• Title/Summary/Keyword: human-to-human (H2H)

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Validation of LC-MS/MS Method for Determination of Rabeprazole in Human Plasma : Application of Pharmacokinetics Study (인체 혈장중 라베프라졸의 정량을 위한 LC-MS/MS 분석법 검증 및 단일 용량 투여에 의한 약물동태 연구)

  • Tak, Sung-Kwon;Seo, Ji-Hyung;Ryu, Ju-Hee;Choi, Sang-Joon;Lee, Myung-Jae;Kang, Jong-Min;Lee, Jin-Sung;Hong, Seung-Jae;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.73-78
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    • 2009
  • A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

Effects of Chronic Treatments with 5-HT Uptake Inhibitors on the [$^3H$]Imipraine and [$^3H$]Paroxetine Binding, [$^3H$]5-HT Uptake, and 5-HT Content of the Rabbit Platelet (5-HT 흡수억제성 항우울제들이 가토혈소판의 [$^3H$]Imipramine과 [$^3H$]Paroxetine Binding, [$^3H$]5-HT 흡수, 및 5-HT함량에 미치는 영향)

  • Won, Kyong-Sik;Lee, Min-Soo;Shin, Kyung-Ho;Chun, Boe-Gwun;Kwak, Dong-Il
    • Korean Journal of Biological Psychiatry
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    • v.1 no.1
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    • pp.88-97
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    • 1994
  • Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

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Optimal Culture Conditions for Photosynthetic Microalgae Nannochloropsis oculata (광합성 미세조류 Nannochloropsis oculata의 최적배양 조건)

  • Park, Hyun-Jin;Jin, Eun-Jung;Jung, Tae-Man;Joo, Hyun;Lee, Jae-Hwa
    • Applied Chemistry for Engineering
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    • v.21 no.6
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    • pp.659-663
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    • 2010
  • Microalgae has been seen all over the seawater and several species are used for human food. Specially, Nannochloropsis oculata, a photosynthetic microalgae, has been focused for a vast array of valuable nutritious compounds. In order to find high mass Nannochloropsis oculata culture conditions, some of important growth factors of pH, temperature, culture media, and $CO_2$ effect were tested. The optimal growth condition was found to be as follows : 3% artificial seawater, initial pH 8.5, and temperature $25^{\circ}C$. The alga mass and chlorophyll content were dramatically increased by applying 5% flue $CO_2$ gas (1.50 g/L algae in a continuous $CO_2$ flue; 0.76 g/L alga without $CO_2$). It was shown that the chlorophyll biosynthesis was also closely associated with alga growth.

Optimal Fermentation Conditions of Hyaluronidase Inhibition Activity on Asparagus cochinchinensis Merrill by Weissella cibaria

  • Kim, Minji;Kim, Won-Baek;Koo, Kyoung Yoon;Kim, Bo Ram;Kim, Doohyun;Lee, Seoyoun;Son, Hong Joo;Hwang, Dae Youn;Kim, Dong Seob;Lee, Chung Yeoul;Lee, Heeseob
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.701-708
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    • 2017
  • This study was conducted to evaluate the hyaluronidase (HAase) inhibition activity of Asparagus cochinchinesis (AC) extracts following fermentation by Weissella cibaria through response surface methodology. To optimize the HAase inhibition activity, a central composite design was introduced based on four variables: the concentration of AC extract ($X_1$: 1-5%), amount of starter culture ($X_2$: 1-5%), pH ($X_3$: 4-8), and fermentation time ($X_4$: 0-10 days). The experimental data were fitted to quadratic regression equations, the accuracy of the equations was analyzed by ANOVA, and the regression coefficients for the surface quadratic model of HAase inhibition activity in the fermented AC extract were estimated by the F test and the corresponding p values. The HAase inhibition activity indicated that fermentation time was most significant among the parameters within the conditions tested. To validate the model, two different conditions among those generated by the Design Expert program were selected. Under both conditions, predicted and experimental data agreed well. Moreover, the content of protodioscin (a well-known compound related to anti-inflammation activity) was elevated after fermentation of the AC extract at the optimized fermentation condition.

