• 제목/요약/키워드: P-M interaction

검색결과 671건 처리시간 0.032초

Effect of Korean Red Ginseng extracts on drug-drug interactions

  • Kim, Se-Jin;Choi, Seungmok;Kim, Minsoo;Park, Changmin;Kim, Gyu-Lee;Lee, Si-On;Kang, Wonku;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • 제42권3호
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    • pp.370-378
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    • 2018
  • Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

Lanthanides-Benzoylformate 착물 형성에 관한 열역학적 연구 (Thermodynamic Properties of Lanthanides Complexes with Benzoylformate Anion)

  • 김영인;박선금
    • 대한화학회지
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    • 제37권4호
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    • pp.442-447
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    • 1993
  • 수용액 내에서 란탄(Ⅲ)-benzoylformate 착물 형성 반응의 열역학적 파라메타들(${\Delta}$G, ${\Delta}$H 및 ${\Delta}$S)을 pH 및 엔탈피 적정 방법을 사용하여 이온세기 $0.1M NaClO_4$, 25$^{\circ}C$ 조건하에서 구하였다. 란탄-benzoylformate 착물의 안정도 상수(1:1) 값으로부터 benzoylformate가 두자리 리간드로 작용함을 알 수 있었다. 열역학적 실험 결과는 카르복실기와 함께 케톤기 산소원자가 결합에 참여하여 킬레이트를형성하는 것으로 판단되었으며, 이는 benzoylformate 리간드 내에 존재하는 벤젠고리의 공액 효과에 의해 케톤기의 산소원자의 전하량이 증가된 결과로 해석되었다. 착물의 안정도는 엔트로피 효과 뿐 아니라, 금속-산소결합 형성에 따른 엔탈피 효과에도 기인하였다.

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Inhibition of Aminopeptidase N by Two Synthetic Tripeptides

  • Chung, Myung Chul;Hyo Kon Chun;Ho Jae Lee;Choong Hwan Lee;Su Il Kim;Yung Hee Kho
    • Journal of Microbiology and Biotechnology
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    • 제6권1호
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    • pp.7-11
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    • 1996
  • MR-387Al (ARPA-Val-Pro) and A2 (AHPA-Val-Hyp) were prepared as aminopeptidase N inhibitors through the synthesis of peptide MR-387A and B analogues which contained 3-amino-2-hydroxy-4-phenyl butanoic acid (ARPA) as a zinc-chelating moiety. They are competitive inhibitors of aminopeptidase N with inhibition constants(Ki) of 4.1 $\times 10^{-7}\;and 1.1 \times 10^{-6}$ M, respectively. MR-387Al also strongly inhibited aminopeptidase B of human myelogenous leukemia K-562 cell with $IC_50$ of 0.35 $\mu$ M. Inhibitions of aminopeptidase N activity by ARPA-bearing inhibitors of various peptide chain lengths also have been studied. $IC_ 50$ values of AHPA-Val (bestatin), ARPA-Val-Pro (MR-387Al) and ARPA-Val-Pro-Leu (MR-387C) compared against porcine kidney aminopeptidase N were 20.1, 0.60 and 0.08 $\mu$ M, respectively. These results support that a multiple interaction between the $S_1\to S'_3$ sites of aminopeptidase N and the $P_1\to P'_3$ of the inhibitor plays a crucial role in stabilizing strongly the enzyme-inhibitor complex.

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Chemotherapeutic Response and Survival for Patients With an Anal Squamous Cell Carcinoma and Low Hemoglobin Levels

  • Naqvi, A.;Platt, E.;Jitsumura, M.;Evans, M.;Coleman, M.;Smolarek, S.
    • Annals of Coloproctology
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    • 제34권6호
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    • pp.312-316
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    • 2018
  • Purpose: Anemia is associated with poor treatment results for a variety of cancers. The effect of low hemoglobin levels on long-term outcomes after the treatment of patients with an anal squamous cell carcinoma (SCC) remains unclear. For that reason, this study aimed to investigate the effect of anemia on treatment outcomes following chemoradiation for an anal SCC. Methods: This was a retrospective study of all patients who underwent curative treatment for an anal SCC between 2009 and 2015 at 2 trusts in the United Kingdom. Data were collated from prospectively collected cancer databases and were cross-checked with operating-room records and records in the hospitals' patient management systems. Results: We identified 103 patients with a median age of 63 years (range, 36-84 years). The median overall survival was 39 months (range, 9-90 months), and the disease-free survival was 36 months (range, 2-90 months). During the follow-up period, 16.5% patients died and 13.6% patients developed recurrence. Twenty-two people were anemic prior to treatment, with a female preponderance (20 of 22). No differences in disease-free survival (P = 0.74) and overall survival (P = 0.12) were noted between patients with anemia and those with normal hemoglobin levels. On regression the analysis, the combination of anemia, the presence of a defunctioning colostomy, lymph-node involvement and higher tumor stage correlated with poor overall survival. Conclusion: In this study, anemia did not influence disease-free survival or overall survival. We suggest that the interaction between anemia and survival is more complex than previously demonstrated and potentially reliant on other coexisting factors.

