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  1. Article ; Online: Blood immune cells from people with HIV on antiviral regimens that contain tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) have differential metabolic signatures.

    Ritou, Eleni / Satta, Sandro / Petcherski, Anton / Daskou, Maria / Sharma, Madhav / Vasilopoulos, Hariclea / Murakami, Eisuke / Shirihai, Orian S / Kelesidis, Theodoros

    Metabolism: clinical and experimental

    2023  Volume 141, Page(s) 155395

    Abstract: Background: Mitochondria regulate immune and organ function. It is unknown whether higher intracellular drug levels observed in peripheral blood mononuclear cells (PBMCs) treated with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate ...

    Abstract Background: Mitochondria regulate immune and organ function. It is unknown whether higher intracellular drug levels observed in peripheral blood mononuclear cells (PBMCs) treated with tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) may alter mitochondrial function and energy production in immune cells in HIV
    Methods: Cellular bioenergetics were determined in PBMCs from HIV-1
    Results: PBMCs from HIV-1
    Conclusions: Compared to TDF, TAF may alter bioenergetics in immune cells from PWH in vitro and in vivo. The clinical significance in terms of the differential impact caused by TAF versus TDF on mitochondrial function and energy production in immune cells, a regulator of immune function, requires further studied in HIV, preexposure prophylaxis and hepatitis B.
    MeSH term(s) Humans ; Adenine/therapeutic use ; Alanine/pharmacology ; Alanine/therapeutic use ; Anti-HIV Agents/therapeutic use ; HIV Infections/drug therapy ; Leukocytes, Mononuclear ; Tenofovir/therapeutic use
    Chemical Substances Adenine (JAC85A2161) ; Alanine (OF5P57N2ZX) ; Anti-HIV Agents ; Tenofovir (99YXE507IL)
    Language English
    Publishing date 2023-01-14
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80230-x
    ISSN 1532-8600 ; 0026-0495
    ISSN (online) 1532-8600
    ISSN 0026-0495
    DOI 10.1016/j.metabol.2022.155395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uc I Zs.316: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Endoscopic transsphenoidal surgery for biochemically and clinically non-functioning adenohypophyseal tumours in the elderly: experience from a single UK centre.

    Quah, Boon Leong / Edwards-Bailey, Andrew / Gnanalingham, Kanna / Pathmanaban, Omar / Vasilopoulos, Hariclea / Roncaroli, Federico / Kearney, Tara / Balogun, James / Karabatsou, Konstantina

    Endocrine

    2021  Volume 75, Issue 3, Page(s) 872–882

    Abstract: Purpose: To assess and compare outcome of surgical management of non-functioning pituitary adenohypophyseal tumours in patients under 65-years, and 65-years and older at tertiary neurosurgical referral centre.: Methods: Data was retrospectively ... ...

    Abstract Purpose: To assess and compare outcome of surgical management of non-functioning pituitary adenohypophyseal tumours in patients under 65-years, and 65-years and older at tertiary neurosurgical referral centre.
    Methods: Data was retrospectively analysed from pituitary database. Forty-four patients aged 65 or older (Group 1) and 93 patients under 65 (Group 2) underwent endoscopic trans-sphenoidal surgery (ETSS) between January 2017 and July 2019. The surgical, endocrinological, ophthalmological and radiological outcomes were compared.
    Results: 6.8% of Group 1 patients had peri-operative surgical complications compared to 12.9% in Group 2 (p = 0.29). Improved visual fields and acuity were seen in 65.2% and 82.8% of Group 1 and Group 2 respectively (p = 0.124), although there were pre-existing ocular problems in 15.9% of Group 1. New hormone deficiencies were observed in 31.8% of Group 1 patients, and 24.7% of Group 2 (p = 0.555). Tumour regrowth/recurrence was seen in 2.3% of Group 1 (p = 0.553). The rate of repeat surgery was 6.8% in the Group 1 and 12.9% in Group 2 (p = 0.28). There was no significant relationship between extent of resection, complications or hormonal deficiency. The mean duration of follow-up was 10.5 ± 13.0 months for Group 1 patients and 13.0 ± 16.0 months for Group 2 patients (p = 0.526).
    Conclusions: ETSS for non-functioning pituitary adenohypophyseal tumours is safe and well tolerated in the patients aged 65 and older. Advanced age by itself should not be a contra-indication for ETSS. It is however highly recommended that the care of such patients to be offered at a high volume, dedicated pituitary surgical units.
    MeSH term(s) Adenoma/pathology ; Aged ; Humans ; Neoplasm Recurrence, Local/complications ; Pituitary Neoplasms/pathology ; Retrospective Studies ; Treatment Outcome ; United Kingdom
    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1194484-5
    ISSN 1559-0100 ; 1355-008X ; 0969-711X
    ISSN (online) 1559-0100
    ISSN 1355-008X ; 0969-711X
    DOI 10.1007/s12020-021-02910-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Mitoquinone mesylate targets SARS-CoV-2 infection in preclinical models.

    Petcherski, Anton / Sharma, Madhav / Satta, Sandro / Daskou, Maria / Vasilopoulos, Hariclea / Hugo, Cristelle / Ritou, Eleni / Dillon, Barbara Jane / Fung, Eileen / Garcia, Gustavo / Scafoglio, Claudio / Purkayastha, Arunima / Gomperts, Brigitte N / Fishbein, Gregory A / Arumugaswami, Vaithilingaraja / Liesa, Marc / Shirihai, Orian S / Kelesidis, Theodoros

    bioRxiv : the preprint server for biology

    2022  

    Abstract: To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against ... ...

