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Article ; Online: An in vitro evaluation of e-vapor products: The contributions of chemical adulteration, concentration, and device power.

Johne, Stephanie / van der Toorn, Marco / Iskandar, Anita R / Majeed, Shoaib / Torres, Laura O / Hoeng, Julia / Peitsch, Manuel C

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2023 Volume 175, Page(s) 113708

Abstract: Homemade e-liquids and power-adjustable vaping devices may carry higher risks than commercial formulations and fixed-power devices. This study used human macrophage-like and bronchial epithelial (NHBE) cell cultures to investigate toxicity of homemade e- ... ...

Abstract	Homemade e-liquids and power-adjustable vaping devices may carry higher risks than commercial formulations and fixed-power devices. This study used human macrophage-like and bronchial epithelial (NHBE) cell cultures to investigate toxicity of homemade e-liquids containing propylene glycol and vegetable glycerin (PG/VG), nicotine, vitamin E acetate (VEA), medium-chain fatty acids (MCFAs), phytol, and cannabidiol (CBD). SmallAir™ organotypic epithelial cultures were exposed to aerosols generated at different power settings (10-50 W). Carbonyl levels were measured, and endpoints reflecting epithelial function (ciliary beating frequency [CBF]), integrity (transepithelial electrical resistance [TEER]), and structure (histology) were investigated. Treatment with nicotine or VEA alone or with PG/VG did not impact cell viability. CBD, phytol, and lauric acid caused cytotoxicity in both culture systems and increased lipid-laden macrophages. Exposure of SmallAir™ organotypic cultures to CBD-containing aerosols resulted in tissue injury and loss of CBF and TEER, while PG/VG alone or with nicotine or VEA did not. Aerosols generated with higher power settings had higher carbonyl concentrations. In conclusion, the presence and concentration of certain chemicals and device power may induce cytotoxicity in vitro. These results raise concerns that power-adjustable devices may generate toxic compounds and suggest that toxicity assessments should be conducted for both e-liquid formulations and their aerosols.
MeSH term(s)	Humans ; Nicotine/toxicity ; Nicotine/chemistry ; Electronic Nicotine Delivery Systems ; Vaping ; Bronchi ; Vegetables ; Aerosols/toxicity ; Glycerol/chemistry ; Propylene Glycol/chemistry
Chemical Substances	Nicotine (6M3C89ZY6R) ; Aerosols ; Glycerol (PDC6A3C0OX) ; Propylene Glycol (6DC9Q167V3)
Language	English
Publishing date	2023-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2023.113708
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Article ; Online: An in vitro evaluation of e-vapor products: The contributions of chemical adulteration, concentration, and device power

Johne, Stephanie / van der Toorn, Marco / Iskandar, Anita R. / Majeed, Shoaib / Torres, Laura O. / Hoeng, Julia / Peitsch, Manuel C.

Food and Chemical Toxicology. 2023 May, v. 175 p.113708-

2023

Abstract	Homemade e-liquids and power-adjustable vaping devices may carry higher risks than commercial formulations and fixed-power devices. This study used human macrophage-like and bronchial epithelial (NHBE) cell cultures to investigate toxicity of homemade e-liquids containing propylene glycol and vegetable glycerin (PG/VG), nicotine, vitamin E acetate (VEA), medium-chain fatty acids (MCFAs), phytol, and cannabidiol (CBD). SmallAir™ organotypic epithelial cultures were exposed to aerosols generated at different power settings (10–50 W). Carbonyl levels were measured, and endpoints reflecting epithelial function (ciliary beating frequency [CBF]), integrity (transepithelial electrical resistance [TEER]), and structure (histology) were investigated. Treatment with nicotine or VEA alone or with PG/VG did not impact cell viability. CBD, phytol, and lauric acid caused cytotoxicity in both culture systems and increased lipid-laden macrophages. Exposure of SmallAir™ organotypic cultures to CBD-containing aerosols resulted in tissue injury and loss of CBF and TEER, while PG/VG alone or with nicotine or VEA did not. Aerosols generated with higher power settings had higher carbonyl concentrations. In conclusion, the presence and concentration of certain chemicals and device power may induce cytotoxicity in vitro. These results raise concerns that power-adjustable devices may generate toxic compounds and suggest that toxicity assessments should be conducted for both e-liquid formulations and their aerosols.
Keywords	acetates ; adulterated products ; cannabidiol ; cell viability ; cytotoxicity ; dodecanoic acid ; electrical resistance ; epithelium ; glycerol ; histology ; humans ; macrophages ; nicotine ; propylene glycol ; toxicology ; vegetables ; vitamin E ; E-vapor ; e-liquids ; Bronchial epithelium ; Air–liquid interface ; Vitamin E acetate ; Phytol
Language	English
Dates of publication	2023-05
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2023.113708
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Article ; Online: Development and testing of a new-generation aerosol exposure system: The independent holistic air-liquid exposure system (InHALES).

