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  1. Article: Clinical features of pulmonary arterial hypertension associated with systemic sclerosis.

    Tuhy, Tijana / Hassoun, Paul M

    Frontiers in medicine

    2023  Volume 10, Page(s) 1264906

    Abstract: Systemic sclerosis is an autoimmune disorder of the connective tissue characterized by disordered inflammation and fibrosis leading to skin thickening and visceral organ complications. Pulmonary involvement, in the form of pulmonary arterial hypertension ...

    Abstract Systemic sclerosis is an autoimmune disorder of the connective tissue characterized by disordered inflammation and fibrosis leading to skin thickening and visceral organ complications. Pulmonary involvement, in the form of pulmonary arterial hypertension and/or interstitial lung disease, is the leading cause of morbidity and mortality among individuals with scleroderma. There are no disease-specific therapies for pulmonary involvement of scleroderma, and pulmonary arterial hypertension in this cohort has typically been associated with worse outcomes and less clinical response to modern therapy compared to other forms of Group I pulmonary hypertension in the classification from the World Symposium on Pulmonary Hypertension. Ongoing research aims to delineate how pathologic microvascular remodeling and fibrosis contribute to this poor response and offer a window into future therapeutic targets.
    Language English
    Publishing date 2023-09-27
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2023.1264906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Double-Negative (PF4-Negative/SRA-Negative) Heparin-Induced Thrombocytopenia.

    Starke, Samuel J / Streiff, Michael B / Brown, Dannielle / Latifi, Ardian / Tuhy, Tijana

    The American journal of medicine

    2022  Volume 136, Issue 2, Page(s) e32–e33

    MeSH term(s) Humans ; Thrombocytopenia/chemically induced ; Thrombocytopenia/diagnosis ; Heparin/adverse effects ; Anticoagulants/adverse effects ; Enzyme-Linked Immunosorbent Assay
    Chemical Substances Heparin (9005-49-6) ; Anticoagulants
    Language English
    Publishing date 2022-10-15
    Publishing country United States
    Document type Case Reports
    ZDB-ID 80015-6
    ISSN 1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
    ISSN (online) 1555-7162 ; 1873-2178
    ISSN 0002-9343 ; 1548-2766
    DOI 10.1016/j.amjmed.2022.09.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Aberrant Long-Chain Fatty Acid Metabolism Associated with Evolving Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

    Coursen, Julie C / Tuhy, Tijana / Naranjo, Mario / Woods, Adrianne / Hummers, Laura K / Shah, Ami A / Suresh, Karthik / Visovatti, Scott H / Mathai, Stephen C / Hassoun, Paul M / Damico, Rachel L / Simpson, Catherine E

    American journal of physiology. Lung cellular and molecular physiology

    2024  

    Abstract: We sought to investigate differential metabolism in patients with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) versus those who do not, as a method of identifying potential disease biomarkers. In a nested case-control design, ...

    Abstract We sought to investigate differential metabolism in patients with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) versus those who do not, as a method of identifying potential disease biomarkers. In a nested case-control design, serum metabolites were assayed in SSc subjects who developed right heart catheterization-confirmed PAH (n=22) while under surveillance in a longitudinal cohort from Johns Hopkins, then compared to metabolites assayed in matched SSc patients who did not develop PAH (n=22). Serum samples were collected at "proximate" (within 12 months) and "distant" (within 1-5 years) time points relative to PAH diagnosis. Metabolites were identified using liquid chromatography-mass spectroscopy (LC-MS). An LC-MS dataset from SSc subjects with either mildly elevated pulmonary pressures or overt PAH from the University of Michigan was compared. Differentially abundant metabolites were tested as predictors of PAH in two additional validation SSc cohorts. Long-chain fatty acid metabolism (LCFA) consistently differed in SSc-PAH versus SSc without PH. LCFA metabolites discriminated SSc-PAH patients with mildly elevated pressures in the Michigan cohort and predicted SSc-PAH up to two years prior to clinical diagnosis in the Hopkins cohort. Acylcholines containing LCFA residues and linoleic acid metabolites were most important for discriminating SSc-PAH. Combinations of acylcholines and linoleic acid metabolites provided good discrimination of SSc-PAH across cohorts. Aberrant lipid metabolism is observed throughout the evolution of PAH in SSc. Lipidomic signatures of abnormal LCFA metabolism distinguish SSc-PAH patients from those without PH, including prior to clinical diagnosis and in mild disease.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1013184-x
    ISSN 1522-1504 ; 1040-0605
    ISSN (online) 1522-1504
    ISSN 1040-0605
    DOI 10.1152/ajplung.00057.2024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Spatial and temporal resolution of metabolic dysregulation in the Sugen hypoxia model of pulmonary hypertension.

    Simpson, Catherine E / Ambade, Anjira S / Harlan, Robert / Roux, Aurelie / Graham, David / Klauer, Neal / Tuhy, Tijana / Kolb, Todd M / Suresh, Karthik / Hassoun, Paul M / Damico, Rachel L

    Pulmonary circulation

    2023  Volume 13, Issue 3, Page(s) e12260

    Abstract: Although PAH is partially attributed to disordered metabolism, previous human studies have mostly examined circulating metabolites at a single time point, potentially overlooking crucial disease biology. Current knowledge gaps include an understanding of ...

    Abstract Although PAH is partially attributed to disordered metabolism, previous human studies have mostly examined circulating metabolites at a single time point, potentially overlooking crucial disease biology. Current knowledge gaps include an understanding of temporal changes that occur within and across relevant tissues, and whether observed metabolic changes might contribute to disease pathobiology. We utilized targeted tissue metabolomics in the Sugen hypoxia (SuHx) rodent model to investigate tissue-specific metabolic relationships with pulmonary hypertensive features over time using regression modeling and time-series analysis. Our hypotheses were that some metabolic changes would precede phenotypic changes, and that examining metabolic interactions across heart, lung, and liver tissues would yield insight into interconnected metabolic mechanisms. To support the relevance of our findings, we sought to establish links between SuHx tissue metabolomics and human PAH -omics data using bioinformatic predictions. Metabolic differences between and within tissue types were evident by Day 7 postinduction, demonstrating distinct tissue-specific metabolism in experimental pulmonary hypertension. Various metabolites demonstrated significant tissue-specific associations with hemodynamics and RV remodeling. Individual metabolite profiles were dynamic, and some metabolic shifts temporally preceded the emergence of overt pulmonary hypertension and RV remodeling. Metabolic interactions were observed such that abundance of several liver metabolites modulated lung and RV metabolite-phenotype relationships. Taken all together, regression analyses, pathway analyses and time-series analyses implicated aspartate and glutamate signaling and transport, glycine homeostasis, lung nucleotide abundance, and oxidative stress as relevant to early PAH pathobiology. These findings offer valuable insights into potential targets for early intervention in PAH.
    Language English
    Publishing date 2023-07-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2638089-4
    ISSN 2045-8940 ; 2045-8932
    ISSN (online) 2045-8940
    ISSN 2045-8932
    DOI 10.1002/pul2.12260
    Database MEDical Literature Analysis and Retrieval System OnLINE

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