• Title/Summary/Keyword: Laboratory tests

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18-year Follow-up of Extended Newborn Screening for Metabolic and Endocrine Disorders (대사 및 내분비 질환에 대한 광범위 신생아 선별 검사의 18년 추적 관찰)

  • Song, Wung Joo;Lee, Sunho;Jeon, Young Mi;Kim, Sook Za;Jang, Mea Young
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.18 no.2
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    • pp.35-42
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    • 2018
  • Purpose: To follow up Korean patients with metabolic and endocrine disorders ascertained by Korea Genetics Research Center, and assess the long-term effectiveness of extended newborn screening program in Korea. Methods: From January 2000 to December 2017, tandem mass spectrometry and fluoroimmunoassay were employed in extended newborn screening (NBS). The NBS program obtained dried blood spots from 283,626 babies, 48 hours after birth, and screened for galactosemia, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and 50 preventable inborn errors of amino acid, fatty acid, and organic acid metabolism. Results: 28 cases of amino acid disorders, 75 cases of organic acid disorders, 27 cases of fatty acid disorders, 51 cases of urea cycle disorders, 127 cases of CH, 14 cases of CAH, and 15 cases of galactosemia were ascertained through NBS and subsequent confirmatory laboratory tests. Patients with amino acid metabolic disorders, galactosemia, CH, or CAH were more likely to have a better long-term outcome if detected early. Early management of MSUD led to much better outcome in over 90%. Despite early intervention, 32% of other organic acidemia cases still resulted in developmental delay and neurological problems. Fatty acid disorders showed varied results; those with EMA and MCAD had a good outcome, but those with VLCAD had serious neurological problems and considerably higher mortality. 75% with UCD experienced serious neurological complications and higher mortality. Conclusion: The nation-wide NBS program must be accompanied by comprehensive long-term management and physician and family education of inborn errors of metabolism for a better outcome.

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Comparison Analysis of The results of IRMA Test among Different Equipment According to Algorithm change. (IRMA 검사법 중 알고리즘 변경에 따른 장비 간 결과값 비교분석)

  • Kim, Jung In;Kwon, Won Hyun;Lee, Kyung Jae
    • The Korean Journal of Nuclear Medicine Technology
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    • v.23 no.2
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    • pp.43-50
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    • 2019
  • Purpose The principle of nuclear medicine test is divided into two main categories: competition(radioimmunoassay, RIA) and noncompetitive reaction(Immunoradiometric assay, IRMA). It is known that the curve fitting method, which is commonly used in inspection field, uses Spline interpolation in RIA method and Linear interpolation method in IRMA method. Among them, the insulin test using the IRMA test showed a significant difference, especially at low concentrations, despite the same algorithm of linear interpolation between fully automated radio immunoassay analyzers. In this study, we aim to obtain results from applying two different of algorithm using fully automated radio immunoassay analyzers including Gamma pro, Gamma 10, Cobra, and SR300. Materials and Methods A total of 30 test samples were selected for the test of TSH, ferritin, C-peptide, and insulin serum levels. Test was performed by IRMA method. We compared the difference in the results of applying the linear interpolation method and the spline interpolation method to Gamma Pro, Gamma 10, Cobra, and SR300 equipment. Results Two-way ANOVA was used for statistical analysis. The significance level was applied as P <0.05. The results of TSH, ferritin, C-peptide, and insulin tests were compared between the fully automated radio immunoassay analyzers. There was a significant difference between ferritin, C-peptide, and insulin serum levels(P<0.001). TSH didn't show any significant different between the devices(P=0.29). In the difference between linear and spline interpolation, there was no significant difference between insulin test(P=0.08), TSH test(P=0.81), and Ferritin test(P=0.06). However, C-peptide test showed a significant difference(P=0.03). Especially, the insulin test showed significant difference in lower ranges. As a result of comparing and analyzing the difference between the two interpolation methods, the devices in the low concentration group showed significant difference(P<0.001). Conclusion In case of new equipment in the laboratory it is necessary to recognize that there is a difference in the curve fitting method for each automated radio immunoassay analyzers in the low concentration area when the principle of inspection is IRMA method.

