, 007 in Japan(13% more than in Korea). (2) The numbers of tillers per 3.3 square meters at the stage of maximum tillering are 1, 150 in Korea, but in Japan they showed 19% more than in Korea. (3) The ratio of effective tillers to total tillers is 77.5% in Korea and 74.7% in Japan, which seems to be higher in Korea than in Japan. But the ratio in Korea is very low when considered the numbers of total tillers in both countries. (4) The ratio of grain to straw is 85.4% in Korea and 96.3% in Japan. 3. The average temperatures during the growing season at the area of Suwon, Kwangjoo and Taegu are almost same as those in the district of Jookokoo(Fookoo yama) in Japan, i.e., the temperatures during the rice-growing season in Korea are similar to those in the southern-warm regions of Japan. 4. Considering the minimum temperatures at the stage of limiting transplanting, 13$^{\circ}C$, the time of transplanting might be 30 to 40 days earlier than presently practicing transplanting time, which comes around June 10. 5. The temperatures during the vegetative growth in Korea were higher than those temperatures that needed in the protein synthesis which ate the main metabolism during this stage. However, the temperatures at the time of reproductive growth was lower than the temperatures that needed in the sugar assimilation which is main metabolism in this stage. In this point of view, it might be considered that the proper time of growing rice plant in Korea would be rather earlier. 6. The temperatures and the day light conditions at the time of first tillering stage of rice plant, when planted as presenting transplanting practices, are very satisfactory, but the poor day light length, high temperatures and too wet conditions in the time of last-tillering stage(mid or last July) might cause the occurrence of disease such as blast. 7. The heading stage of rice plants at each region through nations when planted as presently practicing method comes when the day light length is short. 8. It was shown that the accumulated average air-temperature at the time of maturing stage was not enough and the heading time was too late, when considered the annual deviations of mean temperatures and low minimum temperatures. 9. The nitrogen content of each plant part at the each growing stage was very high at the stage of vegetative growth when compared with the nitrogen content at the stage of reproductive growth after heading. In this respect it was believed to be important to prevent the nutrient shortages at the reproductive stages, especially after the heading. 10. The area of unsatisfactory irrigation paddy fields and natural rain-fed paddy fields are getting reduced in Korea. The correlation between the rate of reducing unsatisfactory irrigation and natural rain-fed paddy fields and the rate of yield increase were computed. The correlation coefficients(r) between the area of unsatisfactory irrigation paddy fields and yield increase were +0.525, and between the natural rain-fed paddy fields and yield increase, +0.832 and between the unsatisfactory irrigation plus natural rain-fed paddy fields and yield increase, +0.84. And there were. highly significant positive correlations between natural rain-fed paddy fields and yield increases indicating that the less the area of natural rain-fed paddy fields, the greater the yields per unit area. 11. The results obtained from the fertilizer experiments (yield performance trials) conducted in both Korea and Japan showed that the yield of non-fertilized plots per 10 are was 231 kg in Korea and 360 kg in Japan. On the basis of this it might be concluded that the fertility of soil in Korea is lower than that in Japan. Furthermore it was. also found that the yields of non-nitrogen applied plots per 10 are were 236 kg in Korea and 383 kg in Japan. This also indicates that the yields of rice in Korea are largely depending on the nitrogen content in the soil. 12. The followings were obtained when the chemical natures of soils in both Korea and Japan were compared. (1) The content of organic matter, total nitrogen, exchangeable calcium, and magnesium in Korea were no more than the half those in Japan. (2) The content of N/2 chloride and soluble silicate in low-land soil were on the average lower in Korea. (3) The exchange capacity of bases in Korea was no more than half that in Japan. 13. It was also observed by comparing the soil nature of the soil with high yielding capacity with the soil with low yielding capacity that the exchange capacity of bases, exchangeable calcium and magnesium, potassium, phosphorus, manganese, silicate and iron were low in the soil with low yielding capacity. 14. The depth of furrow slice was always deeper in the soil with high yielding capacity, and the depth of furrow slice in Korea was also shallower than that in Japan. 15. Summarizing the various conditions mentioned previously and considering the effects of silicate and trace elements such as manganese and iron besides three elements on the physiological and plant type formation of rice crops, more realistic and more ideal fertilizing practices were proposed. proposed.