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  1. Article ; Online: CSL112 (Apolipoprotein A-I [Human]) Reduces the Elevation in Neutrophil-to-Lymphocyte Ratio Induced by Acute Myocardial Infarction.

    Kingwell, Bronwyn A / Duffy, Danielle / Clementi, Regina / Velkoska, Elena / Feaster, John / Gibson, C Michael

    Journal of the American Heart Association

    2024  Volume 13, Issue 9, Page(s) e033541

    MeSH term(s) Neutrophils/metabolism ; Humans ; Lymphocytes/metabolism ; Apolipoprotein A-I/blood ; Myocardial Infarction/blood ; Male ; Lymphocyte Count
    Chemical Substances Apolipoprotein A-I ; APOA1 protein, human
    Language English
    Publishing date 2024-05-03
    Publishing country England
    Document type Research Support, Non-U.S. Gov't ; Letter ; Journal Article
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.123.033541
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Apolipoprotein A-I for Cardiac Recovery Post-Myocardial Infarction.

    Richart, Adele L / Calkin, Anna C / Kingwell, Bronwyn A

    JACC. Basic to translational science

    2021  Volume 6, Issue 9-10, Page(s) 768–771

    Language English
    Publishing date 2021-10-25
    Publishing country United States
    Document type Journal Article
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2021.08.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rethinking good cholesterol: a clinicians' guide to understanding HDL.

    Xiang, Angie S / Kingwell, Bronwyn A

    The lancet. Diabetes & endocrinology

    2019  Volume 7, Issue 7, Page(s) 575–582

    Abstract: Low HDL cholesterol dyslipidaemia affects about half of people with type 2 diabetes and represents a major independent risk factor for atherosclerotic cardiovascular disease. The "good cholesterol" label was coined decades ago on the basis of a presumed ... ...

    Abstract Low HDL cholesterol dyslipidaemia affects about half of people with type 2 diabetes and represents a major independent risk factor for atherosclerotic cardiovascular disease. The "good cholesterol" label was coined decades ago on the basis of a presumed causal role of HDL cholesterol in atherosclerotic cardiovascular disease. However, this view has been challenged by the negative results of several studies of HDL cholesterol-raising drugs, creating a paradox for clinicians regarding the value of HDL cholesterol as a risk biomarker and therapeutic target, and seemingly contradicting decades of evidence substantiating an inverse relation between HDL cholesterol and cardiovascular disease risk. We seek to resolve this issue by revisiting the history of the HDL hypothesis, chronicling how this paradox is ultimately rooted in the progressive erroneous blurring of the distinction between HDL and HDL cholesterol. We describe the compositional complexity of HDL particles beyond their cholesterol cargo and focus on their role in lipid transport. We discuss the evidence regarding novel HDL functions, including effects on glucose metabolism, and speculate on the implications for type 2 diabetes. HDL cholesterol is an imperfect biomarker of a highly complex and multifunctional lipid transport system, and we should now consider how new HDL markers more causally linked to cardiovascular complications could be adapted for clinical use. In the absence of a superior alternative, HDL cholesterol generally has value as a component of primary cardiovascular disease risk prediction models, including in people with type 2 diabetes. However, to avoid prognostic overgeneralisations, it is high time that the good cholesterol label is dropped.
    MeSH term(s) Cholesterol, HDL/blood ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Dyslipidemias/complications ; Dyslipidemias/drug therapy ; Humans
    Chemical Substances Cholesterol, HDL
    Language English
    Publishing date 2019-03-22
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2213-8595
    ISSN (online) 2213-8595
    DOI 10.1016/S2213-8587(19)30003-8
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  4. Article ; Online: A method for detection of anti-drug antibodies to a biotherapeutic (CSL112) with endogenous counterpart (apolipoprotein A-I) using a novel sample pre-treatment electrochemiluminescence assay

    Davis, Roslyn / Velkoska, Elena / McCallum, Helen / Majcen, Belinda / Gille, Andreas / Kingwell, Bronwyn A. / Martin, Kirstee

    Journal of Immunological Methods. 2023 Feb., v. 513 p.113411-

    2023  

    Abstract: There are numerous challenges encountered during clinical testing for an immunogenic response to a plasma-derived therapeutic. Distinguishing between antibodies that recognize endogenous versus therapeutic protein can be particularly difficult. This ... ...