Combined effect of recombinant human bone morphogenetic protein-2 and low level laser irradiation on bisphosphonate-treated osteoblasts

  • Jeong, Seok-Young;Hong, Ji-Un;Song, Jae Min;Kim, In Ryoung;Park, Bong Soo;Kim, Chul Hoon;Shin, Sang Hun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.44 no.6
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    • pp.259-268
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    • 2018
  • Objectives: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. Materials and Methods: Human fetal osteoblast cells (hFOB 1.19) were cultured with $100{\mu}M$ alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. Results: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. Conclusion: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.

Effects of Omahwan Administration in Aged Human Immune System (오마환(烏麻丸)이 노인(老人)의 면역기능(免疫機能)에 미치는 영향(影響))

  • Lee Song-Shil;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.4 no.2
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    • pp.57-71
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    • 2000
  • BACGROUND: To examine effect of omahwan(烏麻丸)-赤何首烏(Polygonum multiflorum THUNB.), 白何首烏(Cynanchum wilfordii H.), 黑芝流(Sesamum indicum L.)-on the aged human immune system a series of humoral immunological parameters was compared in aged female (age 60-70 years) before and after administration of omahwan(烏麻丸). METHODS: Peripheral blood was obtained from fifteen healthy young (age 20-29, mean=66.3) female volunteers. B cell, T cell(T cells, T helper, and T suppressor/ cytotoxic) subsets was examined with specific monoclonal antibodies and isotype controls, using dural color flow cytometer IL-2 was examined with ELISA kit RESULT: By comparing the immune characteristics of the younger and elder groups the total ratio of T-cell, CD8 T-cell and quantify of IL-2 was significantly lower while CD4/CDB ratio was considerably greater in the elder group. ( p(0.05, student t-test) After giving Omahwan for 30 days to the elder group, by comparing the ratio before and after Prescription the total T cell and CD8 T cell ratio was considerably greater after prescription (p(0.05, Paired t-test) The quantity of IL-2 tended to increase after prescription but has no statistical meaning. CONCLUSION: The results indicate that administration of Omahwan(烏麻丸) differentially affects various aspects of the immune system in aged human.

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The Effect of Natural Color Difference and Mordanting in the Onion Coats Dye (양파외피에 의한 천연색소에 관한 실험적 연구)

  • Hong, Kyung-Ok;Shin, In-Soo
    • Korean Journal of Human Ecology
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    • v.7 no.1
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    • pp.167-173
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    • 1998
  • Having silk dyed with some pigment extracted from the skin of an onion, examined the change of color by time and frequency of dyeing and a mordanted cloth, and the antibiosis of a dyed cloth and a mordanted cloth. The result of this were as follows ; 1. The pigment of an onion was easily extracted in the hot water of $40^{\circ}C$ and much more extracted as the temperature of water rises($70^{\circ}C$). 2. As a result of dyeing it by the change of time, 30minutes, 60minutes, 90minutes and the frequency of dyeing, once, twice, three times after filtering the extracted solution, the one dyed three times for 30minutes was the best. 3. The difference of color of a mordanted cloth was the highest in the mordant of $SnCl_2\;2H_2O$ on the basis of the value of L of the non-mordant dyed three times. 4. The mordant of copper sulfate was proved to have the highest antibiosis in the antibiosis of a dyed cloth and a mordanted cloth, and it was proved that the pigment of the skin of an onion had excellent antibiosis.

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Activity Determination, Kinetic Analyses and Isoenzyme Identification of Gamma Glutamyltransferase in Human Neutrophils

