18 research outputs found

    The Metapolis Dictionary of Advanced Architecture

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    Tassonomia interdisciplinare degli nuovi paradigmi contemporani della Architettura e la citt\ue0

    Antidepressant-like effects of a new dihydro isoquinoline and its chemical precursors in mice. Involvement of serotonin and dopaminergic systems.

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    Abstract This study was aimed to synthesize novel 2-(2-bromophenyl)-N-phenethylacetamides and benzylisoquinoline (BIQ) derivatives to be evaluated as antidepressant-like agents in mice. The N-phenethylacetamides derivatives were synthesized by coupling aromatic amides to the backbone of 2-bromophenylacetyl chloride. The synthesis of BIQ was achieved by the reaction between synthesized phenethylacetamides and 2-chloropyridine. The structures of the compounds were established mainly by 1D and 2D NMR spectra. Those compounds obtained with moderate to good yields were evaluated as antidepressant-like agents in the forced swimming test and the open field paradigms in mice. The possible mechanism of those active derivatives was explored by antagonist experiments in combination with p-chloro-phenylalanine methyl ester, reserpine, sulpiride, and dopamine D1 antagonist SCH23390. Also, MAO A and B inhibition assay were performed. Docking studies of the human dopamine D3 receptor with the most active compound was performed. The results showed that the (2-bromophenyl) (3,4-dihydroisoquinoline-1-yl)methanone (4a) presented the most potent antidepressant-like effects without modifying the ambulatory activity of experimental mice. Antagonist experiments showed that 4a acted on the serotonergic and dopaminergic receptors. Docking studies indicated a strong affinity of the human dopamine D3 receptor for 4a. Our results showed that benzylisoquinoline 4a has an antidepressant-like effect that is mediated at least in part by an interaction with the presynaptic serotonin receptors, and dopaminergic D1, D2, and D3, receptors. This study highlights the pharmacological potential of halogenated BIQ’s in the treatment of some depressive disorders.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    Transcriptome Analysis Identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in Nasal Polyp Epithelial Cells of Patients Suffering from Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (AERD)

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    Background: Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterised by chronic rhinosinusitis, nasal polyps, asthma and aspirin intolerance. An imbalance of eicosanoid metabolism with anover-production of cysteinyl leukotrienes (CysLTs) has been associated with AERD. However, the precise mechanisms underlying AERD are unknown. Objective: To establish the transcriptome of the nasal polyp airway epithelial cells derived from AERD patients to discover gene expression patterns in this disease. Methods: Nasal airway epithelial cells were isolated from 12 AERD polyps and 8 AERD non-polyp nasal mucosa samples as controls from the same subjects. Utilising the Illumina HiSeq 2500 platform, RNA samples were sequenced. Potential gene candidate DMRT3 was selected from the differentially-expressed genes for validation. Results: Comparative transcriptome profiling of nasal epithelial cells was accomplished in AERD. A total of 20 genes had twofold mean regulation expression differences or greater. In addition, 8 genes were upregulated, including doublesex and mab-3 related transcription factor 3 (DMRT3), and 12 genes were downregulated. Differentially regulated genes comprised roles in inflammation, defence and immunity. Metabolic process and embryonic development pathways were significantly enriched. Enzyme-linked immune sorbent assay (ELISA) results of DMRT3 in AERD patients were significantly upregulated compared to controls (p = 0.03). Immunohistochemistry (IHC) of AERD nasal polyps localised DMRT3 and was predominantly released in the airway epithelia. Conclusion: Findings suggest that DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. However, further studies are imperative to confirm the exact mechanism of polyp formation in AERD patients

    Transcriptome Analysis Identifies Doublesex and Mab-3 Related Transcription Factor (DMRT3) in Nasal Polyp Epithelial Cells of Patients Suffering from Non-Steroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease (AERD)

