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  1. Book ; Online: Impact of maternal high fat on neurovascular unit of adult offspring

    Hawkes, Cheryl A. / Goss, Victoria / Zotova, Elina / Monfort, Tual / Postle, Anthony / Mahajan, Sumeet / Nicoll, James A. R. / Weller, Roy O. / Carare, Roxana O.

    2024  

    Abstract: Maternal obesity is associated with increased risk of diabetes, cardiovascular disease and hypertension in adult offspring. Midlife hypercholesterolemia and hypertension are risk factors for Alzheimer's disease, suggesting that the ageing brain may be ... ...

    Abstract Maternal obesity is associated with increased risk of diabetes, cardiovascular disease and hypertension in adult offspring. Midlife hypercholesterolemia and hypertension are risk factors for Alzheimer's disease, suggesting that the ageing brain may be impacted by early life environment. We found that exposure to a high fat diet during gestation and lactation induced changes in multiple components of the neurovascular unit, including a downregulation in apolipoprotein E and fibronectin, an upregulation in markers of astrocytes and perivascular macrophages and altered blood vessel morphology in the brains of adult mice. Feeding of high fat diet after weaning increased lipid droplets in the brain and influenced the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine species, but did not affect the neurovascular unit. Sustained high fat diet over the entire lifespan resulted in additional decreases in levels of pericytes and collagen IV, changes in phospholipid composition and impaired perivascular clearance of Beta-amyloid (A-Beta) from the brain. In humans, vascular A-Beta load was significantly increased in the brains of aged individuals with a history of hypercholesterolemia. These results support a critical role for early dietary influence on the brain vasculature across the lifespan, with consequences for the development of age-related cerebrovascular and neurodegenerative diseases.

    Comment: 45 pages, 7 figures
    Keywords Quantitative Biology - Tissues and Organs ; 14J60 ; F.2.2
    Subject code 610
    Publishing date 2024-01-09
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Proinflammatory cytokines and the clinical features of dementia with lewy bodies.

    Clough, Zoe / Jeyapaul, Prem / Zotova, Elina / Holmes, Clive

    Alzheimer disease and associated disorders

    2015  Volume 29, Issue 1, Page(s) 97–99

    MeSH term(s) Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Cytokines/blood ; Female ; Humans ; Inflammation Mediators/blood ; Lewy Body Disease/blood ; Lewy Body Disease/diagnosis ; Lewy Body Disease/psychology ; Male ; Retrospective Studies
    Chemical Substances Cytokines ; Inflammation Mediators
    Language English
    Publishing date 2015-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1002700-2
    ISSN 1546-4156 ; 0893-0341
    ISSN (online) 1546-4156
    ISSN 0893-0341
    DOI 10.1097/WAD.0b013e3182969905
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  3. Article: High-Throughput Urinary Neopterin-to-Creatinine Ratio Monitoring of Systemic Inflammation.

    Stuart, Charlotte M / Zotova, Elina / Koster, Grielof / Varatharaj, Aravinthan / Richardson, Grace / Cornick, Faye R / Weal, Mark / Newman, Tracey A / Postle, Anthony D / Galea, Ian

    The journal of applied laboratory medicine

    2019  Volume 5, Issue 1, Page(s) 101–113

    Abstract: Background: Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a nonspecific marker of systemic inflammation. Expression as urinary neopterin-to- ... ...

    Abstract Background: Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a nonspecific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status. Major attractions include (a) urine vs blood sampling, (b) integration of inflammation over a longer period compared with serum sampling, and (c) high stability of neopterin and creatinine.
    Methods: A high-throughput ultraperformance LC-MS method was developed to measure neopterin and creatinine together from the same urine sample. The assay was applied in several clinical scenarios: healthy controls, symptomatic infections, and multiple sclerosis. Area under the curve was compared between weekly and monthly sampling scenarios. Analysis of a single pooled sample was compared with averaging results from analysis of individual samples.
    Results: The assay has excellent intraassay and interassay precision, linearity of dilution, and spike and recovery. Higher UNCR was demonstrated in female vs male individuals, older age, inflammatory disease (multiple sclerosis), and symptomatic infections. In healthy controls, fluctuations in inflammatory state also occurred in the absence of symptomatic infection or other inflammatory triggers. Analysis of a single pooled sample, made up from weekly urine samples, integrates inflammatory activity over time.
    Conclusions: UNCR is a useful biomarker of systemic inflammation. The method presented offers simplicity, speed, robustness, reproducibility, efficiency, and proven utility in clinical scenarios. UNCR fluctuations underline the importance of longitudinal monitoring, vs a single time point, to capture a more representative estimate of an individual's inflammatory state over time.
    MeSH term(s) Aged ; Area Under Curve ; Biomarkers/urine ; Creatinine/urine ; Female ; Humans ; Infections/diagnosis ; Infections/urine ; Inflammation/urine ; Male ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/urine ; Neopterin/urine ; Prognosis ; Reproducibility of Results ; Treatment Outcome
    Chemical Substances Biomarkers ; Neopterin (670-65-5) ; Creatinine (AYI8EX34EU)
    Language English
    Publishing date 2019-11-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2576-9456
    ISSN 2576-9456
    DOI 10.1373/jalm.2019.030007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy.

