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  • 1
    Online Resource
    Online Resource
    Circulating LOXL2 Levels Reflect Severity of Intestinal Fibrosis and GALT CD4+ T Lymphocyte Depletion in Treated HIV Infection
    Case Western Reserve University ; 2017
    In:  Pathogens and Immunity Vol. 2, No. 2 ( 2017-06-21), p. 239-
    Details
    In: Pathogens and Immunity, Case Western Reserve University, Vol. 2, No. 2 ( 2017-06-21), p. 239-
    Abstract: Background: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4+ T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation.Methods: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies. Relationships among biomarker levels, clinical and demographic variables, GALT lymphoid aggregate (LA) collagen deposition, and LA CD4+ T lymphocyte density were analyzed using simple regression. Biomarker levels were also compared to levels in HIV+ viremic SCOPE participants and a convenience sample of HIV-uninfected (HIV-) samples. Results: HIV+ aviremic participants (n=39) were 92% male and 41% non-white, with median age 48 years, CD4+ T lymphocyte count 277 cells/mm3, and 17 years since HIV diagnosis. Most biomarkers were lower in HIV− (n=36) vs HIV+ aviremic individuals, although CXCL4 levels were higher. HIV+ viremic individuals (N=18) had higher median TGF-ß3, CIC-C1Q, and TIMP-1 (P 〈 0.05) and lower LOXL2 levels (P=0.08) than HIV+ aviremic individuals. Only higher LOXL2 levels correlated with more GALT collagen deposition (R=0.44, P=0.007) and lower LA CD4+ T lymphocyte density (R=−0.32, P=0.05) among aviremic individuals.Conclusions: Circulating LOXL2 levels may be a noninvasive measure of intestinal fibrosis and GALT CD4+T lymphocyte depletion in treated HIV infection. LOXL2 crosslinks elastin and collagen, and elevated LOXL2 levels occur in pathologic states, making LOXL2 inhibition a potential interventional target for intestinal fibrosis and its sequelae. 
    Type of Medium: Online Resource
    ISSN: 2469-2964
    URL: Issue
    URL: Article
    DOI: 10.20411/pai.v2i2
    DOI: 10.20411/pai.v2i2.180
    Language: Unknown
    Publisher: Case Western Reserve University
    Publication Date: 2017
    detail.hit.zdb_id: 3032410-5
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  • 2
    Online Resource
    Online Resource
    Prospective Analysis of Lipid Composition Changes with Antiretroviral Therapy and Immune Activation in Persons Living with HIV
    Case Western Reserve University ; 2017
    In:  Pathogens and Immunity Vol. 2, No. 3 ( 2017-10-06), p. 376-
    Details
    In: Pathogens and Immunity, Case Western Reserve University, Vol. 2, No. 3 ( 2017-10-06), p. 376-
    Abstract: Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lysophosphatidylcholine, LPC) and their saturated (SaFA), monounsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described. Methods: Plasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (N=13) matched for age and sex. Results: The levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants (P 〈 0.01), and levels of these PUFAs were increased following 48 weeks of ART. Levels of PUFAs were often inversely related to immune activation. Levels of LPC were increased in HIV+ participants, both pre- and post-ART vs HIV- participants, and the composition of LPC was enriched for SaFAs among HIV+ individuals. At week 48, several LPC molecules containing SaFAs were positively correlated with levels of sCD14, D-dimer, and TNFR1 (P 〈 0.01), and levels of PUFA-containing LPC (18:3, 20:5, 22:5, 22:6) were positively correlated with CD4+ T cell counts and inversely correlated with sCD14 and IL-6 (P 〈 0.01). Conclusions: The composition of the lipidome is altered in HIV infection and changes when ART is administered. Alterations in SaFAs were generally associated with inflammatory markers and may contribute to comorbid disease pathogenesis.
    Type of Medium: Online Resource
    ISSN: 2469-2964
    URL: Issue
    URL: Article
    DOI: 10.20411/pai.v2i3
    DOI: 10.20411/pai.v2i3.218
    Language: Unknown
    Publisher: Case Western Reserve University
    Publication Date: 2017
    detail.hit.zdb_id: 3032410-5
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  • 3
    Online Resource
    Online Resource
    Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV
    Case Western Reserve University ; 2020
    In:  Pathogens and Immunity Vol. 5, No. 1 ( 2020-12-30), p. 364-
    Details
    In: Pathogens and Immunity, Case Western Reserve University, Vol. 5, No. 1 ( 2020-12-30), p. 364-
    Abstract: Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels  〈 20 copies/mL. FMT was safe and well-tolerated. Alpha diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest alpha diversity at week 0. At week 26, alpha diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low alpha diversity that improved between weeks 0 and 6 with a shift in distribution.Conclusions: Weekly FMT was safe and well-tolerated. Alpha diversity increased in participants with the lowest baseline alpha diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560
    Type of Medium: Online Resource
    ISSN: 2469-2964
    URL: Issue
    URL: Article
    DOI: 10.20411/pai.v5i1
    DOI: 10.20411/pai.v5i1.388
    Language: Unknown
    Publisher: Case Western Reserve University
    Publication Date: 2020
    detail.hit.zdb_id: 3032410-5
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