• Title/Summary/Keyword: basis conversion

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Metabolism of $C^{14}-1-glucose$ and $C^{14}-6-glucose$ by the Ehrlich Ascites Turner Tissue (에르릿히 복수종양의 $C^{14}-1-$ 포도당 및 $C^{14}-6-$포도당 대사에 관한 연구)

  • Kwon, Chang-Rak
    • The Korean Journal of Physiology
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    • v.1 no.1
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    • pp.33-41
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    • 1967
  • The metabolic patterns of C-1 and C-6-carbon atoms of glucose were observed in the tissue homogenates of the Ehrlich ascites tumor tissue which was incubated for 3 hours in the Dubnuff metabolic shaking incubator. $C^{14}-1-and\;C^{14}-6-glucose$ were used as tracers. The glucose media in which tissue homogenate was incubated was kept at a concentration of 200mg% glucose of carrier and appropriate amount of $C^{14}-1-or\;C^{14}-6-tracer$. At the end of 3 hour incubation, respiratory $CO_2$ samples trapped by alkaline which is placed in the tenter well of incubation flask were analyzed for the total $CO_2$ production rates and their radioactivities. The tissue homogenate samples after incubation were analyzed for their concentrations of glucose, lactate, pyruvate and glycogen and calculations were made on the glucose consumption rate, pyruvate and lactate accumulation rates. The following results were obtained. Data obtained in each group are as follows: 1. In the tissue homogenate, which was incubated with $C^{14}-1-glucose as a substrate, total $CO_2$ production rate averaged $19.0{\pm}5.0{\mu}M/hr/gm$ and the mean specific activity of respiratory $CO_2$ was $840{\pm}296\;cpm/mgC.$ Relative specific activity (RSA) which means the fraction of $CO_2$ derived from medium $C^{14}-1-glucose$ to total $CO_2$ production rate was calculated by ratio of SA of respiratory $CO_2$ and medium $C^{14}-1-glucose.$ RSA was $14.3{\pm}5.0%,$ Accordingly actual $CO_2$ production rate from medium $C^{14}-1-glucose$ showed a mean value of $2.79{\pm}1.35\;{\mu}m$ of which amount was equivalent to the mean value of total glucose consumption rate $(RGDco_2)$, namely, $5.1{\pm}1.3%.$ Lactate and pyruvate appearance rates averaged $7.13{\pm}1.26\;and\;0.21{\pm}0.02{\mu}M/hr/gm,$ respectively. Assuming that these 3 carbon compounds appeared in the medium were derived from glucose, calculations were made that relative glucose disappearance rate into lactate $(RGD_L)$ was $38.0{\pm}5.4%\;and\;RGD_P$ was $1.23{\pm}0.03%.$ Therefore, about 43.3% of the total glucose consumed were accounted for by conversion into the respiratory $CO_2$, lactate and pyruvate. 2. In the second group, which was incubated with $C^{14}-1-glucose$ as a substrate, glucose consumption rate, lactate and pyruvate appearance rates showed almost the same order as the values of the $C^{14}-1-glucose$ substrate group. However, RSA was remarkably decreased showing a mean value of $1.02{\pm}0.13%.$ This fact means that the C-6 carbon of glucose take the minor part in the oxidative metabolism of glucose. The glycogen level in both substrate tissue homogenate showed less than 0.3% of tissue weight. These low value suggested that there was an inhibition of carbohydrate synthesis in the Ehrlich ascites tumor tissue. 3. The catabolic pathway of glucose in the tumor tissue were analyzed on the basis of Bloom's principle from the values of RSA. It was found that in the tumor tissue more than 90% of $CO_2$ derived from glucose were oxidized via the alternate pathway other than principal EMP-TCA cycle such as hexose monophosphate pathway (HMP). From the data described above, it was assumed that in the Ehrlich tumor tissue anaerobic glycolysis proceeds normally although, the oxidation of products of anaerobic glycolysis via the TCA cycle is inhibited resulting in the accumulation of lactate and almost all of oxidative energy from glucose is released by oxidative pathway such as HMP.

