• Title/Summary/Keyword: metabolic interaction

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DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes

  • Shon, Jong Cheol;Joo, Jeongmin;Lee, Taeho;Kim, Nam Doo;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.1
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    • pp.24-29
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    • 2018
  • DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

The Effects of Combined Exercise and Peony Drinking on Inflammatory Factors in Middle Aged Women (복합운동과 작약 음료 섭취가 중년여성들의 염증인자에 미치는 영향)

  • Eo, Kyung-Tae;Kim, Chan-Hoi;Kim, Ji-Won
    • Journal of the Korea Convergence Society
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    • v.9 no.11
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    • pp.425-431
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    • 2018
  • The middle aged women in their 40s and 50s were the subjects for this study. There were 6 women for the group of complex exercise. There were 6 women for the group of complex exercise and intake of peony beverage. There were 5 women for controlled group. This study compares and analyzes the effect of complex exercise program, in which the subjects exercise 60 minutes a day for three times a week, on the physical structure, inflammation factors and metabolic syndrome of middle aged women. The result is as shown in the following. there were significant difference (p<.001) for fibrinogen of each group in the change of inflammation factors due to regular complex exercise program and intake of peony beverage. But there were not significant difference in the period, period x the effect of groups' interaction. It is believed that there could be polluted variables, as the number of subjects for this study is not enough. So there should be a study that has more subjects to make it more significant.

Regulation of Hepatic Gluconeogenesis by Nuclear Receptor Coactivator 6

  • Oh, Gyun-Sik;Kim, Si-Ryong;Lee, Eun-Sook;Yoon, Jin;Shin, Min-Kyung;Ryu, Hyeon Kyoung;Kim, Dong Seop;Kim, Seung-Whan
    • Molecules and Cells
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    • v.45 no.4
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    • pp.180-192
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    • 2022
  • Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general Ncoa6 knockout mouse was previously shown to be embryonic lethal, but we here generated liver-specific Ncoa6 knockout (Ncoa6 LKO) mice to investigate the metabolic function of NCOA6 in the liver. These Ncoa6 LKO mice exhibited similar blood glucose and insulin levels to wild type but showed improvements in glucose tolerance, insulin sensitivity, and pyruvate tolerance. The decrease in glucose production from pyruvate in these LKO mice was consistent with the abrogation of the fasting-stimulated induction of gluconeogenic genes, phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc). The forskolin-stimulated inductions of Pck1 and G6pc were also dramatically reduced in primary hepatocytes isolated from Ncoa6 LKO mice, whereas the expression levels of other gluconeogenic gene regulators, including cAMP response element binding protein (Creb), forkhead box protein O1 and peroxisome proliferator-activated receptor γ coactivator 1α, were unaltered in the LKO mouse livers. CREB phosphorylation via fasting or forskolin stimulation was normal in the livers and primary hepatocytes of the LKO mice. Notably, it was observed that CREB interacts with NCOA6. The transcriptional activity of CREB was found to be enhanced by NCOA6 in the context of Pck1 and G6pc promoters. NCOA6-dependent augmentation was abolished in cAMP response element (CRE) mutant promoters of the Pck1 and G6pc genes. Our present results suggest that NCOA6 regulates hepatic gluconeogenesis by modulating glucagon/cAMP-dependent gluconeogenic gene transcription through an interaction with CREB.

Definition, Role and Method of Yinyang Pattern Differentiation (음양변증(陰陽辨證)의 정의와 기능 및 판별방법 연구)

  • Chi, Gyoo-yong;Park, Shin-hyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.35 no.2
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    • pp.47-55
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    • 2021
  • In order to ensure the fact that eight principle pattern differentiation is used clinically as a basic guideline for Korean medicine practice, the definition, role and method of yin-yang pattern differentiation with its case report were explored at first. Yinyang Pattern Differentiation is a method of discriminating human tendencies or morbidity based on the yin and yang characteristics expressed in living bodies. And yin and yang are the two contrasting characteristics and aspects of the interaction when certain physical conditions that have a lasting effect on the human physiological metabolic function are correlated with the morbidity. Specific methods of yinyang pattern differentiation can be divided into several types of yin and yang indicators. First, time and space factors like day and night, hot and cold seasons, above and below, topographical districts. Second, colors and pulse and their/or relative clearness and muddiness, hardness and softness, moving and resting. Third, diagnose yin and yang patterns through distinguishing the true and false of a fever and cold in an emergency phase such as increase of brain pressure and shock state. Fourth, general characteristics of the propensity and constitution of a subject such as body type, speech, behavior, and physiological metabolism. And for clinical use, these were summarized again as a symptom indicators of physical signs and color, pulse, tongue and questionnaire indicators of propensity, body type, and space-time characteristics. Conclusively, it was confirmed that yinyang pattern differentiation has its own diagnostic significance which is distinct from exterior-interior, cold-heat and deficiency-excess pattern differentiation.

