• Title/Summary/Keyword: Standard metabolism

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Determination of 5-HT2C agonist KKHQ80114 and KKHQ80109 in Rat Plasma and Urine by Gas-Chromatography/Mass Spectrometry

  • Im, Hye-Yeon;Park, Hye-Sil;Choo, Hyun-Ah;Pae, Ae-Nim;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.321-325
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    • 2009
  • 5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80114 (K14) and KKHQ80109 (K09), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate analytical methods of these compounds in the plasma and urine of rats by gas chromatography/mass spectrometry. In this experiment, K14 was determined in plasma and urine by using K09 as internal standard. Calibration curves give a good linearity in plasma (r$^2$=0.9993) and urine (r$^2$=0.9988). Among hexane, ethyl acetate and diethyl ether, the highest peak was observed in diethyl ether. However, ethyl acetate was used since more interfering peaks were observed with diethyl ether. Inter-day precision and accuracy were determined in the ranges of 50-500 ng/mL for plasma and 10-500 ng/ml for urine. Quantitation limits were 50 ng/mL plasma and 25 ng/ mL urine. These data may be applicable for further studies of these compounds including absorption and metabolism due to no pharmacokinetic or analytical data available.

Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses

  • Lee, Seungho;Choi, Seohee;Kim, Sang Yong;Yun, Mi Jin;Kim, Hyoung-Il
    • Journal of Gastric Cancer
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    • v.17 no.4
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    • pp.384-393
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    • 2017
  • Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

The Educational Needs and Perception of the Mothers of High Risk Infant and Normal Neonate (정상 신생아 어머니와 고위험 신생아 어머니의 신생아에 대한 지각 및 교육요구도 비교)

  • Lee Mee-Ja;Suh Hyun-Sun;Hong Yoo-Hee;Kim So-Yeon;Yoo Eun-Joo;Park Song-Ja
    • Child Health Nursing Research
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    • v.9 no.1
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    • pp.18-27
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    • 2003
  • The purpose of this study is to compare the educational needs and perception of mothers of normal neonates and high risk infants. This research was designed as a descriptive study. Data were collected for two months from April 2002 to March 2002. Subjects were 41 mothers of high risk infants and 60 mothers of normal neonates in one general hospital in Seoul participated in the study. Measurement tools used in this study were the educational needs scale developed by Cho Kyoul Ja et al and the neonatal perceptive inventories scale developed by Broussard. They ask mothers to rate each item on a four point Likert type scale. The collected data were analyzed using SPSS 8.0 program. The variables were listed as frequency, mean, standard deviation, X2 test, t-test, ANOVA. The results were as follows: The educational needs of the mothers of primi pregnancy was higher than the mothers of multi pregnancy. The educational needs on management of diseases such as prevention of infection, symptoms of disease, mental development, attachment promotion, congenital metabolism test, management of convulsion, care of vomiting and fever were higher than general care of infants such as immunization, measurement of temperature, hiccough care, follow up care. The informations must be included in nursing intervention program to reduce the mothers' stress level. In conclusion, in order to promote positive mother infant relationship, nurse need to give information and educate the mothers of high risk infant and normal neonate.

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A Minireview on Carbohydrate in Weight Management Diet : The Quantity and the Quality (체중조절 식이에서 탄수화물의 비중 : 그 질과 양)