Antiproliferative Effects of Free and Encapsulated Hypericum Perforatum L. Extract and Its Potential Interaction with Doxorubicin for Esophageal Squamous Cell Carcinoma

  • Amjadi, Issa;Mohajeri, Mohammad;Borisov, Andrei;Hosseini, Motahare-Sadat
    • 대한약침학회지
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    • 제22권2호
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    • pp.102-108
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    • 2019
  • Objectives: Esophageal squamous cell carcinoma (ESCC) is considered as a deadly medical condition that affects a growing number of people worldwide. Targeted therapy of ESCC has been suggested recently and required extensive research. With cyclin D1 as a therapeutic target, the present study aimed at evaluating the anticancer effects of doxorubicin (Dox) or Hypericum perforatum L. (HP) extract encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles on the ESCC cell line KYSE30. Methods: Nanoparticles were prepared using double emulsion method. Cytotoxicity assay was carried out to measure the anti-proliferation activity of Dox-loaded (Dox NPs) and HP-loaded nanoparticles (HP NPs) against both cancer and normal cell lines. The mRNA gene expression of cyclin D1 was evaluated to validate the cytotoxicity studies at molecular level. Results: Free drugs and nanoparticles significantly inhibited KYSE30 cells by 55-73% and slightly affected normal cells up to 29%. The IC50 of Dox NPs and HP NPs was ~ 0.04-0.06 mg/mL and ~ 0.6-0.7 mg/mL, respectively. Significant decrease occurred in cyclin D1 expression by Dox NPs and HP NPs (P < 0.05). Exposure of KYSE-30 cells to combined treatments including both Dox and HP extract significantly increased the level of cyclin D1 expression as compared to those with individual treatments (P < 0.05). Conclusion: Dox NPs and HP NPs can successfully and specifically target ESCC cells through downregulation of cyclin D1. The simultaneous use of Dox and HP extract should be avoided for the treatment of ESCC.

Evaluation of photon radiation attenuation and buildup factors for energy absorption and exposure in some soils using EPICS2017 library

  • Hila, F.C.;Javier-Hila, A.M.V.;Sayyed, M.I.;Asuncion-Astronomo, A.;Dicen, G.P.;Jecong, J.F.M.;Guillermo, N.R.D.;Amorsolo, A.V. Jr.
    • Nuclear Engineering and Technology
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    • 제53권11호
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    • pp.3808-3815
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    • 2021
  • In this paper, the EPICS2017 photoatomic database was used to evaluate the photon mass attenuation coefficients and buildup factors of soils collected at different depths in the Philippine islands. The extraction and interpolation of the library was accomplished at the recommended linear-linear scales to obtain the incoherent and total cross section and mass attenuation coefficient. The buildup factors were evaluated using the G-P fitting method in ANSI/ANS-6.4.3. An agreement was achieved between XCOM, MCNP5, and EPICS2017 for the calculated mass attenuation coefficient values. The buildup factors were reported at several penetration depths within the standard energy grid. The highest values of both buildup factor classifications were found in the energy range between 100 and 400 keV where incoherent scattering interaction probabilities are predominant, and least at the region of predominant photoionization events. The buildup factors were examined as a function of different soil silica contents. The soil samples with larger silica concentrations were found to have higher buildup factor values and hence lower shielding characteristics, while conversely, those with the least silica contents have increased shielding characteristics brought by the increased proportions of the abundant heavier oxides.

Donor-Site Morbidity Analysis of Thenar and Hypothenar Flap

  • Dong Chul Lee;Ho Hyung Lee;Sung Hoon Koh;Jin Soo Kim;Si Young Roh;Kyung Jin Lee
    • Archives of Plastic Surgery
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    • 제51권1호
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    • pp.94-101
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    • 2024
  • Background For the small glabrous skin defect, Thenar and Hypothenar skin are useful donors and they have been used as a free flap. Because of similar skin characteristics, both flaps have same indications. We will conduct comparative study for the donor morbidity of the Free thenar flap and Hypothenar free flap. Methods From January 2011 to December 2021, demographic data, characteristics of each flap, and complications using retrospective chart review were obtained. Donor outcomes of the patient, who had been followed up for more than 6 months, were measured using photographic analysis and physical examination. General pain was assessed by Numeric Rating Scale (NRS) score, neuropathic pain was assessed by Douleur Neuropathique 4 Questions (DN4) score, scar appearance was assessed by modified Vancouver Scar Scale (mVSS), and patient satisfaction was assessed on a 3-point scale. Statistical analysis was performed on the outcomes. Results Out of the 39 survey respondents, 17 patients received Free thenar flaps, and 22 patients received Hypothenar free flaps. Thenar group had higher NRS, DN4, and mVSS (p < 0.05). The average scores for the Thenar and Hypothenar groups were 1.35 and 0.27 for NRS, 2.41 and 0.55 for DN4, and 3.12 and 1.59 for mVSS, respectively. Despite the Hypothenar group showing greater satisfaction on the 3-point scale (1.82) compared with the Thenar group (1.47), the difference was not significant (p = 0.085). Linear regression analysis indicated that flap width did not have a notable impact on the outcome measures, and multiple linear regression analysis revealed no significant interaction between flap width and each of the outcome measures. Conclusion Despite the limited number of participants, higher donor morbidity in general pain, neuropathic pain, and scar formation was noted in the Thenar free flap compared with the Hypothenar free flap. However, no difference in overall patient satisfaction was found between the two groups.

