• Title/Summary/Keyword: Co-metabolites

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Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, and Inflammation

  • Kim, Chang H.;Park, Jeongho;Kim, Myunghoo
    • IMMUNE NETWORK
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    • v.14 no.6
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    • pp.277-288
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    • 2014
  • T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We review the current status of our understanding of SCFA functions in regulation of peripheral T cell activity and discuss their impact on tissue inflammation.

A Systematic Review on Potential Drug Interactions of Korean Ginseng Based upon Cytochrome P450 and P-Glycoprotein (고려인삼의 Cytochrome P450 및 P-Glycoprotein 매개 약물 상호작용에 미치는 영향)

  • Nam, Ki Yeul;Yang, Byung Wook;Shin, Wang Soo;Park, Jong Dae
    • Korean Journal of Pharmacognosy
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    • v.49 no.2
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    • pp.85-102
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    • 2018
  • A drug interaction is a situation in which a substance affects the activity of a drug, synergistically or antagonistically, when both are administered together. It has been shown that orally taken ginsenosides are deglycosylated by intestinal bacteria to give ginsenosides metabolites, which has been considered to be genuine pharmacological constituents and to exhibit drug interactions. Animal experimental results demonstrated that ginsenoside metabolites play an important role in the inhibitory or inductive action of both CYPs (cytochrome p450) and P-gp (p-glycoprotein), thereby can be applied as metabolic modulator to drug interactions. Very few are known on the possibility of drug interaction if taken the recommended dose of ginseng, but it has been found to act as CYPs inductor and P-gp inhibitor in any clinical trial, suggesting the risk that side effects will occur. It has been recently reported that interactions might also exist between ginseng and drugs such as warfarin, phenelzine, imatinib and raltegravir. Moreover, medicinal plants are increasingly being taken in a manner more often associated with prescription medicines. Therefore, considering the extensive applications of ginseng for safety, the aim of this review is to present a comprehensive overview of ginseng and drug interactions based upon pharmacodynamic and pharmacokinetic evidences.

Bioequivalence of Commercially available Sustained Release Tablets of Diltiazem Hydrochloride (시판 염산 딜티아젬 서방형 정제의 생물학적 동등성)

  • Lee, Young-Bok;Koh, Ik-Bae;Seo, Se-Min;Yoon, Heong-Tung
    • Korean Journal of Clinical Pharmacy
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    • v.3 no.1
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    • pp.79-88
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    • 1993
  • Bioequivalence(BE) test of commercially available sustained release tablets of diltiazem hydrochloride(DTZ) was performed to give some guidelines to BE test in korea in case of which drugs with low oral bioavaiiability(BA) due to substantial first-pass hepatic loss form pharmacologically active metabolites. In such cases, the pharmacologic activity after oral administration is greater than anticipated from BA data, based on chemical assay of drug alone. Therefore, this paper explores the use and meaning of area under the plasma concentration-time(AUC) data of parent and its metabolites to access BA if sustained release tablets. Normal healthy male volunteers(n=14) were randomly divided into 2 groups, and sustained release reference$(Herbesser^{(R)})$ and test$(Herben^{(R)})$ tablets of DTZ-30mg were given orally by balanced two-period cross-over dosing schedule. The plasma concentration of DTZ and and its active metabolite, desacetyldiitiazem(DAD), were determined by high performance liquid chromatography, and, $AUC_{DTZ},\;AUC_{DAD},\;AUC_{DTZ+DAD},\;C_{max}\;and\;T_{max}$ obtained. Analysis of varlance(ANOVA) showed that $AUC_{DTZ}\;and\;C_{max}$ passed the standard $(\alpha=0.05,\;1-\beta\geq0.8,\;\Delta\leq0.2)$ of BE test of korea, but $AUC_{DAD}$ was not satisfied from the standpoint of power. On the other hand, $AUC_{DTZ\midDAD}$ may be more avaliable than $AUC_{DAD}$ from the standpoint of statistics and pharmacologic equivalence.

