• 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 Agricultural Science
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• v.12 no.2
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• pp.356-369
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• 1985

In Korea, inevitable researches for the blast control exactly started from 1927 by the organization of Office of Rural Development with the local extensive outbreak of panicle blast at Jeonlla Buk-Do Province in 1926. At present, the rice blast is still one of the most destructive and widespread diseases in spite of considerable contributions by rice scientists, particularly plant pathologists during last 55 years in Korea. Rice blast control and management are very difficult because of the marked variability in pathogenicity of the blast fungus. From the results obtained through the disease surveys during last 70 years, different 3 prevalence type of blast such as bimodal leaf-blast type, bimodal panicle-blast type and bimodal continual blast type were recognized. In generally speaking, pattern of blast outbreak is said to be characterized by severe outbreak of panicle blast after slight outbreak of leaf blast with discontinuity between leaf and panicle blast. So we have to pay much attention for successful management of panicle blast giving direct influence to rice yield. Main factors induce blast epidemic were pointed out to be breakdown of the disease resistance, nutritional unbalance such as excess application of nitrogen, delay of transplantation and longspell of rain fall by extensive surveys and researches on blast during last 70 years in Korea. The fact some of Japonica varieties such as Kokuryomiyako, Tamanishiki, Ginbozu and Pungok belong to varietal group A had been cultivated with extensive acrage over 30 years in this country should be mentioned by Korean rice scientists. Differences in field resistance between varieties in the same group are detectable and apparently small but sometimes epidemiologically significant differential effects may be found out in case of blast. Much more attention should be payed to accumulate the knowledges on field resistance for successful management of blast. Excess application of nitrogen is more effective to outbreak of panicle blast than that of leaf blast of IR varieties. In comparatively low level application of nitrogen infection rate of panicle blast of IR varieties is considerably high. Low temperature effects on outbreak of blast is very great. It results in remarkable increase of the inoculum potential on the leaf lesions and infection of panicle blast in leaf sheathes of IR varieties during the booting stage. In economic point of view, it is concluded that 5 times sprays of effective fungicides including 3 times before and 2 times after heading is good enough to control blast. We have experienced no one of control measures for blast is superior to all others. The integrated control measures was established as guideline of blast control around 1950 in Korea. This guideline must be helpful for rice growers as long as rice growing continue.

• Parasites, Hosts and Diseases
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• v.29 no.3
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• pp.235-244
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• 1991

An epidemiological study and mass treatments of Enterobius vermicularis infection among children near Wonju area of Kangwon province were carried out. The children were divided into 4 groups according to their residing localities; children in the mountainous area, rural area, urban area and in orphanage. They were examined by adhesive cellotape anal swab technique, and egg positive rates were obtained. The rates of egg reduction and re-infection rates after repeated mass treatments were also observed. The results obtained were as follows: 1. The overall egg Positive rate of E. vermicularis in the first screening was 19.9% (251 out of 1, 262 examinees; 19.7% in males and 20.1% in females). The positive rates were 13.0% in the mountainous area, 11 9% in the rural area, 15.1% in the urban (medium-sized) area and 61.9% in orphanages. 2. The highest positive rates were observed in the kindergarten children, and 1st and 2nd grade children of primary schools (26.2~32.2%), and the lowest rate (13.6%) in 6-year grade children of primary schools. 3. Cumulative detection rates from 3 repeated anal swabs at 4~5 days interval were higher (70.8%) than those from single anal swabs (50.0~59.2%). 4. Out of the examinees who showed the highest cumulative positive rate (70.8%), about 39.2% were consecutively positive in 3 anal swabs. Among different groups of children, the higher the total egg detection rates (87.5%), the higher the consecutive positive rates (71.9%) . 5. A total of 2, 609 (male : female=1 : 12.4) worms were collected from 17 egg-positive cases treated with anthelinintics. The mean number of worms per child was 153 (range: 4-824) . 6. The egg-positive cases in several studied groups (180 children) were treated with anthelmintics 6 times at 3-week intervals. In this case, the overall positive rate was decreased from 54.8% to 2.2% at 15 weeks after the treatments, but no complete negative conversion was experienced. However, in a group of children (154 children) including egg Positive and negative cases who were both treated with anthelmintics at 3-week interval, a complete egg-negative conversion was observed in the 9th week after treatments. 7. The egg-detection rate in the brothers or sisters of egg Positive children was 70.0% (28 out of 40 examined), and the egg-positive rate according to the family unit was 69.7%. In summarizing the above results, it is concluded that Enterobius vermicularis infection is still highly prevalent among children in Korea, and that repeated mass treatments of more than 3 times will be effective for control of this infection.