Effects of endurance exercise under hypoxia on acid-base and ion balance in healthy males

  • Nam, Sang-Seok;Park, Hun-Young
    • Korean Journal of Exercise Nutrition
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    • v.24 no.3
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    • pp.7-12
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    • 2020
  • [Purpose] This study was performed to investigate the acid-base and ion balance at rest and after exercise in healthy males under normoxia, moderate hypoxia, and severe hypoxia. [Methods] Ten healthy Korean males completed three different trials on different days, comprising exercise under normoxia (FiO2 = 20.9%, N trial), moderate hypoxia (FiO2 = 16.5%, MH trial), and severe hypoxia (FiO2 = 12.8%, SH trial). They undertook endurance exercise for 30 min on a cycle ergometer at the same relative exercise intensity equivalent to 80% maximal heart rate under all conditions. Capillary blood samples were obtained to determine acid-base and ion balance at rest and after exercise. [Results] Exercise-induced blood lactate elevations were significantly increased as hypoxic conditions became more severe; SH > MH > N trials (P = 0.003). After exercise, blood glucose levels were significantly higher in the SH trial than in the N and MH trials (P = 0.001). Capillary oxygen saturation (SCO2) levels were significantly lowered as hypoxic conditions became more severe; SH > MH > N trials (P < 0.001). The pH levels were significantly lower in the MH trial than that in the N trial (P = 0.010). Moreover, HCO3- levels were significantly lower in the SH trial than in the N trial, with significant interaction (P = 0.003). There were no significant differences in blood Na+, K+, and Ca2+ levels between the trials. [Conclusion] MH and SH trials induced greater differences in glucose, lactate, SCO2, pH, and HCO3- levels in capillary blood compared to the N trial. Additionally, lactate, SCO2, and HCO3- levels showed greater changes in the SH trial than in the MH trial. However, there were no significant differences in Na+, K+, and Ca2+ levels in MH and SH trials compared to the N trial.

Blood biochemical parameters and organ development of brown layers fed reduced dietary protein levels in two rearing systems

  • Viana, Eduardo de Faria;Mello, Heloisa Helena de Carvalho;Carvalho, Fabyola Barros;Cafe, Marcos Barcellos;Leandro, Nadja Susana Mogyca;Arnhold, Emmanuel;Stringhini, Jose Henrique
    • Animal Bioscience
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    • v.35 no.3
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    • pp.444-452
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    • 2022
  • Objective: An experiment was conducted to evaluate the effect of different levels of crude protein (CP) and two rearing systems (cage and floor), on blood parameters and digestive and reproductive organ development of brown laying hens. Methods: A total of 400 Hisex Brown laying hens between 30 and 45 weeks of age were distributed in a completely randomized design and a 2×4 factorial arrangement, with main effects including two rearing systems (cage and floor) and levels of CP (140, 150, 160, and 180 g/kg), in a total of eight treatments and five replicates of 10 birds each with initial body weight of 1,877 g (laying hen in cage) and 1,866 g (laying hens in floor). The parameters evaluated were plasma total protein, albumin, uric acid, total cholesterol, relative weights of oviduct, abdominal fat, liver, gizzard, crest and dewlap, length of small intestine and oviduct. Results: The blood parameters were similar in birds reared in cage and floor systems. The birds reared on the floor showed greater small intestine and oviduct weight (%) and lower liver and pancreas weight (%). A significant interaction was observed between factors for the relative gizzard, crest and dewlap weight, serum protein, uric acid, and total cholesterol (p<0.05). The diets with 140 g/kg CP resulted in lower serum protein and lower cholesterol in birds reared in floor system, while birds reared in cage system showed no effect of CP on both parameters. Birds reared in cage and fed with 140 and 150 g/kg CP presented lower uric acid. The group of birds reared in floor system fed 180 g/kg had greater uric acid. Conclusion: The dietary protein level can be reduced up to 140 g/kg for Hisex Brown hens (30 to 45 weeks of age) without an important effect on metabolic profile and organ development in both rearing systems.

