• Journal of Life Science
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• v.19 no.11
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• pp.1529-1537
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• 2009

To elucidate further the antitumor effects of a natural L-arginine analogue, L-canavanine, the mechanism underlying apoptogenic activity of L-canavanine and its modulation by protein tyrosine kinase $p56^{lck}$ was investigated in human Jurkat T cells. When the cells were treated with 1.25 to 2.5 mM L-canavanine for 36 h, several apoptotic events including mitochondrial membrane potential (${\Delta\Psi}m$) loss, activation of caspase-9, -3, -8, and -7, poly (ADP-ribose) polymerase (PARP) degradation, and DNA fragmentation were induced without alteration in the levels of Fas or FasL. These apoptotic changes were more significant in $p56^{lck}$-deficient Jurkat clone JCaM1.6 than in $p56^{lck}$-positive Jurkat clone E6.1. The L-canavanine-induced apoptosis observed in $p56^{lck}$-deficient JCaM1.6 cells was significantly reduced by introducing $p56^{lck}$ gene into JCaM1.6 cells by stable transfection. Treatment of JCaM1.6/lck cells with L-canavanine caused a transient 1.6-fold increase in the kinase activity of $p56^{lck}$. Both FADD-positive wild-type Jurkat T cell clone A3 and FADD-deficient Jurkat T cell clone I2.1 exhibited a similar susceptibility to the cytotoxicity of L-canavanine, excluding involvement of Fas/FasL system in triggering L-canavanine-induced apoptosis. The L-canavanine-induced apoptotic sub-$G_1$ peak and activation of caspase-3, -8, and -7 were abrogated by pan-caspase inhibitor (z-VAD-fmk), whereas L-canavanine-induced activation of caspase-9 was not affected. These results demonstrated that L-canavanine caused apoptosis of Jurkat T cells via the loss of ${\Delta\Psi}m$, and the activation of caspase-9, -3, -8, and -7, leading to PARP degradation, and that the $p56^{lck}$ kinase attenuated the ${\Delta\Psi}m$ loss and activation of caspases, and thus contributed as a negative regulator to L-canavanine-induced apoptosis.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.191-199
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• 1996

Purpose : To evaluate 5-year survival rate, patterns of failure and complications of cervical cancer treatment, fifty nine patients treated by curative radiotherapy for the uterine cervical cancer were analyzed retrospectively. Materials and Methods : From March 1986 to May 1990, fifty nine patients with histologically proven uterine cervical cancer were analyzed. According to FIGO stage, there were 2 patients ($3.4\%$) in stage Ib, 2 patients ($3.4\%$) in stage IIa, 31 patients ($52.5\%$) in stage IIb, 15 patients ($25.4\%$) in stage IIIb, 9 patients ($15.3\%$) in stage IV. External RT was per formed by 6 MVLINAC with daily 1.8 Gy, 5 times per week and followed by ICR. A point dose of ICR was calculated to 30-43.66 Gy (median: 34.6 Gy). These techniques delivered total A Point dose of 80.4 to 109.8 Gy (median: 85 Gy). Patients had been followed up from 2 to 110 months (median: 61 months) Results : The overall 5-year survival rate & disease free survival rate were $55.9\%$ and $55.0\%$ respectively. According to FIGO stage, the 5-year survival rate for less than IIa, IIb, IIIb, IV were $75.0\%$, $74.8\%$, $26.7\%$, $33.3\%$, respectively. In univariate analysis, the 5-year survival rate for stage IIb and below versus stage IIIa and above revealed $74.8\%$, $29.2\%$ respectively (P<0.005). According to the hemoglobin level during RT, the 5-rear survival rate of was $73.3\%$ for patients with Hg 10 gm/dL or higher, in contrast to $0\%$ for those with lower than 10 gm/dL (p<0.005). In 18 patients with nonbulky tumor (<5cm), the 5-year survival rates were $71.8\%$. The 5-rear survival rates for 18 patients with 5 cm or greater in tumor diameter were $22.2\%$ (p<0.005). The 5-year survival rate for Patient age of above 50 years and below were $65.3\%$ $34.2\%$ respectively (p<0.05). ECOG performance status. pathologic finding, total dose, total treatment time were not statistically significant factors. The significant prognostic factors affecting overall 5-year survival rate by multivariate analysis showed the hemoglobin level during RT (P=0.0001), tumor size (p=0.0390), FIGO stage (p=0.0468). Total recurrence rate was $23.7\%$ local failure $15.2\%$ (9/59), distant metastasis $6.8\%$ (4/59), local and distant metastasis $1.7\%$ (1/59). According to the RTOG/EORTC Soma Scales, the late complication rate was $23.8\%$ (14/59) The late complication rate of colorectum and genitourinary tract were $15.3\%$ (9/59), $8.5\%$ (5/59), respectively: 10 patients ($17.0\%$) were grade 2, 3 Patients ($5.1\%$) were grade 3 and one patient ($1.7\%$) was grade 4. The late complications were radiation proctitis, rectal bleeding, radiation colitis, diarrhea and radiation cystitis in decreasing order. Conclusion : For improvement of therapeutic results, prospective randomized trials are recomended to discover new prognostic factors and more aggressive radiation therapeutic methods are needed for poor prognostic patients. The adjuvant chemotherapy or radiation-sensitizing agents must be considered to inhibit regional and distant metastasis.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.257-264
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• 2000