  • Sener, Azize;Yardimci, Turay
    • BMB Reports
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    • v.38 no.3
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    • pp.343-349
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    • 2005
  • Gamma-glutamyltransferase (GGT, EC 2.3.2.2) which hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH concentration. GGT is a membrane enzyme present in leukocytes and platelets. Its activity has also been observed in human neutrophils. In this study, GGT was purified from Triton X-100 solubilized neutrophils and its kinetic parameters were determined. For kinetic analyses of transpeptidation reaction, $\gamma$-glutamyl p-nitroanilide was used as the substrate and glycylglycine as the acceptor. Apparent $K_m$ values were determined as 1.8 mM for $\gamma$-glutamyl p-nitroanilide and 16.9 mM for glycylglycine. The optimum pH of GGT activity was 8.2 and the optimum temperature was $37^{\circ}C$. It had thermal stability with 58% relative activity at $56^{\circ}C$ for 30 min incubation. L-serine, in the presence of borate, was detected as the competetive inhibitor. Bromcresol green inhibited neutrophil GGT activity as a noncompetetive inhibitor. The neutrophils seem to contain only the isoenzyme that is present in platelets. We characterized the kinetic properties and compared the type of the isoenzyme of neutrophil GGT with platelet GGT via polyacrylamide gel electrophoresis (PAGE) under a standart set of conditions.

Anti-tumor and Anti-inflammatory Activity of the Methanol Extracts from Adlay Bran

  • Lee, Ming-Yi;Tsai, Shu-Hsien;Kuo, Yueh-Hsiung;Chiang, Wenchang
    • Food Science and Biotechnology
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    • v.17 no.6
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    • pp.1265-1271
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    • 2008
  • Adlay bran is a waste product previously thought to have no commercial value, Its methanolic extract was fractionated using n-hexane (ABM-Hex), ethyl acetate (ABM-EtOAc), 1-butanol (ABM-BuOH), and water (ABM-$H_2O$). The ABM-EtOAc fraction exhibited a strongest inhibition against growth of human lung cancer cell A549 and human colorectal carcinoma cells HT-29 and COLO 205. Inhibition of cell cycle progression at $G_0/G_1$ transition, increase of cells at the sub-$G_1$ phase, and DNA ladders were observed in cells treated with ABM-EtOAc. The ABM-BuOH fraction showed the strongest inhibition of proinflammatory cytokines tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-$1{\beta}$ in stimulated RAW 264.7 macrophages. Further, ABM-EtOAc and ABM-BuOH inhibited cyclooxygenase (COX)-2 expression in A549 and HT-29 carcinoma cells, while COX-l expression was not affected. These results reveal that both ABM-EtOAc and ABM-BuOH may aid the prevention of cancers and the applications in cancer chemotherapy.

Synthesis and radiolabeling of PEGylated dendrimer-G2-Gemifloxacin with 99mTc to Biodistribution study in rabbit

  • Mohtavinejad, Naser;Dolatshahi, Shaya;Amanlou, Massoud;Ardestani, Mehdi Shafiee;Asadi, Mehdi;Pormohammad, Ali
    • Advances in nano research
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    • v.10 no.5
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    • pp.461-470
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    • 2021
  • Infection is one of the major mortality causes throughout the globe. Nuclear medicine plays an important role in diagnosis of deep infections such as osteomyelitis, arthritis infection, heart valve and heart prosthesis infections. Techniques such as labeled leukocytes are sensitive and selective for tracking the inflammations but they are not suitable for differentiating infection from inflammation. Anionic linear-globular dendrimer-G2 was synthesized then conjugation to gemifloxacin antibiotic. The structures were identified by FT-IR, 1H-NMR, C-NMR, LC-MS and DLS. The toxicity of gemifloxacin and dendrimer-gemifloxacin complex was compared by MTT test. Dendrimer-G2-gemifloxacin was labeled by Technetium-99m and its in-vitro stability and radiochemical purity were investigated. In-vivo biodistribution and SPECT imaging were studied in a rabbit model. Identify and verify the structure of the each object was confirmed by FT-IR, 1H-NMR, C-NMR and LC-MS, also, the size and charge of this compound were 128 nm and -3/68 mv respectively. MTT test showed less toxicity of the dendrimer-G2-gemifloxacin than free gemifluxacin (P < 0.001). Radiochemical yield was > %98. Human serum stability was 84% up to 24 h. Biodistribution study at 50 min, 24 and 48 h showed that the complex is significantly absorbed by the intestine and accumulation in the lungs and affects them, finally excreted through the kidneys, biodistribution results are consistent with results from full image means of SPECT/CT technique.