Nationwide "Pediatric Nutrition Day" survey on the nutritional status of hospitalized children in South Korea

  • Lee, Yoo Min;Ryoo, Eell;Hong, Jeana;Kang, Ben;Choe, Byung-Ho;Seo, Ji-Hyun;Park, Ji Sook;Jang, Hyo-Jeong;Lee, Yoon;Chang, Eun Jae;Chang, Ju Young;Lee, Hae Jeong;Kim, Ju Young;Lee, Eun Hye;Kim, Hyun Jin;Chung, Ju-Young;Choi, You Jin;Choi, So Yoon;Kim, Soon Chul;Kang, Ki-Soo;Yi, Dae Yong;Moon, Kyung Rye;Lee, Ji Hyuk;Kim, Yong Joo;Yang, Hye Ran
    • Nutrition Research and Practice
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    • v.15 no.2
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    • pp.213-224
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    • 2021
  • BACKGROUND/OBJECTIVES: To evaluate the nutritional status and prevalence of malnutrition in hospitalized children at admission and during hospitalization in South Korea. SUBJECTS/METHODS: This first cross-sectional nationwide "Pediatric Nutrition Day (pNday)" survey was conducted among 872 hospitalized children (504 boys, 368 girls; 686 medical, 186 surgical) from 23 hospitals in South Korea. Malnutrition risk was screened using the Pediatric Yorkhill Malnutrition Score (PYMS) and the Screening Tool Risk on Nutritional status and Growth. Nutritional status was assessed by z-scores of weight-for-age for underweight, weight-for-height for wasting, and height-for-age for stunting as well as laboratory tests. RESULTS: At admission, of the 872 hospitalized children, 17.2% were underweight, and the prevalence of wasting and stunting was 20.2% and 17.3%, respectively. During hospitalization till pNday, 10.8% and 19.6% experienced weight loss and decreased oral intake, respectively. During the aforementioned period, fasting was more prevalent in surgical patients (7.5%) than in medical patients (1.6%) (P < 0.001). According to the PYMS, 34.3% and 30% of the children at admission and on pNday, respectively, had a high-risk of malnutrition, requiring consultation with the nutritional support team (NST). However, only 4% were actually referred to the NST during hospitalization. CONCLUSIONS: Malnutrition was prevalent at admission and during hospitalization in pediatric patients, with many children experiencing weight loss and poor oral intake. To improve the nutritional status of hospitalized children, it is important to screen and identify all children at risk of malnutrition and refer malnourished patients to the multidisciplinary NST for proper nutritional interventions.

The Validation of a Commercial Testosterone RIA Test Kits (Testosterone RIA 검사 kit 별 유효성 비교평가)

  • Ryu, Hwa-jin;Shin, Seon-yeong;Cho, Seong-uk
    • The Korean Journal of Nuclear Medicine Technology
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    • v.26 no.1
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    • pp.38-41
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    • 2022
  • Purpose Testosterone is a steroid hormone synthesized by the Leydig cells of the testes in men, and by the adrenal cortex and ovaries in women. Testosterone production is regulated by luteinzing hormone secreted by the anterior pituitary gland. In this experiment, the effectiveness of testosterone radioimmunoassay (RIA) kits produced by three companies was evaluated and compared in case the production of testosterone kits was stopped or supply problems occurred. Materials and Methods In October 2021, samples were collected from the patients (n=49) who requested the testosterone RIA test. The experiment was conducted by dividing the patient's sample into low concentration (1.0 ng/mL or less), medium concentration (2.0-4.0 ng/mL) and high concentration (6.0 ng/mL or more). The Testosterone RIA test compared and evaluated the validity of Company A kits used in this hospital and those of Company B and C used in other hospitals. The precision, sensitivity, recovery, linearity and correlation were evaluated for each kit. The testosterone RIA test was carried out in accordance with the insert kit manual for each manufacturer. Results As a result of measuring the precision of the intra assay, the Coefficient of Variation (CV) value of the company A kit was high at 11.4% only in the low concentration sample, and in the case of the company B and C kits, the CV value was less than 10% at low, medium, and high concentrations. In the inter-assay precision measurement, the CV value was less than 15% in both A and C kits, but in the case of the B kit, the CV value exceeded 15% at low and medium concentrations. Sensitivity was 0.13 ng/mL for company A, 0.01 ng/mL for company B, and 0.01 ng/mL for company C, and the linearity of all three kits showed excellent linearity. In the case of recovery rate, all of the A, B, and C company kits showed results that were out of 90-110%. In the case of correlation test, when compared with the company A kit currently use in here, the correlation coefficient (R2) value for the company B kit was 0.9508, and for the company C kit was 0.9352 Conclusion As a result, there was a slight difference in precision at the low concentration sample. The correlation test showed an excellent correlation coefficient. However, it was difficult to secure samples of various concentrations because there were not many tests of testosterone requested at this hospital. So, additional experiments should be carried out by acquiring samples of various concentrations on each laboratory later.

