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951.
Matsuda Yasuhiro Masuda Masaharu Asai Mitsutoshi Iida Osamu Okamoto Shin Ishihara Takayuki Nanto Kiyonori Kanda Takashi Tsujimura Takuya Okuno Shota Hata Yosuke Uematsu Hiroyuki Mano Toshiaki 《Journal of interventional cardiac electrophysiology》2021,61(1):171-179
Journal of Interventional Cardiac Electrophysiology - Cardiac conduction disturbance necessitating pacemaker implantation is common among elderly patients. However, patients often have... 相似文献
952.
953.
Young-Hoon Kim Young-Ji Bae Hyung Soo Kim Hey-Jin Cha Jae-Suk Yun Ji-Soon Shin Won-Keun Seong Yong-Moon Lee Kyoung-Moon Han 《Biomolecules & therapeutics.》2015,23(5):486-492
Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery. 相似文献
954.
Koji Matsuo Suguru Yamamoto Takuya Wakamatsu Yoshimitsu Takahashi Kazuko Kawamura Yoshikatsu Kaneko Shin Goto Junichiro J. Kazama Ichiei Narita 《Toxins》2015,7(8):3155-3166
One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD. 相似文献
955.
Jaesuk Yun Eunyong Chung Ki Hwan Choi Dae Hyun Cho Yun Jeong Song Kyoung Moon Han Hey Jin Cha Ji Soon Shin Won-Keun Seong Young-Hoon Kim Hyung Soo Kim 《Biomolecules & therapeutics.》2015,23(4):386-389
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation. 相似文献
956.
The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits 下载免费PDF全文
Michelle Khai Khun Yap Nget Hong Tan Si Mui Sim Shin Yee Fung Choo Hock Tan 《Basic & clinical pharmacology & toxicology》2015,117(4):274-279
The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab′)2] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab′)2 and venom antigens, as the terminal half‐life and volume of distribution of the F(ab′)2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence. 相似文献
957.
Quantitative Relationships Between the Cytotoxicity of Flavonoids on the Human Breast Cancer Stem‐Like Cells MCF7‐SC and Their Structural Properties 下载免费PDF全文
Hyeryoung Jung Soon Young Shin Yearam Jung Thao Anh Tran Hye Ok Lee Kang‐Yeoun Jung Dongsoo Koh Somi Kim Cho Yoongho Lim 《Chemical biology & drug design》2015,86(4):496-508
As some breast cancer‐related deaths can be attributed to the metastasis of cancer stem cells, chemotherapeutic agents targeting breast cancer stem cells are of interest as a potential treatment. Flavonoids that exhibit cytotoxicity on breast cancer stem cells have rarely been observed. Thus, the objective of this study was to measure potential cytotoxic effects of 42 different flavonoids on the human breast cancer stem‐like cell line, MCF7‐SC. The relationship between flavonoid structural properties and cytotoxicity has not been reported previously; therefore, we determined quantitative structure–activity relationships using both comparative molecular field analysis and comparative molecular similarity analysis. Further biological experiments including Western blot analysis, flow cytometry, and immunofluorescence microscopy were also conducted on the most cytotoxic 8‐chloroflavanone. 相似文献
958.
Zhenxing Yu Junjie Wang Na Zhang Jungwoo Shin Qiye Zheng Subing Qu Xiaoqing He Angus Rockett Hong Yang Paul V. Braun 《RSC advances》2018,8(68):38745
Here we show that dendritic architectures are attractive as the basis of hierarchically structured battery electrodes. Dendritically structured FeS2, synthesized via simple thermal sulfidation of electrodeposited dendritic α-Fe, was formed into an electrode and cycled vs. lithium. The reversible capacities of the dendritic FeS2 cathode were 560 mA h g−1 at 0.5C and 533 mA h g−1 at 1.0C after 50 cycles over 0.7–3.0 V. Over 0.7–2.4 V, where the electrode is more stable, the reversible capacities are 348 mA h g−1 at 0.2C and 179 mA h g−1 at 1.0C after 150 cycles. The good cycling performance and high specific capacities of the dendritic FeS2 cathodes are attributed to the ability of a dendritic structure to provide good ion and electron conducting pathways, and a large surface area. Importantly, the dendritic structure appears capable of accommodating volume changes imposed by the lithiation and delithiation process. The presence of a Li2−xFeS2 phase is indicated for the first time by high-resolution transmission electron microscopy (HRTEM) and scanning transmission electron microscopy (STEM) electron energy loss spectroscopy (EELS). We suspect this phase is what enables electrochemical cycling to possess high reversibility over 0.7–2.4 V.High performance dendritically structured FeS2 cathodes are systemically studied. The dendritic structure is resistant to volume changes during cycling, increasing cyclability. The presence of Li2–xFeS2, which also enhances cyclability, is confirmed. 相似文献
959.
960.
Kazuo Tarao Akito Nozaki Makoto Chuma Masataka Taguri Shin Maeda 《World journal of hepatology》2021,13(1):144-150
BACKGROUND The oral nucleos(t)ide analogue,entecavir(ETV) was demonstrated to reduce the rate of hepatocellular carcinoma(HCC) in patients with hepatitis B virus(HBV)-associated liver cirrhosis.However,the reduction of HCC differs in various regions of the world.AIM To investigate the reduction of HCC development due to ETV therapy by metaanalysis.METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed(2004-2019).RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain(1.0 %/year) and Canada(Southern part,1.3 %/year),and the most ineffective areas were South Korea(3.6 %-3.8 %/year),China(3.3 %/year),Taiwan(2.4 %-3.1 %/year),and Hong Kong(2.8 %/year).Following ETV administration,the incidence of HCC in genotype D regions(1.89 %±0.28 %/year,mean ± SE) was significantly lower than that in genotype C regions(2.91%±0.24%/year,P 0.01).With regard to the initial HBV-DNA level,in genotype C patients(average:5.61 Log_(10)IU/mL) this was almost the same as that in genotype D patients(average:5.46 Log_(10)IU/mL).Moreover,there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment.CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent. 相似文献