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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    • 제9권1호
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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.

Indigenous Fungivorous Nematodes Affect the Biocontrol Efficacy of Trichoderma harzianum through Reducing the Hyphal Density

  • Kim, Tae Gwan;Knudsen, Guy R.
    • Journal of Microbiology and Biotechnology
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    • 제31권6호
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    • pp.815-822
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    • 2021
  • Indigenous fungus-feeding nematodes may adversely affect the growth and activity of introduced biocontrol fungi. Alginate pellets of the biocontrol fungus Trichoderma harzianum ThzID1-M3 and sclerotia of the fungal plant pathogen Sclerotinia sclerotiorum were added to nonsterile soil at a soil water potential of -50 or -1,000 kPa. The biomass of ThzID1-M3, nematode populations, and extent of colonization of sclerotia by ThzID1-M3 were monitored over time. The presence of ThzID1-M3 increased the nematode population under both moisture regimes (p < 0.05), and fungivores comprised 69-75% of the nematode population. By day 5, the biomass of ThzID1-M3b and its colonization of sclerotia increased and were strongly correlated (R2 = 0.98), followed by a rapid reduction, under both regimes. At -50 kPa (the wetter of the two environments), fungal biomass and colonization by ThzID1-M3 were less, in the period from 5 to 20 days, while fungivores were more abundant. These results indicate that ThzID1-M3 stimulated the population growth of fungivorous nematodes, which in turn, reduced the biocontrol ability of the fungus to mycoparasitize sclerotia. However, colonization incidence reached 100% by day 5 and remained so for the experimental period under both regimes, although hyphal fragments disappeared by day 20. Our results suggest that indigenous fungivores are an important constraint for the biocontrol activity of introduced fungi, and sclerotia can provide spatial refuge for biocontrol fungi from the feeding activity of fungivorous nematodes.

Microarray를 이용한 작약(芍藥)의 인간치은섬유모세포 유전자 발현 조절 연구 (Gene expression microarray analysis of Paeoniae radix on IL-$1{\beta}$-stimulated primary human gingival fibroblast)

  • 김경호;최영곤;홍연미;여수정;최지훈;김영홍;이제현;임사비나
    • 대한한의학회지
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    • 제31권2호
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    • pp.91-108
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    • 2010
  • Background & Objective: The aim of this study was to investigate the effect of P. radix on the inflammatory related gene expression in IL-$1{\beta}$-stimulated primary human gingival fibroblast using Whole Transcript Sense Target (WT-ST). Method: Human gingival fibroblast was incubated with P. radix [100 or $200\;{\mu}g/ml$], and IL-$1{\beta}$ [$1ng/m{\ell}$] added an hour later. After 24h, total RNA was extracted using RNeasy Mini Kit and the whole gene expression patterns were performed using WT-ST Labeling $Assay^{(R)}$. Result: In the DEG results, 782 genes were up-regulated in the IL-$1{\beta}$-treated group as compared to control and among those, 43 genes were associated with inflammation. 981 genes were down-regulated after treatment with IL-$1{\beta}$ and of those 7 genes were associated with inflammation. 1439 genes were up-regulated after treatment with P. radix plus IL-$1{\beta}$-treated when compared to IL-$1{\beta}$-treated alone group and 1225 genes were down-regulated in the same condition. Among the down-regulated genes, 5 were associated with inflammation- and inhibitor genes such as GDF15 and LIF. In the analysis of the P. radix plus IL-$1{\beta}$-treated group, the most significant pathways were the cytokine-cytokine receptor interaction, toll-like receptor signaling, JAK-STAT signaling and tyrosine metabolism. The gene expression patterns in the P. radix $200{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group appear to be more involved in the metabolism-related pathways than in the $100{\mu}g/m{\ell}$ plus IL-$1{\beta}$-treated group. Conclusion & Discussion: By microarray analysis of gene expression data, we are able to identify gene expression patterns associated with not only anti-inflammation effect but also transcription function of P. radix.