• 제목/요약/키워드: interaction curve

검색결과 366건 처리시간 0.029초

Effect of Ginsenoside Rc on the Pharmacokinetics of Mycophenolic Acid, a UGT1A9 Substrate, and its Glucuronide Metabolite in Rats

  • Park, So-Young;Jeon, Ji-Hyeon;Jang, Su-Nyeong;Song, Im-Sook;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • 제12권2호
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    • pp.53-58
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    • 2021
  • Previous in vitro studies have demonstrated that ginsenoside Rc inhibits UGT1A9, but there are no available data to indicate that ginsenoside Rc inhibits UGT1A9 in vivo. The effect of single and repeated intravenous injection of ginsenoside Rc was evaluated on the pharmacokinetics of mycophenolic acid. After injection of ginsenoside Rc (5 mg/kg for one day or 3 mg/kg for five days), 2-mg mycophenolic acid was intravenously injected, and the pharmacokinetics of mycophenolic acid and mycophenolic acid-β-glucuronide were determined. Concentrations of mycophenolic acid and its metabolite from rat plasma were analyzed using a liquid chromatography-triple quadrupole mass spectrometry. Single or repeated pretreatment with ginsenoside Rc had no significant effects on the pharmacokinetics of mycophenolic acid (P > 0.05): The mean difference in maximum plasma concentration (Cmax) and area under the concentration-time curve (AUCinf) were within 0.83- and 0.62-fold, respectively, compared with those in the absence of the ginsenoside Rc. These results indicate that ginsenoside Rc has a negligible effect on the disposition of mycophenolic acid in vivo despite in vitro findings indicating that ginsenoside Rc is a selective UGT1A9 inhibitor. As a result, ginsenoside Rc has little possibility of interacting with drugs that are metabolized by UGT1A9, including mycophenolic acid.

Induction of Systemic Resistance against Bacterial Leaf Streak Disease and Growth Promotion in Rice Plant by Streptomyces shenzhenesis TKSC3 and Streptomyces sp. SS8

  • Hata, Erneeza Mohd;Yusof, Mohd Termizi;Zulperi, Dzarifah
    • The Plant Pathology Journal
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    • 제37권2호
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    • pp.173-181
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    • 2021
  • The genus Streptomyces demonstrates enormous promise in promoting plant growth and protecting plants against various pathogens. Single and consortium treatments of two selected Streptomyces strains (Streptomyces shenzhenensis TKSC3 and Streptomyces sp. SS8) were evaluated for their growth-promoting potential on rice, and biocontrol efficiency through induced systemic resistance (ISR) mediation against Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of rice bacterial leaf streak (BLS) disease. Seed bacterization by Streptomyces strains improved seed germination and vigor, relative to the untreated seed. Under greenhouse conditions, seed bacterization with consortium treatment TKSC3 + SS8 increased seed germination, root length, and dry weight by 20%, 23%, and 33%, respectively. Single and consortium Streptomyces treatments also successfully suppressed Xoc infection. The result was consistent with defense-related enzyme quantification wherein single and consortium Streptomyces treatments increased peroxidase (POX), polyphenol oxidase, phenylalanine ammonia-lyase, and β,1-3 glucanase (GLU) accumulation compared to untreated plant. Within all Streptomyces treatments, consortium treatment TKSC3 + SS8 showed the highest disease suppression efficiency (81.02%) and the lowest area under the disease progress curve value (95.79), making it the best to control BLS disease. Consortium treatment TKSC3 + SS8 induced the highest POX and GLU enzyme activities at 114.32 µmol/min/mg protein and 260.32 abs/min/mg protein, respectively, with both enzymes responsible for plant cell wall reinforcement and resistant interaction. Our results revealed that in addition to promoting plant growth, these Streptomyces strains also mediated ISR in rice plants, thereby, ensuring protection from BLS disease.

