• 제목/요약/키워드: Large strain

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Analysis of Tidal Deflection and Ice Properties of Ross Ice Shelf, Antarctica, by using DDInSAR Imagery (DDInSAR 영상을 이용한 남극 로스 빙붕의 조위변형과 물성 분석)

  • Han, Soojeong;Han, Hyangsun;Lee, Hoonyol
    • Korean Journal of Remote Sensing
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    • v.35 no.6_1
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    • pp.933-944
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    • 2019
  • This study analyzes the tide deformation of land boundary regions on the east (Region A) and west (Region B) sides of the Ross Ice Shelf in Antarctica using Double-Differential Interferometric Synthetic Aperture Radar (DDInSAR). A total of seven Sentinel-1A SAR images acquired in 2015-2016 were used to estimate the accuracy of tide prediction model and Young's modulus of ice shelf. First, we compared the Ross Sea Height-based Tidal Inverse (Ross_Inv) model, which is a representative tide prediction model for the Antarctic Ross Sea, with the tide deformation of the ice shelf extracted from the DDInSAR image. The accuracy was analyzed as 3.86 cm in the east region of Ross Ice Shelf and it was confirmed that the inverse barometric pressure effect must be corrected in the tide model. However, in the east, it is confirmed that the tide model may be inaccurate because a large error occurs even after correction of the atmospheric effect. In addition, the Young's modulus of the ice was calculated on the basis of the one-dimensional elastic beam model showing the correlation between the width of the hinge zone where the tide strain occurs and the ice thickness. For this purpose, the grounding line is defined as the line where the displacement caused by the tide appears in the DDInSAR image, and the hinge line is defined as the line to have the local maximum/minimum deformation, and the hinge zone as the area between the two lines. According to the one-dimensional elastic beam model assuming a semi-infinite plane, the width of the hinge region is directly proportional to the 0.75 power of the ice thickness. The width of the hinge zone was measured in the area where the ground line and the hinge line were close to the straight line shown in DDInSAR. The linear regression analysis with the 0.75 power of BEDMAP2 ice thickness estimated the Young's modulus of 1.77±0.73 GPa in the east and west of the Ross Ice Shelf. In this way, more accurate Young's modulus can be estimated by accumulating Sentinel-1 images in the future.

Genotoxicity of Therapeutic Dose of $^{131}I$ Analyzed by Micronuclei Test in the Mouse Bone Marrow (생쥐골수세포 미소핵검사에 의한 치료용량 방사성옥소($^{131}I$)의 유전독성 평가)

  • Bom, Hee-Seung;Kim, Ji-Yeul
    • The Korean Journal of Nuclear Medicine
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    • v.27 no.1
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    • pp.112-117
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    • 1993
  • Background Radioiodine ($^{131}I$), a major component of nuclear fallout and a valuable therapeutic agent for thyrotoxicosis and thyroid cancer, has been regarded as a mutagen or a carcinogen without any convincing evidence. To evaluate the genotoxicity of radioiodine ($^{131}I$) we performed a micronuclei test in mice bone marrow. Materials and methods : Mice (ICR strain, $25{\sim}30 g$) were divided to 4 groups: control, group 1 (0.17 mCi/kg, usual therapeutic dose for thyrotoxicosis), group 2 (1.67 mCi/kg, usual therapeutic dose for thyroid cancer), and group 3 (16.67 mCi/kg, usual accumulated dose causing bone marrow suppression). $^{131}I$ was administered intraperitoneally. Ten mice of each group were sacrificed at days 1 and 3. Bone marrow were smeared and stained with May-Grunwald Giemsa method. One thou-sand polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were counted under the light microscope, and the number of micronucleated PCEs were recorded. Results : The frequency of micronuclei in PCE (and NCE in parenthesis) in the control group was $0.25{\pm}0.07$ ($0.23{\pm}0.07$)% in day 1 and $0.24{\pm}0.07$ ($0.21{\pm}0.07$)% in day 3. Those in group 1 was $0.27{\pm}0.1$ ($0.23{\pm}0.09$)% in day 1 and $0.28{\pm}0.07$ ($0.25{\pm}0.06$)% in day 3. Micronuclei was noted in $0.29{\pm}0.08$ ($0.26{\pm}0.09$)% in day 1 and $0.31{\pm}0.05$ ($0.29{\pm}0.06$)% in day 3 in group 2, and in $0.32{\pm}0.06$ ($0.25{\pm}0.09$)% in day 1 and $0.33{\pm}0.08$ ($0.3{\pm}0.06$)% in day 3 in group 3. There was no difference in the frequency of micronuclei between each groups (p> 0.05). Conclusion : Radioiodine ($^{131}I$) did not cause any genotoxicity in mice bone marrow even at the large dose (16.67 mCi/kg).