    Abstract There are numerous challenges encountered during clinical testing for an immunogenic response to a plasma-derived therapeutic. Distinguishing between antibodies that recognize endogenous versus therapeutic protein can be particularly difficult. This study focused on CSL112 (human plasma-derived apolipoprotein A-I; apoA-I), which is in clinical development for reducing the risk of recurrent major adverse cardiovascular events following acute myocardial infarction. To develop and validate a high-throughput, highly sensitive and specific assay to detect antibodies to CSL112 that can be used for immunogenicity assessment in large clinical studies. We developed a clinical anti-drug antibody (ADA) assay utilizing an immunoglobulin purification step that improved specificity and drug tolerance, demonstrating that measurement of pre-existing or treatment emergent ADAs was highly dependent on assay format. The Sample Pre-treatment Electrochemiluminescence (ECL; SPECL) assay incorporates a protein A extraction of serum samples before a bridging assay is performed on an ECL platform. The assay is qualitative, sensitive (lower limit of quantification <39 ng/mL) and has a drug tolerance of 0.5 mg/mL in line with U.S. Food and Drug Administration requirements for clinical immunogenicity assays for therapeutic proteins. Importantly, the SPECL assay demonstrated the absence of antibodies to both apoA-I and CSL112 both prior to drug exposure and after repeated dosing across multiple trials (n = 970 subjects). The SPECL method has been validated and applied to support the CSL112 preclinical and clinical development program and has broader application to similar protein therapeutics. Attributes of the methodology include high drug tolerance, high sensitivity, selectivity, and precision. This format is amenable to automation providing the high throughput and reduced variability required to support large scale clinical studies that span extended time periods.
    Keywords Food and Drug Administration ; antibodies ; apolipoprotein A-I ; automation ; blood serum ; drug resistance ; electrochemiluminescence ; humans ; immunogenicity ; immunoglobulins ; myocardial infarction ; risk ; therapeutics ; Anti-drug antibodies ; Biotherapeutics ; CSL112 ; Sample pre-treatment electrochemiluminescence ; ADA ; AMI ; apoA-I ; CKD ; ECL ; ELISA ; EMA ; FDA ; HPC ; IgG ; IV ; LPC ; MAD ; MPC ; NC ; NHS ; PD ; PK ; RU ; SPECL
    Language English
    Dates of publication 2023-02
    Publishing place Elsevier B.V.
    Document type Article ; Online
    Note Use and reproduction
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2022.113411
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    Zs.A 795: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Vascular Aging Is Accelerated in Hematological Cancer Survivors Who Undergo Allogeneic Stem Cell Transplant.

    Climie, Rachel E / Dillon, Hayley T / Horne-Okano, Yuki / Wallace, Imogen / Avery, Sharon / Kingwell, Bronwyn A / La Gerche, Andre / Howden, Erin J

    Hypertension (Dallas, Tex. : 1979)

    2023  Volume 80, Issue 9, Page(s) 1881–1889

    Abstract: Background: Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the ... ...

    Abstract Background: Survivors of allogeneic stem cell transplant (SCT) receive intensive cancer treatments that are associated with cardiovascular dysfunction. Markers of vascular age can indicate early signs of adverse (cardio)vascular changes; however, the impact of SCT on these makers is unknown. We aimed to determine the short (3 months) and longer-term (≥2 years) effect of SCT on markers of vascular age in hematologic cancer survivors compared with an age-matched noncancer control group.
    Methods: The short-term effects of SCT, markers of vascular age (aortic compliance, arterial elastance, and ventricular-vascular coupling) were assessed via cardiac magnetic resonance imaging (cardiac and aortic volumes) before and ≈3 months post-SCT in 13 short-term survivors and compared with 11 controls. The longer-term impact was assessed by comparing 14 long-term survivors (6.5 [2-20] years post-SCT) to the short-term survivors (post-SCT) and controls (n=16).
    Results: The groups were similar for age and body mass index. In the short-term survivors, no significant group-by-time interactions were observed for any markers of vascular aging from pretransplant to posttransplant (net difference for change in compliance between groups -0.07 [95% CI, -1.49 to 1.35]). For the time-course analysis, aortic compliance was significantly lower in both SCT groups (overall
    Conclusion: This study provides evidence of an accelerated vascular aging phenotype in allogeneic SCT survivors and provides insight into the increased burden of cardiovascular disease among hematologic cancer survivors.
    MeSH term(s) Humans ; Stem Cell Transplantation/adverse effects ; Hematologic Neoplasms/complications ; Hematologic Neoplasms/therapy ; Survivors ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Aging
    Language English
    Publishing date 2023-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.123.21115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1488: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Reply: High Pulse Pressure: Complex PCI or Complex Patients?

