• 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 Weed Science
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• v.16 no.4
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• pp.264-281
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• 1996

As a consequence of wide use of herbicides, Eleocharis kuroguwai Ohwi became a dorminant problem weed for rice cultivation in Korea. To understand the establishment of the weed, experiments on physio-ecological characteristics were carried out sprouting and occurrence, the results could be summarized as follows: Sprouting percentage remained 68 to 73% until the time of field emergence, indicating many of the them are still dormant. The proportion of the dormant tubers were greater for the smaller than the bigger tubers. Apical dominance was apparent in sprouting, with 84% of tuber sprouted from only one of the apical buds. Tubers sprouted from 2 or 3 buds were less than 20%, and were mostly from the bigger tubers. When the shoot growth was compared, by controlling the others, ones from apical and the next 3 buds showed similar vigorous growth, but the later ones showed poorer growth. For the longevity of tubers, deep soil storage appeared to be better than storage in temperature controlled room to 2~$3^{\circ}C$. Emergence of E. kuroguwai was better in clay soil than in sand, and the possible depth for emergence in clay soil appeared to be up to 21cm, but was 15cm in sand. When tubers were exposed to salt solutions before emergence tests, E. kuroguwai appeared to be much sensitive to salts than S.planiculmis. Among the tubers formed in previous year, 12.7% remained still viable until the end of next crop season, but with relatively strong dormancy. The first emergence was about 10 days after planting at ordinary cropping seasons, and the days to the maximum shoot number stage were 60~90 from planting. The duration was extended at early transplanting, and shoot number, leaves per shoot, and tubers developed per plant were also greater at early plantings. The 6th order offshoots were developing when E. kuroguwai was planted at early season. When planted at later seasons, generation and the number of offshoots was reduced planted at early season. When planted at later seasons, generation and the number of offshoots was reduced and the number of tubers, runner and rhizome lengths was also reduced.

• Economic and Environmental Geology
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• v.51 no.3
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• pp.213-222
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• 2018

Metasediment-hosted Pb-Zn mineralized zone has been found in Dyusembay of Kazakhstan. Its petrological properties, metal index, alteration index and redox-sensitivity are compared with those of SEDEX type deposit. Mineralization is developed along foliation of host rock (graphitic phyllite) and controlled by folds and faults; major ore minerals including pyrite, pyrrhotite, sphalerite, and galena are disseminated or interlayered with fine-grained quartz. The margin of the mineralized zone is metamorphosed accompanying sericite and chlorite. Hydrothermal brecciation and Pb-Zn mineralization formed in quartz-calcite stockworks are confirmed at the around of Maytyubin granitoid intrusions. The mineralization is classified into three types according to those of occurrence, paragenesis, chemical composition and isotopic characteristics. Type 1 whose fine-grained pyrite, pyrrhotite and sphalerite are formed in parallel yet discontinuous to well-developed foliations of the host rock; its geochemistry is similar to those of the earlier stage in SEDEX-type mineralization. In case of type 2, the ore minerals of which are concentrated being parallel to a foliation by regional metamorphism, and most of them associated with quartz and muscovite (${\pm}$ biotite) paragenetically. Type 3 is formed in the hydrothermal breccia zone whose ore minerals are controlled by foliation and breccia and developed in quartz ${\pm}$ calcite veins having a form such as stratification, stockwork or veinlets. Host rocks in the mineralized zone indicate homogeneous metamorphic grade and there is no specific alteration zonation. Also, all types (type 1, type 2, and type 3) represent similar REEs patterns, it can be interpreted that these are originated from a same source. Sulphides occurred in mineralized zone indicate a limited range of sulphur isotope values (type 2, ${\delta}^{34}S=-13.3{\sim}-11.7$‰; type 3, ${\delta}^{34}S=-13.9{\sim}-8.2$‰), and a result of geothermometry presents different temperature ranges: type 2($251{\pm}38^{\circ}C{\sim}277{\pm}40^{\circ}C$); type 3($360{\pm}2^{\circ}C$ to $537{\pm}29^{\circ}C$). It is estimated to be due to the effect of metamorphism and Maytyubin granitoid intrusions, respectively. In addition, ternary chart of thorium, scandium, and zircon for discrimination of tectonic setting and redox sensitivity using V/Mo values indicate that hydrothermal sediments put on reduction environment after precipitation, before being affected by metamorphism and intrusion activity. Geochemical data are plotted on a distal trend of SEDEX-type with discrimination plot using SEDEX index. As a result, petrological-geochemical properties demonstrate that Dyusembay Pb-Zn mineralized zone is comparable to distal-type of SEDEX deposit.

• Journal of Animal Science and Technology
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• v.46 no.2
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• pp.261-272
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• 2004

This study was conducted to investigate indices affecting composts maturity for swine manure compost produced in a commercial composting facility with air-forced from the bottom. The composting was made of swine manure mixed with puffing rice hull(6: 4) and turned by escalating agitator twice a day. Composting samples were collected periodically during a 45-d composting cycle at that system, showing that indices of Ammonium-N to Nitrate-N ratio were sensitive indicators of composting quality. Pile temperature maintained more than 62$^{\circ}C$ and water contents decreased about 20% for 25days of composting. A great variety and high numbers of aerobic thermophilic heterotropic microbes playing critical roles in stability of composts have been examined in the final composts, sbowing that they were detected $10^8$ to $10^{10}$ $CFUg^{-1}$ in mesophilic bacteria, $10^3$ - $10^4$ in fungi and $10^6$ - $10^8$ in actinomycetes, respectively. The results of this study for detennining a factor affecting compost stability evaluations based on composting steps were as follows; 1. Ammonium-N concentrations were highest at the beginning of composting, reaching approximately 421mg/kg. However Ammonium-N concentrations were lower during curing, reaching approximately l04mg/kg just after 45 day. The ratio between $NH_4-N$ and $NO_3-N$ was above II at the beginning of composting and less than 2 at the final step(45 day). 2. Seed germination Index was dependent upon the compost phytotoxicity and its nutrition. The phytotocity caused the GI to low during the period of active composting(till 25 days of composting time) depending on the value of the undiluted. After 25 days of composting time, the GI was dependent upon compost nutrition. The Gennination index of the final step was calculated at over 80 without regard to treatments. 3. E4: E6 ratio in humic acid of composts was correlatively decreased from 8.86 to 6.76 during the period of active composting. After 25 days of composting time, the E4: E6 was consistently decreased from 6.76 to 4.67($r^2$ of total composting period was 0.95). 4. Water soluble carbon had a tendency to increase from 0.54% to 0.78%during the period of active composting. After 25 days of composting time, it was consistently decreased from 0.78% to 0.42%. Water soluble nitrogen increased from 0.22% to 0.32% during the period of 15 days after initial composting while decreased from 0.32% to 0.21% after 15days of composting. In consequence, the correlation coefficient($r^2$) between water soluble carbon and water soluble nitrogen was 0.12 during the period of active composting mule was 0.50 after 25 days of composting time