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Pharmacological Studies of Cefoperazone(T-1551) (Cefoperazone(T-1551)의 약리학적 연구)

  • Lim J.K.;Hong S.A.;Park C.W.;Kim M.S.;Suh Y.H.;Shin S.G.;Kim Y.S.;Kim H.W.;Lee J.S.;Chang K.C.;Lee S.K.;Chang K.C.;Kim I.S.
    • 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.

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Soil Classification of Paddy Soils by Soil Taxonomy (미국신분류법(美國新分類法)에 의(依)한 답토양의 분류(分類)에 관한 연구)

  • Joo, Yeong-Hee;Shin, Yong-Hwa
    • Korean Journal of Soil Science and Fertilizer
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    • v.11 no.2
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    • pp.97-104
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    • 1979
  • According to Soil Taxonomy which has been developed over the past 20 years in the soil conservation service of the U. S. D. A, Soils in Korea are classified. This system is well suited for the classification of the most of soils. But paddy field soils have some difficulties in classification because Soil Taxonomy states no proposals have yet been developed for classifying artificially irrigated soils. This paper discusses some problems in the application of Taxonomy and suggestes the classification of paddy field soils in Korea. Following is the summary of the paper. 1. Anthro aquic, Aquic Udipsamments : The top soils of these soils are saturated with irrigated water at some time of year and have mottles of low chroma(2 or less) more than 50cm of the soil surface. (Ex. Sadu, Geumcheon series) 2. Anthroaquic Udipsamments : These sails are like Anthroaquic, Aquic Udipsamments except for the mottles of low chroma within 50cm of the soil surface. (Ex. Baegsu series) 3. Halic Psammaquents : These soils contain enough salts as distributed in the profile that they interfere with the growth of most crop plants and located on the coastal dunes. The water table fluctuates with the tides. (Ex. Nagcheon series) 4. Anthroaquic, Aquic Udifluvents : They have some mottles that have chroma of 2 or less in more than 50cm of the surface. The upper horizon is saturated with irrigated water at sometime. (Ex. Maryeong series) 5. Anthro aquic Udifluvents : These soils are saturated with irrigated water at some time of year and have mottles of low chroma(2 or less) within 50cm of the surface soils. (Ex. Haenggog series) 6. Fluventic Haplaquepts : These soils have a content of organic carbon that decreases irregularly with depth and do not have an argillic horizon in any part of the pedon. Since ground water occur on the surface or near the surface, they are dominantly gray soils in a thick mineral regolith. (Ex Baeggu, Hagseong series) 7. Fluventic Thapto-Histic Haplaquepts : These soils have a buried organic matter layer and the upper boundary is within 1m of the surface. Other properties are same as Fluventic Haplaquepts. (Ex. Gongdeog, Seotan series) 8. Fluventic Aeric Haplaquepts : These soils have a horizon that has chroma too high for Fluventic Haplaquepts. The higher chroma is thought to indicate either a shorter period of saturation of the whole soils with water or some what deeper ground water than in the Fluventic Haplaquepts. The correlation of color with soil drainage classes is imperfect. (Ex. Mangyeong, Jeonbug series) 9. Fluventic Thapto-Histic Aeric Haplaquepts : These soils are similar to Fluventic Thapto Histic Haplaquepts except for the deeper ground water. (Ex. Bongnam series) 10. Fluventic Aeric Sulfic Haplaquepts : These soils are similar to Fluventic Aeric Haplaquepts except for the yellow mottles and low pH (<4.0) in some part between 50 and 150cm of the surface. (Ex. Deunggu series) 11. Fluventic Sulfaquepts : These soils are extremely acid and toxic to most plant. Their horizons are mostly dark gray and have yellow mottles of iron sulfate with in 50cm of the soil surface. They occur mainly in coastal marshes near the mouth of rivers. (Ex. Bongrim, Haecheog series) 12. Fluventic Aeric Sulfaquepts : They have a horizon that has chroma too high for Fluventic Sulfaquepts. Other properties are same as Fluventic Sulfaquepts. (Ex. Gimhae series) 13. Anthroaquic Fluvaquentic Eutrochrepts : These soils have mottles of low chroma in more than 50cm of the surface due to irrigated water. The base saturation is 60 percent or more in some subhroizon that is between depth of 25 and 75cm below the surface. (Ex. Jangyu, Chilgog series) 14. Anthroaquic Dystric Fluventic Eutrochrepts : These soils are similar to Anthroaquic Fluvaquentic Eutrochrepts except for the low chroma within 50cm of the surface. (Ex. Weolgog, Gyeongsan series) 15. Anthroaquic Fluventic Dystrochrepts : These soils have mottles that have chroma of 2 or less within 50cm of the soil surface due to artificial irrigation. They have lower base saturation (<60 percert) in all subhorizons between depths of 25 and 75cm below the soil surface. (Ex. Gocheon, Bigog series) 16. Anthro aquic Eutrandepts : These soils are similar to Anthroaquic Dystric Fluventic Eutrochrepts except for lower bulk density in the horizon. (Ex. Daejeong series) 17. Anthroaquic Hapludalfs : These soils' have a surface that is saturated with irrigated water at some time and have chroma of 2 or less in the matrix and higher chroma of mottles within 50cm of the surface. (Ex. Hwadong, Yongsu series) 18. Anthro aquic, Aquic Hapludalfs : These soils are similar to Anthro aquic Hapludalfs except for the matrix that has chroma 2 or less and higher chroma of mottles in more than 50cm of the surface. (Ex. Geugrag, Deogpyeong se ries)