Purpose: For early stage non-small-cell lung cancer, surgical resection is the treatment of choice. But when the patients are not able to tolerate it because of medical problem and when refuse surgery, radiation therapy is considered an acceptable alternative. We report on the treatment results and the effect of achieving local control of primary tumors on survival end points, and analyze factors that may influence survival and local control. Materials and Method : We reviewed the medical records of 32 patients with medically inoperable non-small cell lung cancer treated at our institution from June, 1987 through June, 1997. All patients had a pathologic diagnosis of non-small cell lung cancer and were not candidate for surgical resection because of either patients refusal (4), old age (2), lung problem (21), chest wail invasion (3) and heart problems (3). In 8 patients, there were more than 2 problems. The median age of the patients was 68 years (ranging from 60 to 86 years). Histologic cell type included souamous (24), adenocarcinoma (6) and unclassiried squamous cell (2). The clinical stages of the patients were 71 in 5, 72 in 25, 73 in 2 patients. Initial tumor size was 3.0 cm in 11, between 3.0 cm and 5.0 cm in 13 and more than 5.0 cm in 8 patients. Ail patients had taken chest x-rays, chest CT, abdomen USG and bone scan. Radiotherapy was delivered using 6 MV or 10 MV linear accelerators. The doses of primary tumor were the ranging from 54.0 Gy to 68.8 Gy (median; 61.2 Gy). The duration of treatment was from 37 days through 64 days (median; 0.5 days) and there was no treatment interruption except 1 patient due to poor general status. In 12 patients, concomitant boost technique was used. There were no neoadjuvant or adjuvant treatments such as surgery or chemotherapy. The period of follow-up was ranging from 2 months through 93 months (median; 23 months). Survival was measured from the date radiation therapy was initiated. Results : The overall survival rate was 44.6$\%$ at 2 years and 24.5$\%$ at 5 years, with the median survival time of 23 months. of the 25 deaths, 7 patients died of intercurrent illness, and cause-specific survival rate was 61.0$\%$ at 2 years and 33.5$\%$ at 5 years. The disease-free survival rate was 38.9$\%$ at 2 years and 28.3$\%$ at 5 years. The local-relapse-free survival rate was 35.1$\%$, 28.1$\%$, respectively. On univariate analysis, tumor size was significant variable of overall survival (p=0.0015, 95$\%$ C.1.; 1.4814-5.2815), disease-free survival (P=0.0022, 95$\%$ C.1., 1.4707-5.7780) and local-relapse-free survival (p=0.0015, 95$\%$ C.1., 1.2910- 4.1197). 7 stage was significant variable of overall survival (p=0.0395, 95$\%$ C.1.; 1.1084-55.9112) and had borderline significance on disease-free survival (p=0.0649, 95$\%$ C.1.; 0.8888-50.7123) and local-relapse-free survival (p=0.0582, 95$\%$ C,1.; 0.9342-52.7755). On multivariate analysis, tumor size had borderline significance on overall survival (p=0.6919, 955 C.1., 0.9610-5.1277) and local-relapse-free survival ( p=0.0585, 95$\%$ C.1.; 0.9720-4.9657). Tumor size was also significant variable of disease-free survival (p=0.0317, 95% C.1.; 1.1028-8.4968). Conclusion : Radical radiotherapy is an effective treatment for small (71 or f3 cm) tumors and can be offered as alternative to surgery in elderly or infirmed patients. But when the size of tumor is larger than 5 cm, there were few long-term survivors treated with radiotherapy alone. The use of hypefractionated radiotherapy, endobronchial boost, radisensitizer and conformal or IMRT should be consider to improve the local control rate and disease-specific survival rate.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.311-323
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• 1998