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Studies on the Fermentation on Soy Sauce by Bacteria (세균(細菌)을 이용(利用)한 간장 제조(製造)에 관(關)한 연구(硏究))

  • Ju, Hyun-Kyu;Ro, Sin-Kyu;Im, Moo-Hyun
    • Korean Journal of Food Science and Technology
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    • v.4 no.4
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    • pp.276-284
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    • 1972
  • A strain of Bacillus sp. which has powerful enzymatic activity and sets free a little amount of ammonia nitrogen and large amount of amino nitrogen was separated from Meju, Denzang, Chungkukjang, and paddy straw to make the soy-sauce rapidly and conveniently in the various mixing ratio of steamed soy-bean and wheat parched or steamed. Total nitrogen and amino nitrogen were increased during the maturing. The acidity of soy-sauce was increased to $1.15{\sim}1.98%$ than ordinary soy-sauce. pH were ranged in $4.6{\sim}6.0%$. The fermenting time takes 30 days while it takes at least 4 monthes in ordinary method. The best results were obtained with the mixed ratio of 1 : 1 or 1 : 2 (wheat : soy-bean).

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Experimental Studies on the Properties of Epoxy Resin Mortars (에폭시 수지 모르터의 특성에 관한 실험적 연구)

  • 연규석;강신업
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.26 no.1
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    • pp.52-72
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    • 1984
  • This study was performed to obtain the basic data which can be applied to the use of epoxy resin mortars. The data was based on the properties of epoxy resin mortars depending upon various mixing ratios to compare those of cement mortar. The resin which was used at this experiment was Epi-Bis type epoxy resin which is extensively being used as concrete structures. In the case of epoxy resin mortar, mixing ratios of resin to fine aggregate were 1: 2, 1: 4, 1: 6, 1: 8, 1:10, 1 :12 and 1:14, but the ratio of cement to fine aggregate in cement mortar was 1 : 2.5. The results obtained are summarized as follows; 1.When the mixing ratio was 1: 6, the highest density was 2.01 g/cm$^3$, being lower than 2.13 g/cm$^3$ of that of cement mortar. 2.According to the water absorption and water permeability test, the watertightness was shown very high at the mixing ratios of 1: 2, 1: 4 and 1: 6. But then the mixing ratio was less than 1 : 6, the watertightness considerably decreased. By this result, it was regarded that optimum mixing ratio of epoxy resin mortar for watertight structures should be richer mixing ratio than 1: 6. 3.The hardening shrinkage was large as the mixing ratio became leaner, but the values were remarkably small as compared with cement mortar. And the influence of dryness and moisture was exerted little at richer mixing ratio than 1: 6, but its effect was obvious at the lean mixing ratio, 1: 8, 1:10,1:12 and 1:14. It was confirmed that the optimum mixing ratio for concrete structures which would be influenced by the repeated dryness and moisture should be rich mixing ratio higher than 1: 6. 4.The compressive, bending and splitting tensile strenghs were observed very high, even the value at the mixing ratio of 1:14 was higher than that of cement mortar. It showed that epoxy resin mortar especially was to have high strength in bending and splitting tensile strength. Also, the initial strength within 24 hours gave rise to high value. Thus it was clear that epoxy resin was rapid hardening material. The multiple regression equations of strength were computed depending on a function of mixing ratios and curing times. 5.The elastic moduli derived from the compressive stress-strain curve were slightly smaller than the value of cement mortar, and the toughness of epoxy resin mortar was larger than that of cement mortar. 6.The impact resistance was strong compared with cement mortar at all mixing ratios. Especially, bending impact strength by the square pillar specimens was higher than the impact resistance of flat specimens or cylinderic specimens. 7.The Brinell hardness was relatively larger than that of cement mortar, but it gradually decreased with the decline of mixing ratio, and Brinell hardness at mixing ratio of 1 :14 was much the same as cement mortar. 8.The abrasion rate of epoxy resin mortar at all mixing ratio, when Losangeles abation testing machine revolved 500 times, was very low. Even mixing ratio of 1 :14 was no more than 31.41%, which was less than critical abrasion rate 40% of coarse aggregate for cement concrete. Consequently, the abrasion rate of epoxy resin mortar was superior to cement mortar, and the relation between abrasion rate and Brinell hardness was highly significant as exponential curve. 9.The highest bond strength of epoxy resin mortar was 12.9 kg/cm$^2$ at the mixing ratio of 1:2. The failure of bonded flat steel specimens occurred on the part of epoxy resin mortar at the mixing ratio of 1: 2 and 1: 4, and that of bonded cement concrete specimens was fond on the part of combained concrete at the mixing ratio of 1 : 2 ,1: 4 and 1: 6. It was confirmed that the optimum mixing ratio for bonding of steel plate, and of cement concrete should be rich mixing ratio above 1 : 4 and 1 : 6 respectively. 10.The variations of color tone by heating began to take place at about 60˚C, and the ultimate change occurred at 120˚C. The compressive, bending and splitting tensile strengths increased with rising temperature up to 80˚ C, but these rapidly decreased when temperature was above 800 C. Accordingly, it was evident that the resistance temperature of epoxy resin mortar was about 80˚C which was generally considered lower than that of the other concrete materials. But it is likely that there is no problem in epoxy resin mortar when used for unnecessary materials of high temperature resistance. The multiple regression equations of strength were computed depending on a function of mixing ratios and heating temperatures. 11.The susceptibility to chemical attack of cement mortar was easily affected by inorganic and organic acid. and that of epoxy resin mortar with mixing ratio of 1: 4 was of great resistance. On the other hand, when mixing ratio was lower than 1 : 8 epoxy resin mortar had very poor resistance, especially being poor resistant to organicacid. Therefore, for the structures requiring chemical resistance optimum mixing of epoxy resin mortar should be rich mixing ratio higher than 1: 4.