One-Dimensional Consolidation Simulation of Kaolinte using Geotechnical Online Testing Method (온라인 실험을 이용한 카올리나이트 점토의 일차원 압밀 시뮬레이션)

  • Kwon, Youngcheul
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.26 no.4C
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    • pp.247-254
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    • 2006
  • Online testing method is one of the numerical experiment methods using experimental information for a numerical analysis directly. The method has an advantage in that analysis can be conducted without using an idealized mechanical model, because mechanical properties are updated from element test for a numerical analysis in real time. The online testing method has mainly been used for the geotechnical seismic engineering, whose major target is sand. A testing method that may be applied to a consolidation problem has recently been developed and laboratory and field verifications have been tried. Although related research thus far has mainly used a method to update average reaction for a numerical analysis by positioning an element tests at the center of a consolidation layer, a weakness that accuracy of the analysis can be impaired as the thickness of the consolidation layer becomes more thicker has been pointed out regarding the method. To clarify the effectiveness and possible analysis scope of the online testing method in relation to the consolidation problem, we need to review the results by applying experiment conditions that may completely exclude such a factor. This research reviewed the results of the online consolidation test in terms of reproduction of the consolidation settlement and the dissipation of excess pore water pressure of a clay specimen by comparing the results of an online consolidation test and a separated-type consolidation test carried out under the same conditions. As a result, the online consolidation test reproduced the change of compressibility according effective stress of clay without a huge contradiction. In terms of the dissipation rate of excess pore water pressure, however, the online consolidation test was a little faster. In conclusion, experiment procedure needs to improve in a direction that hydraulic conductivity can be updated in real time so as to more precisely predict the dissipation of excess pore water pressure. Further research or improvement should be carried out with regard to the consolidation settlement after the end of the dissipation of excess pore water pressure.

Enhanced immunity effect of Korean Red Ginseng capsule: A randomized, double-blind and placebo-controlled clinical trial

  • Yi Yang;Jing Li;Shengyuan Zhou;Daoyan Ni;Cailing Yang;Xu Zhang;Jian Tan;Jingrui Yan;Na Wang
    • Journal of Ginseng Research
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    • v.48 no.5
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    • pp.504-510
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    • 2024
  • Background: As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status. Methods: This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration). Results: After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (P < 0.01), (2) CD3 and CD4/CD8 increased significantly after the test (P < 0.05), (3) IgG, IgA, IgM and WBC increased significantly in the mid-term and after the test (P < 0.01); the results of the secondary efficacy indicators: (1) TNF-α decreased significantly in the midterm (P < 0.05), IFN-γ decreased significantly in the mid-term (P < 0.01), (2) NK increased significantly in the mid-term and after the test (P < 0.05), (3) monocyte increased significantly in the mid-term and after the test (P < 0.01). Inter-group comparison of the test group and the control group, the results of the main efficacy indicators: (1) immune related health scores were higher than that of the control group in the mid-term and after the test (P < 0.01), (2) IgA of the test group was higher than that of the control group in the mid-term and after the test (P < 0.05); the results of the secondary efficacy indicators: (1) WBC of the test group was higher than that of the control group in the mid-term (P < 0.05); (2) monocytes of the test group were higher than that of the control group in the mid-term and after the test (P < 0.05), neutrophils of the test group were higher than that of the control group in the mid-term (P < 0.05). Conclusion: Taking KRG has no adverse effects on the health of the subjects. According to the standard of clinical trial scheme, the immune related health scores and IgA in the main efficacy indicators were positive, which shows that KRG is helpful in enhancing human immunity.

Analysis of Variation for Parallel Test between Reagent Lots in in-vitro Laboratory of Nuclear Medicine Department (핵의학 체외검사실에서 시약 lot간 parallel test 시 변이 분석)