Purpose : Prospective, single arm, Phase I/II clinical trial was performed to assess the efficacy and toxicity of the concurrent chemotherapy and definitive radiotherapy (RT) in patients with previously untreated locally advanced carcinoma of the uterine cervix. Methods and Materials : From Mar 1992 to January 1997, a total of 73 patients with advanced cervical carcinoma were entered on the protocol but 5 patients were excluded in analysis because of patients' refusal of treatment. Their ages ranged from 31 to 77 years, median 58 years. The International Federation of Gynecology and Obstetrics (FIGO) stage distribution was as follows: IIB 46, IIIA 2, IIIB 15 and IVA 5. RT consisted of external beam irradiation to 4,140-5,040 cGy/23-28 fractions plus high dose rate intracavitary treatments to deliver a dose of 30-35 Gy to point A in 6-7 fractions. During the intracavitary treatments parametrial boost was delivered for point B dose of 60 Gy in stage IIB and 65 Gy in stage IIIB. Two cycles of concurrent 5-fluorouracil and cisplatin (FP) chemotherapy (5-fluorouracil 1,000 mg/$m^2$/day continuous infusion for 4 days, day 1-4, 29-32 and cisplatin 20 mg/$m^2$/day intravenous bolus for 3 days day 1-3, 29-31) administered starting on day 1 of RT. Results : The median follow-up was 24 months (range 4-68+). Sixty-four patients were evaluable for survival rate in this protocol: The 5-year actuarial and disease-free survival rate were 52$\%$ and 64$\%$, respectively. The 5-rear actuarial survival for stage IIB and III+IVA patients were 58$\%$ and 36$\%$, respectively The 5-year disease-free survival rate for stage IIB and III+IVA patients were 71$\%$ and 40$\%$, respectively. Of the 68 patients evaluated for patterns of failure, overall recurrence rate was 27.9$\%$ (19/68) : local failure in 5.9$\%$ (4/68), distant metastasis in 10.3$\%$ (7/68) and both in 11.8$\%$ (8/68). Of the 64 patients evaluated for response at one month after the completion of treatment the complete response rate was 78$\%$ (50/64). Concurrent chemoradiation appear to be a well-tolerated regimen but there were two treatment-related deaths. Conclusion : Concurrent chemotherapy of FP with high-dose definitive RT in locally advanced carcinoma of the uterine cervix is feasible and effective with acceptable toxicities. This chemoradiation regimen may offer a modest survival benefit for advanced stage. Further follow-up of these patients will evaluate the impact of this regimen on the long-term local control and their survival.

• Korean Journal of Agricultural and Forest Meteorology
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• v.14 no.4
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• pp.207-221
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• 2012