Moment-rotational analysis of soil during mining induced ground movements by hybrid machine learning assisted quantification models of ELM-SVM

  • Dai, Bibo;Xu, Zhijun;Zeng, Jie;Zandi, Yousef;Rahimi, Abouzar;Pourkhorshidi, Sara;Khadimallah, Mohamed Amine;Zhao, Xingdong;El-Arab, Islam Ezz
    • Steel and Composite Structures
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    • 제41권6호
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    • pp.831-850
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    • 2021
  • Surface subsidence caused by mining subsidence has an impact on neighboring structures and utilities. In other words, subsurface voids created by mining or tunneling activities induce soil movement, exposing buildings to physical and/or functional destruction. Soil-structure is evaluated employing probability distribution laws to account for their uncertainty and complexity to estimate structural vulnerability. In this study, to investigate the displacement field and surface settlement profile caused by mining subsidence, on the basis of a Winklersoil model, analytical equations for the moment-rotation response ofsoil during mining induced ground movements are developed. To define the full static moment-rotation response, an equation for the uplift-yield state is constructed and integrated with equations for the uplift- and yield-only conditions. The constructed model's findings reveal that the inverse of the factor of safety (x) has a considerable influence on the moment-rotation curve. The maximal moment-rotation response of the footing is defined by X = 0:6. Despite the use of Winkler model, the computed moment-rotation response results derived from the literature were analyzed through the ELM-SVM hybrid of Extreme Learning Machine (ELM) and Support Vector Machine (SVM). Also, Monte Carlo simulations are used to apply continuous random parameters to assess the transmission of ground motions to structures. Following the findings of RMSE and R2, the results show that the choice of probabilistic laws of input parameters has a substantial impact on the outcome of analysis performed.

The Coordinative Locomotor Training Intervention Strategy Using the ICF Tool to Improve the Standing Posture in Scoliosis: A Case Report

  • Lee, Jeong-a;Kim, Jin-cheol
    • The Journal of Korean Physical Therapy
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    • 제33권1호
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    • pp.7-15
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    • 2021
  • Purpose: This study was examined to improve the standing posture of a scoliosis client using the ICF Tool. Methods: For examination, the study subject was a 16-year-old female student diagnosed with 3curve-pelvic (3CP) type scoliosis. Information about her were collected through a client interview and based on international Classification of Functioning, Disability and Health (ICF). The ICF core set was for post-acute musculoskeletal conditions, and the ICF level 2 items suggested by National Rehabilitation Information Center (NARIC) were added to the recommendations for scoliosis. For evaluation, the ICF assessment sheet was used to identify the interaction among the problems. For the diagnosis, the client's functional problems were described in ICF terms. For the prognosis, the global goals for reaching the client's functional activity and participation level were presented as the long-and short-term goals. For the intervention, a coordinative locomotor training program composed of warm-up, main exercise, and cool-down was applied 3 times a week, 50 minutes a day, for 5 weeks. For the outcome, the differences between before and after the intervention were compared with the ICF qualifier and are shown with the ICF evaluation display. Results: Clinical advantages were observed in body function and structure (7° decrease of thoracic angle, 7 score increase of trunk muscle power, 6.47s improve of one leg standing, 4 score decrease of neck pain). The activity for maintaining the standing posture, in which the client had a primary limitation, was improved. Conclusion: Applying the coordinative locomotor training program is expected to improve scoliosis client's standing posture.

Antibacterial activity of enrofloxacin loaded gelatin-sodium alginate composite nanogels against intracellular Staphylococcus aureus small colony variants

  • Luo, Wanhe;Liu, Jinhuan;Algharib, Samah Attia;Chen, Wei
    • Journal of Veterinary Science
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    • 제23권3호
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    • pp.48.1-48.12
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    • 2022
  • Background: The poor intracellular concentration of enrofloxacin might lead to treatment failure of cow mastitis caused by Staphylococcus aureus small colony variants (SASCVs). Objectives: In this study, enrofloxacin composite nanogels were developed to increase the intracellular therapeutic drug concentrations and enhance the efficacy of enrofloxacin against cow mastitis caused by intracellular SASCVs. Methods: Enrofloxacin composite nanogels were formulated by an electrostatic interaction between gelatin (positive charge) and sodium alginate (SA; negative charge) with the help of CaCl2 (ionic crosslinkers) and optimized by a single factor test using the particle diameter, zeta potential (ZP), polydispersity index (PDI), loading capacity (LC), and encapsulation efficiency (EE) as indexes. The formation mechanism, structural characteristics, bioadhesion ability, cellular uptake, and the antibacterial activity of the enrofloxacin composite nanogels against intracellular SASCVs strain were studied systematically. Results: The optimized formulation was comprised of 10 mg/mL (gelatin), 5 mg/mL (SA), and 0.25 mg/mL (CaCl2). The size, LC, EE, PDI, and ZP of the optimized enrofloxacin composite nanogels were 323.2 ± 4.3 nm, 15.4% ± 0.2%, 69.6% ± 1.3%, 0.11 ± 0.02, and -34.4 ± 0.8 mV, respectively. Transmission electron microscopy showed that the enrofloxacin composite nanogels were spherical with a smooth surface and good particle size distributions. In addition, the enrofloxacin composite nanogels could enhance the bioadhesion capacity of enrofloxacin for the SASCVs strain by adhesive studies. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibitory concentration, and minimum biofilm eradication concentration were 2, 4, 4, and 8 ㎍/mL, respectively. The killing rate curve had a concentration-dependent bactericidal effect as increasing drug concentrations induced swifter and more radical killing effects. Conclusions: This study provides a good tendency for developing enrofloxacin composite nanogels for treating cow mastitis caused by intracellular SASCVs and other intracellular bacterial infections.