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Biliary Atresia in Korea - A Survey by the Korean Association of Pediatric Surgeons - (담도폐색증 - 대한소아외과학회회원 대상 전국조사 -)

  • Choi, Kum-Ja;Kim, S.C.;Kim, S.K.;Kim, W.K.;Kim, I.K.;Kim, J.E.;Kim, J.C.;Kim, H.Y.;Kim, H.H.;Park, K.W.;Park, W.H.;Song, Y.T.;Oh, S.M.;Lee, D.S.;Lee, M.D.;Lee, S.K.;Lee, S.C.;Jhung, S.Y.;Jhung, S.E.;P.M., Jung;S.O., Choi;Choi, S.H.;Han, S.J.;Huh, Y.S.;Hong, C.;Hwbang, E.H.
    • Advances in pediatric surgery
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    • v.8 no.2
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    • pp.143-155
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    • 2002
  • A survey on biliary atresia was made among 26 members of the Korean Association of Pediatric Surgeons. The members were required to complete a questionnaire and a case registration form for each patient during the twentyone-year period of 1980-2000. Three hundred and eighty patients were registered from 18 institutions. The average number of patients per surgeon was one to two every year. The male to female ratio was 1:1.3. The age of patients on diagnosis with biliary atresia was on average $65.4{\pm} 36.2$ days old. The national distribution was 32.8% in Seoul, 25.3% in Gyoungki-Do, 21.6% in Gyoungsang-Do, 9.27% in Choongchung-Do, etc. in order. The most common clinical presentation was jaundice (98.4%) and change of stool color (86.2%) was second. Two hundred eighty (74.7%) of 375 patients were operated by 80 days of age. Three hundred thirty six (9 1.9%) of 366 patients were operated on by the original Kasai procedure, and 305 (84.3%) of 362 patients were observed by bile-drainage postoperatively. The overall postoperative complication rate was 18.5% and the overall postoperative mortality rate was 6.8%. The associated anomalies were observed in 72 cases (22.5%). One hundred ninty five (64.7%) of 302 patients have been alive in follow-up and 49 (25.1%) have survived over 5 years without problem after operation. Ascending cholangitis, varices and ascites affected survival significantly, and the important long-term prognostic factor was the occurrence of complications.

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Effects of Boliing, Steaming, and Chemical Treatment on Solid Wood Bending of Quercus acutissima Carr. and Pinus densiflora S. et. Z. (자비(煮沸), 증자(蒸煮) 및 약제처리(藥劑處理)가 상수리나무와 소나무의 휨가공성(加工性)에 미치는 영향(影響))