• Economic and Environmental Geology
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• v.35 no.3
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• pp.211-220
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• 2002

The Xiaoxinancha Cu-Au deposit in the Jilin province, located in NNE 800 km of Beijing, is hosted by diorite. The ore mineralization of Xiaoxinancha Cu-Au deposit show a stockwork occurrence that is concentrated on the potassic and phyllic alteration zones. The Xiaoxinancha Cu-Au deposit in the south is being mined with its reserves grading 0.8% Cu, 3.64 g/t Au and 16.8 g/t Ag and in the north, grading 0.63% Cu, 3.80 g/t Au and 6.8 glt Ag. The alteration assemblage occurs as a supergene blanket over deposit. Hydrothermal alteration at the Xiaoxinancha Cu-Au deposit is centered about the stock and was extensively related to the emplacement of the stock. Early hydrothermal alteration was dominantly potassic and followed by propylitic alteration. Chalcocite, often associated with hematite, account for the ore-grade copper, while chalcopyrite, bornite, quartz, epidote, chlorite and calcite constitute the typical gangue assemblage. Other minor opaque phases include pyrite, marcasite, native gold, electrum, hessite, hedleyite, volynskite, galenobismutite, covellite and goethite. Fluid inclusion data indicate that the formation of this porphyry copper deposit is thought to be a result of cooling followed by mixing with dilute and cooler meteoric water with time. In stage II vein, early boiling occurred at 497$^{\circ}$C was succeeded by the occurrence of halite-bearing type III fluid inclusion with homogenization temperature as much as 100$^{\circ}$C lower. The salinities of type 1II fluid inclusion in stage II vein are 54.3 to 66.9 wt.% NaCI + KCI equiv. at 383$^{\circ}$ to 495$^{\circ}$C, indicating the formation depth less than 1 km. Type I cupriferous fluids in stage III vein have the homogenization temperatures and salinity of 168$^{\circ}$ to 365$^{\circ}$C and 1.1 to 9.0 wt.% NaCI equiv. These fluid inclusions in stage III veins were trapped in quartz veins containing highly fractured breccia, indicating the predominance of boiling evidence. This corresponds to hydrostatic pressure of 50 to 80 bars. The $\delta$$^{34}S$ value of sulfide minerals increase slightly with paragenetic time and yield calculated $\delta$$^{34}S_{H2S}$ values of 0.8 to 3.7$\textperthousand$. There is no mineralogical evidence that fugacity of oxygen decreased, and it is thought that the oxygen fugacity of the mineralizing fluids have been buffered through reaction with magnetite. We interpreted the range of the calculated $\delta$$^{34}S_{H2S}$ values for sulfides to represent the incorporation of sulfur from two sources into the Xiaoxinancha Cu-Au hydrothermal fluids: (1) an isotopically light source with a $\delta$$^{34}S$ value of I to 2$\textperthousand$, probably a Mesozoic granitoid related to the ore mineralization. We can infer from the fact that diorite as the host rock in the Xiaoxinancha Cu-Au deposit area intruded plagiogranite; (2) an isotopically heavier source with a $\delta$$^{34}S$ value of > 4.0$\textperthousand$, probably the local porphyry.

• Journal of Korean Society of Forest Science
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• v.42 no.1
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• pp.1-38
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• 1979

The woody species of Genus Ilex which are endemic to Korea are distributed on limited area due to solely temperature factor. There is some differences according to species, however in general, the evergreen Ilex are found along southern coastal area of Korean Peninsula and near islands where the cold index does not exceed $-5^{\circ}C$. But Ilex macropoda and the variety, only deciduous ones, are grown in temperate zone of the peninsula and some islands. The list of Ilex species of Korea are as follows. Ilex cornuta Lindley et Pax., I. crenata Thunb. var. microphylla Max., I. crenata Thunb., I. rotunda Thunb., I. macropoda Miq., I. macropoda Miq. var. pseudo-macropoda Loensner, I. integra Thunb. The author surveyed the populations of Ilex species as many as possible and data of some characters such as leaf shape, spine, fruit shape, stomata density, sex ratio in natural communities, etc. are collected. Almost all the Ilex species in Korea show sporadic distribution. This means quite small sized populations isolate distantly each other eliminating the change of gene exchange in between. Particularly Ilex conuta and I. crenata show the morphological differentiation among populations as well as significant individual variation within a population. These were true with such characteristics, leaf shape, leaf dimension, leaf margin, fruit shape, spine, and stomata density. The founded are that the fruit length and the stomata density counted on the beneath surface of leaves of Ilex cornuta increased with the decrease of latitude. These are naturally closely related with the cold index values. The table shown below indicates the correlation between mean stomata density per $0.3642mm^2$ and cold index values. These relation however were not observed on Ilex crenata. The most dominated natured in relation to individual variation were outline of leaf, the number of marginal spine, the shape of leaf cross section and the degree of luster of the upper leaf surface. As shown in photos 5~7, these variations are agreed at a glance. There are reports that the development of marginal spines in some Ilex species is associated with the juvenility and topophysis. In present study, these two factors were neglected because of the intended sampling procedure. Of Ilex rotunda, population difference with the characteristics of leaf length is recognized but not for leaf width, petiole length, and fruit size. However, individual variations within a population were significantly large. In case of Ilex integra, only individual differences within population were calculated statistically for such characteristics as leaf length, leaf width, and petiole length. As to natural population, the sex ratio was 1:2 (female to male) for Ilex cornuta, and 1:1 for Ilex crenata. The tendency of more male than female in I. cornuta was agreed to other observations. Preparing the tip cutting of length 10cm, and treating with IBA, then attaching earth ball to the cut end, very successful rooting percentages were obtained. Asexual propagation has the advantages of maintaining the heterozygosity of existing varieties and overcoming the difficulties of delayed seed germination frequently encountered with Ilex species. Considering a great deal of variation in morphological traits, a good possibility of selection breeding for decorative and ornamental purposes exists. At present, these evergreen Ilex are ignored by local people as nuisance weedy shrubs. So the proper protection measures should promptly be taken.