    Warren, Josephine / Kingwell, Bronwyn A / Duffy, Stephen J

    Journal of the American College of Cardiology

    2019  Volume 74, Issue 15, Page(s) 2012–2013

    MeSH term(s) Angioplasty, Balloon, Coronary ; Blood Pressure ; Coronary Artery Disease ; Humans ; Percutaneous Coronary Intervention
    Language English
    Publishing date 2019-09-28
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 605507-2
    ISSN 1558-3597 ; 0735-1097
    ISSN (online) 1558-3597
    ISSN 0735-1097
    DOI 10.1016/j.jacc.2019.08.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1846: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 196: Show issues

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  7. Article ; Online: Building an Academic-Industry Partnership to Tackle Australia's Biggest Health Burden.

    Climie, Rachel E / Kingwell, Bronwyn A / Figtree, Gemma A

    Heart, lung & circulation

    2019  Volume 28, Issue 8, Page(s) 1144–1147

    Abstract: Cardiovascular disease (CVD) poses a highly significant health and economic burden in Australia and worldwide, with the latest global burden of disease study identifying cardiovascular disease as an "expanding threat to global health" [1]. Australian ... ...

    Abstract Cardiovascular disease (CVD) poses a highly significant health and economic burden in Australia and worldwide, with the latest global burden of disease study identifying cardiovascular disease as an "expanding threat to global health" [1]. Australian cardiovascular researchers are recognised internationally for their broad expertise spanning from fundamental molecular and cellular biology, through innovative bioengineering approaches, patient-focussed clinical trials, and impactful community interventions for improved public health. However, funding challenges have resulted in a fragmented research sector struggling to survive, let alone work together as an effective national team with strategic leadership and collaboration. The Australian Cardiovascular Alliance have successfully advocated for a federally supported Mission for Cardiovascular Helath ($220 Million). A key element of success in their goal of enhancing the CV health of Austrlaians, is partnering with industry.
    MeSH term(s) Australia/epidemiology ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/therapy ; Global Health ; Health Policy ; Humans
    Language English
    Publishing date 2019-06-21
    Publishing country Australia
    Document type Editorial
    ZDB-ID 2020980-0
    ISSN 1444-2892 ; 1443-9506
    ISSN (online) 1444-2892
    ISSN 1443-9506
    DOI 10.1016/j.hlc.2019.05.174
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    Zs.A 4988: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Blood Pressure Down Under, but Down Under What? US and Australian Hypertension Guideline Conversation.

    Hoare, Erin / Kingwell, Bronwyn A / Jennings, Garry L R

    Hypertension (Dallas, Tex. : 1979)

    2018  Volume 71, Issue 6, Page(s) 972–975

    MeSH term(s) Adult ; American Heart Association ; Australia ; Blood Pressure ; Humans ; Hypertension ; Proliferating Cell Nuclear Antigen ; United States
    Chemical Substances Proliferating Cell Nuclear Antigen
    Language English
    Publishing date 2018-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.118.11026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1488: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Potential implications of the new American hypertension guidelines in Australia.

    Jennings, Garry Lr / Kingwell, Bronwyn A / Hoare, Erin

    The Medical journal of Australia

    2018  Volume 209, Issue 3, Page(s) 108–109

    MeSH term(s) Antihypertensive Agents/therapeutic use ; Australia ; Humans ; Hypertension/drug therapy ; Practice Guidelines as Topic ; United States
    Chemical Substances Antihypertensive Agents
    Language English
    Publishing date 2018-08-02
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 186082-3
    ISSN 1326-5377 ; 0025-729X
    ISSN (online) 1326-5377
    ISSN 0025-729X
    DOI 10.5694/mja18.00104
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    Ua VI Zs.398: Show issues Location:
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  10. Article ; Online: Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity.

    Kingwell, Bronwyn A / Nicholls, Stephen J / Velkoska, Elena / Didichenko, Svetlana A / Duffy, Danielle / Korjian, Serge / Gibson, C Michael

    Journal of the American Heart Association

    2022  Volume 11, Issue 8, Page(s) e024754

    Abstract: Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic ... ...

    Abstract Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90-day post-AMI high-risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A-I, which is rapidly lipidated to form high-density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma-derived apolipoprotein A-I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti-inflammatory/immune-regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high-risk early post-AMI period.
    MeSH term(s) Apolipoprotein A-I ; Cholesterol/metabolism ; Humans ; Lipoproteins, HDL/therapeutic use ; Myocardial Infarction/drug therapy ; Plaque, Atherosclerotic/drug therapy
    Chemical Substances Apolipoprotein A-I ; CSL112 ; Lipoproteins, HDL ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-04-12
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2653953-6
    ISSN 2047-9980 ; 2047-9980
    ISSN (online) 2047-9980
    ISSN 2047-9980
    DOI 10.1161/JAHA.121.024754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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