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Mechanical and Rheological Properties of Rice Plant (수도(水稻)의 역학적(力學的) 및 리올러지 특성(特性)에 관(關)한 연구(硏究))

  • Huh, Yun Kun;Cha, Gyun Do
    • Korean Journal of Agricultural Science
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    • v.14 no.1
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    • pp.98-133
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    • 1987
  • The mechanical and rheological properties of agricultural materials are important for engineering design and analysis of their mechanical harvesting, handling, transporting and processing systems. Agricultural materials, which composed of structural members and fluids do not react in a purely elastic manner, and their response when subjected to stress and strain is a combination of elastic and viscous behavior so called viscoelastic behavior. Many researchers have conducted studies on the mechanical and rheological properties of the various agricultural products, but a few researcher has studied those properties of rice plant, and also those data are available only for foreign varieties of rice plant. This study are conducted to experimentally determine the mechanical and the rheological properties such as axial compressive strength, tensile strength, bending and shear strength, stress relaxation and creep behavior of rice stems, and grain detachment strength. The rheological models for the rice stem were developed from the test data. The shearing characteristics were examined at some different levels of portion, cross-sectional area, moisture content of rice stem and shearing angle. The results obtained from this study were summarized as follows 1. The mechanical properties of the stems of the J aponica types were greater than those of the Indica ${\times}$ Japonica hybrid in compression, tension, bendingand shearing. 2. The mean value of the compressive force was 80.5 N in the Japonica types and 55.5 N in the Indica ${\times}$ Japonica hybrid which was about 70 percent to that of the Japonica types, and then the value increased progressively at the lower portion of the stems generally. 3. The average tensile force was about 226.6 N in the Japonica types and 123.6 N in the Indica ${\times}$ Japonica hybrid which was about 55 percent to that of the Japonica types. 4. The bending moment was $0.19N{\cdot}m$ in the Japonica types and $0.13N{\cdot}m$ in the Indica ${\times}$ Japonica hybrid which was 68 percent to that of the Japonica types and the bending strength was 7.7 MPa in the Japonica types and 6.5 MPa in the Indica ${\times}$ Japonica hybrid respectively. 5. The shearing force was 141.1 N in Jinju, the Japonica type and 101.4 N in Taebaeg, the Indica ${\times}$ Japonica hybrid which was 72 percent to that of Jinju, and the shearing strength of Taebaeg was 63 percent to that of Jinju. 6. The shearing force and the shearing energy along the stem portion in Jinju increased progressively together at the lower portions, meanwhile in Taebaeg the shearing force showed the maximum value at the intermediate portion and the shearing energy was the greatest at the portion of 21 cm from the ground level, and also the shearing strength and the shearing energy per unit cross-sectional area of the stem were the greater values at the intermediate portion than at any other portions. 7. The shearing force and the shearing energy increased with increase of the cross-sectional area of the rice stem and with decrease of the shearing angie from $90^{\circ}$ to $50^{\circ}$. 8. The shearing forces showed the minimum values of 110 N at Jinju and of 60 N at Taebaeg, the shearing energy at the moisture content decreased about 15 percent point from initial moisture content showed value of 50 mJ in Jinju and of 30 mJ in Taebaeg, respectively. 9. The stress relaxation behavior could be described by the generalized Maxwell model and also the compression creep behavior by Burger's model, respectively in the rice stem. 10. With increase of loading rate, the stress relaxation intensity increased, meanwhile the relaxation time and residual stress decreased. 