  • So, Won-Tek
    • Journal of the Korean Wood Science and Technology
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    • v.13 no.1
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    • pp.19-62
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    • 1985
  • This study was performed to investigate: (i) the bending processing properties of silk worm oak (Quercus acutissima Carr.) and Korean red pine (Pinus densiflora S. et Z.) by boiling and steaming treatments; (ii) the effects of interrelated factors - sapwood and heartwood, annual ring placement, softening temperature and time, moisture content. and wood defects on bending processing properties; (iii) the changing rates of bending radii after release from a tension strap, and (iv) the improving methods of bending process by treatment with chemicals. The size of specimens tested was $15{\times}15{\times}350mm$ for boiling and steaming treatments and $5{\times}10{\times}200mm$ for treatments with chemicals. The specimens were green for boiling treatments and dried to 15 percent for steaming treatments. The specimens for treatments with chemicals were soaked in saturated urea solution, 35 percent formaldehyde solution, 25 percent polyethylene glycol -400 solution, and 25 percent ammonium hydroxide solution for 5 days and immediately followed the bending process, respectively. The results obtained were as follows: 1. The internal temperature of silk worm oak and Korean red pine by boiling and steaming time was raised slowly to $30^{\circ}C$ but rapidly from $30^{\circ}C$ to $80-90^{\circ}C$ and then slowly from $80-90^{\circ}C$ to $100^{\circ}C$. 2. The softening time required to the final temperature was directly proportional to the thickness of specimen. The time required from $25^{\circ}C$ to $100^{\circ}C$ for 15mm-squared specimen was 9.6-11.2 minutes in silk worm oak and 7.6-8.1 minutes in Korean red pine. 3. The moisture content (M.C.) of specimen by steaming time was increased rapidly first 4 minutes in the both species, and moderately from 4 to 20 minutes and then slowly and constantly in silk worm oak, and moderately from 4 to 15 minutes and then slowly and constantly in Korean red pine. The M.C. of 15mm-squared specimen in 50 minutes of steaming was increased to 18.0 percent in the oak and 22.4 percent in the pine from the initial conditioned M.C. of 15 percent The rate of moisture adsorption measured was therefore faster in the pine than in the oak. 4. The mechanical properties of the both species were decreased significantly with the increase of boiling rime. The decrement by the boiling treatment for 60 minutes was measured to 36.6-45.0 percent in compressive strength, 12.5-17.5 percent in tensile strength, 31.6-40.9 percent in modulus of rupture, and 23.3-34.6 percent in modulus of elasticity. 5. The minimum bending radius (M.B.R.) of sapwood and heartwood was 60-80 mm and 90 mm in silk worm oak, and 260 - 300 mm and 280 - 300 mm in Korean red pine, respectively. Therefore, the both species showed better bending processing properties in sapwood than in heartwood. 6. The M.B.R. of edge-grained and flat-grained specimen in suk worm oak was 60-80 mm, but the M.B.R. in Korean red pine was 240-280 mm and 260-360 mm, respectively. Comparing the M.B.R. of edge-grained with flat-grained specimen, in the pine the edge-grained showed better bending processing property than the flat-grained. 7. The bending processing properties of the both species were improved by the rising of softening temperature from $40^{\circ}C$ to $100^{\circ}C$. The minimum softening temperature for bending was $90^{\circ}C$ in silk worm oak and $80^{\circ}C$ in Korean red pine, and the dependency of softening temperature for bending was therefore higher in the oak than in the pine. 8. The bending processing properties of the both species were improved by the increase of softening time as well as temperature, but even after the internal temperature of specimen reaching to the final temperature, somewhat prolonged softening was required to obtain the best plastic conditions. The minimum softening time for bending of 15 mm-squared silk worm oak and Korean red pine specimen was 15 and 10 minutes in the boiling treatment, and 30 and 20 minutes in the steaming treatment, respectively. 9. The optimum M.C. for bending of silk worm oak was 20 percent, and the M.C. above fiber saturation point rather degraded the bending processing property, whereas the optimum M.C. of Korean red pine needed to be above 30 percent. 10. The bending works in the optimum conditions obtained as seen in Table 24 showed that the M.B.R. of silk worm oak and Korean red pine was 80 mm and 240 mm in the boiling treatment, and 50 mm and 280 mm in the steaming treatment, respectively. Therefore, the bending processing property of the oak was better in the steaming than in the boiling treatment, but that of the pine better in the boiling than in the steaming treatment. 11. In the bending without a tension strap, the radio r/t of the minimum bending radius t to the thickness t of silk worm oak and Korean red pine specimen amounted to 16.0 and 21.3 in the boiling treatment, and 17.3 and 24.0 in the steaming treatment, respectively. But in the bending with a tension strap, the r/t of the oak and the pine specimen decreased to 5.3 and 16.0 in t he boiling treatment, and 3.3 and 18.7 in the steaming treatment, respectively. Therefore, the bending processing properties of the both species were significantly improved by the strap. 12. The effect of pin knot on the degradation of bending processing property was very severe in silk worm oak by side, e.g. 90 percent of the oak specimens with pin knot on the concave side were ruptured when bent to a 100 mm radius but only 10 percent of the other specimens with pin knot on the convex side were ruptured. 13. The changing rate in the bending radius of specimen bent to a 300 mm radius after 30 days of exposure to room temperature conditions was measured to 4.0-10.3 percent in the boiling treatment and 13,0-15.0 percent in the steaming treatment. Therefore, the degree of spring back after release was higher in the steaming than in the boiling treatment. And the changing rate of moisture-proofing treated specimen by expoxy resin coating was only -1.0.0 percent. 14. Formaldehyde, 35 percent solution, and 25 percent polyethylene glycol-400 solution found no effect on the plasticization of the both species, but saturated urea solution and 25 percent ammonium hydroxide solution found significant effect in comparison to non-treated specimen. But the effect of the treatment with chemicals alone was inferior to that of the steaming treatment, and the steaming treatment after the treatment with chemicals improved 10-24 percent over the bending processing property of steam-bent specimen. 15. Three plasticity coefficients - load-strain coefficient, strain coefficient, and energy coefficient - were evaluated to be appropriate for the index of bending processing property because the coefficients had highly significant correlation with the bending radius. The fitness of the coefficients as the index was good at load-strain coefficient, energy coefficient, and strain coefficient, in order.

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