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Effect of Breed (Lean or Fat Pigs) and Sex on Performance and Feeding Behaviour of Group Housed Growing Pigs in a Tropical Climate

  • Renaudeau, D.;Giorgi, M.;Silou, F.;Weisbecker, J.L.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.4
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    • pp.593-600
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    • 2006
  • The effects of breed and sex on individual growth performance and feeding behaviour were studied between 45 and 90 kg BW in two replicates of forty group-housed pigs. The first and the second replicates were carried out during the warm season (i.e. between February and April 2003) and during the hot season (i.e. between August and October 2003), respectively. During the warm season, ambient temperature and relative humidity averaged $25.3^{\circ}C$ and 86.0%. The corresponding values for the hot season were $27.9^{\circ}C$ and 83.6%. The pigs were grouped in pens of 10 animals on the basis of breed (Creole or Large White) and sex (gilt or castrated male) and given ad libitum access to a grower diet (9.0 MJ/kg net energy and 158 g/kg crude protein) via feed intake recording equipment (Acema 48). An ear-tag transponder was inserted into each pig and this allowed the time, duration, and size of individual visits to be recorded. The growth performance and feeding pattern were significantly affected by breed, sex, and season. The Creole pigs (CR) had a lower average daily gain (ADG) (642 vs. 861 g/d, p<0.01) and carcass lean content ($LC_{90kg}$) (35.4 vs. 54.5%; p<0.01) and a higher backfat thickness at 90 kg BW ($BT_{90kg}$) (23.4 vs. 10.4 mm; p<0.01) than Large White pigs (LW) whereas the average daily feed intake (ADFI) was not affected by breed (2.34 vs. 2.22 kg/d, respectively for CR and LW pigs; p>0.10). Consequently, the food:gain ratio was higher in CR than in LW (3.65 vs. 2.58; p<0.01). CR had less frequent meals but ate more feed per meal than LW (5.9 vs. 8.8 meals/d and 431 vs. 279 g/meal; p<0.01). The rate of feed intake was lower (27.6 vs. 33.9 g/min; p<0.01) and the ingestion time per day and per meal were higher in CR than in LW (87.1 vs. 69.7 min/d and 15.8 vs. 8.4 min/meal; p<0.01). The ADFI and BT90 kg were higher (2.38 vs. 2.17 kg/d and 18.1 vs. 15.9 mm; p<0.05) and LC90 kg was lower (43.5 vs. 46.4%; p<0.01) in castrated males (CM) than in gilts (G) whereas ADG was not affected by sex (p = 0.12). The difference in lean content between CM and G was greater in CR than in LW. The ADFI and ADG were reduced during the hot season (2.18 vs.2.38 kg/d and 726 vs. 777 g/d, respectively; p<0.05) whereas feed conversion and carcass lean content were not affected by season (p>0.05). Average feeding time per meal and meal size decreased during the hot season (10.9 vs. 13.2 min/meal and 316 vs. 396 g/meal; p<0.01) whereas the rate of feed intake was not affected by season (p = 0.83). On average, 0.69 of total feed intake was consumed during the diurnal period. However, this partition of feed intake was significantly affected by breed, sex, and season. In conclusion, the breed, sex and season significantly affect performance and feeding pattern in growing pigs raised in a tropical climate. Moreover, the results obtained in the present study suggest that differences observed in BW composition between CR and LW are associated with difference in feeding behaviour, in particular, the short-term regulation of feed intake.

Nutritional Evaluation of Tofu Containing Dried Soymilk Residue(DSR) 1. Evaluation of Protein Quality (건조비지 첨가 두부의 영양적 품질평가 1. 단백질의 영양가)

  • Kweon, Mi-Na;Ryu, Hong-Soo;Moon, Jeung-Hye
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.22 no.3
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    • pp.255-261
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    • 1993
  • The effect of dried soymilk residue (DSR) on protein quality of tofu was studied. The amount of added DSR into soybean water extract was corresponding 10% (dry basis) of soybean used in tofu manufacturing. Proximate composition and in vitro protein qualities of soybeans at different stages of the conversion into tofu have also been investigated. Partially substituted tofu with DSR (TDSR) had higher moisture content (80.6%) than that of tofu prepared in traditional manner (TT). TDSR contained lower content of protein (38.9%) and total lipid (26.9%) compared to 45.8% of protein and 34.3% of total lipid for TT. A large amount of trypsin inhibitor (TI) in raw soybeans was diminished and extracted through tofu processing, and only 10~13% of TI in raw soybean remained in both tofu products (TDSR and TT). There was not a considerable difference in amino acid profiles between TT and TDSR, but TDSR had a higher content of lysine than that in TT. in vitro studies showed that TDSR and TT were comparable in terms of both in vitro digestibilities (90% over for four-enzyme digestibility and predicted digestibility) and discriminant computed protein efficiency ratio (2.07~2.14, DC-PER). Unlike those in vitro indices for protein quality, computed protein efficiency ratio (C-PER) of TDSR was much lower (1.4) than that of TT (1.95). It was revealed that C-PERs of tofu products were not in agreement with rat-PERs (1.7~1.9) in previous reports except for TT. However, DC-PER assay was more recommendable for protein quality of tofu products than C-PER assay.