Steiner, Sandro / Herve, Pierre / Pak, Claudius / Majeed, Shoaib / Sandoz, Antonin / Kuczaj, Arkadiusz / Hoeng, Julia

Toxicology in vitro : an international journal published in association with BIBRA

2020 Volume 67, Page(s) 104909

Abstract: The dose of inhaled materials delivered to the respiratory tract is to a large extent a function of the kinetics of particle deposition and gas dissolution on or in the airway and lung epithelia, and therefore of the structural and functional properties ... ...

Abstract	The dose of inhaled materials delivered to the respiratory tract is to a large extent a function of the kinetics of particle deposition and gas dissolution on or in the airway and lung epithelia, and therefore of the structural and functional properties of the respiratory tract. In vitro aerosol exposure systems commonly do not simulate these properties, which may result in the delivery of non-realistic, non-human-relevant doses of inhalable test substances to the in vitro biological test systems. We developed a new-generation in vitro aerosol exposure system, the InHALES, that can, like the human respiratory tract, actively breathe, operate medical inhalers, or take puffs from tobacco products. Due to its structural and functional similarity to the human respiratory tract, the system is expected to deliver human-relevant doses of inhalable materials to cell cultures representing respiratory tract epithelia. We here describe the proof of concept of the InHALES with respect to aerosol delivery and compatibility with oral, bronchial, and alveolar cell cultures. The results indicate that the system structure and function translate into complex patterns of test atmosphere delivery that, with increasing system complexity, may closely mimic the patterns observable in the human respiratory tract.
MeSH term(s)	Administration, Inhalation ; Aerosols/administration & dosage ; Air ; Cell Culture Techniques ; Humans ; Lung ; Models, Biological
Chemical Substances	Aerosols
Language	English
Publishing date	2020-06-05
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2020.104909
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Article: Effects of whitening toothpaste and bleaching treatment on resin composite discoloration caused by cigarette smoke and electronic vapor aerosol.

Zhao, Xiaoyi / Zanetti, Filippo / Wang, Linchuan / Malmstrom, Hans / Majeed, Shoaib / Peitsch, Manuel C / Hoeng, Julia / Ren, Yanfang

American journal of dentistry

2021 Volume 34, Issue 2, Page(s) 63–69

Abstract: Purpose: To compare the effects of whitening toothpaste and bleaching with 6% hydrogen peroxide (H2O2) on discoloration of dental resin composite caused by cigarette smoke (CS) and electronic vapor product (EVP) aerosol.: Methods: 40 resin composite ... ...

Abstract	Purpose: To compare the effects of whitening toothpaste and bleaching with 6% hydrogen peroxide (H2O2) on discoloration of dental resin composite caused by cigarette smoke (CS) and electronic vapor product (EVP) aerosol. Methods: 40 resin composite discs were divided into three groups: 15 each for CS and EVP aerosol exposure and 10 for air exposure (control). Exposures were performed for 15 days, with daily brushing with regular toothpaste. Two whitening sessions, including 21 days of brushing with whitening toothpaste and 3 days of treatments with take-home bleaching (6% H2O2), were performed after the exposure. Color and gloss were assessed before exposure, at every 5 days of exposure, and after each whitening session. Results: After 15 days of exposure, marked discoloration of resin composite was observed in the CS group (ΔE = 23.66 ± 2.31), minimal color change in the EVP group ((ΔE = 2.77 ± 0.75), and no color change in the control group. Resin composites exposed to CS did not recover their original color after treatment with whitening toothpaste ((ΔE = 20.17 ± 2.68) or take-home bleaching ((ΔE = 19.32 ± 2.53), but those exposed to EVP aerosol reverted to baseline after treatment with whitening toothpaste ((ΔE = 0.98 ± 0.37), and no further change in color was observed following take-home bleaching. The gloss of resin composites exposed to CS, EVP aerosol, and air decreased equally with exposure time. Brushing with whitening toothpaste recovered the gloss similarly in all groups, but no further change was observed following take-home bleaching. Clinical significance: Aerosol from electronic vapor products induced minimal discoloration of resin composites that can be completely reverted by brushing with whitening toothpaste alone. Bleaching with 6% H2O2 did not revert discoloration caused by cigarette smoke. Whitening toothpaste could help revert the decreased gloss of resin composites.
MeSH term(s)	Aerosols ; Electronics ; Hydrogen Peroxide/adverse effects ; Smoking ; Toothpastes
Chemical Substances	Aerosols ; Toothpastes ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2021-05-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	645142-1
ISSN	0894-8275
ISSN	0894-8275
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Article ; Online: A new fluorescence-based method for characterizing in vitro aerosol exposure systems.