    Zotova, Elina / Nicoll, James Ar / Kalaria, Raj / Holmes, Clive / Boche, Delphine

    Alzheimer's research & therapy

    2010  Volume 2, Issue 1, Page(s) 1

    Abstract: Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this ... ...

    Abstract Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this hypothesis, the inflammatory reaction is still considered to be a downstream effect of the accumulated proteins (amyloid beta (Abeta) and tau). This review aims to highlight the importance of the immune processes involved in AD pathogenesis based on the outcomes of the two major inflammation-relevant treatment strategies against AD developed and tested to date in animal studies and human clinical trials - the use of anti-inflammatory drugs and immunisation against Abeta.
    Language English
    Publishing date 2010-01-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/alzrt24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Inflammatory components in human Alzheimer's disease and after active amyloid-β42 immunization.

    Zotova, Elina / Bharambe, Viraj / Cheaveau, Matthew / Morgan, William / Holmes, Clive / Harris, Scott / Neal, James W / Love, Seth / Nicoll, James A R / Boche, Delphine

    Brain : a journal of neurology

    2013  Volume 136, Issue Pt 9, Page(s) 2677–2696

    Abstract: Inflammatory processes are important in the pathogenesis of Alzheimer's disease and in response to amyloid-β immunotherapy. We investigated the expression of multiple inflammatory markers in the brains of 28 non-immunized patients with Alzheimer's ... ...

    Abstract Inflammatory processes are important in the pathogenesis of Alzheimer's disease and in response to amyloid-β immunotherapy. We investigated the expression of multiple inflammatory markers in the brains of 28 non-immunized patients with Alzheimer's disease and 11 patients with Alzheimer's disease immunized against amyloid-β42 (AN1792): microglial ionized calcium-binding adaptor Iba-1, lysosome marker CD68, macrophage scavenger receptor A, Fcγ receptors I (CD64) and II (CD32); and also immunoglobulin IgG, complement C1q and the T lymphocyte marker CD3 using immunohistochemistry. The data were analysed with regard to amyloid-β and phospho-tau pathology, severity of cerebral amyloid angiopathy and cortical microhaemorrhages. In non-immunized Alzheimer's disease cases, amyloid-β42 correlated inversely with CD32 and Iba-1, whereas phospho-tau correlated directly with all microglial markers, IgG, C1q and the number of T cells. In immunized Alzheimer's disease cases, amyloid-β42 load correlated directly with macrophage scavenger receptor A-positive clusters and inversely with C1q. The severity of cerebral amyloid angiopathy and microhaemorrhages did not relate to any of the analysed markers. Overall, the levels of CD68, macrophage scavenger receptor A, CD64, CD32 and the number of macrophage scavenger receptor A-positive plaque-related clusters were significantly lower in immunized than non-immunized cases, although there was no significant difference in Iba-1 load, number of Iba-1-positive cells, IgG load, C1q load or number of T cells. Our findings indicate that different microglial populations co-exist in the Alzheimer's disease brain, and that the local inflammatory status within the grey matter is importantly linked with tau pathology. After amyloid-β immunization, the microglial functional state is altered in association with reduced amyloid-β and tau pathology. The results suggest that, in the long term, amyloid-β immunotherapy results in downregulation of microglial activation and potentially reduces the inflammation-mediated component of the neurodegeneration of Alzheimer's disease.
    MeSH term(s) Aged ; Aged, 80 and over ; Alzheimer Disease/immunology ; Alzheimer Disease/metabolism ; Alzheimer Disease/therapy ; Amyloid beta-Peptides/immunology ; Antigens, CD/metabolism ; Calcium-Binding Proteins ; Complement C1q/metabolism ; DNA-Binding Proteins/metabolism ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin G/metabolism ; Male ; Microfilament Proteins ; Middle Aged ; Peptide Fragments/immunology ; Receptors, Scavenger/metabolism ; Statistics, Nonparametric ; Vaccination/methods ; tau Proteins/metabolism
    Chemical Substances AIF1 protein, human ; Amyloid beta-Peptides ; Antigens, CD ; Calcium-Binding Proteins ; DNA-Binding Proteins ; Immunoglobulin G ; Microfilament Proteins ; Peptide Fragments ; Receptors, Scavenger ; amyloid beta-protein (1-42) ; tau Proteins ; Complement C1q (80295-33-6)
    Language English
    Publishing date 2013-08-13
    Publishing country England
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awt210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ui II Zs.26: Show issues Location:
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  6. Article ; Online: Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial.