  • Chae, Hong Joo;Cheon, Jun Hong;Lee, Sun Ho;Yoo, So Yeon;Yoo, Seon Hee;Park, Ji Hye;Lim, Soo Yeon
    • The Korean Journal of Nuclear Medicine Technology
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    • v.23 no.2
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    • pp.51-58
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    • 2019
  • Purpose In in-vitro laboratories of nuclear medicine department, when the reagent lot or reagent lot changes Comparability test or parallel test is performed to determine whether the results between lots are reliable. The most commonly used standard domestic laboratories is to obtain %difference from the difference in results between two lots of reagents, and then many laboratories are set the standard to less than 20% at low concentrations and less than 10% at medium and high concentrations. If the range is deviated from the standard, the test is considered failed and it is repeated until the result falls within the standard range. In this study, several tests are selected that are performed in nuclear medicine in-vitro laboratories to analyze parallel test results and to establish criteria for customized percent difference for each test. Materials and Methods From January to November 2018, the result of parallel test for reagent lot change is analyzed for 7 items including thyroid-stimulating hormone (TSH), free thyroxine (FT4), carcinoembryonic antigen (CEA), CA-125, prostate-specific antigen (PSA), HBs-Ab and Insulin. The RIA-MAT 280 system which adopted the principle of IRMA is used for TSH, FT4, CEA, CA-125 and PSA. TECAN automated dispensing equipment and GAMMA-10 is used to measure insulin test. For the test of HBs-Ab, HAMILTON automated dispensing equipment and Cobra Gamma ray measuring instrument are used. Separate reagent, customized calibrator and quality control materials are used in this experiment. Results 1. TSH [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(low concentration) [14.8 / 4.4 / 3.7 / 0.0 ] C-2(middle concentration) [10.1 / 4.2 / 3.7 / 0.0] 2. FT4 [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(low concentration) [10.0 / 4.2 / 3.9 / 0.0] C-2(high concentration) [9.6 / 3.3 / 3.1 / 0.0 ] 3. CA-125 [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(middle concentration) [9.6 / 4.3 / 4.3 / 0.3] C-2(high concentration) [6.5 / 3.5 / 4.3 / 0.4] 4. CEA [%diffrence Max / Mean / median] (P-value by t-test > 0.05) C-1(low concentration) [9.8 / 4.2 / 3.0 / 0.0] C-2(middle concentration) [8.7 / 3.7 / 2.3 / 0.3] 5. PSA [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(low concentration) [15.4 / 7.6 / 8.2 / 0.0] C-2(middle concentration) [8.8 / 4.5 / 4.8 / 0.9] 6. HBs-Ab [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(middle concentration) [9.6 / 3.7 / 2.7 / 0.2] C-2(high concentration) [8.9 / 4.1 / 3.6 / 0.3] 7. Insulin [%diffrence Max / Mean / Median] (P-value by t-test > 0.05) C-1(middle concentration) [8.7 / 3.1 / 2.4 / 0.9] C-2(high concentration) [8.3 / 3.2 / 1.5 / 0.1] In some low concentration measurements, the percent difference is found above 10 to nearly 15 percent in result of target value calculated at a lower concentration. In addition, when the value is measured after Standard level 6, which is the highest value of reagents in the dispensing sequence, the result would have been affected by a hook effect. Overall, there was no significant difference in lot change of quality control material (p-value>0.05). Conclusion Variations between reagent lots are not large in immunoradiometric assays. It is likely that this is due to the selection of items that have relatively high detection rate in the immunoradiometric method and several remeasurements. In most test results, the difference was less than 10 percent, which was within the standard range. TSH control level 1 and PSA control level 1, which have low concentration target value, exceeded 10 percent more than twice, but it did not result in a value that was near 20 percent. As a result, it is required to perform a longer period of observation for more homogenized average results and to obtain laboratory-specific acceptance criteria for each item. Also, it is advised to study observations considering various variables.

Depositional Environment and Formation Ages of Eurimji Lake Sediments in Jaechon City, Korea (제천 의림지 호저퇴적물 퇴적환경과 형성시기 고찰)

  • 김주용;양동윤;이진영;김정호;이상헌
    • The Korean Journal of Quaternary Research
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    • v.14 no.1
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    • pp.7-31
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    • 2000
  • Quaternary Geological and geophysical investigation was performed at the Eurimji reservoir of Jaechon City in order to interprete depositional environment and genesis of lake sediments. For this purpose, echo sounding, bottom sampling and columnar sampling by drilling on board and GPR survey were employed for a proper field investigation. Laboratory tests cover grain size population analysis, pollen analysis and $^{14}C$ datings for the lake sediments. The some parts of lake bottom sediments anthropogenically tubated and filled several times to date, indicating several mounds on the bottom surface which is difficult to explain by bottom current. Majority of natural sediments were accumulated both as rolling and suspended loads during seasonal flooding regime, when flash flow and current flow are relatively strong not only at bridge area of the western part of Eurimji, connected to stream valley, but at the several conduit or sewage system surrounding the lake. Most of uniform suspend sediments are accumulated at the lake center and lower bank area. Some parts of bottom sediments indicate the existence of turbid flow and mudflow probably due to piezometric overflowing from the lake bottom, the existence of which are proved by CM patterns of the lake bottom sediments. The columnar samples of the lake sediments in ER-1 and ER-3-1 boreholes indicate good condition without any human tubation. The grain size character of borehole samples shows poorly sorted population, predominantly composed of fine sand and muds, varying skewness and kurtosis, which indicate multi-processed lake deposits, very similar to lake bottom sediments. Borehole columnar section, echo sounding and GPR survey profilings, as well as processed data, indicate that organic mud layers of Eurimji lake deposits are deeper and thicker towards lower bank area, especially west of profile line-9. In addition the columnar sediments indicate plant coverage of the Eurimji area were divided into two pollen zones. Arboreal pollen ( AP) is predominant in the lower pollen zone, whreas non-aboreal pollen(NAP) is rich in the upper pollen zone. Both of the pollen zones are related to the vegetation coverage frequently found in coniferous and deciduous broad-leaved trees(mixed forest) surrounded by mountains and hilly areas and prevailing by aquatic or aquatic margin under the wet temperate climate. The $^{14}C$ age of the dark gray organic muds, ER1-12 sample, is 950$\pm$40 years B.P. As the sediments are anthropogenetically undisturbed, it is assumed that the reliability of age is high. Three $^{14}C$ ages of the dark gray organic muds, including ER3-1-8, ER3-1-10, ER3-1-11 samples, are 600$\pm$30 years B.P., 650$\pm$30 years B.P., 800$\pm$40 years B.P. in the descending order of stratigraphic columnar section. Based on the interpretation of depositional environments and formation ages, it is proved that Eurimji reservoir were constructed at least 950$\pm$40 years B.P., the calibrated ages of which ranges from 827 years, B.P. to 866 years B.P. Ancient people utilize the natural environment of the stream valley to meet the need of water irrigation for agriculture in the local valley center and old alluvium fan area.