Development of Modified Flexibility Ratio - Racking Ratio Relationship of Box Tunnels Subjected to Earthquake Loading Considering Rocking

  • Duhee Park;Van-Quang Nguyen;Gyuphil Lee;Youngsuk Lee
    • 한국지반환경공학회 논문집
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    • 제24권2호
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    • pp.13-24
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    • 2023
  • Tunnels may undergo a larger or a smaller response compared with the free-field soil. In the pseudo-static procedure, the response of the tunnel is most often characterized by a curve that relates the racking ratio (R) with the flexibility ratio (F), where R represents the ratio of the tunnel response with respect to the free-field vibration and F is the relative stiffness of the tunnel and the surrounding soil. A set of analytical and empirical curves that do not account for the depth and the aspect ratio of the tunnel are typically used in practice. In this study, a series of dynamic analyses are conducted to develop a set of F-Rm relations for use in a frame analysis method. Rm is defined as an adjusted R where the rocking mode of deformation is removed and only the racking deformation is extracted. The numerical model is validated against centrifuge test recordings. The influence of aspect ratio, buried depth of tunnel on results is investigated. The results show that Rm increases with the increase of the buried depth and the aspect ratio. The widely used F-R relations are highlighted to be different compared with the obtained results in this study. Therefore, the updated F-Rm relations with proposed equations are recommended to be used in practice design. The rocking response decreases with either the decrease of the difference of stiffness between surrounding soil and tunnel or the larger aspect ratio of the tunnel section.

Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction

  • Hyeon Gyeom Choi;So Yeon Park;Sung Hun Bae;Sun-Young Chang;So Hee Kim
    • Biomolecules & Therapeutics
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    • 제32권5호
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    • pp.601-610
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    • 2024
  • Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance. Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

반응표면분석법을 이용한 Thermotoga neapolitana β-glucosidase의 당전이 활성을 통한 glycosyl aesculin 합성 최적화 (Optimization of Glycosyl Aesculin Synthesis by Thermotoga neapolitana β-Glucosidase Using Response-surface Methodology)

  • 박현수;박영돈;차재호
    • 생명과학회지
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    • 제27권1호
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    • pp.38-43
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    • 2017
  • 강한 항 염증 활성을 갖는 glycosyl aesculin이 Thermotoga neapolitana ${\beta}-glucosidase$의 당전이 활성을 통하여 aesculin을 수용체로 이용하여 합성되었다. 약 $2{\mu}g$의 효소를 이용하여 반응표면분석법을 통한 주요 반응 매개변수들의 최적화가 시도되었다. 각 반응 변수들의 통계분석 결과 2차 다항식모델이 적용된 유의값(p<0.05)에 잘 맞았다. Aesculin과 다른 매개변수사이의 상호관계를 의미하는 반응표면곡선 그래프는 glycosyl aesculin의 수율이 주로 aesculin의 농도와 반응시간에 영향을 받음을 나타내었다. Glycosyl aesculin의 생산을 위한 반응최적조건은 aesculin의 농도 9.5 g/l, 온도 $84^{\circ}C$, 반응시간 81분, 그리고 pH 8.2로 나타났으며, 이러한 조건하에서 효소반응시 61.7%의 전환율로 5.86 g/l 의 수율이 예상되었다. 실험을 통한 실질적인 수율은 6.02 g/l으로 나타났다. 실질적인 수율과 가까운 값을 예측 가능하다는 것을 통하여 반응표면분석법이 효소반응의 전환율을 최적화하는데 타당하다는 것이 입증되었다. 본 연구에서는 반응표면분석법을 활용하여 최적화 이전에 비하여 약 1.6배의 glycosyl aesculin을 얻을 수 있었다. 이러한 결과들은 반응표면분석법이 미생물유래 당화효소를 이용한 생물학적 활성을 갖는 배당체 합성의 생산 최적화에 효과적으로 활용할 수 있다는 것을 보여준다.