Air temperature in Korea has increased by $1.5^{\circ}C$ over the last 100 years, which is nearly twice the global average rate during the same period. Moreover, it is projected that such change in temperature will continue in the 21st century. The objective of this study was to evaluate the potential impacts of future climate change on the rice production and adaptation methods in Korea. Climate data for the baseline (1971~2000) and the three future climate (2011~2040, 2041~2070, and 2071~2100) at fifty six sites in South Korea under IPCC SRES A1B scenario were used as the input to the rice crop model ORYZA2000. Six experimental schemes were carried out to evaluate the combined effects of climatic warming, $CO_2$ fertilization, and cropping season on rice production. We found that the average production in 2071~2100 would decrease by 23%, 27%, and 29% for early, middle, and middle-late rice maturing type, respectively, when cropping seasons were fixed. In contrast, predicted yield reduction was ~0%, 6%, and 7%, for early, middle, and middle-late rice maturing type, respectively, when cropping seasons were changed. Analysis of variation suggested that climatic warming, $CO_2$ fertilization, cropping season, and rice maturing type contributed 60, 10, 12, and 2% of rice yield, respectively. In addition, regression analysis suggested 14~46 and 53~86% of variations in rice yield were explained by grain number and filled grain ratio, respectively, when cropping season was fixed. On the other hand, 46~78 and 22~53% of variations were explained respectively with changing cropping season. It was projected that sterility caused by high temperature would have no effect on rice yield. As a result, rice yield reduction in the future climate in Korea would resulted from low filled grain ratio due to high growing temperature during grain-filling period because the $CO_2$ fertilization was insufficient to negate the negative effect of climatic warming. However, adjusting cropping seasons to future climate change may alleviate the rice production reduction by minimizing negative effect of climatic warming without altering positive effect of $CO_2$ fertilization, which improves weather condition during the grain-filling period.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.85-96
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• 1993

To investigate the alteration of transferrin receptor (TfR) in the proliferating or transformed liver cells, $^{125}I-transferrin$ binding experiment was carried out in the isolated parenchymal cells (PC) or nonparenchymal cells (NPC) from normal regenerated rat liver after partial hepatectomy and from the liver of 3-methyl-4-dimethyl-aminoazobenzene (3-Me-DAB) treated rat. With the administration of 3-Me-DAB for 8 weeks, the liver tissue showed marked morphologic changes of oval cell proliferation, regenerations of hepatocytes, and atypical proliferations of bile ducts, but these changes were little affected by partial hepatectomy. Transferrin binding values in PC or NPC homogenate from the regenerated liver of normal rat, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With the treatement of 3-Me-DAB for 8 weeks, transferrin binding sites in homogenates were higher than those of normal rat liver and increased by 7th day after partial hepatectomy. Transferrin binding sites (Bmax) in the cell membrane of NPC were higher than those of PC of normal rat liver, but there was no significant difference in Kd values between both groups (5.05, 6.3 nM). In the normal resenerated rat liver, transferrin binding sites in the PC or NPC plasma membrane, were increased by 3rd day and diminished to control level at 7th day after partial hepatectomy. With 3-Me-DAB tratment, transferrin binding sites in both liver NPC and PC plasma membrane were increased about 3 folds, compared to those in each plasma membrane of normal rat liver. And after partial hepatectomy of 3-Me-DAB trated rat, transferrin binding sites were increased by the 3rd day in the NPC plasma membrane but increased by the 7th day in the PC plasma membrane. In the transferrin binding sites of the PC or NPC plasma membrane of 3-Me-DAB treated liver, two kinds of Kd values $(3.1{\sim}4.7\;nM,\;25.4{\sim}54.1\;nM)$ were detected. The present results suggest that 1) TfRs are distributed in the liver PC as well as NPC; 2) Increased TfRs in PC or NPC plasma membrane of normal regenerated liver after partial hepatectomy and 3-Me-DAB treated rat liver, may be due to increased intracellular synthesis; 3) Increased TfRs in normal regenerated liver after partial hepatectomy might be related to the expression of a single type of high affinity site $(Kd,\;3.1{\sim}7.5\;nM)$, but in 3-Me-DAB treated rat liver might be related to the expression of high and low affinity types of receptors $(Kd,\;25.4{\sim}54.1\;nm)$.

