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瞬时受体电位通道TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性和神经病理性疼痛模型中的镇痛作用(英文)

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第3期16卷 167-178页

作者： Kinga SALAT Barbara FILIPEK Department of Pharmacodynamics Faculty of PharmacyJagiellonian University

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇... 详细信息

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇痛作用;通过建立紫杉醇诱导的小鼠神经病理性疼痛模型,对TRP通道拮抗剂的抗痛觉(冷、热、触觉)过敏效应进行评估;通过旋转法实验对小鼠的运动协调性进行评估。结论:TRP通道家族包含了不同的小鼠疼痛模型。TRP通道拮抗剂能减轻神经源性、持续性和神经病理性疼痛,但是其镇痛效果与疼痛模型有关。

关键词：异硫氰酸烯丙酯辣椒素福尔马林神经源性疼痛瞬时受体电位通道紫杉醇诱导的感觉神经病变

Can molecular targeting the TNFα-ERK-ETS1- IL27Rα pathway keep us young and healthy by protecting HSCs from aging?

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Blood Science 2020年第4期2卷 148-149页

作者： Yonghan He Daohong Zhou Department of Pharmacodynamics College of PharmacyUniversity of FloridaGainesvilleFLUSA

The world’s older population grows at an unprecedented rate.Today,there are about 8.5%of people worldwide(617 million)aged 65 and older today,which is projected to continue growing to nearly 17%of the world’s population by 2050(1.6 billion).World population aging has profound implications because aging represents a progressive deterioration of physiological function accompanied by an increase in vulnerability for disease and mortality.

关键词： mortality aging young

One extraction tool for in vitro-in vivo extrapolation?SPME-based metabolomics of in vitro 2D,3D,and in vivo mouse melanoma models

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Journal of Pharmaceutical Analysis 2021年第5期11卷 667-674页

作者： Karol Jaroch Paulina Taczynska Marta Czechowska Joanna Bogusiewicz KamilŁuczykowski Katarzyna Burlikowska Barbara Bojko Department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun Poland85-089BydgoszczPoland

Solid phase microextraction(SPME)in combination with high-resolution mass spectrometry was employed for the determination of metabolomic profile of mouse melanoma growth within in vitro 2D,in vitro 3D,and in vivo models.Such multi-model approach had never been investigated before.Due to the low-invasiveness of SPME,it was possible to perform time-course analysis,which allowed building time profile of biochemical reactions in the studied material.Such approach does not require the multiplication of samples as subsequent analyses are performed from the very same cell culture or from the same individual.SPME already reduces the number of animals required for experiment;therefore,it is with good concordance with the 3Rs rule(replacement,reduction,and refinement).Among tested models,the largest number of compounds was found within the in vitro 2D cell culture model,while in vivo and in vitro 3D models had the lowest number of detected compounds.These results may be connected with a higher metabolic rate,as well as lower integrity of the in vitro 2D model compared to the in vitro 3D model resulting in a lower number of compounds released into medium in the latter model.In terms of in vitro-in vivo extrapolation,the in vitro 2D model performed more similar to in vivo model compared to in vitro 3D model;however,it might have been due to the fact that only compounds secreted to medium were investigated.Thus,in further experiments to obtain full metabolome information,the intraspheroidal assessment or spheroid dissociation would be necessary.

关键词： Solid-phase microextraction In vitro-in vivo extrapolation Metabolomics Melanoma B16F0 C57BL6 mouse model

Photosafety testing of dermally-applied chemicals based on photochemical and cassette-dosing pharmacokinetic data

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 237-238页

作者： Hiroto Ohtake Yukiko Suzuki Masashi Kato Yoshiki Seto Satomi Onoue department of Pharmacokinetics and pharmacodynamics School of Pharmaceutical Sciences University of Shizuoka

Drug-induced phototoxicity is elicited by exposure of skin and/or eyes to topical or systemic administration of chemicals,followed by exposure to sunlight.For photosafety testing,a new screening strategy,employing in vitro photochemical/photobiological and in vivo cassette-dosing pharmacokinetic(PK)studies,was proposed[1,2].The screening system provided reliable phototoxic predictions of tested chemicals at least within the same chemical series;however,the applicability of the proposed strategy is not fully understood.

关键词： Photosafety assessment Phototoxicity Photoreactivity Pharmacokinetics

Solid-phase microextraction of endogenous metabolites from intact tissue validated using a Biocrates standard reference method kit

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Journal of Pharmaceutical Analysis 2023年第1期13卷 55-62页

作者： Runshan Will Jiang Karol Jaroch Janusz Pawliszyn department of Chemistry University of WaterlooWaterlooN2L 3G1Canada Department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in TorunBydgoszcz85-089Poland

Improved analytical methods for the metabolomic profiling of tissue samples are constantly needed.Currently,conventional sample preparation methods often involve tissue biopsy and/or homogenization,which disrupts the endogenous metabolome.In this study,solid-phase microextraction(SPME)fibers were used to monitor changes in endogenous compounds in homogenized and intact ovine lung tissue.Following SPME,a Biocrates AbsoluteIDQ assay was applied to make a downstream targeted metabolomics analysis and confirm the advantages of in vivo SPME metabolomics.The AbsoluteIDQ kit enabled the targeted analysis of over 100 metabolites via solid-liquid extraction and SPME.Statistical analysis revealed significant differences between conventional liquid extractions from homogenized tissue and SPME results for both homogenized and intact tissue samples.In addition,principal component analysis revealed separated clustering among all the three sample groups,indicating changes in the metabolome due to tissue homogenization and the chosen sample preparation method.Furthermore,clear differences in free metabolites were observed when extractions were performed on the intact and homogenized tissue using identical SPME procedures.Specifically,a direct comparison showed that 47 statistically distinct metabolites were detected between the homogenized and intact lung tissue samples(P<0.05)using mixed-mode SPME fibers.These changes were probably due to the disruptive homogenization of the tissue.This study's findings highlight both the importance of sample preparation in tissue-based metabolomics studies and SPME's unique ability to perform minimally invasive extractions without tissue biopsy or homogenization while providing broad metabolite coverage.