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Effects of Dietary Carbohydrase Enzyme Complex and Microbial Phytase Supplementation on Productivity and Nutrient Digestibility in Growing Pigs (탄수화물 분해 복합효소제와 미생물 파이테이즈의 첨가가 육성돈의 생산성 및 영양소 소화율에 미치는 영향)

  • Shim, Y.H.;Chae, B.J.;Lee, J.H.
    • Journal of Animal Science and Technology
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    • v.45 no.4
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    • pp.569-576
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    • 2003
  • An experiment was conducted to investigate the effect of microbial phytase (Natuphos$^{\circledR}$) supplementation, individually and in combination with carbohydrase enzyme complex (composed of enzymes targeted to SBM dietary components such as $\alpha$-galactosides and galactomannans; ENDO-POWER$^{\circledR}$) to corn-soy basis diet with low nutrient levels on growth performance and nutrient digestibility of growing pigs. A total of 48 crossbred weaned pigs (Landrace${\times}$Yorkshire${\times}$Duroc), 29.1$\pm$0.14 kg of initial body weight, were randomly allotted to four dietary treatments, based on weight and age, according to a Randomized Complete Block Design. There were three pens per treatment and 4 pigs per pen. The dietary treatments were 1) CON (control diet with 3,380 kcal/kg of metabolizable energy, 18.96% of crude protein, 1.10% of lysine, 0.75% of calcium and 0.35% of available phosphorus), 2) LP+NTPS (CON diet with 0.15% unit lower available P levels+0.1% phytase (500 FTU/kg; Natuphos$^{\circledR}$)), 3) LEL+ENP (CON diet with 3.0% unit lower ME and lysine levels + 0.1% carbohydrase enzyme complex (ENDO-POWER$^{\circledR}$), and 4) LPEL+ENZ (CON diet with 0.15% unit lower available P levels and 3.0% unit lower ME and lysine levels+0.1% ENDO-POWER$^{\circledR}$ and 0.1% Natuphos$^{\circledR}$ (500 FTU/kg). There was no significant difference (p〉0.05) in average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) among dietary treatments during the whole experimental period (0 to 4 weeks). Apparent digestibility of gross energy was greater in LP+NTPS and LPEL+ENZ groups than in the LEL+ENP (p<0.05). Apparent digestibility of phosphorus was greater in LP+NTPS than in LEL+ENP (p<0.05). Dry matter excretion was lowest in LPEL+ENZ and phosphorus excretion was lowest in LP+NTPS (p<0.05). Overall, pigs fed on LPEL+ENZ group tended to have better nutrient digestibility (dry matter, gross energy, crude protein and phosphorus) than pigs fed on control group. All dietary enzyme treatment groups showed lower feed cost/body weight gain of pigs than control group. In conclusion, the results from the present study suggest that the simultaneous inclusion of phytase and carbohydrase enzyme complex to diets is advantageous with respect to reducing nutrient excretion of growing pigs and may contribute to increased economic return when added to corn-soy based growing pig diets.

