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Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats

  • Rojas-Armas, Juan;Arroyo-Acevedo, Jorge;Ortiz-Sanchez, Manuel;Palomino-Pacheco, Miriam;Castro-Luna, Americo;Ramos-Cevallos, Norma;Justil-Guerrero, Hugo;Hilario-Vargas, Julio;Herrera-Calderon, Oscar
    • Toxicological Research
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    • v.35 no.3
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    • pp.225-232
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    • 2019
  • Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

Growth of ε-Ga2O3 film and fabrication of high quality β-Ga2O3 films by phase transition (ε-Ga2O3 박막의 성장과 상전이를 이용한 고품질 β-Ga2O3 박막의 제조)

  • Lee, Hansol;Kim, Soyoon;Lee, Jungbok;Ahn, Hyungsoo;Kim, Kyounghwa;Yang, Min
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.31 no.1
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    • pp.1-7
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    • 2021
  • ε-Ga2O3, a metastable phase of Ga2O3, has excellent compatibility with substrates having a hexagonal structure or a quasi-hexagonal structure, so that a film having a relatively lower surface roughness and defect density than β-Ga2O3 can be obtained easily. Accordingly, we attempted to fabricate a high-quality β-Ga2O3 film with a low surface roughness and defect density using the property of phase transition to β-Ga2O3 when ε-Ga2O3 is annealed at a high temperature. For this, the growth of high-quality ε-Ga2O3 films must be preceded. In this study, the optimal flow rate was investigated by analyzing the structural and morphological characteristics of the ε-Ga2O3 film according to the supplied precursor ratio. In addition, the annealing condition and the effect of β-Ga2O3 mixed in the ε-Ga2O3 film on the crystallinity of β-Ga2O3 after phase transition were also investigated.

Crystal structural property and chemical bonding nature of cellulose nanocrystal formed by high-pressure homogenizer (고압 균질기를 이용하여 형성된 셀룰로오스 나노결정의 결정 구조 및 화학적 결합 특성 연구)

  • Chel-Jong Choi;Nae-Man Park;Kyu-Hwan Shim
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.34 no.3
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    • pp.79-85
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    • 2024
  • We investigated the crystal structural property and chemical bonding nature of cellulose nanocrystal extracted directly from cotton cellulose using high-pressure homogenizer. The nanowire-like cellulose nanocrystals were randomly distributed in the form of a dense mesh. Based on calculating the interplanar distance of the Bragg-diffracted crystal plane observed through X-ray diffraction (XRD) analysis, it was found that the cellulose nanocrystals formed by high-pressure homogenizer had a monoclinc crystal structure, corresponding to the cellulose Iβ sub-polymorph. Solid-state nuclear magnetic resonance (NMR) analysis for the quantitatively evaluation of the amorphous region in cellulose nanocrystals revealed that the crystallinity index of cellulose nanocrystals was calculated to be 53.06 %. The O/C ratio of the surface of cellulose nanocrystal was estimated to be 0.82. Further analysis showed that chemical bonds of C-C bond or C-H bond, C-O bond, O-C-O bond or C=O bond, and O-C=O bond were the main chemical bonding states of the cellulose nanocrystal surface.

Precipitation of $CaCO_3$ Crystals from Variously Supersaturated Solutions (다양한 과포화 조건하에서의 탄산염광물의 합성에 대한 연구)

  • Hyeon Yoon;Kim, Soo-Jin
    • Journal of the Mineralogical Society of Korea
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    • v.17 no.1
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    • pp.11-21
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    • 2004
  • Crystallization of CaC $O_3$ from the solutions of various degrees of supersaturation was carried out by a spontaneous precipitation method. The solution was kept at $25^{\circ}C$ and pH 6.9∼8.8. The solution compositions were varied in two ways: (1) The total carbonate, [C $O_3$]$_{Τ}$, to total calcium. [Ca]$_{Τ}$, ratios vary as ; [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$ >1. [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$=1, and [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$<1. (2) The total calcium concentration, [Ca]$_{Τ}$, held at 0.02 mo1/d $m^3$, 0.2 mo1/d $m^3$, and 0.4 mo1/d $m^3$. We found that the CaC $O_3$ phase crystallized from the solutions of [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$ $\geq$ 1 was mostly calcite with less than 1% of vaterite, while the CaC $O_3$ crystals precipitated from low carbonate concentration toward calcium concentration, [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$ < 1, were dominated by vaterite crystals. It appears that the polymorph of CaC $O_3$ precipitate was mainly controlled not by the calcium concentration but by the carbonate concentration during the spontaneous precipitation. Also, we found that the surface roughness of vaterite increased with decreasing carbonate concentration from 0.8 or 0.5 of [C $O_3$]$_{Τ}$/[Ca]$_{Τ}$ ratios and the surface area of vaterite increased from 5.64∼7.34 $\mu\textrm{m}$ to 8.39∼10.3 $\mu\textrm{m}$.

Variability in Drug Interaction According to Genetic Polymorph isms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • Environmental Mutagens and Carcinogens
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    • v.23 no.4
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    • pp.131-134
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    • 2003
  • There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

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