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  1. Article ; Online: The cholinergic anti-inflammatory pathway in chronic kidney disease-review and vagus nerve stimulation clinical pilot study.

    Hilderman, Marie / Bruchfeld, Annette

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2020  Volume 35, Issue 11, Page(s) 1840–1852

    Abstract: Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro- ... ...

    Abstract Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro-immune circuit that upholds the homoeostatic balance of inflammatory activity in response to cell injury and pathogens. CAP models have been examined in preclinical studies to investigate its significance in a range of clinical inflammatory conditions and diseases. More recently, cervical vagus nerve stimulation (VNS) implants have been shown to be of potential benefit for patients with chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. We have previously shown that dialysis patients have a functional CAP ex vivo. Here we review the field and the potential role of the CAP in acute kidney injury and chronic kidney disease (CKD) as well as in hypertension. We also present a VNS pilot study in haemodialysis patients. Controlling inflammation by neuroimmune modulation may lead to new therapeutic modalities for improved treatment, outcome, prognosis and quality of life for patients with CKD.
    MeSH term(s) Acute Kidney Injury/immunology ; Acute Kidney Injury/pathology ; Acute Kidney Injury/therapy ; Aged ; Aged, 80 and over ; Female ; Humans ; Hypertension/immunology ; Hypertension/pathology ; Hypertension/therapy ; Inflammation/immunology ; Inflammation/pathology ; Inflammation/therapy ; Male ; Middle Aged ; Neuroimmunomodulation ; Pilot Projects ; Quality of Life ; Renal Insufficiency, Chronic/immunology ; Renal Insufficiency, Chronic/pathology ; Renal Insufficiency, Chronic/therapy ; Vagus Nerve Stimulation/methods
    Language English
    Publishing date 2020-11-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfaa200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2198: 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)
    Zs.MO 329: Show issues

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  2. Article ; Online: The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation.

    Hilderman, Marie / Qureshi, Abdul Rashid / Abtahi, Farhad / Witt, Nils / Jägren, Christina / Olbers, Joakim / Delle, Martin / Lindecrantz, Kaj / Bruchfeld, Annette

    Molecular medicine (Cambridge, Mass.)

    2019  Volume 25, Issue 1, Page(s) 39

    Abstract: Background: Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits ... ...

    Abstract Background: Renal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF.
    Methods: Ten patients treated with RDN (Medtronic Inc), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC).
    Results: Baseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up.
    Conclusion: RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.
    MeSH term(s) Aged ; Blood Pressure/physiology ; Cytokines/analysis ; Cytokines/metabolism ; Denervation/methods ; Female ; Humans ; Hypertension/surgery ; Inflammation/metabolism ; Kidney/innervation ; Male ; Middle Aged ; Neuroimmunomodulation/physiology
    Chemical Substances Cytokines
    Language English
    Publishing date 2019-08-15
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1283676-x
    ISSN 1528-3658 ; 1076-1551
    ISSN (online) 1528-3658
    ISSN 1076-1551
    DOI 10.1186/s10020-019-0097-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4456: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Rituximab for minimal change disease in adults: long-term follow-up.

    Bruchfeld, Annette / Benedek, Samiha / Hilderman, Marie / Medin, Charlotte / Snaedal-Jonsdottir, Sunna / Korkeila, Maarit

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2013  Volume 29, Issue 4, Page(s) 851–856

    Abstract: Background: Minimal change nephropathy or disease (MCD) accounts for 10-15% of cases of the nephrotic syndrome in adults with frequent relapses occurring in up to 25% of cases. The drug of choice is glucocorticoids (GCs), but GC-dependence is seen in 25- ...

    Abstract Background: Minimal change nephropathy or disease (MCD) accounts for 10-15% of cases of the nephrotic syndrome in adults with frequent relapses occurring in up to 25% of cases. The drug of choice is glucocorticoids (GCs), but GC-dependence is seen in 25-30%. Treatment with rituximab has been found to be effective in relapsing and GC-dependent cases, but little data are available regarding long-term outcome in adults.
    Patients: We present nine female and seven male patients, ranging from 19 to 73 years of age with multirelapsing, GC-dependent or GC-resistant disease with a kidney biopsy consistent with MCD. Twelve patients were steroid-dependent with a lowest daily GC dose between 5 and 20 mg/day.
    Treatment and outcomes: Rituximab with a total dose 1000-2800 mg divided in two to four doses was given together with GC achieving B-cell depletion before the second dose. No major side-effects occurred. Thirteen of the patients responded with complete remission enabling discontinuation or tapering of GC significantly below levels, where relapses had occurred in the past (P < 0.001). Two patients reached partial remission and one had no response to therapy. Follow-up was 12-70 months (median 44). Eight patients have remained in remission, whereas relapses occurred in seven patients after 9-28 months with repeated rituximab treatment in four of these.
    Conclusions: Our study reinforces the role of rituximab as a GC-sparing agent in the challenging GC-dependent and multirelapsing MCD patients. In this emerging therapeutic field randomized studies with extended follow-up will add important information regarding optimal treatment, relapse and safety.
    MeSH term(s) Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/administration & dosage ; Antigens, CD20 ; Biopsy ; Chronic Disease ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glucocorticoids/administration & dosage ; Humans ; Immunologic Factors/administration & dosage ; Injections, Intravenous ; Kidney/pathology ; Male ; Middle Aged ; Nephrosis, Lipoid/drug therapy ; Nephrosis, Lipoid/pathology ; Recurrence ; Remission Induction ; Rituximab ; Time Factors ; Treatment Outcome ; Young Adult
    Chemical Substances Antibodies, Monoclonal, Murine-Derived ; Antigens, CD20 ; Glucocorticoids ; Immunologic Factors ; Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2013-10-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gft312
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2198: 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)
    Zs.MO 329: Show issues

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  4. Article: Cholinergic anti-inflammatory pathway activity in dialysis patients: a role for neuroimmunomodulation?

