The Experts below are selected from a list of 248904 Experts worldwide ranked by ideXlab platform
Izumi Hide - One of the best experts on this subject based on the ideXlab platform.
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protein kinase c α mediates tnf Release Process in rbl 2h3 mast cells
British Journal of Pharmacology, 2005Co-Authors: Ihab T Abdelraheem, Izumi Hide, Yuhki Yanase, Yukari Shigemotomogami, Norio Sakai, Yasuhito Shirai, Naoaki Saito, Farid M Hamada, Nagh A ElmahdyAbstract:1 To clarify the mechanism of mast cell TNF secretion, especially its Release Process after being produced, we utilized an antiallergic drug, azelastine (4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)- phthalazinone), which has been reported to inhibit TNF Release without affecting its production in ionomycin-stimulated RBL-2H3 cells. 2 Such inhibition was associated with the suppression of an ionomycin-induced increase in membrane-associated PKC activity rather than the suppression of Ca2+ influx, suggesting that PKC might be involved in TNF Release Process. 3 To see whether conventional PKC family (cPKCs) are involved, we investigated the effects of a selective cPKC inhibitor (Go6976) and an activator (thymeleatoxin) on TNF Release by adding them 1 h after cell stimulation. By this time, TNF mRNA expression had reached its maximum. Go6976 markedly inhibited TNF Release, whereas thymeleatoxin enhanced it, showing a key role of cPKC in TNF post-transcriptional Process, possibly its releasing step. 4 To determine which subtype of cPKCs could be affected by azelastine, Western blotting and live imaging by confocal microscopy were conducted to detect the translocation of endogenous cPKC (α, βI and βII) and transfected GFP-tagged cPKC, respectively. Both methods clearly demonstrated that 1 μM azelastine selectively inhibits ionomycin-triggered translocation of αPKC without acting on βI or βIIPKC. 5 In antigen-stimulated cells, such a low concentration of azelastine did not affect either αPKC translocation or TNF Release, suggesting a functional link between αPKC and the TNF-releasing step. 6 These results suggest that αPKC mediates the TNF Release Process and azelastine inhibits TNF Release by selectively interfering with the recruitment of αPKC in the pathway activated by ionomycin in RBL-2H3 cells. British Journal of Pharmacology (2005) 145, 415–423. doi:10.1038/sj.bjp.0706207
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calcium signaling and protein kinase c for tnf α secretion in a rat mast cell line
Life Sciences, 1998Co-Authors: Yoshihiro Nakata, Izumi HideAbstract:Abstract In mast cells, like other nonexcitable cells, receptor activation produces Ca2+-mobilizing second messengers such as inositol 1,4,5-triphosphate or sphingosine-1-phosphate, which induce Ca2+ Release from internal stores. The resulting depletion of Ca2+ stores activates Ca2+ channels in plasma membranes designated as Ca2+ Release-activated Ca2+ (CRAC) channels. lonomycin appears to cause activation of CRAC channels by depleting intracellular Ca2+ stores rather than by acting as an ionophore. We compared the effects of azelastine, an anti-allergic drug, on TNF-α secretion, on Ca2+ signal, and on degranulation in an antigen- or ionomycin-stimulated rat mast RBL-2H3 cell line. Azelastine inhibited TNF-α Release at concentrations lower than those needed for the inhibition of degranulation. In antigen-stimulated cells, azelastine also inhibited equipotently TNF-α mRNA expression/protein synthesis, TNF-α Release and Ca2+ influx. In ionomycin-stimulated cells, however, azelastine inhibited TNF-α Release to a greater extent than TNF-α mRNA expression/ protein synthesis and Ca2+ influx, indicating that azelastine inhibits the Release Process more potently than transcription or production of TNF-α by interfering with a signal other than Ca2+. Pretreatment with 1 μM azelastine inhibited ionomycin-induced, but not antigen-induced, protein kinase C translocation to the membranes. These results suggest that TNF-α transcription/production is mainly regulated by Ca2+ influx, but the Release Process of TNF-α is regulated by additional mechanism(s) possibly involving activation of protein kinase C.