11. In the compression creep test, the logarithmic creep occured at the stress less than 2.0 MPa and the steady-state creep at the stress larger than 2.0 MPa. 12. The stress level had not a significant effect on the relaxation time, while the relaxation intensity and residual stress increased with increase of the stress level. 13. In the compression creep test of the rice stem, the instantaneous elastic modulus of Burger's model showed the range of 60 to 80 MPa and the viscosities of the free dashpot were very large numerical value which was well explained that the rice stem was viscoelastic material. 14. The tensile detachment forces were about 1.7 to 2.3 N in the Japonica types while about 1.0 to 1.3 N in Indica ${\times}$ Japonica hybrid corresponding to 58 percent of Japonica types, and the bending detachment forces were about 0.6 to 1.1 N corresponding to 30 to 50 percent of the tensile detachment forces, and the bending detachment of the Indica ${\times}$ Japonica hybrid was 0.1 to 0.3 N which was 7 to 21 percent of Japonica types. 15. The detachment force of the lower portion was little bigger than that of the upper portion in a penicle and was not significantly affected by the harvesting period from September 28 to October 20. 16. The tensile and bending detachment forces decreased with decrease of the moisture content from 23 to 13 percent (w.b.) by the natural drying, and the decreasing rate of detachment forces along the moisture content was the greater in the bending detachment force than the tensile detachment force.

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Transformation is Mechanism of Gene Transfer in Soil (토양에서 Transformation에 의한 유전자 전이)

  • ;Stotzky, G.
    • Korean Journal of Microbiology
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    • v.28 no.3
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    • pp.210-218
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    • 1990
  • The survival and transfer of chromosomal genes coding for the synthesis of amino acids (threonine, tryptophan, histidine, leucine, methionine) and of plasmid-borne genes coding for resistance to antibiotics (chloramphenicol, kanamycin, erythromycin) by transformation in sterile and nonsterile soil (the soil was amended to 12% vol/vol with the clay mineral, montmorillonite) was studied. In pure culture, the numbers of vegetative cells of the Bacillus subtilis strains decreased by 1 to 1.5 orders of magnitude within one week, but spores of each strain showed lesser decreases. In sterile soil, the populations of vegetative cells and spores decreased by 1.5 to 3 orders of magnitude within 2 to 4 days and then showed little additional decreased. The transformation frequencies (number of transformants/numbers of donors and recipients) of individual amino acid-genes invitro ranged from $1.3{\pm}0.6{\times}10^{-6}$ to $6.0{\pm}2.36{\times}10^{-6}$, of two amino acid-genes from $8.5{\pm}0.7{\times}10^{-8}$ to $3.1{\pm}0.6{\times}10^{-7}$, and of the antibiotic-resistance genes from $1.5{\pm} 0.2{\itmes} 10^{-7}$ to $1.4{\pm} 0.4{\times} 10^{-5}$ . In sterile soil, the frequencies of transfer of individual amino acid-genes ranged from $2.0{\times} 10^{-7}$ to $2.0{\times} 10^{-5}$ and of the antibiotic-resistance genes from $2.0{\times} 10^{-7}$ to $9.4{\pm} 4.7{\times} 10^{-6}$. The transfer of two amino acid-genes in sterile soil was detected at a frequency of $2.0{\times} 10^{-6}$ to $4.5{\times} 10^{-6}$, but only in three instances. The transformation frequencies of antibiotic-resistance genes in nonsterile soil were essentially similar to those in sterile soil. However, to detect transformants in nonsterile soil, higher concentrations of antibiotics were needed, as the result of the large numbers of indigenous soil bacteria resistant to the concentration of antibiotics used in the sterile soil and in vitro studies. The results of these studies show that genes can be transferred by transformation in soil and that this mechanism of transfer must be considered in risk assessment of the release of genetically engineered microorganisms to the environment.