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Effects of feeding sodium metabisulfite-treated fruit and vegetable discards to Hanwoo heifers and cows

  • Lee, Won Hee;Ahmadi, Farhad;Kim, Young Il;Park, Jong Moon;Kwak, Wan Sup
    • Animal Bioscience
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    • v.35 no.3
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    • pp.410-421
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    • 2022
  • Objective: Two series of experiments were conducted to determine how the incremental levels of sodium metabisulfite (SMB)-treated fruit and vegetable discards (FVD) in diet of Hanwoo heifers and cows affect their performance and health. Methods: In Exp. 1, 36 Hanwoo heifers were stratified by age (13.3±0.83 mo) and initial body weight (305±19.7 kg), and divided randomly to one of three diets containing 0%, 10%, or 20% SMB-treated FVD (as-fed basis). The experiment lasted 110 d, including 20 d of adaptation. In Exp. 2, 24 multiparous Hanwoo cows were divided into three groups based on age (48.2±2.81 mo) and initial body condition score (2.64±0.33). Cows in each block were assigned randomly to one of three diets containing 0%, 11%, or 22% SMB-treated FVD (as-fed basis). The experiment lasted 80 d, including a 20-d adaptation period. In both experiments, SMB-treated FVD was used as a replacement for wet brewers grain in total mixed ration (TMR). Results: Growing heifers exhibited no differences in their daily feed intake (6.58±0.61 kg/d dry matter [DM]), average daily gain (0.60±0.07 kg/d), and body condition score when they consumed the incremental levels of SMB-treated FVD. Although most blood metabolites were unaffected by treatments, blood urea-N and β-hydroxybutyrate levels decreased linearly as the SMB-treated FVD level increased in TMR. Similar to Exp. 1, minor differences were found in daily feed intake (8.27±0.72 kg DM/d) and body condition score of Hanwoo cows. Most blood metabolites remained unaffected by treatments, but blood urea-N decreased as the SMB-treated FVD level in TMR increased. Conclusion: Our findings suggest that SMB-treated FVD could be safely incorporated into the diet of Hanwoo heifers and cows, potentially improving N-use efficiency in the body while not impairing performance or health.

Inhibitory Effect of Lichen Metabolites and their Synthetic Analogues on Melanin Biosynthesis in Cultured B-16 Mouse Melanoma Cells

  • Matubara, H.;Miharu, K.;Kinoshita, K.;Koyama, K.;Ye, Yang;Takahashi, K.;Yoshimura, I.;Yamamoto, Y.;Miura, Y.;Kinoshita, Y.
    • Natural Product Sciences
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    • v.4 no.3
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    • pp.161-169
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    • 1998
  • The analogues of lichen components showing anti-tyrosinase activities were synthesized. 4-Alkylresorcinol derivatives showed both the inhibitory activity and cytotoxicity in B-16 melanoma cells at the doses of 10 mM to 1.2 mM. Resorcinol and 4-methylresorcinol showed the inhibitory effect with a low cytotoxicity at the doses of 2.5 mM and $600\;{\mu}M$ among 4-alkylresorcinols, respectively. Some diphenylmethane derivatives (Type A, B, and C) had strong activities with a low cytotoxicity. While xanthine derivatives had no effect. Glucosides of 4,5-alkylresorcinol and the diphenylmethane derivative (Type B) were prepared to decrease the cytotoxicity. As a result, no effect were observed. Liposome of the diphenylmethane derivative (Type B) was prepared for the same purpose, and the latter showed a remarkable effect at the dose of $15\;{\mu}M$ with a low cytotoxicity.

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A Case of Propionic Acidemia with Gait Disturbance (보행장애를 주소로 4세에 진단된 프로피온산혈증)

  • Lee, Jung Hyun;Ko, Jung Min;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.6 no.1
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    • pp.6-14
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    • 2006
  • Propionic acidemia is an autosomal recessive metabolic disorder caused by a defect of propionyl CoA carboxylase with resultant accumulation of toxic organic acid metabolites. This disorder is biochemically characterized by metabolic acidosis, ketoacidosis, hyperglycinemia and hyperammonemia. Clinical symptoms are very heterogeneous and present as a severe neonatal-onset or a late-onet form. We describe one case of propionic acidemia in a 4-year-old boy who has developed gait disturbance after acute metabolic decompensation.