Interactive effect of dietary levels of calcium and 25-hydroxy vitamin D3 on the performance, serum biochemical concentration and digestibility of laying hens from 61 to 70 weeks of age

  • Lim, Chun Ik;Ryu, Kyeong Seon
    • Animal Bioscience
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    • v.35 no.9
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    • pp.1426-1433
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    • 2022
  • Objective: The present research was conducted to evaluate the interactive effect of dietary concentration of calcium (Ca) and 25-hydroxy vitamin D3 (25OHD3) on the performance, blood composition and digestibility of laying hens. Methods: A total of 540 Hy-line brown laying hens aged 61 to 70 weeks were randomly allotted in a 3×3 factorial arrangement, consisting of three levels of 25OHD3 (0, 25, and 50 ㎍/kg) and three levels of Ca (3.5%, 4.0%, and 4.5%). All diets had basal concentration of 3,000 IU/kg of vitamin D3 including the 2,800 kcal/kg of metabolic energy and 16% of crude protein. Results: The results showed that interactive effect (p<0.05) between Ca and 25OHD3 was such that dietary 25OHD3 linearly increased interleukin-6 at all levels of Ca inclusion. Interaction (p<0.05) occurred with the highest parathyroid hormone in laying hens that received dietary concentration of Ca (3.5%) with 25OHD3 (50 ㎍/kg), and Ca (4.0%) with 25OHD3 (50 ㎍/kg). Egg production and egg weight significantly (p<0.05) increased in the 4.5% Ca group compared to the 3.5% to 4.0% Ca groups. Egg shell thickness and tibia bone length also increased (p<0.05) in groups fed a high-Ca diet (4.0% to 4.5%). Phosphorus digestibility significantly (p<0.05) increased along with dietary Ca level. Among the tested 25OHD3 groups, higher (p<0.05) egg production and tibia thickness were present in hens fed 50 ㎍/kg of 25OHD3. Furthermore, Ca digestibility serum Ca and 25OHD3 were significantly increased in group offered 50 ㎍/kg of 25OHD3. Conclusion: The results gathered in this study indicate that dietary concentrations of 4.0% to 4.5% Ca and 50 ㎍/kg 25OHD3 improve the performance of hens from 61 to 70 weeks of age.

Clinical Applications and Efficacy of Korean Ginseng (고려인삼의 주요 효능과 그 임상적 응용)

  • Nam, Ki-Yeul
    • Journal of Ginseng Research
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    • v.26 no.3
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    • pp.111-131
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    • 2002
  • Korean ginseng (Panax ginseng C.A. Meyer) received a great deal of attention from the Orient and West as a tonic agent, health food and/or alternative herbal therapeutic agent. However, controversy with respect to scientific evidence on pharmacological effects especially, evaluation of clinical efficacy and the methodological approach still remains to be solved. Author reviewed those articles published since 1980 when pharmacodynamic studies on ginseng have intensively started. Special concern was paid on metabolic disorders including diabetes mellitus, circulatory disorders, malignant tumor, sexual dysfunction, and physical and mental performance to give clear information to those who are interested in pharmacological study of ginseng and to promote its clinical use. With respect to chronic diseases such as diabetes mellitus, atherosclerosis, high blood pressure, malignant disorders, and sexual disorders, it seems that ginseng plays preventive and restorative role rather than therapeutics. Particularly, ginseng plays a significant role in ameliorating subjective symptoms and preventing quality of life from deteriorating by long term exposure of chemical therapeutic agents. Also it seems that the potency of ginseng is mild, therefore it could be more effective when used concomitantly with conventional therapy. Clinical studies on the tonic effect of ginseng on work performance demonstrated that physical and mental dysfunction induced by various stresses are improved by increasing adaptability of physical condition. However, the results obtained from clinical studies cannot be mentioned in the indication, which are variable upon the scientist who performed those studies. In this respect, standardized ginseng product and providing planning of the systematic clinical research in double-blind randomized controlled trials are needed to assess the real efficacy for proposing ginseng indication. Pharmacological mode of action of ginseng has not yet been fully elucidated. Pharmacodynamic and pharmacokinetic researches reveal that the role of ginseng not seem to be confined to a given single organ. It has been known that ginseng plays a beneficial role in such general organs as central nervous, endocrine, metabolic, immune systems, which means ginseng improves general physical and mental conditons. Such multivalent effect of ginseng can be attributed to the main active component of ginseng,ginsenosides or non-saponin compounds which are also recently suggested to be another active ingredients. As is generally the similar case with other herbal medicines, effects of ginseng cannot be attributed as a given single compound or group of components. Diversified ingredients play synergistic or antagonistic role each other and act in harmonized manner. A few cases of adverse effect in clinical uses are reported, however, it is not observed when standardized ginseng products are used and recommended dose was administered. Unfavorable interaction with other drugs has also been suggested, which the information on the products and administered dosage are not available. However, efficacy, safety, interaction or contraindication with other medicines has to be more intensively investigated in order to promote clinical application of ginseng. For example, daily recommended doses per day are not agreement as 1-2g in the West and 3-6 g in the Orient. Duration of administration also seems variable according to the purpose. Two to three months are generally recommended to feel the benefit but time- and dose-dependent effects of ginseng still need to be solved from now on. Furthermore, the effect of ginsenosides transformed by the intestinal microflora, and differential effect associated with ginsenosides content and its composition also should be clinically evaluated in the future. In conclusion, the more wide-spread use of ginseng as a herbal medicine or nutraceutical supplement warrants the more rigorous investigations to assess its effacy and safety. In addition, a careful quality control of ginseng preparations should be done to ensure an acceptable standardization of commercial products.