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    Background: Aspirin-exacerbated respiratory disease (AERD) is a syndrome characterised by chronic rhinosinusitis, nasal polyps, asthma and aspirin intolerance. An imbalance of eicosanoid metabolism with anover-production of cysteinyl leukotrienes (CysLTs) has been associated with AERD. However, the precise mechanisms underlying AERD are unknown. Objective: To establish the transcriptome of the nasal polyp airway epithelial cells derived from AERD patients to discover gene expression patterns in this disease. Methods: Nasal airway epithelial cells were isolated from 12 AERD polyps and 8 AERD non-polyp nasal mucosa samples as controls from the same subjects. Utilising the Illumina HiSeq 2500 platform, RNA samples were sequenced. Potential gene candidate DMRT3 was selected from the differentially-expressed genes for validation. Results: Comparative transcriptome profiling of nasal epithelial cells was accomplished in AERD. A total of 20 genes had twofold mean regulation expression differences or greater. In addition, 8 genes were upregulated, including doublesex and mab-3 related transcription factor 3 (DMRT3), and 12 genes were downregulated. Differentially regulated genes comprised roles in inflammation, defence and immunity. Metabolic process and embryonic development pathways were significantly enriched. Enzyme-linked immune sorbent assay (ELISA) results of DMRT3 in AERD patients were significantly upregulated compared to controls (p = 0.03). Immunohistochemistry (IHC) of AERD nasal polyps localised DMRT3 and was predominantly released in the airway epithelia. Conclusion: Findings suggest that DMRT3 could be potentially involved in nasal polyp development in AERD patients. Furthermore, several genes are downregulated, hinting at the dedifferentiation phenomenon in AERD polyps. However, further studies are imperative to confirm the exact mechanism of polyp formation in AERD patients

    Does owning a \u201cfatter\u201d virtual body increase body anxiety in college students?

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    This study aimed to assess the ability of a virtual reality (VR)-based software to produce body anxiety responses in a non-clinical sample. 23 college students (5 male) were exposed to an immersive VR environment displayed with an HMD, where the illusion of ownership of a virtual body was induced by means of visuomotor synchronization. Each participant was exposed to three body sizes (from first-person perspective and from third-person perspective reflected in a mirror placed in the virtual environment): an avatar with the same body measurements as the participant, an avatar 20% larger than the participant, and another avatar 40% larger than the participant. BMI, drive for thinness (EDI 3-DT) and body dissatisfaction (EDI3-BD) were assessed before exposure, while body anxiety (PASTAS), fear of gaining weight (Visual analogue scale [VAS], from 0 to 100) and ownership illusion (VAS from 0 to 100) were assessed after exposure to each avatar. Students reported significantly higher levels of body anxiety and fear of gaining weight after owning a 40% larger virtual body than after owning a virtual body with their real measurements. When body dissatisfaction and drive for thinness was considered, only participants with higher scores in these scales showed a significant increment of body anxiety and fear of weight gain after exposure to the largest avatar. BMI had no effect on the results. This study provides evidence of the usefulness of virtual body ownership illusions to provoke weight and body related anxiety responses in individuals worried about their weight and body image and opens the door to its therapeutic use in patients with anorexia nervosa

    How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU.

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    Funding: This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733032 HBM4EU, and co-funding from the authors’ organisations. The results presented here are based on a huge body of work performed as part of Task 5.3 of the HBM4EU in 2017–2022. First and foremost, we would like to acknowledge all our Task 5.3 colleagues for their valuable contribution to the project work, including the individual RAs and EBoD calculations. In addition, we would like to thank all our other HBM4EU colleagues, the HBM4EU-aligned study data owners, and the other stakeholders who provided support for and feedback on our work during its course.One of the aims of the European Human Biomonitoring Initiative, HBM4EU, was to provide examples of and good practices for the effective use of human biomonitoring (HBM) data in human health risk assessment (RA). The need for such information is pressing, as previous research has indicated that regulatory risk assessors generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols, cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/poly-fluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.publishersversionpublishe
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