• Title/Summary/Keyword: RANO 2.0

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Phenotyping of Flavin-Containing Monooxygenase (FMO) Activity and Factors Affecting FMO Activity in Korean

  • Jeon, Sun-Ho;Park, Chang-Shin;Cha, Young-Nam;Chung, Woon-Gye
    • Toxicological Research
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    • v.17
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    • pp.127-133
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    • 2001
  • Together with cytochrome P450 (CYP), flavin-containing monooxygenase (FMO) present in liver microsomes oxidizes various endogenous and exogenous chemicals. In an effort to determine the human FMO activity, we have developed two non-invasive urine analysis methods using caffeine (CA) and ranitidine (RA) as the probe compounds. As the production of theobromine (TB) and ranitidine N-oxide (RANO) from CA and RA is catalyzed primarily by the hepatic FMO, we have assigned the urinary molar ratios of TB/CA and RA/RANO as the in vivo FMO activity. In 200 age-matched Korean volunteers, the obtained TB/CA ratio ranged from 0.4 to 15.2 (38-fold difference) and the RA/RANO ratio from 5.7 to 27.2 (4.8-fold). The FMO activity of 20's, determined by caffeine metabolism, was the highest (2.5$\pm$l.9) and those of 30's, 40's, 50's, 60's and 70's were 40%, 50%, 24%, 39% and 36% of the 20's, respectively. Intake of grapefruit juice, known to contain flavonoids, inhibited the in vivo FMO (TB/CA) activity by 79%. Addition of the flavonoids like naringin, quercitrin and kaempferol, present in grapefruit juice, to the in vitro microso-mal FMO assay, thiobenzamide S-oxidation, produced 75%, 70% and 60% inhibition, respectively. Obtained Ki values of quercitrin, kaempferol and naringin on the in vitro FMO activity were 6.2, 12.0 and 13.9 $\mu\textrm{M}$, respectively. This suggested that the dose of drug should need to be adjusted to suit the individual FMO activities when the drugs metabolized by FMO are given to patients. As the intake of grapefruit juice has been identified to inhibit the FMO as well as CYP3A4 and lA2 activities, patients taking drugs metabolized by these enzymes should not drink grapefruit juice as the carrier.

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Relationship of Maximal Take-off Speed to Power and Shortening llelocitv of Hindlimb Muscle in Anuran Amphibians (무미양서류의 도약속도와 다리근육의 동력 및 수축속도와의 관계)

  • 최인호
    • The Korean Journal of Zoology
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    • v.39 no.2
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    • pp.132-138
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    • 1996
  • To learn how maximal locomotory speed of animals is defined in terms of hindlimb structure and muscle contractile function, take-off speed, hindlimb length, thigh muscle mass, shortening velocity and power of the sastrocnemius muscle were measured with one fast species, Rono nigromaculota and one relatively slowresponding species, Bombina orientalis. Take-off speed (m.sec-1) was greater in R. nigromoculata $(2.4\pm0.2SD, $ n: 14) than in the Bombino $(1.6\pm0.1SD, $ n=8). Stvle of the take-off response was a long-iump type in the Rano and a short-ranged hopping in the Bombing. Faster take-off capacity of the ranid frogs was supported by the longer hindlimb length (relative to body length) and the more massive thigh muscles (relative to body mass), compared to the Bombina. Further, the ranids exhibited faster maximal shortening velocity and Breater maximal power generateion than the Bombina [Vmax $(ML.sec-1)=11.79\pm1.69SD$ for the Runa and $9.74\pm1.27SD$ for the Bombina; Pmax $nW.kg-1)=222.42\pm42.42SD$ for the Rono and $169.03\pm34.52SD$ for the Bombinal. With more massive thigh muscles and greater mechanical power, the ranids would generate greater total power and thus higher energy release per unit time to muscle tissues for the burst take-off. As a consequence, biomechanical properties seen in the ranids seem to be more effective for frost take-off than in the Bombina.

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Tumor Habitat Analysis Using Longitudinal Physiological MRI to Predict Tumor Recurrence After Stereotactic Radiosurgery for Brain Metastasis

  • Da Hyun Lee;Ji Eun Park;NakYoung Kim;Seo Young Park;Young-Hoon Kim;Young Hyun Cho;Jeong Hoon Kim;Ho Sung Kim
    • Korean Journal of Radiology
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    • v.24 no.3
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    • pp.235-246
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    • 2023
  • Objective: It is difficult to predict the treatment response of tissue after stereotactic radiosurgery (SRS) because radiation necrosis (RN) and tumor recurrence can coexist. Our study aimed to predict tumor recurrence, including the recurrence site, after SRS of brain metastasis by performing a longitudinal tumor habitat analysis. Materials and Methods: Two consecutive multiparametric MRI examinations were performed for 83 adults (mean age, 59.0 years; range, 27-82 years; 44 male and 39 female) with 103 SRS-treated brain metastases. Tumor habitats based on contrast-enhanced T1- and T2-weighted images (structural habitats) and those based on the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) images (physiological habitats) were defined using k-means voxel-wise clustering. The reference standard was based on the pathology or Response Assessment in Neuro-Oncologycriteria for brain metastases (RANO-BM). The association between parameters of single-time or longitudinal tumor habitat and the time to recurrence and the site of recurrence were evaluated using the Cox proportional hazards regression analysis and Dice similarity coefficient, respectively. Results: The mean interval between the two MRI examinations was 99 days. The longitudinal analysis showed that an increase in the hypovascular cellular habitat (low ADC and low CBV) was associated with the risk of recurrence (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.46-4.91; P = 0.001). During the single-time analysis, a solid low-enhancing habitat (low T2 and low contrast-enhanced T1 signal) was associated with the risk of recurrence (HR, 1.54; 95% CI, 1.01-2.35; P = 0.045). A hypovascular cellular habitat was indicative of the future recurrence site (Dice similarity coefficient = 0.423). Conclusion: After SRS of brain metastases, an increased hypovascular cellular habitat observed using a longitudinal MRI analysis was associated with the risk of recurrence (i.e., treatment resistance) and was indicative of recurrence site. A tumor habitat analysis may help guide future treatments for patients with brain metastases.