  • Lee, Myung-Jong;Kim, Ho-Jun
    • Journal of Korean Medicine for Obesity Research
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    • v.5 no.1
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    • pp.121-131
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    • 2005
  • During last few decades dietary guidelines for the weight management mainly have focused on a low-fat, high carbohydrate diet. Carbohydrate was supposed to be low-dense, highly satiating as well as it affects little on the lipogenesis. Although low-fat diet has significant weight-reducing effect, the loss was modest and usually regained after cessation of the diet. Furthermore, low-fat, modest-carbohydrate diet did not impact on the ever increasing rates of overweight and obesity. Alternative approaches include low-carbohydrate diet, high-carbohydrate diet and low-glycemic index diet. Although none of above mentioned diet have sufficient evidence for standard weight management diet, short-term efficacy and safety are being approved continuously. Low-carbohydrate diet contains less than 45% of carbohydrate in daily energy consumption, it is claimed to have more satiating effect and to improve metabolism. However, low compliance due to the limitation of food choice should be considered on prescribing the diet. High-carbohydrate which contains 90% of carbohydrate in total daily energy consumption, is effective in providing satiety and lowering total calorie intake and cholesterol. On the other hand, nutritional unbalance should be took into account. Low-glycemic index diet is based on the theory that contemporary diet contains significantly less fiber and unrefined carbohydrate, therefore insulin secretion is disturbed. Because low glycemic index food slowly increase blood glucose and insulin level, it induces much satiating effect and may decrease calorie ultimate intake. However, poor standardization of glycemic index is one of the main obstacle for the diet to be applied in the clinic. Meanwhile, high fructose food and beverage should be discouraged because it has little satiating effect and may cause insulin resistance. High fiber food is another recommendation for healthy, lean diet.

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Biotransformation of major ginsenosides in ginsenoside model culture by lactic acid bacteria

  • Park, Seong-Eun;Na, Chang-Su;Yoo, Seon-A;Seo, Seung-Ho;Son, Hong-Seok
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.36-42
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    • 2017
  • Background: Some differences have been reported in the biotransformation of ginsenosides, probably due to the types of materials used such as ginseng, enzymes, and microorganisms. Moreover, most microorganisms used for transforming ginsenosides do not meet food-grade standards. We investigated the statistical conversion rate of major ginsenosides in ginsenosides model culture during fermentation by lactic acid bacteria (LAB) to estimate possible pathways. Methods: Ginsenosides standard mix was used as a model culture to facilitate clear identification of the metabolic changes. Changes in eight ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg2) during fermentation with six strains of LAB were investigated. Results: In most cases, the residual ginsenoside level decreased by 5.9-36.8% compared with the initial ginsenoside level. Ginsenosides Rb1, Rb2, Rc, and Re continuously decreased during fermentation. By contrast, Rd was maintained or slightly increased after 1 d of fermentation. Rg1 and Rg2 reached their lowest values after 1-2 d of fermentation, and then began to increase gradually. The conversion of Rd, Rg1, and Rg2 into smaller deglycosylated forms was more rapid than that of Rd from Rb1, Rb2, and Rc, as well as that of Rg1 and Rg2 from Re during the first 2 d of fermentation with LAB. Conclusion: Ginsenosides Rb1, Rb2, Rc, and Re continuously decreased, whereas ginsenosides Rd, Rg1, and Rg2 increased after 1-2 d of fermentation. This study may provide new insights into the metabolism of ginsenosides and can clarify the metabolic changes in ginsenosides biotransformed by LAB.

Substrate reduction therapy as a new treatment option for patients with Gaucher disease type 1: A review of literatures

  • Sohn, Young Bae;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.13 no.2
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    • pp.59-64
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    • 2016
  • Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficiency of acid ${\beta}$-glucosidase. The diminished enzyme activity leads to the accumulation of substrates and results in multi-systemic manifestations including hepatosplenomegaly, anemia, thrombocytopenia, and bone diseases. Enzyme replacement therapy (ERT) by infusion of recombinant protein has been the standard treatment for over 20 years. Despite the successful long-term treatment with ERT, several unmet needs remain in the treatment of GD1 such as severe pulmonary and skeletal manifestations. Substrate reduction therapy (SRT) reduces the accumulation of substrates by inhibiting their biosynthesis. Eliglustat, a new oral SRT, was approved in United States and Europe as a first-line therapy for treating adult patients with GD1 who have compatible CYP2D6 metabolism phenotypes. Although eliglustat is not yet available in Korea, introduction and summary of this new treatment modality are provided in this paper by review of literatures. Despite the fact that there are only limited studies to draw resolute conclusions, the current data demonstrated that eliglustat is not inferior to ERT in terms of its clinical efficacy. The approval of eligustat enables eligible adult GD1 patients to have the option of oral therapy although it still needs further studies on long-term outcomes. The individual patient should be assessed carefully for the choice of treatment modality when eliglustat becomes available in Korea. Furthermore, the clinical guidelines for Korean patients with GD1 regarding the use of eliglustat needs to be developed in near future.