    Hilderman, Marie / Qureshi, Abdul R / Al-Abed, Yousef / Abtahi, Farhad / Lindecrantz, Kaj / Anderstam, Björn / Bruchfeld, Annette

    Clinical kidney journal

    2015  Volume 8, Issue 5, Page(s) 599–605

    Abstract: Background: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and ... ...

    Abstract Background: The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through the vagus nerve and the α-7-nicotinic acetylcholine receptor (α7nAChR) on macrophages and immune cells. Sympathetic/parasympathetic imbalance and chronic inflammation are both linked to poor outcome in dialysis patients. The aim of this study was to investigate CAP activity in these patients.
    Methods: Twenty dialysis patients, 12 hemodialysis (HD) and 8 peritoneal dialysis (PD) patients (12 male, 8 female; age range 47-83 years) and 8 controls (5 male, 3 female; age range 31-52 years) were analyzed for C-reactive protein (CRP), tumor necrosis factor (TNF), interleukin-1b (IL-1b), IL-6 and IL-10 at baseline. The cytokines were then assessed after whole blood stimulation ex vivo with lipopolysaccharide (LPS) (10 and 100 ng/mL) and again in the presence of 45 and 90 μmol/L GTS-21, a cholinergic α7nAChR agonist.
    Results: CRP, TNF, IL-1 and IL-6 were significantly higher, whereas IL-10 was significantly lower at baseline in patients compared with controls. After LPS stimulation, TNF increased significantly more in patients than in controls but decreased to similar levels in both groups after addition of GTS-21. IL-6 attenuation was comparable with TNF and the IL-1b pattern was similar but remained significantly higher in patients. Interestingly, IL-10 increased after GTS-21 in a dose-dependent manner, but only in patients. Results in HD and PD patients did not differ.
    Conclusions: The response of immune cells after LPS exposure and cholinergic stimulation suggests a functional CAP in dialysis patients. It may thus be possible to target the α7nAChR control of cytokine release as an anti-inflammatory strategy and thereby improve outcome in these patients.
    Language English
    Publishing date 2015-08-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2655800-2
    ISSN 2048-8513 ; 2048-8505
    ISSN (online) 2048-8513
    ISSN 2048-8505
    DOI 10.1093/ckj/sfv074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6587: Show issues Location:
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  5. Article ; Online: Rituximab for multirelapsing, steroid-dependent or steroid-resistant, minimal-change nephropathy – a report of nine adult cases

    Maarit Korkeila / Charlotte Medin / Marie Hilderman / Samiha Benedek / Annette Bruchfeld

    Nephrology Reviews, Vol 2, Iss 1, Pp e2-e

    2010  Volume 2

    Abstract: Minimal-change nephropathy (MCN) accounts for 10-15% of cases of the nephrotic syndrome in adults. Frequent relapses occur in 10-25% of cases and steroid dependence is seen in 25-30%. Rituximab is a chimeric mono-clonal antibody directed against CD20- ... ...

    Abstract Minimal-change nephropathy (MCN) accounts for 10-15% of cases of the nephrotic syndrome in adults. Frequent relapses occur in 10-25% of cases and steroid dependence is seen in 25-30%. Rituximab is a chimeric mono-clonal antibody directed against CD20-positive B-cells with reported benefit in immune-mediated renal disease. We present six female and three male patients, ranging from 27-70 years of age, with multirelapsing, steroid-dependant or steroid-resistant MCN, with previous multiple courses of cortico-steroids (CS) and second-line therapies. Five patients were steroid dependant with the lowest daily CS dose between 5-20 mg/day. All patients were given two doses of rituximab, each a flat dose of 500 mg except for one case who received a dose of 1000 mg. All patients were B-cell depleted before the second dose. No major side effects occurred. Seven of the patients responded to therapy with normalized plasma albumin and no albuminuria enabling discontinuation or tapering of CS significantly below levels where relapses had occurred in the past (P=0.03). One patient reached partial remission and another had no response to therapy. Follow-up was 6-33 months. There were three relapses after 9, 12, and 20 months, respectively. In conclusion, frequency of relapses and steroid dependency or resistance in MCN remain therapeutic challenges to physicians. The current case series suggests that B-cell depletion may induce long-lasting remissions and, as a result, has a potential as a steroid-sparing agent in the treatment of steroid-dependent and multirelapsing MCN patients.
    Keywords Diseases of the genitourinary system. Urology ; RC870-923 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Urology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Publishing date 2010-11-01T00:00:00Z
    Publisher PAGEPress Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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