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Behaviors of Soft Bangkok Clay behind Diaphragm Wall Under Unloading Compression Triaxial Test (삼축압축 하에서 지중연속벽 주변 방콕 연약 점토의 거동)

  • Le, Nghia Trong;Teparaksa, Wanchai;Mitachi, Toshiyuki;Kawaguchi, Takayuki
    • Journal of the Korean Geotechnical Society
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    • v.23 no.9
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    • pp.5-16
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    • 2007
  • The simple linear elastic-perfectly plastic model with soil parameters $s_u,\;E_u$ and n of undrained condition is usually applied to predict the displacement of a constructed diaphragm wall(DW) on soft soils during excavation. However, the application of this soil model for finite element analysis could not interpret the continued increment of the lateral displacement of the DW for the large and deep excavation area both during the elapsed time without activity of excavation and after finishing excavation. To study the characteristic behaviors of soil behind the DW during the periods without excavation, a series of tests on soft Bangkok clay samples are simulated in the same manner as stress condition of soil elements happening behind diaphragm wall by triaxial tests. Three kinds of triaxial tests are carried out in this research: $K_0$ consolidated undrained compression($CK_0U_C$) and $K_0$ consolidated drained/undrained unloading compression with periodic decrement of horizontal pressure($CK_0DUC$ and $CK_0UUC$). The study shows that the shear strength of series $CK_0DUC$ tests is equal to the residual strength of $CK_0UC$ tests. The Young's modulus determined at each decrement step of the horizontal pressure of soil specimen on $CK_0DUC$ tests decreases with increase in the deviator stress. In addition, the slope of Critical State Line of both $CK_0UC$ and $CK_0DUC$ tests is equal. Moreover, the axial and radial strain rates of each decrement of horizontal pressure step of $CK_0DUC$ tests are established with the function of time, a slope of critical state line and a ratio of deviator and mean effective stress. This study shows that the results of the unloading compression triaxial tests can be used to predict the diaphragm wall deflection during excavation.

Microbiological and Enzymological Studies on the Flavor Components of Sea Food Pickles (젓갈등속(等屬)의 정미성분(呈味成分)에 관(關)한 미생물학적(微生物學的) 및 효소학적(酵素學的) 연구(硏究))