Possible Use of the Animal By-product Mixture as n Dietary Fish meal Relpacer in Growing Common Carp (Cyprinus carpio) (잉어 사료에 있어 축산 가공 부산 혼합물의 어분 대체 가능성)

  • BAI Sungchul;JANG Hye-Kyung;CHO Eun-Sun
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.31 no.3
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    • pp.380-385
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    • 1998
  • This study evaluated the possible utilization and the replacing range of animal by-product mixture (ABPM) as a dietary fish meal replacer in growing common carp (Cyprinus carpio). ABPM is a mixture of leather meal, meat and bone meal, blood meal and squid liver powder at a specific weight based ratio. Five different diets were formulated on isonitrogenous and isocaloric basis of $40\%$ crude protein and 15.3 KJ/g diet in which white fish meal (WFM) protein was substituted with the ABPM Protein as follows: diet 1, $100\%$ WFM ($0\%$ ABPM, control); diet 2, $75\%$ WFM+$25\%$ ABPM ($25\%$ ABPM); diet $3,\;50\%$ WFM+$50\%$ ABPM ($50\%$ ABPM); diet 4 $25\%$ WFM+$75\%$ ABPM ($75\%$ ABPM); diet $5.0\%$ WFM+$100\%$ ABPM ($100\%$ ABPM). As the dietary protein sources, each diet contained $34.7\%$ of animal protein supplied by white fish meal and/or ABPM and $65.3\%$ of plant protein. After one week of conditioning period, fish averaging 10 g were randomly assigned to each diet treatment as triplicate groups and fed one of the experimental diets for 12 weeks. Weight gain of fish fed diet 1 (control) and 3 were significantly higher than those of fish fed diet 2, 4 and 5 during the first 4 weeks (P< 0.05), while there were no significant differences among all diet groups during the third 4 weeks (P>0.05). Feed conversion ratio of fish fed diet 1 was significantly higher than those fed diet 2, 3, 4 and 5 during the second 4 weeks (P<0.05), while there were no significant differences among all diet groups during the first and the third 4 weeks (P<0.05). There were no significant differences in proximate analysis among fish fed the experimental diets either for the second 4 weeks or the third 4 weeks (P>0.05). These results indicated that ABPM could be used as a fish meal replacer up to $100\%$ in growing common carp.

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Economic Feasibility of Hill Land Development (산지개발(山地開發)의 경제성)

  • Kim, Dong-Min
    • Korean Journal of Soil Science and Fertilizer
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    • v.11 no.4
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    • pp.283-295
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    • 1979
  • A new Farmland Expansion and Development Promotion Law was enacted in 1975. This law authorizes the Government to undertake development within a declared "reclamation area", wherever the land owners are unable to do so. In order to give additional impetus to conversion of waste hilly land into productive farmland, these hilly land development projects were conducted as large scale scheme which include soil fertility improvements such as the application of lime and phosphate. Farmland Expansion and Development Promotion Corps has attempted to undertake annual farm surveys in order to obtain some information about hilly land agriculture and farming operations within the reclamation project areas since 1976. As survey data accumulates, more and more clear picture of hilly land farming come to appear and enable us to conduct in-depth study. Effects of such upland reclamation include converting of previously unproductive slopeland into cultivable farmland for lucrative and commercial farming or food production. Furthermore, idle or marginal resources such as farm labor, equipment and compost would be fully employed. Socio-economic effects would include increases in land value and attitude change of farmers. On the other hand the preservation of natural environments might be damaged to the some extend by the projects. As shown in Table 7, the average farm size increased from 3,156 pyeong($3.3m^2$) to 5,562 pyeong, a 76.2% increase. The proportion of small farms with less than I ha dropped from 59.8% to 34.4%, but that of the large farms over 2 ha rose from 13.1% to 32.0% (See Table 8). The survey results indicate that as the farming on reclaimed uplands become time-honored, the acreage devoted for food crop production decreases against the economic crop growing acreage (see Table 6). For example, in the case of uplands reclaimed in 1972, the ratio of food crop acreages decreased from 99.7% in 1972 to 62.5% in 1977, whereas that of economic crop acreages increased from 0.3% in 1972 to 37.5% in 1977. The government used to actively encourage the farmers to carry out food crop production in the reclaimed upland targting toward the realization of self-sufficiency in food grains. It is, however, apparent that the farmers did hardly take the government advises as far as their economic interest were concerned. Yield per 10a. of various crops from the reclaimed uplands by year were surveyed as seen in Table 12. On the average, barley production in the reclaimed areas achieved 83.3% of the average unit yield from the existing upland in its 5 th year. Soybean yields showed a modest increase from 64% in the first year to 95%, in the 5 th year. In contrast, economic crops such as red pepper, totacco and radish achieved their maximum target yields in 3 years from starting to cultivate on the reclaimed farms. In order to test the post economic viability, an economic analysis was performed for each of selected subprojects on the basis of the data obtained through survey. The average actual internal economic rate of return on upland reclamation investments was found to be 20.3% which exceeded other types of projects of land and water development such as tidal land reclamation, irrigation or paddy rearrangement. The actual IRRs of subcategories of upland reclamation projects varied from 17.9% to 21.4% depending upon the kinds of cropping system adopted in each reclaimed areas such as food, economic, fruit or forage crops.