• The Journal of Korean Society for Radiation Therapy
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• v.26 no.1
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• pp.127-135
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• 2014

Purpose : By taking advantage of each imaging modality, the use of fused CT/MRI image has increased in prostate cancer radiation therapy. However, fusion uncertainty may cause partial target miss or normal organ overdose. In order to complement such limitation, our hospital acquired MRI image (Planning MRI) by setting up patients with the same fixing tool and posture as CT simulation. This study aims to evaluate the usefulness of the Planning MRI through comparing and analyzing the diagnostic MRI image and Planning MRI image. Materials and Methods : This study targeted 10 patients who had been diagnosed with prostate cancer and prescribed nonhormone and definitive RT 70 Gy/28 fx from August 2011 to July 2013. Each patient had both CT and MRI simulations. The MRI images were acquired within one half hour after the CT simulation. The acquired CT/MRI images were fused primarily based on bony structure matching. This study measured the volume of prostate in the images of Planning MRI and diagnostic MRI. The diameters at the craniocaudal, anteroposterior and left-to-right directions from the center of prostate were measured in order to compare changes in the shape of prostate. Results : As a result of comparing the volume of prostate in the images of Planning MRI and diagnostic MRI, they were found to be $25.01cm^3$(range $15.84-34.75cm^3$) and $25.05cm^3$(range $15.28-35.88cm^3$) on average respectively. The diagnostic MRI had an increase of 0.12 % as compared with the Planning MRI. On the planning MRI, there was an increase in the volume by $7.46cm^3$(29 %) at the transition zone directions, and there was a decrease in the volume by $8.52cm^3$(34 %) in the peripheral zone direction. As a result of measuring the diameters at the craniocaudal, anteroposterior and left-to-right directions in the prostate, the Planning MRI was found to have on average 3.82cm, 2.38cm and 4.59cm respectively and the diagnostic MRI was found to have on average 3.37cm, 2.76cm and 4.51cm respectively. All three prostate diameters changed and the change was significant in the Planning MRI. On average, the anteroposterior prostate diameter decrease by 0.38cm(13 %). The mean right-to-left and craniocaudal diameter increased by 0.08cm(1.6 %) and 0.45cm(13 %), respectively. Conclusion : Based on the results of this study, it was found that the total volumes of prostate in the Planning MRI and the diagnostic MRI were not significantly different. However, there was a change in the shape and partial volume of prostate due to the insertion of prostate balloon tube to the rectum. Thus, if the Planning MRI images were used when conducting the fusion of CT/MRI images, it would be possible to include the target in the CTV without a loss as much as the increased volume in the transition zone. Also, it would be possible to reduce the radiation dose delivered to the rectum through separating more clearly the reduction of peripheral zone volume. Therefore, the author of this study believes that acquisition of Planning MRI image should be made to ensure target delineation and localization accuracy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.1
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• pp.96-101
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• 2003

This study was done to analyze the contents of minerals, to compare the measured values of calcium and the labeled values in food labeling and to analyze the ratio of calcium to other minerals in 43 calcium-fortified Food products sold in markets in Seoul, Korea. Content of minerals such as Ca, P, Mg, Na, K, Fe, Cu, Zn was measured by atomic absorption or colorimetric method after dry-ashing or wet-ashing. The measured values of calcium were ranged 65.5~343.9% of the labeled values in 43 calcium-fortified products. In 21 calcium-fortified food products, the measured calcium values were ranged 120～160% of the labeled values, and in three drinks those were less than 80% of the labeled, which is not acceptable to the food regulation. The ratios of Ca:P were 2.63$\pm$1.99 (mean$\pm$SD) in grain Products, 1.79$\pm$0.39 in Ramyuns, 2.80$\pm$0.53 in retort pouch food products and 8.35$\pm$12.87 in drinks. The Ca:Fe ratios were 126.33$\pm$44.36 in grain products, 130.65$\pm$34.67 in Ramyuns, 120.31$\pm$71.15 in retort pouch food products and 700.25$\pm$553.70 in drinks. The ratios of Ca:Mg were 11.86$\pm$5.40 in grain products, 9.29$\pm$1.34 in Ramyuns, 9.09$\pm$2.09 in retort pouch food products and 32.50$\pm$41.35 in drinks. The P:Mg ratios were 4.11$\pm$1.54 in grain products, 4.17$\pm$0.67 in Ramyuns, 2.58$\pm$0.45 in retort pouch food Products and 2.59$\pm$2.50 in drinks. These results suggest calcium contents and the ratio of calcium contents to other minerals in calcium-fortified food products should be strictly controlled.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.659-666
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• 2005