关键词： Solid-phase microextraction Solvent extraction Metabolomics Sample preparation In vivo sampling

Time-course monitoring of in vitro biotransformation reaction via solid-phase microextraction-ambient mass spectrometry approaches

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Journal of Pharmaceutical Analysis 2022年第1期12卷 186-191页

作者： Karol Jaroch Janusz Pawliszyn department of Chemistry University of WaterlooWaterlooN2L 3G1Canada Department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Toruń Poland85090BydgoszczPoland

The solid-phase microextraction technique quantifies analytes without considerably affecting the sample composition.Herein,a proof-of-concept study was conducted to demonstrate the use of coated probe electrospray ionization(coated-PESI)and coated blade spray(CBS)as ambient mass spectrometry approaches for monitoring drug biotransformation.The ability of these methods was investigated for monitoring the dephosphorylation of a prodrug,combretastatin A4 phosphate(CA4P),into its active form,combretastatin A4(CA4),in a cell culture medium supplemented with fetal bovine serum.The CBS spot analysis was modified to achieve the same extraction efficiency as protein precipitation and obtained results in 7 min.Because coated-PESI performs extraction without consuming any samples,it is the preferred technique in the case of a limited sample volume.Although coated-PESI only extracts small quantities of analytes,it uses the desorption solvent volume of 5-10 pL,resulting in high sensitivity,thus allowing the detection of compounds after only 1 min of extraction.The biotransformation of CA4P into CA4 via phosphatases occurs within the simple matrix,and the proposed sample preparation techniques are suitable for monitoring the biotransformation.

关键词： Solid-phase microextraction Coated probe electrospray ionization Coated blade spray Combretastatin Biotransformation Prodrug activation

In vitro discrimination between sedative and non-sedative histamine H1 receptor antagonists by an intact cell binding assay.

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In vitro discrimination between sedative and non-sedative hi...

Sensitization Properties of Propolis and Balsam of Peru in Guinea Pig Maximization Test(GPMT)

第十五届国际药理学大会

作者： Hishinuma Shigeru Saito Masaki Department of Pharmacodynamics Meiji Pharmaceutical University Department of Pharmacodynamics Meiji Pharmaceutical University

＜正＞ We investigated the changes in the binding properties of sedative and non - sedative antihistamines by histamine（HA） - induced intemalization of histamine H1 receptors （H1Rs） in intact human U373 MG astrocytoma cells. Intemalization of H1Rs was induced without their degradation by treatment with 0.1 mM HA for 30 min at 37℃. The binding properties of [3H]mepyramine. a cell - penetrating radioligandfor H1Rs. were not changed by the HA pretreatment. The displacement curves for sedative antihistamines （6 drugs tested） against [3H]mepyramine binding were not changed by the HA pretreatment. In contrast, the displacement analyses for non - sedative antihistamines （5 drugs tested） showed that their affinities for H1Rs were reduced by the HA pretreatment. which was prevented under hy- pertonic conditions where the clathrin - mediated receptor intemalization was inhibited. These results suggest that non - sedative antihistamines have the lower affinities for the intracellular H1Rs than for the cell surface H1Rs. possibly due to their less accessibility through the biomembrane. This intact cell binding assay might provide us a novel method for screening sedative and non - sedative antihistamines in vitro.

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Food and Nutrition Sciences 2017年第7期8卷 714-724页

作者： Katarzyna Basista-Soltys Barbara Filipek Monika Zadrozna Barbara Nowak Agata Pietrzycka Grzegorz Kazek Department of Pharmacodynamics Medical College of Jagiellonian UniversityKrakowPoland department of Pharmacobiology Medical College of Jagiellonian UniversityKrakowPoland

Introduction: Propolis is used in Poland as an active ingredient of some drugs administered externally, dietary supplements and cosmetics. According to the literature, propolis is a non-toxic and safe substance, although it may cause allergic contact dermatitis. Aim: The aim of this study was to assess the allergenic properties of propolis and Balsam of Peru. Material and methods: The study was conducted according to the OECD Guideline for testing of chemicals-Skin sensitization with use of Guinea pig maximization test (GPMT). Guinea pigs have similar sensitivity to allergens as human body. Sensitization properties of propolis were tested in comparison with sensitization properties of Balsam of Peru because of the possibility of cross-reaction between those two substances. Results: The skin of guinea pigs in the propolis group showed no visible change compared to the control group during the first (48 h) and second observation (72 h). The skin of guinea pigs from Balsam of Peru group showed discrete erythema in only one case at the first observation (8.33% of the animals). During the second observation, no visible changes were observed compared to the control group. Conclusions: Guinea pig maximization test showed no sensitizing properties of propolis and weak sensitizing properties of Balsam of Peru in concentration of 5%.

关键词： Propolis Balsam of Peru Guinea Pig Maximization Test Sensitization Properties Allergic Contact Dermatitis

Hormone replacement therapy decreases noradrenaline release in human myometrium

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Hormone replacement therapy decreases noradrenaline release ...