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Effects of Dietary Supplementation of Vitamin C and Sea Buckthorn on the Performance and Meat Quality in Old Laying Hens (비타민 C와 비타민나무 부산물 첨가가 산란 성계의 생산성 및 계육 품질에 미치는 영향)

  • Kang, Hwan Ku;Kim, Ji-Hyuk;Hwangbo, Jong;Kim, Chan Ho
    • Korean Journal of Poultry Science
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    • v.42 no.2
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    • pp.181-189
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    • 2015
  • The objective of this study was to investigate the effect of dietary supplementation of vitamin C and Sea buckthorn on the performance, blood biochemistry and meat quality in old laying hens. A total 200 Hy-Line Brown laying hens (101 weeks old) were randomly allotted to 1 of 5 dietary treatments : (1) Basal : basal diet, (2) Vit. C : basal diet + 0.1% vitamin C, (3) SB 0.1 : basal diet + 0.1% Sea buckthorn, (4) SB 0.5 : basal diet + 0.5% Sea buckthorn, and (5) SB 1.0 : basal diet + 1.0% Sea buckthorn. Each treatment was replicated 4 times with 10 birds units were arranged according to randomized block design. Feeding trial lasted 4 weeks under 16L:8D lighting regimen. The diets were fed to hens on an ad libitum basis for 4 weeks. Result indicated that during feeding trial of the experiment, hen-day egg production and feed conversion ratio were not significantly influenced by treatments. However, feed intake was significantly (P<0.05) higher in Vit. C and SB treated groups than the basal during 1 wks and 3 wks. Egg weight was significantly (P<0.05) higher in basal and Vit. C than the SB 1.0 treatment. There were no differences in carcass yield during feeding trials. However, partial ratio (breast and neck) was significantly (P<0.05) higher in SB 0.5 than other treatment. There were no differences in the level of leukocytes and erythrocytes. There were no significant differences on proximate analysis (DM, crude protein, crude fat, and crude ash), meat color, water holding capacity, cooking loss, and fatty acids concentrations. In conclusion, dietary supplementation of vitamin C and Sea buckthorn to the diet of old laying hens might be a potential ingredient for increasing partial weight (breast) in old laying hens.

Effects of Increasing Supplementation of Lycii fructus and Glycyrrhiza uralensis Mixture in Diets on Growth Performance, Blood Parameter, Immune Response and Intestinal Microflora in Broilers (사료 내 감초, 구기자 복합제 급여가 육계의 생산성, 혈액성상, 면역성상 및 장내 미생물 균총에 미치는 영향)

  • Kim, Chan Ho;Kim, Ji-Hyuk;Paik, In Kee;Kang, Hwan Ku
    • Korean Journal of Poultry Science
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    • v.42 no.2
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    • pp.139-145
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    • 2015
  • The objective of this experiment was to investigate the effects of dietary supplementation of Lycii fructus (LF) and Glycyrrhiza uralensis (GU) mixture on growth performance, blood parameter, immune response and intestinal microflora in broiler. A total 750 1-d old ROSS 308 was randomly allotted to 1 of 3 dietary treatments with 5 replicates during d 35 of the feeding trial. Two additional diets were prepared by adding 0.5 or 1.0% of LF and GU mixture to the basal diet. The experimental diets were fed on an ad libitum basis to the birds during 35 d. Results indicated that increasing inclusion level of LF and GU mixture in diets improved BW gain (quadratic, P<0.05) and improved feed conversion ratio (quadratic, P<0.05) of birds during to 0 to 21 d. Increasing inclusion level of LF and GU mixture in diets improved BW gain (linear and quadratic, P<0.05) of birds during to 0 to 35 d. The leukocyte concentrations were not affected by increasing inclusion level of LF and GU mixture in diets. Plasma IgG concentration was increased (linear, P<0.05) as the concentrations of LF and GU mixture in diets increased. The concentrations of Lactobacillus spp. in the ileal content of birds increased (linear, P<0.05), but those of Escherichia coli decreased (quadratic, P<0.01). These results suggest that dietary LF and GU mixture may be used as a functional ingredient to improve growth performance, plasma IgG and intestinal health of birds.