The purpose of this study was to compare the intake status of calcium, phosphorus, iron, and zinc of Korean adults residing in different regions. Subjects were recruited and divided into three groups according to the districts where they lived, which included rural (n=137), coastal (n=100), and urban district (n=117). Subjects were interviewed using a general questionnaire and 24-hour recall method for dietary intake. The average age of the subjects were 58.1 years for rural district, 57.7 years for coastal district, and 48.6 years for urban district. There was no significance in total food intake by regions. The food intakes from cereals, mushrooms, vegetables of rural district, that from fishes of coastal district, and those from sugars, milks, oils of urban area were the highest among three districts. The calcium, phosphorus, iron, and zinc intakes were $60.1\%,\;123.9\%,\;95.2\%,\;and\;73.1\%$ of RDAs, respectively. The calcium intakes as percentage of RDA in rural and coastal district were significantly (p<0.01) lower than that in urban district. A larger number of subjects from coastal or urban district ate under $75\%$ of zinc RDA compared to those from rural village. Major sources of dietary calcium in total subjects were anchovy, kimchi, milk, soybean curd, rice, ice cream, sea mustard, yogurt, loach, and welsh onion. Rice supplied $15.5\%$ for phosphorus, $22.1\%$ for iron, and $35.9\%$ for zinc of total intake. Except for rice, major sources of dietary zinc were pork, beef, small red bean, dog meat, chicken, jacopever, soybean curd, glutinous millet, and kimchi. In conclusion, the food and mineral intakes of adults differed according to the regions in which they resided. The food and nutrient intakes of coastal district were not satisfactory, and calcium and zinc intakes of three regions did not meet RDAs. Therefore, it is required unique and discriminatory nutritional education with each region for increasing intakes of calcium and zinc.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.2
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• pp.269-277
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• 2003

Effects of soy protein concentrate (SPC) containing isoflavone and casein diets on plasma phospholipid (PLs)-fatty acid patterns were investigated in 7-& 40- wk old female rats. Diets containing 16% SPC (soy/young:SY, soy/old: SO) and casein (casein/young : CY, casein/ old: CO) supplemented with 0.5% cholesterol were fed for 4 wks. Fatty acid compositions of plasma PLs were determined by TLC and GLC. Compared to the dietary protein effects, age effects on serum lipids were more profound. The levels of total cholesterol (Chol.), triglyceride, HDL-Chol., (LDL+VLDL)-Chol. and atherogenic index (AI) were higher in older groups (OC & OS) than younger groups (YC &. YS). Soy groups had higher Ell)L-Chol. level and lower (LDL+ VLDL)-Chol. and AI, compared with casein groups. The compositions of C22:0, Cl8:1 $\omega$9 and sum of MUFA in plasma PLs were significantly higher in casein group (CY & CO) than soy group (SY & SO), but those of sum of SFA were higher in soy group. The compositions of C22:0, Cl8:1 $\omega$9, C22:1, Cl8:3$\omega$3 and C22:4$\omega$6 were higher and those of C22:6$\omega$3, sum of $\omega$3, Cl8: 2$\omega$6 C20:4$\omega$6, sum of $\omega$6 and sum of PUFA were lower in plasma PLs of younger rats. The average P/S and $\omega$3/$\omega$6 ratio in older group was higher. The $\Delta$-7 desaturation index (16:0⇒16:1$\omega$7) and $\Delta$-9 desaturation index (18:0⇒18:1$\omega$9) were lower in soy group than casein group, while $\Delta$-6 and $\Delta$-5 desaturation index were not affected by dietary protein. The $\Delta$-4 desaturation index (22:4$\omega$6⇒22:5$\omega$6) were higher and elongation index (20:4$\omega$6⇒22:4$\omega$6) were lower in older group. The ratio of the products of $\omega$3 fatty acid series (Cl8:3) was significantly higher in older group, which indicated that age affected the plasma PUFA metabolism. On the other hand, older rats had higher serum cholesterol level compared with younger rats. Taken together, these changes in fatty acid composition might cause minimal changes in tile membrane fluidity induced by the increase serum cholesterol level.