Effects of Practical Variations in Fasting, Stress and Chilling Regime on Post-slaughter Metabolic Rate and Meat Quality of Pork Loin (절식, 스트레스 및 냉각속도가 돼지도체의 사후 대사속도와 등심근의 육질에 미치는 영향)

  • Hwang, I.H.;Park, B.Y.;Cho, S.H.;Kim, J.H.;Lee, J.M.
    • Journal of Animal Science and Technology
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    • v.46 no.1
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    • pp.97-106
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    • 2004
  • The study was conducted to investigate the effects of practical variations in feed restriction, pre-slaughter handing and chilling regime on pork quality during ageing. A total of twenty male landraces were allocated into three treatments(i.e., pre-slaughter feeding, stress and chilling regime) in a factorial arrangement. pH, temperature, free calcium ions, WB-shear force, sarcomere length, cooking loss, drip loss and objective color were determined during rigor development and/or 1, 3, 7 d postmortem. Pre-slaughter chasing stress for approximately 15 min had no effects on pH/temperature profile and objective meat quality. There was an interaction(P < 0.05) between the fasting treatment and chi1ling regime for muscle temperature at pH 6.2. Sarcomere length indicated that the current experiment conditions did not induce muscle shortening, with 1.7 to 1.8 ${\mu}m$, in spite of a significant effect of the fasting treatment (P<0.01). Pigs fed until the morning of slaughter showed a low WB-shear force(P < 0.05) until 3 d at I "C. The treatment also resulted in a higher Hunter L* and a*(P < 0.05) at 24 h and 7 d. Fasted pigs showed a significantly(P < 0.05) reduced cooking loss. The current results indicated that feeding upon the morning of slaughter became detrimental on meat color and the negative effect on cooking loss were linearly elevated with increased ageing time. On the other hand, WB-shear force did not distinguishable after 3 d. Collectively, it appeared that feed restriction from a day before slaughter could produce more a desirable meat quality at the time of consuming. However, the limited effect of animal handling and chilling rate on meat quality is not necessarily to extend to that these do not affect pork quality, as that largely depends on experimental design.

Effects of Nitrogen Sources on RNA, DNA and other Phosphorus Fractions of Soybean Cultivars Different in Phosphorus Sensitivity (인산감수성(燐酸感受性)이 다른 대두품종(大豆品種)의 RNA, DNA 및 기타 인산형태(燐酸形態)에 대(對)한 질소원(窒素源)의 영향(影響)에 관한 연구(硏究))

  • Park, Hoon;Stutte, Charls A.
    • Applied Biological Chemistry
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    • v.19 no.3
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    • pp.172-183
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    • 1976
  • RNA, DNA and other phosphorus fractions were determined in the leaf and root of soybean plants different in phosphorus sensitivity grown in $NH_4-N,\;NO_3-N$ and urea medium. The phosphorus sensitive cultivars contained higher ASIP (acid soluble inorganic phosphorus) than the tolerant cultivars with all nitrogen sources. ASIP was highest in the urea treated plants and lowest in the nitrate treated plants. Total phosphorus content was mostly affected with increase in ASIP. When ASIP increased, acid solsuble organic phosphorus(ASOP), phospholipids (L-P), RNA-P, residual phosphorus (R-P) tended to increase, while DNA-P showed little change. The percent RNA-P or DNA-P of total phosphorus in the nitrate treated plant was twice that in the ammonium treated plant, which were also higher in tolerant cultivars regardless of nitrogen sources. The percent ASOP in total acid soluble phosphorus $(ASOP/ASP{\times}100)$ decreased as phosphorus sensitivity decreased. Indications are that phosphorus sensitivity depends on the relative sizes of phosphorus metabolic pools. Total dry matter yield was negatively correlated with total phosphorus (r=0.84 significant at 0.01P), ASIP (0.84 significant at 0.01P) and residual phosphorus (0.69 significant at 0.05P). ASOP showed positive correlation with L-P, RNA-P and DNA-P but negative with R-P. RNA-P was significanly correlated only with L-P (0.63 at P=0.01). There was significant interaction (0.01) among nitrogen sources, cultivars and phosphorus metabolic pools. Phosphorus sensitivity and ammonium toxicity appear to be same in view of energy metabolism, that is, the former inhibits the conversion of ATP to ADP (energy releasing) through phosphate potential while the latter inhibits ATP formation (energy storing).

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