성향정기산(星香正氣散)이 가토의 경동맥(頸動脈) 평활근(平滑筋) 긴장(緊張) 및 $Ca^{2+}$ 대사(代謝)에 미치는 영향(影響) (Effect of Sunghyangchungisan on Contractile Reactivity and $Ca^{2+}$ metabolism in Isolated Rabbit Carotid Artery)

  • 김영균;권정남;김종훈
    • 대한한방내과학회지
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    • 제21권3호
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    • pp.377-388
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    • 2000
  • Objective : This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone and $Ca^{2+}$ metabolism in arterial tissues. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities, endothelial function and $Ca^{2+}$ metabolism were determined. Methods : In phentobarbital sodium-anesthetized rabbits, SHCS administered through ear vein (100 mg/Kg body wt.) or intragastric dwelling tube (300 mg/Kg body wt.) attenuated phenylephrine (PE, 10 ${\mu}g$/Kg, i.v.)-induced increases in both systolic and diastolic cartoid arterial blood pressure. Results : In experiments with isolated arterial strips, SHCS relaxed arterial rings which were pre-contracted by phenylephrine (PE, 1 ${\mu}M$). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50)$ of PE oh its dose-response curve ruled out the possible interaction of SHCS with ${\alpha}$-receptors. The relaxant effect of SHCS was not affected by removal of endothelium or a nitric oxide synthase inhibitor, L-NAME. Methylene blue, an inhibitor of the soluble guanylate cyclase, did not affect the relaxant effect of SHCS. These results suggest that the action of SHCS is not mediated by the endothelium nor soluble guanylate cyclase. Constant cGMP production determined in arterial strips in the presence or absence of SHCS is consistent with this conclusion. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}$-free solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. SHCS partially blocked $Ca^{2+}$ influx stimulated by PE and high $K^+$ which was determined by 5-min ^{45}Ca$ uptake, while it did not affect $Ca^{2+}$ efflux. Conclusions : From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium independent manner, andinhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

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합성보 전단연결부의 구조거동에 대한 비교 분석 (Analysis of a Load Carrying Behavior of Shear Connection at the Interface of the Steel-Concrete Composite Beam)

  • 신현섭
    • 한국강구조학회 논문집
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    • 제17권6호통권79호
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    • pp.737-747
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    • 2005
  • 강재 보와 콘크리트 슬래브로 구성되어 지는 합성보에서 두 부재는 일반적으로 전단연결재에 의해 서로 합성되어져 일체적인 구조거동을 하게 된다. 현재까지 전단연결재로서는 스터드(stud)가 널리 사용되어지고 있다. 합성보의 구조적 거동은 사용된 부재의 재료적 특성 외에도 스터드에 의한 전단합성작용에 의해 많은 영향을 받게 된다. 합성보 전단연결부에서의 전단합성거동은 합성보에서가 아닌 단순화된 Push-Out 시험체(Push-Out Test Specimen)에 의해 실험적으로 결정되고 있다. 최근의 연구결과에 따르면, Push-Out 실험에서 얻은 전단 스터드의 합성거동과 실제 합성보에서의 전단합성거동에는 분명한 차이점이 존재하며, 특히 부분합성된 합성보에서는 그 차이가 매우 크다는 것이 밝혀지고 있다. 본 연구에서는 표준 Push-Out 시험체 및 합성보의 구조거동 해석을 위해, Push-Out 실험으로부터 결정되는 스터드에 대한 하중-상대변위 곡선의 도입이 필요 없는 3차원 유한요소모델을 개발하였다. 해석결과의 비교 분석으로부터 합성보 전단연결부에서의 합성거동을 평가할 수 있었고, 이를 Push-Out 실험결과와 비교하여 보았으며 전단합성거동의 차이점에 대한 구체적 원인을 찾을 수 있었다.