• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• The Korean Journal of Zoology
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• v.14 no.4
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• pp.199-204
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• 1971

The effect of 400 R total-body X-irradiation on the rate of deoxycytidine-2-$^14 C$(CdR-2-$^14 C$) into DNA and on the degradation of DNA has been studied in the liver, spleen and thymus of the rat. The postirradiation period can be divided into a radiation reaction period followed by a regeneration period. During the period of radiation reaction, which consists of days 1-2, markdely decreased CdR-2-$^14 C$ incorporation into DNA of each organ is observed. Rate of incorporation of labeled precursor in the thymus shows the most profound decrease, whereas those in the liver and spleen show similar decrease when expressed as percent of normal. The change in the amount of DNA as percent of normal exhibits a similar pattern in all organs, but the rate of decrease is larger in the spleen and thymus compared to that in the liver. The period of regeneration as judged by the incorporation experiment appears day 4 to 5, which consists of the second phase of the regeneration period. The second phase is highlighted by a markedly increased rate of CdR-2-$^14 C$ incorporation and by a slow and continued increase in the amount of DNA in all organs. The regeneration occurs faster in the liver and spleen than in the thymus which is the most radiosensitive of the all. The findings of the present experiments are strongly suggestive of the fact that the radiation-induced loss of spleen and thymus DNA as well as the radiation-caused inhibition in the CdR incorporation into DNA of the thymus are the important factors in the elevated levels of CdR in the urine and plasma.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.6
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• pp.561-565
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• 2007

Purpose: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Materials and Methods: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound $[^{18}F]$TPP via two step nucleophilic substitution of no-carrier-added $[^{18}F]$fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and $K_2CO_3$. Result: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound $[^{18}F]$TPP was synthesized in $10\sim15%$ yield. The radiochemical purity of the $[^{18}F]$TPP was $95.57{\pm}0.51%$ (n=11). Conclusion: $[^{18}F]$TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply $[^{18}F]$TPP in preclinical or clinical researches.

• Journal of Nutrition and Health
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• v.55 no.3
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• pp.330-347
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• 2022

Folate, a water-soluble vitamin, acts as a coenzyme for one-carbon metabolism in nucleic acid synthesis and amino acid metabolism. Adequate folate nutritional status during the periconceptional period is known to prevent neural tube defects. In addition, insufficient folate intake is associated with various conditions, such as anemia, hyperhomocysteinemia, cardiovascular disease, cancer, cognitive impairment, and depression. This review discusses the rationale for the revision of the 2020 Korean dietary reference intakes for folate, and suggestions for future revisions. Based on the changes in the standard body weight in 2020, the adequate intake (AI) for infants (5-11 months) and the estimated average requirements (EARs) for 15-18 years of age were revised, but there were no changes in the recommended nutrient intakes (RNIs) and tolerable upper intake levels (ULs) for all age groups. Mean folate intake did not reach RNI in most age groups and was particularly low in women aged 15-29 years, according to the results of the 2016-2018 Korea National Health and Nutrition Examination Survey (KNHANES). The percentages of folate intake to RNI were lower than 60% in pregnant and lactating women, but serum folate concentrations were higher than those in other age groups, presumably due to the use of supplements. Therefore, total folate intake, from both food and supplements, should be evaluated. In addition, the database of folate in raw, cooked, and fortified foods should be further expanded to accurately assess the folate intake of Koreans. Determination of the concentrations of erythrocyte folate and plasma homocysteine as well as serum folate is recommended, and quality control of the analysis is critical.

• Korean Journal of Veterinary Service
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• v.45 no.2
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• pp.79-86
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• 2022

Reproductive disorders in cows cause economic loss in livestock farms. This study was carried out to investigate the incidence of endometriosis in the uterine of Korean indigenous cow (Hanwoo). In the present study, the uterine of 25 cows was provided by the slaughterhouse. As a result on a visual examination of the uterus, 18 out of 25 were visually normal, and 7 uteruses (28%) appeared rather pale and showed purulent or mucosal symptoms in Uterine horn. However, the results of hematological analysis showed that both RBC and WBC were normal and showed no signs of systemic inflammation, indicating 7 cows showed asymptomatic endometriosis. The inflammatory uterus (28%) showed a wide range of pathological conditions that elicit an inflammatory response, such as serous exudate and bleeding. Histological and microscopic analysis in the inflammatory group demonstrated that there was swelling of the uterine glands, and neutrophil, basophil, and lymphocyte appeared in the uterine gland. Moreover, plasma cells and hemosiderin-laden macrophages were increased in the endometrial stroma, which lead to inhibit pregnancy by suppression of the synthesis of pregnancy hormones, and the appearance of hemosiderin-laden macrophages is an indicator of intracellular bleeding. In summary, hematologically, it is a normal diagnosis in Korean indigenous cows, however, when the uterus was extracted and investigated microscopically, the asymptomatic endometriosis were evident. In order to achieve the goal of healthy cow management and breeding within 2 weeks after birth, cows' uterus should be washed, disinfected, and through thorough the hygiene management, it aims to prevent asymptomatic endometriosis to produce healthy offspring and reduce the breeding interval.

• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Journal of Dental Rehabilitation and Applied Science
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• v.25 no.4
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• pp.361-374
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• 2009

For successful osteogenesis around the implants, interaction between implant surface and surrounding tissue is important. Biomechanical bonding and biochemical bonding are considered to influence the response of adherent cells. But the focus has shifted surface chemistry. The purpose of this study is to evaluate the MC3T3-E1 osteoblast like cell responses of magnesium (Mg) ion implanted titanium surface produced using a plasma source ion implantation method. Commercially pure titanium disc was used as substrates. The discs were prepared to produce four different surface, A: Machine turned surface, B: Mg implanted surface, C: sandblasted surface, D: sandblasted and Mg implanted surface. MC3T3 El osteoblastic like cells were cultured on the disc specimens. Cell adhesion, proliferation, differentiation, and synthesis of extracellular matrix were evaluated. The cell adhesion morphology was evaluated by SEM. RT PCR assay was used for assessment of cell adhesion, proliferation and differentiation. ALP activity was measured for cell differentiation. The results of this study were as follows: 1. SEM showed that cell on Mg ion groups was more proliferative than that of non Mg ion groups. On the machine turned surface, cell showed some degree of contact guidance in aligning with the machining grooves. 2. In RT PCR analysis, osteonectin and c-fos mRNA were more expressed on sandblasted and Mg ion implanted group. 3. ALP activity was not significantly different among all groups. Within the limitations of this study, the following conclusions were drawn: It might indicate Mg ion implanted titanium surface induce better bone response than non Mg ion groups.

• Journal of the Korean Chemical Society
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• v.45 no.5
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• pp.461-469
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• 2001

The combinatorial approach has been applied to discover and optimize the composition of the novel or enhanced materials. In this study, we screened the optimum composition of the system SrO-Gd$_2$O$_3$-Al$_2$O$_3$ doped with $Tb^{3+}$ by a polymerized-complex combinatorial chemistry method. Mixtures with compositions of Sr, Gd and Al component that is in the range from 0 to 1 in about 0.05 increments could be tested. The sample powders were synthesized by a polymerized complex method. To prepare appropriately polymeric precursors, we used the metallic nitrates, citric acid and ethylene glycol. The luminescence properties of the synthesized powders are investigated using the UV and VUV (Vacuum-UV: 147 nm) photoluminescence spectrometer. In addition, the crystallinity and morphology of powder were monitored by X-ray diffraction spectrometer and scanning electron microscopy. In result of VUV PL works, there are good luminescent samples with the composition of 0.595 < x < 0.733 and 0.016 < y < 0.017 in Gd1-x-yAlxTbyO$\delta$ and 0.049 < x < 0.064 and 0.02 < y < 0.039 in $Sr_xAl_{1-x-y}Tb_yO_$\delta$$, their materials can be applicable to plasma display panels as the green phosphor.

• The Korean Journal of Nuclear Medicine
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• v.28 no.3
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• pp.364-370
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• 1994

The purpose of this study is to evaluate the clinical application of the no carrier added $[^{51}Cr]Cr(III)$-EDTA complexes, produced at Korea Cancer Center Hospital. The $[^{51}Cr]Cr(III)$-EDTA complexes, usefut for measurement of GFR were prepared at room temperature in the presence of bicarbonate catalysts. The radiochemical purity of $[^{51}Cr]Cr(III)$-EDTA was over 99% by paper electrophoresis. The time activity curves were obtained by counting the blood samples from 5 volunteers and counting the head and neck regions with whole body counter after injection of the $^{51}Cr$-EDTA, respectively. After the nonlinear regression, the area under curve was obtained. The plasma clearance of the $^{51}Cr$-EDTA was calculated with injected dose/AUC. The clearance rate calculated with the head and neck counting data was in good agreement with the result from the plasma sample radioactivity at 1-3 hrs after injection. From this result, the counting of head and neck region and the nonlinear regression by 2-compartment model could be applied for the measurement of the clearance rate. Using MIRD system, the absorbed radiation dose was calculated by residence $time{\times}S$. The absorbed whole body radiation dose was negligibly small.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.573-580
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• 2005

Cholesterol $7\alpha-hydroxylase$ (CYP7A1) is the rate-limiting enzyme in the conversion of cholesterol to bile acids and plays a central role in regulating cholesterol homeostasis. We previously showed that a fermentable $\beta-glucan$ ingestion decreased plasma cholesterol levels due to fecal bile acid excretion elevation involved inincrease of cholesterol $7\alpha-hydroxylase$ mRNA expression and activity. It is proposed that short chain fatty acids (SCFA) produced by cecal and colonic fermentation of soluble fiber are associated with cholesterol-lowering effect of fiber. In the present study, we investigated whether CYP7A1 expression is up-regulated by short chain fatty acids or by hormones in cultured human hepatoma (HepG2) cells. Confluent HepG2 cell were incubated with acetate, propionate, or butyrate at 1 mM concentration for 24 hrs. Acetate as well as propionate increased to 1.8-fold expression of CYP7A1 mRNA than the control. Butyrate also increased 1.5-fold expression of CYP7A1 mRNA. Our data show for the first time that SCFA increase expression of CYP7A1 mRNA. Adding insulin, dexamethasone and triiodothyronine $(1\;{\mu}M)$ to HepG2 cell increased the expression of CYP7A1 mRNA to $150\%,\;173\%,\;141\%$, respectively. These results suggest that SCFA produced by cecal fermentation stimulate enteric nervous system, in which secreted some neuropeptides may be responsible for change in cholesterol and bile acid metabolism. These findings suggest that SCFA are involved in lowering plasma cholesterol levels due to the up-regulation of CYP7A1 and bile acid synthesis.