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suppression of tnf alpha secretion by azelastine in a rat mast rbl 2h3 cell line evidence for differential regulation of tnf alpha Release transcription and degranulation
Journal of Immunology, 1997Co-Authors: Izumi Hide, N Toriu, T Nuibe, Atsuko Inoue, Michihiro Hide, S Yamamoto, Yoshihiro NakataAbstract:The mast cell plays a pivotal role in initiating allergic inflammation by secreting several cytokines including TNF-alpha, in addition to granule mediators such as histamine. Anti-allergic drugs including azelastine prevent immediate-type hypersensitivity by inhibiting mast cell degranulation, as well as blocking histamine H1 receptors. However, their effects on cytokine Release from mast cells remain unknown. In a rat mast RBL-2H3 cell line, azelastine inhibited Ag- and ionomycin-induced TNF-alpha Release with IC50 values of 25.7 +/- 3.4 microM and 1.66 +/- 0.45 microM, respectively. These effects were observed at lower concentrations than needed for the inhibition of degranulation. In Ag-stimulated cells, azelastine also inhibited TNF-alpha mRNA expression, TNF-alpha protein synthesis and Release, and, possibly related to these effects, Ca2+ influx. In ionomycin-stimulated cells, however, azelastine inhibited TNF-alpha Release to a greater extent than mRNA expression/protein synthesis and Ca2+ influx, suggesting that azelastine inhibits the Release Process more potently than transcription or production of TNF-alpha by interfering with a signal other than Ca2+. Azelastine added 1 h after ionomycin stimulation also immediately blocked subsequent Release of TNF-alpha, which had been produced in the cells, without affecting Ca2+ influx. Pretreatment with 1 microM azelastine inhibited ionomycin-induced, but not Ag-induced, protein kinase C translocation to the membranes. These results suggest that the Release Process of TNF-alpha in mast cells is regulated by a mechanism distinct from that of degranulation, and that in Ca2+-ionophore-stimulated cells, it is also different from that of transcription/production, and possibly involves protein kinase C activation.
Margarita Romeroavila - One of the best experts on this subject based on the ideXlab platform.
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two photon triggered no Release via a ruthenium nitrosyl complex with a star shaped architecture
Journal of Physical Chemistry Letters, 2020Co-Authors: Margarita Romeroavila, Andres Felipe Leon Rojas, Pascal G Lacroix, Isabelle Malfant, Norberto Farfan, Rana Mhanna, Rosa Santillan, Gabriel Ramosortiz, Jeanpierre MalvalAbstract:We report herein a molecular engineering strategy based on the design of a multipolar ruthenium-nitrosyl (Ru-NO) complex with a three-branched architecture. The three ruthenium-nitrosyl units are introduced at the periphery of a highly π-delocalized truxene core bearing three terpyridine ligands. The two-photon absorption capabilities of the complex were investigated by the Z-scan technics. The strong electronic coupling among the individual arms gives rise to a very strong two-absorption response (δ800nm ~ 1600 GM), which corresponds to a 16 times enhancement of the capability of a single arm reference, promoting thereby an efficient light-driven NO Release Process in aqueous medium.
Roberto Guzmanzamudio - One of the best experts on this subject based on the ideXlab platform.
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mathematical modeling and parametrical analysis of the temperature dependency of control drug Release from biodegradable nanoparticles
RSC Advances, 2019Co-Authors: Armando Luceroacuna, Cindy Alejandra Gutierrezvalenzuela, Reynaldo Esquivel, Roberto GuzmanzamudioAbstract:In this study we describe a mathematical analysis that considers the temperature effects of the controlled drug Release Process from biodegradable poly-D,L-lactide-co-glycolide (PLGA) nanoparticles. Temperature effects are incorporated and applied to two drug Release models. The first one consists of a two-stage Release Process that considers only simultaneous contributions of initial burst and nanoparticle degradation–relaxation (BR model). The second one is a three Release stage model that considers, additionally, a simultaneous drug diffusion (BRD model) step. In these models, the temperature dependency of the Release parameters, initial burst constant, kb, the rate of degradation–relaxation constant, kr, time to achieve 50% of Release, tmax, and effective diffusion coefficient constant (De), are determined using mathematical expressions analogous to the Arrhenius equation. The temperature dependent models are used to analyze the Release of previously encapsulated Rhodamine 6G dye as a model drug in polyethylene glycol modified PLGA nanoparticles. The experimental data used to develop the mathematical model was obtained from Release studies carried out in phosphate buffer pH 7.4 at 37 °C, 47 °C, and 57 °C. Multiphasic Release behaviors with an overall increase rate associated with the incubation temperature were observed. The study incorporates a parametrical analysis that can evaluate diverse temperature variation effects of the controlled Release parameters for the two models.
Yu Yang - One of the best experts on this subject based on the ideXlab platform.
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a large capacity cationic metal organic framework nanocarrier for physiological ph responsive drug delivery
Molecular Pharmaceutics, 2016Co-Authors: Yanyu Yang, Qi Zhang, Ke Jiang, Wenxin Lin, Yu Yang, Yuanjing Cui, Guodong QianAbstract:A nanoscale cationic porous drug carrier ZJU-101 (ZJU = Zhejiang University), synthesized by the solvothermal method to get the crystal size of ∼300 nm, was used to load diclofenac sodium, an anionic drug. This positively charged host materials showed a large loading capacity of diclofenac sodium (∼0.546 g/g) through ion exchange and penetration procedures. The drug delivery in the inflamed tissues (pH = 5.4) exhibited a more effective Release in comparison with that in the normal tissues (pH = 7.4), demonstrating a physiological pH responsive drug Release. This discriminating drug Release Process was controlled by anion exchange between anions in phosphate buttered saline (PBS) and coordinated/free diclofenac anions.