    Holmes, Clive / Boche, Delphine / Wilkinson, David / Yadegarfar, Ghasem / Hopkins, Vivienne / Bayer, Anthony / Jones, Roy W / Bullock, Roger / Love, Seth / Neal, James W / Zotova, Elina / Nicoll, James A R

    Lancet (London, England)

    2008  Volume 372, Issue 9634, Page(s) 216–223

    Abstract: Background: Immunisation of patients with Alzheimer's disease with full-length amyloid-beta peptide (Abeta(42)) can clear amyloid plaques from the brain. Our aim was to assess the relation between Abeta(42) immune response, degree of plaque removal, and ...

    Abstract Background: Immunisation of patients with Alzheimer's disease with full-length amyloid-beta peptide (Abeta(42)) can clear amyloid plaques from the brain. Our aim was to assess the relation between Abeta(42) immune response, degree of plaque removal, and long-term clinical outcomes.
    Methods: In June, 2003, consent for long-term clinical follow-up, post-mortem neuropathological examination, or both, was sought from 80 patients (or their carers) who had entered a phase I randomised, placebo-controlled trial of immunisation with Abeta(42) (AN1792, Elan Pharmaceuticals) in September, 2000. The follow-up study was completed in September, 2006. Plaques were assessed in terms of the percentage area of the cortex with Abeta immunostaining (Abeta load) and in terms of characteristic histological features reflecting plaque removal. Survival of all 80 individuals until severe dementia or death was assessed with a Cox proportional hazard model.
    Findings: 20 participants--15 in the AN1792 group, five in the placebo group--died before follow-up started. A further 22 patients--19 in the AN1792 group, three in the placebo group--died during follow-up. Nine of the deceased patients, all in the AN1792 group, had given consent for post-mortem analysis; one of these who did not die with Alzheimer's disease was excluded. In the remaining eight participants who received immunisation and who were examined neuropathologically, mean Abeta load was lower than in an unimmunised control group that was matched for age at death (2.1% [SE 0.7] in treated participants vs 5.1% [0.9] in controls; mean difference 3.0%, 95% CI 0.6-5.4; p=0.02). Although there was considerable variation in Abeta load and degree of plaque removal among immunised participants, the degree of plaque removal varied significantly with mean antibody response attained during the treatment study period (Kruskal-Wallis p=0.02). Seven of the eight immunised patients who underwent post-mortem assessment, including those with virtually complete plaque removal, had severe end stage dementia before death. In the whole cohort, there was no evidence of improved survival (hazard ratio 0.93, 95% CI 0.43-3.11; p=0.86) or of an improvement in the time to severe dementia (1.18, 0.45-3.11; p=0.73) in the AN1792 group versus the placebo group.
    Interpretation: Although immunisation with Abeta(42) resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not prevent progressive neurodegeneration.
    MeSH term(s) Aged ; Alzheimer Disease/drug therapy ; Alzheimer Disease/immunology ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/immunology ; Antibody Formation ; Clinical Trials, Phase I as Topic ; Follow-Up Studies ; Humans ; Plaque, Amyloid/drug effects ; Plaque, Amyloid/immunology ; Plaque, Amyloid/pathology ; Randomized Controlled Trials as Topic
    Chemical Substances AN-1792 ; Amyloid beta-Peptides
    Language English
    Publishing date 2008-07-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(08)61075-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 94: Show issues

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  7. Book: Bălgarski bibliografski Institut (Elin Pelin)

    Zotova, Kremena N / Borov, T

    (Poredica otdelni trudove ; 10)

    1955  

    Institution Bălgarski bibliografski Institut
    Author's details [Kremena N. Zotova. T. Borov]
    Series title Poredica otdelni trudove ; 10
    Keywords Bulgarien ; Bibliographie ; Bibliographie der Bibliographien
    Language Bulgarian
    Size 93 S., 8°
    Document type Book
    Note [Das Bulgarisch Bibliographische Institut in den Jahren 1945-1955]
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