  • Lee, Ke-Ho
    • Applied Biological Chemistry
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    • v.11
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    • pp.1-27
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    • 1969
  • More than thirty kinds of sea food pickles have been eaten in Korea. Out of these salted yellow tail pickle, salted clam pickle, salted oyster pickle, and salted cuttlefish pickle were employed for the analysis of their components, identification of main fermenting microbes, and determination of enzyme characteristics concerned. Also studied was the effect of enzymic action of microbes, which are concerned with the fermenting of pickles, on the production of flavorous 5'-mononucleotides and amino acids. The results are summarized as follows: 1. Microflora observed in the pickles are: (a) Total count of viable cells after 1-2 months of pickling was found to be $10^7$ and that after 6 months decreased to $10^4$. (b) Microbial occurence in the early stage of pickling was observed to be 10-20% Micrococcus spp., 10-20% Brevibacterium spp., 0-30% Sarcina spp., 20-30% Leuconostoc spp., ca 30% Bacillus spp., 0-10% Pseudomonas spp., 0-10% Flavobacterium spp., and 0-20% yeast. (c) Following the early stage of pickling, mainly halophilic bacteria such as Bacillus subtilis, Leuconostoc mesenteroides, Pediococcus halophilus and Sarcina litoralis, were found to exhibit an effect on the fermentation of pickle and their enzyme activities were in direct concern in fermentation of pickles. (d) Among the bacteria participating in the fermentation, Sarcina litoralis 8-14 and 8-16 strains were in need of high nutritional requirement and the former was grown only in the presence of purine, pyrimidine and cystine and the latter purine, pyrimidine and glutamic acid. 2. Enzyme characteristics studied in relation to the raw materials and the concerned microbes isolated are as follows: (a) A small amount of protease was found in the raw materials and 30-60% decrease in protease activity was demonstrated at 7% salt concentration. (b) Protease activity of halophilic bacteria, Bacillus subtilis 7-6, 11-1, 3-6 and 9-4 strains, in the complete media decreased by 10-30% at the 7% salt concentration and that of Sarcina litoralis 8-14 and 8-16 strains decreased by 10-20%. (c) Proteins in the raw materials were found to be hydrolyzed to yield free amino acids by protease in the fermenting microbes. (d) No accumulation of flavorous 5'-mononucleotides was demonstrated because RNA-depolymerase in the raw materials and the pickles tended to decompose RNA into nucleoside and phosphoric acid. (e) The enzyme produced in Bacillus subtilis 3-6 strain isolated from the salted clam pickles, was ascertained to be 5'-phosphodiesterase because of its ability to decompose RNA and thus accumulating 5'-mononucleotide. (f) It was demonstrated that the activity of phosphodiesterase in Bacillus subtilis 3-6 strain was enhanced by some components in the corn steep liquor and salted clam pickle. The enzyme activity was found to decrease by 10-30% and 40-60% at the salt concentration of 10% and 20%, respectively. 3. Quantitative data for free amino acids in the pickles are as follows: (a) Amounts of acidic amino acids such as glutamic and aspartic acids in salted clam pickle, were observed to be 2-10 times other pickles and it is considered that the abundance in these amino acids may contribute significantly to the specific flavor of this food. (b) Large amounts of basic amino acids such as arginine and histidine were found to occur in salted yellow tail pickle. (c) It is much interesting that in the salted cuttlefish pickle the contents of sulfur-containing amino acids were exceedingly high compared with those of others: cystine was found to be 17-130 times and methionine, 7-19 times. (d) In the salted oyster pickle a high content of some essential amino acids such as lysine, threonine, isoleucine and leucine, was demonstrated and a specific flavor of the pickle was ascribed to the sweet amino acids. Contents of alanine and glycine in the salted oyster pickle were 4 and 3-14 times as much as those of the others respectively. 4. Analytical data for 5'-mononucleotides in the pickles are as follows: (a) 5'-Adenylic acid and 3'-adenylic acid were found in large amounts in the salted yellow tail pickle and 5'-inosinic acid in lesser amount. (b) 5'-Adenylic acid, especially 3'-adenylic acid predominated in amount in the salted oyster pickle over that in the other pickles. (c) The salted cuttlefish pickle was found to contain only 5'-adenylic acid and 3'-adenylic acid. It has become evident from the above fact that clam and the invertebrate lack of adenylic deaminase and contain high content of adenylic acid. Thus, they were demonstrated to be the AMP-type. (d) 5'-Inosinic acid was contained in the salted yellow tail pickle in a significant concentration, and it might be considered to be IMP-type. 5. Comparative data for flavor with regard to the flavorous amino acids and the contents of 5'-mononucleotides are: (a) A specific flavor of salted yellow tail pickle was ascribed to the abundance in glutamic acid and aspartic acid, and to the existence of a small amount of flavorous 5'-inosinic acid. The combined effect of these components was belived to exhibit a synergistic action in producing a specific fiavor to the pickle. (b) A specific flavor of salted clam pickle has been demonstrated to be attributable to the richness in glutamic acid and aspartic acid rather than to that of 5'-mononucleotides.

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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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