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IN VIVO H-MRS QUANTIFICATION OF BRAIN METABOLITES USING WATER AS AN INTERNAL STANDARD

  • Lee, Jung-Woo;Choe, Bo-Young;Baik, Hyun-Man;Chung, Sung-Taek;Lee, Hyoung-Koo;Suh, Tae-Suk
    • Proceedings of the KSMRM Conference
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    • 2002.11a
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    • pp.79-79
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    • 2002
  • Purpose: The reliability of absolute quantification of average metabolite concentrations in the human brain in vivo by H-MRS using the fully relaxed water signal as an internal standard was evaluated in a number of in vitro as well as in vivo measurements. Method: The experiments were performed on 3T MEDINUS MAGNUM MR-scanner using a STEAM sequence.

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Effects of N-Acetyl Cysteine and Silymarin on 1-Bromopropane-induced Hepatotoxicity in Mice (1-Bromopropane의 간독성에 미치는 N-Acetyl Cysteine과 Silymarin의 영향)

  • Lee, Sang-Kyu;Kang, Mi-Jeong;Jeon, Tae-Won;Jeong, Tae-Cheon
    • YAKHAK HOEJI
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    • v.54 no.2
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    • pp.97-101
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    • 2010
  • Recently, it was found that the formation of reactive metabolites by cytochrome P450s as well as the depletion of glutathione would play important roles in hepatotoxicity induced by 1-bromopropane. In the present study, possible roles of anti-oxidants in 1-bromopropane-induced hepatotoxicity were investigated in male ICR mice. The hepatotoxicity induced by 1-bromopropane was significantly protected by the co-treatment with either N-acetyl cysteine or silymarin. 1-Bromopropane-induced decrease in hepatic glutathione level was significantly protected by the pretreatment with N-acetyl cysteine. Taken together, the present results indicated that the reduction of hepatic glutathione level caused by 1-bromopropane treatment might be associated in 1-bromopropane-induced hepatotoxicity in mice.

First Record of the Complete Mitochondrial Genome of a Saprotrophic and Opportunistic Human Pathogenic Fungus, Scopulariopsis brevicaulis

  • Park, Jongsun;Kwon, Woochan;Hong, Seung-Beom;Han, Kap-Hoon
    • Mycobiology
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    • v.48 no.6
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    • pp.528-531
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    • 2020
  • Scopulariopsis brevicaulis is a widely distributed soil fungus known as a common saprotroph of biodegradation. It is also an opportunistic human pathogen that can produce various secondary metabolites. Here, we report the first complete mitochondrial genome sequence of S. brevicaulis isolated from air in South Korea. Total length of the mitochondrial genome is 28,829 bp and encoded 42 genes (15 protein-coding genes, 2 rRNAs, and 25 tRNAs). Nucleotide sequence of coding region takes over 26.2%, and overall GC content is 27.6%. Phylogenetic trees present that S. brevicaulis is clustered with Lomentospora prolificans with presenting various mitochondrial genome length.

Glutaric Aciduria Type I: Overview

  • Kim, Su Jin
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.5 no.1
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    • pp.8-11
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    • 2021
  • Glutaric aciduria type 1 (GA1; OMIM #231670) is a rare autosomal recessive-inherited neurometabolic disorder caused by the deficiency of glutaryl-CoA dehydrogenase (GCDH), which is encoded by the GCDH gene. It results in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid (3-OH-GA), glutaconic acid, and glutarylcarnitine (C5DC). These metabolites are considered to damage the striatum through an excitotoxic mechanism. The treatments of GA1 known to date are metabolic maintenance treatment based on a low-lysine diet and emergency treatment during acute illness. However, treatment after the onset of neurological symptoms has limited effectiveness and is associated with poor outcomes, and the effect of treatment and disease course after treatment are not good. After the implementation of newborn screening, the incidence of acute encephalopathic crisis fell to 10%-20% with early diagnosis, preventative dietary management, and aggressive medical intervention during acute episodes. Recently, several cohort studies have been published on the natural course and treatment of GA1 patients. This mini review will cover the clinical symptoms, natural history, and treatment of GA1 through a literature review.