Steiner, Sandro / Majeed, Shoaib / Kratzer, Gilles / Hoeng, Julia / Frentzel, Stefan

Toxicology in vitro : an international journal published in association with BIBRA

2017 Volume 38, Page(s) 150–158

Abstract: Knowledge of how an in vitro aerosol exposure system delivers a test aerosols to the biological test system is among the most crucial prerequisites for the interpretation of exposure experiments and relies on detailed exposure system characterization. ... ...

Abstract	Knowledge of how an in vitro aerosol exposure system delivers a test aerosols to the biological test system is among the most crucial prerequisites for the interpretation of exposure experiments and relies on detailed exposure system characterization. Although various methods for this purpose exist, many of them are time consuming, require extensive instrumentation, or offer only limited ability to assess the performance of the system under experimental settings. We present the development and evaluation of a new, highly robust and sensitive fluorometry-based method for assessing the particle size specific delivery of liquid aerosols. Glycerol aerosols of different mean particle sizes and narrow size distributions, carrying the fluorophore disodium fluorescein, were generated in a condensation monodisperse aerosol generator. Their detailed characterization confirmed their stability and the robustness and reproducibility of their generation. Test exposures under relevant experimental settings in the Vitrocell
MeSH term(s)	Aerosols/administration & dosage ; Aerosols/chemistry ; Fluorescein/chemistry ; Fluorescence ; Fluorescent Dyes/chemistry ; Fluorometry/methods ; Glycerol/chemistry ; Particle Size ; Toxicity Tests/methods
Chemical Substances	Aerosols ; Fluorescent Dyes ; Glycerol (PDC6A3C0OX) ; Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2017-02
Publishing country	England
Document type	Journal Article
ZDB-ID	639064-x
ISSN	1879-3177 ; 0887-2333
ISSN (online)	1879-3177
ISSN	0887-2333
DOI	10.1016/j.tiv.2016.09.018
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Article ; Online: Application of Secondary Electrospray Ionization Coupled with High-Resolution Mass Spectrometry in Chemical Characterization of Thermally Generated Aerosols.

Zivkovic Semren, Tanja / Majeed, Shoaib / Fatarova, Maria / Laszlo, Csaba / Pak, Claudius / Steiner, Sandro / Vidal-de-Miguel, Guillermo / Kuczaj, Arkadiusz / Mazurov, Anatoly / Peitsch, Manuel C / Ivanov, Nikolai V / Hoeng, Julia / Guy, Philippe A

Journal of the American Society for Mass Spectrometry

2022 Volume 33, Issue 11, Page(s) 2147–2155

Abstract: Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the past decade. We performed real-time analyses of aerosols using secondary electrospray ionization (SESI) technology interfaced with high- ... ...

Abstract	Inhalation as a route for administering drugs and dietary supplements has garnered significant attention over the past decade. We performed real-time analyses of aerosols using secondary electrospray ionization (SESI) technology interfaced with high-resolution mass spectrometry (HRMS), primarily developed for exhaled breath analysis with the goal to detect the main aerosol constituents. Several commercially available inhalation devices containing caffeine, melatonin, cannabidiol, and vitamin B12 were tested. Chemical characterization of the aerosols produced by these devices enabled detection of the main constituents and screening for potential contaminants, byproducts, and impurities in the aerosol. In addition, a programmable syringe pump was connected to the SESI-HRMS system to monitor aerosolized active pharmaceutical ingredients (APIs) such as chloroquine, hydroxychloroquine, and azithromycin. This setup allowed us to detect caffeine, melatonin, hydroxychloroquine, chloroquine, and cannabidiol in the produced aerosols. Azithromycin and vitamin B12 in the aerosols could not be detected; however, our instrument setup enabled the detection of vitamin B12 breakdown products that were generated during the aerosolization process. Positive control was realized by liquid chromatography-HRMS analyses. The compounds detected in the aerosol were confirmed by exact mass measurements of the protonated and/or deprotonated species, as well as their respective collision-induced dissociation tandem mass spectra. These results reveal the potential wide application of this technology for the real-time monitoring of aerosolized active pharmaceutical ingredients that can be administered through the inhalation route.
MeSH term(s)	Spectrometry, Mass, Electrospray Ionization/methods ; Caffeine ; Melatonin ; Cannabidiol ; Azithromycin ; Hydroxychloroquine ; Aerosols/analysis ; Vitamin B 12
Chemical Substances	Caffeine (3G6A5W338E) ; Melatonin (JL5DK93RCL) ; Cannabidiol (19GBJ60SN5) ; Azithromycin (83905-01-5) ; Hydroxychloroquine (4QWG6N8QKH) ; Aerosols ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2022-10-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.2c00222
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Article ; Online: Assessment of Single-Photon Ionization Mass Spectrometry for Online Monitoring of