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Analysis of Urinary Mass Screening for Elementary, Middle and High School Children Over a 3-year Period(1995-1997) in Seoul (서울지역내 초.중.고 학생들에 실시된 3년 동안의($1995{\sim}1997$) 집단뇨검사 결과 분석)

  • Kang Ho-Seok;Lee Chong-Guk
    • Childhood Kidney Diseases
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    • v.3 no.2
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    • pp.161-169
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    • 1999
  • Purpose : The urinary mass screening program for the detection of proteinuria in school aged population has been performed in Seoul since 1981. Systematic evaluation in corporation with the Seoul School Health Center for students with proteinuria identified in the mass screening has been performed from 1987. The results of urinary mass screening up to 1994 was reported. I report here the results of urinary mass screening from 1995 to 1997 and compare them with previous results and attempt to reveal the significance of urinary mass screening. Objects and Methods : In the 3-year period between 1995 and 1997, annually about 460,000 students comprising 3 different age groups; 5th grade of elementary school, 2nd grade of middle school and 2nd grade of high school were chosen, corresponding to the approximate ages of 11, 14, and 17 years, respectively. These subjects accounted for 26% of total school aged children in Seoul. The screening program was carried out in 3 steps. The 1st test was performed with dipstick at school and the 2nd at the Seoul School Health Center. Those students who showed proteinuria in the 1st and 2nd tests were referred to the hospital. Laboratory examinations including renal biopsies were performed to those students with pathologic proteinuria to clarify the incipient renal diseases. Results : 1) The prevalence of asymptomatic proteinuria was 0.28% in the 1st test. It peaked at the group of 14 years old as 0.34%, compared with 0.26% at the group of 11 years old and 0.24% at the group of 17 years old. It reached to 0.26% in male and 0.30% in female. 2) 25 percent of those having proteinuria at the first test were positive at the second test. 3) The proportion of patients with proteinuria by 3rd test were as follows; 25% of transient proteinuria, 55% of orthostatic proteinuria, 6% of constant proteinuria, 12% of proteinuria with hematuria, and 2% of transient proteinuria with isolated hematuria. Pathologic proteinuria were totaled as 20%. The prevalence of renal diseases among the age group of 7-18 years old was estimated to be 1.4 per 10,000. 4) Renal biopsy performed on 38 children with proteinuria at the third test revealed IgA nephropathy in 17(44%), focal segmental glomerusclerosis in 5(13%), minimal change disease in 4(11%), membranoproliferative glomeronephritis in 3(8%), $Henoch-Sch\"{o}nlein$ purpura nephritis in 3(8%), and others in 6(16%). Therefore, the prevalence of IgA nephropathy among the age group of 7-18 years old was estimated to be 0.64 per 10,000. 5) The prevalence of chronic renal failure was estimated to be 5.7 per 1 million of 7 to 18 years age group. Conclusions : 1) The prevalence of proteinuria in the first screening test was 0.28% and finally only 5% of them showed the pathologic proteinuria at the third test. 2) The prevalence of IgA nephropathy and chronic renal failure were 0.63 per 10,000 and 5.7 per 1 million, respectively among school-aged children in Seoul.

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Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.