Validation of dietary reference intake equations for estimating energy requirements in Korean adults by using the doubly labeled water method

  • Kim, Eun-Kyung;Kim, Jae-Hee;Kim, Myung-Hee;Ndahimana, Didace;Yean, Seo-Eun;Yoon, Jin-Sook;Kim, Jung-Hyun;Park, Jonghoon;Ishikawa-Takata, Kazuko
    • Nutrition Research and Practice
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    • v.11 no.4
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    • pp.300-306
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    • 2017
  • BACKGROUND/OBJECTIVES: The doubly labeled water (DLW) method is considered the gold standard for the measurement of total energy expenditure (TEE), which serves to estimate energy requirements. This study evaluated the accuracy of predictive dietary reference intake (DRI) equations for determining the estimated energy requirements (EER) of Korean adults by using the DLW as a reference method. SUBJECTS/METHODS: Seventy-one participants (35 men and 36 women) aged between 20 and 49 years were included in the study. The subjects' EER, calculated by using the DRI equation ($EER_{DRI}$), was compared with their TEE measured by the DLW method ($TEE_{DLW}$). RESULTS: The DRI equations for EER underestimated TEE by -36.3 kcal/day (-1.3%) in men and -104.5 kcal/day (-4.9%) in women. The percentages of accurate predictions among subjects were 77.1% in men and 62.9% in women. There was a strong linear correlation between $EER_{DRI}$ and $TEE_{DLW}$ (r = 0.783, P < 0.001 in men and r = 0.810, P < 0.001 in women). CONCLUSIONS: The present study supports the use of DRI prediction equations to determine EER in Korean adults. More studies are needed to confirm our results and to assess the validity of these equations in other population groups, including children, adolescents, and older adults.

Amino acid digestibility in plant protein sources fed to growing pigs

  • Son, Ah Reum;Park, Chan Sol;Park, Kyu Ree;Kim, Beob Gyun
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.11
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    • pp.1745-1752
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    • 2019
  • Objective: The objective was to determine standardized ileal digestibility (SID) of amino acids (AA) in 11 plant protein sources fed to growing pigs. Methods: Eleven feed ingredients used were sesame meal, two sources of soybean meal (SBM) produced in the Republic of Korea, a source of SBM produced in India, high-protein distillers dried grains (HPDDG), perilla meal, canola meal, copra meal, corn germ meal, palm kernel expeller, and tapioca distillers dried grains (TDDG). Experimental diets were prepared to contain each test ingredient as a sole source of AA, and a nitrogen-free diet was also prepared to estimate the basal ileal endogenous losses of AA. Twelve barrows surgically fitted with T-cannulas at the distal ileum with an initial body weight of 29.0 kg (standard deviation = 3.0) were individually housed in metabolism crates equipped with a feeder and a nipple drinker. A $12{\times}9$ incomplete Latin square design was employed with 12 experimental diets, 12 animals, and 9 periods. After a 5-d adaptation period, ileal digesta were collected on d 6 and 7 in each experimental period. Results: Values for apparent ileal digestibility of most indispensable AA in three sources of SBM were greater compared with other test ingredients except HPDDG and canola meal (p<0.05). Pigs fed diets containing SBM sources had also greater SID of most indispensable AA compared with those fed diets containing other test ingredients (p<0.05) except for HPDDG and canola meal. There was no difference in the apparent ileal digestibility and SID of AA among sources of SBM. The TDDG had the least value for the SID of methionine among test ingredients (p<0.05). Conclusion: The SID of most AA in SBM, HPDDG, and canola meal were greater than those in sesame meal, perilla meal, copra meal, and TDDG.