Long-term Changes in Soil Chemical Properties in Organic Arable Farming Systems in Korea (작물의 지속적인 유기 재배가 토양의 이화학적 특성변화에 미치는 영향)

  • Lee, Yun-Jeong;Choe, Du-Hoi;Kim, Seung-Hwan;Lee, Sang-Min;Lee, Yong-Hwan;Lee, Byung-Mo;Kim, Tae-Wan
    • Korean Journal of Soil Science and Fertilizer
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    • v.37 no.4
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    • pp.228-234
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    • 2004
  • In organic farming, nutrients for the crop production are mostly supplied by compost containing various organic materials. The long-term organic cultivation would result in continuous changes of soil chemical properties and fertility. The aim of this study was to investigate the contribution of long-term organic cultivation to the soil fertility in Korea focusing on the chemical properties of soil. Soil samples were collected from organic farms that had been cultivated for 8-10 years after certification of organic product through the conversion periods of 2-3 years. Thereby each organic farm had acquired optimal cultivating techniques and soil condition. We separated organic farms into three groups by cultivating crops, i.e. leaf vegetables, fruit vegetables and fruit trees. In each group, five representative farms were chosen in order to investigate the relationships between application rate of compost and nutrient contents in soil. The application rate of compost was approximately $10-15Mg\;10a^{-1}$ for the first 2-3 years at the beginning of organic farming and then reduced to a rate of $3-4Mg\;10a^{-1}$ after stabilization of organic matter content in soil with $30-50g\;10a^{-1}$. However, the continuous organic farming for 8-10 years resulted in accumulation of nutrients, especially of P, in soil probably due to the excessive amounts of compost applied. In conclusion, we suggest that the application rate and organic sources of compost should be decided on the basis of P content in soil by soil testing and thereafter the lack of soil N content for crop cultivation should be compensated by crop rotation with such as legumes. This might be an approach to the original meaning of organic farming as an environmental friendly agriculture.

Video-Assisted Thoracic Surgery Lobectomy for Non-Small Cell Lung Cancer: Experience of 133 Cases (폐암에서의 흉강경 폐엽절제술 치험 133예)

  • Kim, Hyeong-Ryul;Cho, Jeong-Su;Jang, Hee-Jin;Lee, Sang-Cheol;Choi, Eun-Suk;Jheon, Sang-Hoon;Sung, Soak-Whan
    • Journal of Chest Surgery
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    • v.42 no.5
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    • pp.615-623
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    • 2009
  • Background: We evaluated the feasibility and the efficacy of Video-Assisted Thoracic Surgery (VATS) lobectomy for treating patients with non-small cell lung cancer (NSCLC) and we compared the outcomes of VATS lobectomy with those of open lobectomy. Material and Method: From 2003 to March 2008, 133 NSCLC patients underwent VATS lobectomy. The patients were selected on the basis of having clinical stage I disease on the chest CT and PET scan. The outcomes of 202 patients who underwent open lobectomy (OL group) for clinical stage I NSCLC were evaluated to compare their results with those of the patients who underwent VATS lobectomy (the VL group). Result: The number of females and the number of patients with adenocarcinoma and stage IA disease were greater in VL group (p<0.05). There was no operative mortality or major complications in the VL group. Conversion to thoracotomy was needed in 8 cases (6%), which was mostly due to bleeding. The chest tube indwelling time and the length of the postoperative hospital stay were significantly shorter in the VL group (p<0.001). The number of dissected lymph nodes and the size of tumor were significantly smaller in the VL group (p<0.001). For the pathologic stage I patients, there was no significant difference in the three-year survival rates between the two groups (p=0.15). Conclusion: VATS lobectomy is a safe procedure with low operative mortality and morbidity. VATS lobectomy is feasible for early stage NSCLC and it provides outcomes that are comparable to those for open lobectomy. Further long-term data are needed.