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  1. Article: Dimethyl Fumarate as Potential Treatment for Alzheimer's Disease: Rationale and Clinical Trial Design.

    Sharkus, Robert / Thakkar, Richa / Kolson, Dennis L / Constantinescu, Cris S

    Biomedicines

    2023  Volume 11, Issue 5

    Abstract: Alzheimer's Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, ... ...

    Abstract Alzheimer's Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, neuroinflammation and oxidative stress related to sustained microglial activation is thought to play a significant role in the disease process as well. NRF-2 has been identified in modulating the effects of inflammation and oxidative stress in AD. Activation of NRF-2 leads to an increased production of antioxidant enzymes, including heme oxygenase, which has been shown to have protective effects in neurodegenerative disorders such as AD. Dimethyl fumarate and diroximel fumarate (DMF) have been approved for the use in relapsing-remitting multiple sclerosis. Research indicates that they can modulate the effects of neuroinflammation and oxidative stress through the NRF-2 pathway, and as such, could serve as a potential therapeutic option in AD. We propose a clinical trial design that could be used to assess DMF as a treatment option for AD.
    Language English
    Publishing date 2023-05-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11051387
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Utilization of FDA approved treatments for neuromyelitis optica spectrum disorder in clinical practice: A survey study of academic neuroimmunologists.

    Thon, Jesse M / Sharkus, Robert / Thakkar, Richa / Hunter, Krystal / Siegler, James E / Thon, Olga R

    Multiple sclerosis and related disorders

    2023  Volume 80, Page(s) 105076

    Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition for which three treatments have been approved since 2019: eculizumab, inebilizumab, and satralizumab. We conducted a survey of U.S. academic neuroimmunologists to assess ... ...

    Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune condition for which three treatments have been approved since 2019: eculizumab, inebilizumab, and satralizumab. We conducted a survey of U.S. academic neuroimmunologists to assess adoption of these therapies and barriers to use. Thirty-three neuroimmunologists from 18 states completed the survey. Nearly all (88 %) reported using the novel NMOSD treatments (NNTs). They uncommonly switched clinically stable patients to NNTs (69 % switched none, 22 % switched 1-25 % of their patients). For newly diagnosed patients, NNT initiation rates varied. Following relapse, respondents were dichotomized, either switching 75-100 % of patients (60 %) or 0-25 % (40 %). Insurance and cost-related barriers were common.
    MeSH term(s) Humans ; Neuromyelitis Optica/drug therapy ; Autoimmune Diseases ; Cognition ; Rare Diseases ; Aquaporin 4
    Chemical Substances Aquaporin 4
    Language English
    Publishing date 2023-10-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2645330-7
    ISSN 2211-0356 ; 2211-0348
    ISSN (online) 2211-0356
    ISSN 2211-0348
    DOI 10.1016/j.msard.2023.105076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke.

    Kakadia, Bhavika / Thakkar, Richa / Sanborn, Emma / Suero-Abreu, Giselle Alexandra / Jovin, Tudor G / Then, Ryna

    Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

    2021  Volume 30, Issue 8, Page(s) 105883

    Abstract: Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with ... ...

    Abstract Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial.
    MeSH term(s) Antineoplastic Agents/adverse effects ; Functional Status ; Humans ; Infarction, Middle Cerebral Artery/diagnostic imaging ; Infarction, Middle Cerebral Artery/etiology ; Infarction, Middle Cerebral Artery/therapy ; Intracranial Arteriosclerosis/chemically induced ; Intracranial Arteriosclerosis/diagnostic imaging ; Intracranial Arteriosclerosis/therapy ; Ischemic Stroke/diagnostic imaging ; Ischemic Stroke/etiology ; Ischemic Stroke/therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Male ; Middle Aged ; Protein Kinase Inhibitors/adverse effects ; Pyrimidines/adverse effects ; Recovery of Function ; Risk Factors ; Treatment Outcome
    Chemical Substances Antineoplastic Agents ; Protein Kinase Inhibitors ; Pyrimidines ; nilotinib (F41401512X)
    Language English
    Publishing date 2021-06-02
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 1131675-5
    ISSN 1532-8511 ; 1052-3057
    ISSN (online) 1532-8511
    ISSN 1052-3057
    DOI 10.1016/j.jstrokecerebrovasdis.2021.105883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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