    Abstract To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern
    One-sentence summary: Mitoquinone/mitoquinol mesylate has potent antiviral and anti-inflammatory activity in preclinical models of SARS-CoV-2 infection.
    Language English
    Publishing date 2022-06-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.02.22.481100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ApoA-I mimetics reduce systemic and gut inflammation in chronic treated HIV.

    Daskou, Maria / Mu, William / Sharma, Madhav / Vasilopoulos, Hariclea / Heymans, Rachel / Ritou, Eleni / Rezek, Valerie / Hamid, Philip / Kossyvakis, Athanasios / Sen Roy, Shubhendu / Grijalva, Victor / Chattopadhyay, Arnab / Kitchen, Scott G / Fogelman, Alan M / Reddy, Srinivasa T / Kelesidis, Theodoros

    PLoS pathogens

    2022  Volume 18, Issue 1, Page(s) e1010160

    Abstract: Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical ... ...

    Abstract Novel therapeutic strategies are needed to attenuate increased systemic and gut inflammation that contribute to morbidity and mortality in chronic HIV infection despite potent antiretroviral therapy (ART). The goal of this study is to use preclinical models of chronic treated HIV to determine whether the antioxidant and anti-inflammatory apoA-I mimetic peptides 6F and 4F attenuate systemic and gut inflammation in chronic HIV. We used two humanized murine models of HIV infection and gut explants from 10 uninfected and 10 HIV infected persons on potent ART, to determine the in vivo and ex vivo impact of apoA-I mimetics on systemic and intestinal inflammation in HIV. When compared to HIV infected humanized mice treated with ART alone, mice on oral apoA-I mimetic peptide 6F with ART had consistently reduced plasma and gut tissue cytokines (TNF-α, IL-6) and chemokines (CX3CL1) that are products of ADAM17 sheddase activity. Oral 6F attenuated gut protein levels of ADAM17 that were increased in HIV-1 infected mice on potent ART compared to uninfected mice. Adding oxidized lipoproteins and endotoxin (LPS) ex vivo to gut explants from HIV infected persons increased levels of ADAM17 in myeloid and intestinal cells, which increased TNF-α and CX3CL1. Both 4F and 6F attenuated these changes. Our preclinical data suggest that apoA-I mimetic peptides provide a novel therapeutic strategy that can target increased protein levels of ADAM17 and its sheddase activity that contribute to intestinal and systemic inflammation in treated HIV. The large repertoire of inflammatory mediators involved in ADAM17 sheddase activity places it as a pivotal orchestrator of several inflammatory pathways associated with morbidity in chronic treated HIV that make it an attractive therapeutic target.
    MeSH term(s) ADAM17 Protein/drug effects ; Animals ; Anti-HIV Agents/pharmacology ; Apolipoprotein A-I ; HIV Infections/pathology ; Humans ; Inflammation/pathology ; Intestines/drug effects ; Mice ; Peptides/pharmacology
    Chemical Substances 6F peptide ; Anti-HIV Agents ; Apolipoprotein A-I ; Peptides ; ADAM17 Protein (EC 3.4.24.86)
    Language English
    Publishing date 2022-01-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010160
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mitoquinone mesylate targets SARS-CoV-2 and associated lung inflammation through host pathways

    Petcherski, Anton / Sharma, Madhav / Daskou, Maria / Satta, Sandro / Vasilopoulos, Hariclea / Hugo, Cristelle / Ritou, Eleni / Dillon, Barbara Jane / Fung, Eileen / Garcia, Gustavo / Scafoglio, Claudio / Purkayastha, Arunima / Gomperts, Brigitte / Fishbein, Gregory A / Arumugaswami, Vaithilingaraja / Liesa, Marc / Shirihai, Orian S / Kelesidis, Theodoros

    bioRxiv

    Abstract: To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against ... ...

    Abstract To date, there is no effective oral antiviral against SARS-CoV-2 that is also anti-inflammatory. Herein, we show that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has potent antiviral activity against SARS-CoV-2 and its variants of concern in vitro and in vivo. Mito-MES had nanomolar in vitro antiviral potency against the Beta and Delta SARS-CoV-2 variants as well as the murine hepatitis virus (MHV-A59). Mito-MES given in SARS-CoV-2 infected K18-hACE2 mice through oral gavage reduced viral titer by nearly 4 log units relative to the vehicle group. We found in vitro that the antiviral effect of Mito-MES is attributable to its hydrophobic dTPP+ moiety and its combined effects scavenging reactive oxygen species (ROS), activating Nrf2 and increasing the host defense proteins TOM70 and MX1. Mito-MES was efficacious reducing increase in cleaved caspase-3 and inflammation induced by SARS-CoV2 infection both in lung epithelial cells and a transgenic mouse model of COVID-19. Mito-MES reduced production of IL-6 by SARS-CoV-2 infected epithelial cells through its antioxidant properties (Nrf2 agonist, coenzyme Q10 moiety) and the dTPP moiety. Given established safety of Mito-MES in humans, our results suggest that Mito-MES may represent a rapidly applicable therapeutic strategy that can be added in the therapeutic arsenal against COVID-19. Its potential long-term use by humans as diet supplement could help control the SARS-CoV-2 pandemic, especially in the setting of rapidly emerging SARS-CoV-2 variants that may compromise vaccine efficacy.
    Keywords covid19
    Language English
    Publishing date 2022-02-25
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.02.22.481100
    Database COVID19

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