Frege, Carla / Asgari, Mahdi / Steiner, Sandro / Ferreira, Sandra / Majeed, Shoaib / Lucci, Francesco / Frentzel, Stefan / Hoeng, Julia / Kuczaj, Arkadiusz K

Chemical research in toxicology

2020 Volume 33, Issue 2, Page(s) 505–514

Abstract: Chemical and physical characterization of transported evolving aerosols in ... ...

Abstract	Chemical and physical characterization of transported evolving aerosols in an
MeSH term(s)	Aerosols/administration & dosage ; Aerosols/analysis ; Environmental Exposure/analysis ; Environmental Monitoring ; Mass Spectrometry ; Particle Size ; Photons
Chemical Substances	Aerosols
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.9b00381
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Article ; Online: In vitro testing of salt coating of fabrics as a potential antiviral agent in reusable face masks.

Schorderet Weber, Sandra / Bulliard, Xavier / Bonfante, Rosy / Xiang, Yang / Biselli, Silvia / Steiner, Sandro / Constant, Samuel / Pugin, Raphael / Laurent, Alexandra / Majeed, Shoaib / Lebrun, Stefan / Palmieri, Michele / Hogg, Andreas / Kuczaj, Arkadiusz / Peitsch, Manuel C / Hoeng, Julia / Stan, Adrian

Scientific reports

2022 Volume 12, Issue 1, Page(s) 17041

Abstract: During the coronavirus disease (COVID-19) pandemic, wearing face masks in public spaces became mandatory in most countries. The risk of self-contamination when handling face masks, which was one of the earliest concerns, can be mitigated by adding ... ...

Abstract	During the coronavirus disease (COVID-19) pandemic, wearing face masks in public spaces became mandatory in most countries. The risk of self-contamination when handling face masks, which was one of the earliest concerns, can be mitigated by adding antiviral coatings to the masks. In the present study, we evaluated the antiviral effectiveness of sodium chloride deposited on a fabric suitable for the manufacturing of reusable cloth masks using techniques adapted to the home environment. We tested eight coating conditions, involving both spraying and dipping methods and three salt dilutions. Influenza A H3N2 virus particles were incubated directly on the salt-coated materials, collected, and added to human 3D airway epithelial cultures. Live virus replication in the epithelia was quantified over time in collected apical washes. Relative to the non-coated material, salt deposits at or above 4.3 mg/cm
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/prevention & control ; Humans ; In Vitro Techniques ; Influenza A Virus, H3N2 Subtype ; Masks ; SARS-CoV-2 ; Sodium Chloride/pharmacology
Chemical Substances	Antiviral Agents ; Sodium Chloride (451W47IQ8X)
Language	English
Publishing date	2022-10-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-21442-7
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Article ; Online: Pulmonary Delivery of Aerosolized Chloroquine and Hydroxychloroquine to Treat COVID-19: In Vitro Experimentation to Human Dosing Predictions.

Kolli, Aditya R / Semren, Tanja Zivkovic / Bovard, David / Majeed, Shoaib / van der Toorn, Marco / Scheuner, Sophie / Guy, Philippe A / Kuczaj, Arkadiusz / Mazurov, Anatoly / Frentzel, Stefan / Calvino-Martin, Florian / Ivanov, Nikolai V / O'Mullane, John / Peitsch, Manuel C / Hoeng, Julia

The AAPS journal

2022 Volume 24, Issue 1, Page(s) 33

Abstract: In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary ... ...