Genetic relationship between purebred and synthetic pigs for growth performance using single step method

  • Hong, Joon Ki;Cho, Kyu Ho;Kim, Young Sin;Chung, Hak Jae;Baek, Sun Young;Cho, Eun Seok;Sa, Soo Jin
    • Animal Bioscience
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    • v.34 no.6
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    • pp.967-974
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    • 2021
  • Objective: The objective of this study was to estimate the genetic correlation (rpc) of growth performance between purebred (Duroc and Korean native) and synthetic (WooriHeukDon) pigs using a single-step method. Methods: Phenotypes of 15,902 pigs with genotyped data from 1,792 pigs from a nucleus farm were used for this study. We estimated the rpc of several performance traits between WooriHeukDon and purebred pigs: day of target weight (DAY), backfat thickness (BF), feed conversion rate (FCR), and residual feed intake (RFI). The variances and covariances of the studied traits were estimated by an animal multi-trait model that applied the Bayesian inference. Results: rpc within traits was lower than 0.1 for DAY and BF, but high for FCR and RFI; in particular, rpc for RFI between Duroc and WooriHeukDon pigs was nearly 1. Comparison between different traits revealed that RFI in Duroc pigs was associated with different traits in WooriHeukDon pigs. However, the most of rpc between different traits were estimated with low or with high standard deviation. Conclusion: The results indicated that there were substantial differences in rpc of traits in the synthetic WooriHeukDon pigs, which could be caused by these pigs having a more complex origin than other crossbred pigs. RFI was strongly correlated between Duroc and WooriHeukDon pigs, and these breeds might have similar single nucleotide polymorphism effects that control RFI. RFI is more essential for metabolism than other growth traits and these metabolic characteristics in purebred pigs, such as nutrient utilization, could significantly affect those in synthetic pigs. The findings of this study can be used to elucidate the genetic architecture of crossbred pigs and help develop new breeds with target traits.

Statin Intolerance: an Overview of the Current Status and Possible Treatment Options

  • Suh, Sunghwan;Jung, Chang Hee;Hong, Soon-Jun;Kim, Jung-Sun;Choi, Sung Hee
    • Journal of Lipid and Atherosclerosis
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    • v.7 no.2
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    • pp.77-87
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    • 2018
  • Lowering serum low-density lipoprotein cholesterol (LDL-C) is the mainstay for reduction of risk of cardiovascular disease (CVD), the second most common cause of death in Korea. The 2015 Korean guidelines for management of dyslipidemia strongly recommend the use of statins in patients at risk of CVD. Statin therapy, which is the gold standard for CVD, reduces LDL-C level by 40% to 60% and is generally well tolerated. However, many patients are intolerant to statins and discontinue therapy or become nonadherent to therapy because of actual/perceived side effects. The most common of these side effects is the statin-associated muscle symptom (SAMS). Discontinuation and repetitive re-challenge with statins can help identify SAMS. If serum creatinine kinase level is more than 10 times the upper limit of normal, statin therapy must be stopped immediately, and the physician should identify possible causes including rhabdomyolysis and treat appropriately. In other patients, it might help to switch to a less potent statin or to use statins at intermittent non-daily dosing. To achieve target LDL-C level, non-statin lipid-lowering therapies such as dietary modifications, ezetimibe, and bile acid sequestrants may be added. Several new drugs have recently been approved for lowering LDL-C level. Alirocumab and evolocumab are monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, and both drugs cause large reductions in LDL-C, similar to statins. Lomitapide and mipomersen are orphan drugs used as adjuncts to other lipid-lowering therapies in patients with homozygous familial hypercholesterolemia.