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a low cytotoxic cationic metal organic framework carrier for controllable drug Release
Journal of Medicinal Chemistry, 2014Co-Authors: Quan Hu, Jiancan Yu, Min Liu, Aiping Liu, Zhongshang Dou, Yu YangAbstract:A positively charged porous drug carrier MOF-74-Fe(III) (1, MOF = metal–organic framework), which could not be directly synthesized using ferric salts, was prepared through the oxidation of the neutral crystal MOF-74-Fe(II). This cationic host material exhibits very low cytotoxicity upon PC12 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and high drug loading capacity of ibuprofen anions (∼15.9 wt %) through ion exchange and salt penetration procedures. Controlled by anion exchange, two mechanisms were involved in the drug Release Process with different drug delivery rates due to the presence of coordinated or free ibuprofen anions, making the administration of drug Release more flexible.
Liang Fang - One of the best experts on this subject based on the ideXlab platform.
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molecular mechanism of ion pair releasing from acrylic pressure sensitive adhesive containing carboxyl group roles of doubly ionic hydrogen bond in the controlled Release Process of bisoprolol ion pair
Journal of Controlled Release, 2018Co-Authors: Hanqing Zhao, Chao Liu, Degong Yang, Xiaocao Wan, Rui Shang, Peng Quan, Liang FangAbstract:Abstract Though ion-pair strategy has been employed as an effective and promising method for controlling transdermal delivery of drugs, investigations into the underlying mechanisms involved in the controlled Release Process of ion-pairs are still limited. In the present study, a brand-new controlled Release system combining acrylic pressure sensitive adhesive containing carboxyl group (carboxylic PSA) with ion-pair strategy was developed, and the molecular mechanism of ion-pair releasing from carboxylic PSA was systemically elucidated. Bisoprolol (BSP) and bisoprolol-lauric acid ion-pair (BSP-C12) were chosen as model drugs. Carboxylic PSA was designed and synthesized. Effect of ion-pair on controlling BSP Release from carboxylic PSA was evaluated by in vitro drug Release study, in vitro skin permeation study and pharmacokinetic study. Molecular mobility of PSA, along with the strength of drug-PSA interaction was evaluated by thermal analysis and dielectric spectroscopy. Molecular details of drug-PSA interaction were identified by FTIR, XPS and Raman. Roles of drug-PSA interaction in the controlled Release Process were clarified by molecular modeling. Results showed that BSP-C12 patch demonstrated a controlled Release drug plasma profile, with lower Cmax (193 ± 63 ng/mL) and longer MRT (19.9 ± 3.4 h) compared to BSP patch (Cmax,BSP = 450 ± 28 ng/mL, MRTBSP = 7.9 ± 0.9 h). Besides, there was no significant difference between the AUC of BSP-C12 and BSP patch. It turned out that instead of PSA molecular mobility, molecular interaction between ion-pair and PSA played a dominant role in the controlled Release Process of BSP: as illustrated by FTIR, Raman and molecular docking, the ionic interaction between BSP-C12 and PSA determined the amount of BSP Released, namely the thermodynamic Process; while the doubly ionic hydrogen bond between BSP-C12 and PSA-COO– controlled the Release rate, which was the kinetic Process. In conclusion, it was found that the doubly ionic hydrogen bond formed between carboxylic PSA and ion-pair controlled the Release profile of BSP, which broadened our understanding about the molecular mechanisms involved in ion-pair controlled Release transdermal patches and contributed to the design of controlled Release TDDS.
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probing the role of chemical enhancers in facilitating drug Release from patches mechanistic insights based on ft ir spectroscopy molecular modeling and thermal analysis
Journal of Controlled Release, 2016Co-Authors: Wenting Song, Peng Quan, Shanshan Li, Siji Lv, Yongshan Zhao, Liang FangAbstract:Abstract In patches, a drug must Release from patches prior to its percutaneous absorption. Chemical enhancers have been used for several decades, but their roles in drug Release from patches are poorly understood. In this work, the roles of chemical enhancers in bisoprolol tartrate (BSP-T) Release from patches were probed in vitro and in vivo. More importantly, an innovative mechanism insight of chemical enhancers in drug Release Process was provided at molecular level. FT-IR spectroscopy and molecular modeling were employed to investigate the influence of chemical enhancers on drug-adhesive interaction. The results showed chemical enhancers like Span 80, which had a strong ability forming hydrogen bonds, could decrease drug-adhesive interaction leading to the Release of drug from adhesive of patches. Thermal analysis was conducted to research the influence of chemical enhancers on the thermodynamic properties of patch system. It showed that chemical enhancers promoted the formation of free volume of adhesive, which facilitated drug Release Process. By contrast, the influence on the thermodynamic properties of BSP-T was less effective in influencing BSP-T Release Process. In conclusion, chemical enhancers played an important role in facilitating BSP-T Release from the adhesive DURO-TAK® 87-2287 of patches by decreasing drug-adhesive interaction and promoting the formation of free volume of adhesive. This work may be an important step in understanding the important roles of chemical enhancers in drug Release Process.