Abstract	In vitro screening for pharmacological activity of existing drugs showed chloroquine and hydroxychloroquine to be effective against severe acute respiratory syndrome coronavirus 2. Oral administration of these compounds to obtain desired pulmonary exposures resulted in dose-limiting systemic toxicity in humans. However, pulmonary drug delivery enables direct and rapid administration to obtain higher local tissue concentrations in target tissue. In this work, inhalable formulations for thermal aerosolization of chloroquine and hydroxychloroquine were developed, and their physicochemical properties were characterized. Thermal aerosolization of 40 mg/mL chloroquine and 100 mg/mL hydroxychloroquine formulations delivered respirable aerosol particle sizes with 0.15 and 0.33 mg per 55 mL puff, respectively. In vitro toxicity was evaluated by exposing primary human bronchial epithelial cells to aerosol generated from Vitrocell. An in vitro exposure to 7.24 μg of chloroquine or 7.99 μg hydroxychloroquine showed no significant changes in cilia beating, transepithelial electrical resistance, and cell viability. The pharmacokinetics of inhaled aerosols was predicted by developing a physiologically based pharmacokinetic model that included a detailed species-specific respiratory tract physiology and lysosomal trapping. Based on the model predictions, inhaling emitted doses comprising 1.5 mg of chloroquine or 3.3 mg hydroxychloroquine three times a day may yield therapeutically effective concentrations in the lung. Inhalation of higher doses further increased effective concentrations in the lung while maintaining lower systemic concentrations. Given the theoretically favorable risk/benefit ratio, the clinical significance for pulmonary delivery of aerosolized chloroquine and hydroxychloroquine to treat COVID-19 needs to be established in rigorous safety and efficacy studies. Graphical abstract.
MeSH term(s)	Administration, Inhalation ; Animals ; Antimalarials/administration & dosage ; Antimalarials/pharmacokinetics ; Antimalarials/toxicity ; COVID-19/drug therapy ; Cells, Cultured ; Chloroquine/administration & dosage ; Drug Evaluation, Preclinical ; Humans ; Hydroxychloroquine/administration & dosage ; Hydroxychloroquine/pharmacokinetics ; Hydroxychloroquine/toxicity ; Male ; Mice ; Middle Aged ; Models, Chemical ; Rats
Chemical Substances	Antimalarials ; Hydroxychloroquine (4QWG6N8QKH) ; Chloroquine (886U3H6UFF)
Language	English
Publishing date	2022-02-07
Publishing country	United States
Document type	Journal Article
ISSN	1550-7416
ISSN (online)	1550-7416
DOI	10.1208/s12248-021-00666-x
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Article ; Online: Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products.

van der Toorn, Marco / Koshibu, Kyoko / Schlage, Walter K / Majeed, Shoaib / Pospisil, Pavel / Hoeng, Julia / Peitsch, Manuel C

Toxicology reports

2019 Volume 6, Page(s) 1206–1215

Abstract: The adverse effects of cigarette smoking are well documented, and the two main strategies for reducing smoking prevalence are prevention of smoking initiation and promotion of smoking cessation. More recently, a third and complementary avenue, tobacco ... ...

Abstract	The adverse effects of cigarette smoking are well documented, and the two main strategies for reducing smoking prevalence are prevention of smoking initiation and promotion of smoking cessation. More recently, a third and complementary avenue, tobacco harm reduction has emerged, which is aimed to reduce the burden of smoking-related diseases. This has been enabled by the development of novel products such as electronic cigarettes (e-cigarettes) and heated tobacco products, designed to deliver nicotine with significantly reduced levels of the toxicants that are emitted by cigarettes. Several potential modified risk tobacco products (pMRTP) have been reported to emit significantly less toxicants than cigarettes and significantly reduce toxicant exposure in smokers who switch completely to such products. These are two prerequisites for pMRTPs to reduce harm and the risk of smoking-related disease. However, concerns remain regarding the addictive nature of these products. Smoking addiction is a complex phenomenon involving multiple pharmacological and non-pharmacological factors. Although the main pharmacological substance associated with smoking addiction is nicotine, accumulating evidence suggests that nicotine mostly acts as a primary reinforcer and that other factors are involved in establishing smoking addiction. Inhibition of monoamine oxidases (MAO)-mammalian flavoenzymes with a central role in neurotransmitter metabolism-has also been suggested to be involved in this process. Therefore, we aimed to comparatively investigate the ability of several types of pMRTPs and cigarette smoke (3R4F) to inhibit MAO activity. The results showed that the heated tobacco product Tobacco Heating System (THS) 2.2 and the
Language	English
Publishing date	2019-11-13
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	2805786-7
ISSN	2214-7500 ; 2214-7500
ISSN (online)	2214-7500
ISSN	2214-7500
DOI	10.1016/j.toxrep.2019.11.008
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