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Article ; Online: The authors reply.

Gryp, Tessa / Vanholder, Raymond / Glorieux, Griet

2020 Volume 98, Issue 3, Page(s) 784

MeSH term(s)	Gastrointestinal Microbiome ; Humans ; Renal Insufficiency, Chronic ; Toxins, Biological
Chemical Substances	Toxins, Biological
Language	English
Publishing date	2020-08-14
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2020.05.019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease.

Glorieux, Griet / Gryp, Tessa / Perna, Alessandra

Toxins

2020 Volume 12, Issue 4

Abstract: Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. ... ...

Abstract	Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H
MeSH term(s)	Animals ; Bacteria/metabolism ; Bacterial Toxins/blood ; Bacterial Toxins/immunology ; Bacterial Toxins/metabolism ; Colon/immunology ; Colon/metabolism ; Colon/microbiology ; Dysbiosis ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammation Mediators/blood ; Intestinal Absorption ; Permeability ; Renal Insufficiency, Chronic/blood ; Renal Insufficiency, Chronic/immunology ; Renal Insufficiency, Chronic/microbiology ; Uremia/blood ; Uremia/immunology ; Uremia/microbiology
Chemical Substances	Bacterial Toxins ; Inflammation Mediators
Language	English
Publishing date	2020-04-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins12040245
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gut-Derived Metabolites and Their Role in Immune Dysfunction in Chronic Kidney Disease

Griet Glorieux / Tessa Gryp / Alessandra Perna

Toxins, Vol 12, Iss 245, p

2020 Volume 245

Abstract	Several of the uremic toxins, which are difficult to remove by dialysis, originate from the gut bacterial metabolism. This opens opportunities for novel targets trying to decrease circulating levels of these toxins and their pathophysiological effects. The current review focuses on immunomodulatory effects of these toxins both at their side of origin and in the circulation. In the gut end products of the bacterial metabolism such as p-cresol, trimethylamine and H 2 S affect the intestinal barrier structure and function while in the circulation the related uremic toxins stimulate cells of the immune system. Both conditions contribute to the pro-inflammatory status of patients with chronic kidney disease (CKD). Generation and/or absorption of these toxin precursors could be targeted to decrease plasma levels of their respective uremic toxins and to reduce micro-inflammation in CKD.
Keywords	uremic toxins ; gut ; chronic kidney disease ; immune ; Medicine ; R
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Isolation and Quantification of Uremic Toxin Precursor-Generating Gut Bacteria in Chronic Kidney Disease Patients.

Gryp, Tessa / Huys, Geert R B / Joossens, Marie / Van Biesen, Wim / Glorieux, Griet / Vaneechoutte, Mario

International journal of molecular sciences

2020 Volume 21, Issue 6

Abstract: In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), ...

Abstract	In chronic kidney disease (CKD), impaired kidney function results in accumulation of uremic toxins, which exert deleterious biological effects and contribute to inflammation and cardiovascular morbidity and mortality. Protein-bound uremic toxins (PBUTs), such as
MeSH term(s)	Amino Acids, Aromatic/metabolism ; Bacteria/classification ; Bacteria/isolation & purification ; Bacteria/metabolism ; Cresols/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Indican/metabolism ; Indoleacetic Acids/metabolism ; Renal Insufficiency, Chronic/pathology ; Sulfuric Acid Esters/metabolism ; Toxins, Biological/metabolism
Chemical Substances	Amino Acids, Aromatic ; Cresols ; Indoleacetic Acids ; Sulfuric Acid Esters ; Toxins, Biological ; 4-cresol sulfate (56M34ZQY1S) ; indoleacetic acid (6U1S09C61L) ; Indican (N187WK1Y1J)
Language	English
Publishing date	2020-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21061986
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: p-Cresyl Sulfate.

Gryp, Tessa / Vanholder, Raymond / Vaneechoutte, Mario / Glorieux, Griet

Toxins

2017 Volume 9, Issue 2

Abstract: If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. ...

Abstract	If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins.
MeSH term(s)	Animals ; Bacteria/metabolism ; Colon/microbiology ; Cresols/adverse effects ; Cresols/metabolism ; Dietary Proteins/metabolism ; Dysbiosis ; Fermentation ; Gastrointestinal Microbiome ; Humans ; Kidney/drug effects ; Kidney/metabolism ; Kidney/physiopathology ; Prognosis ; Protein Binding ; Renal Insufficiency, Chronic/chemically induced ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology ; Renal Insufficiency, Chronic/therapy ; Renal Replacement Therapy ; Risk Factors ; Sulfuric Acid Esters/adverse effects ; Sulfuric Acid Esters/metabolism
Chemical Substances	Cresols ; Dietary Proteins ; Sulfuric Acid Esters ; 4-cresol sulfate (56M34ZQY1S)
Language	English
Publishing date	2017-01-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins9020052
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Article ; Online: Urea and chronic kidney disease: the comeback of the century? (in uraemia research).

Vanholder, Raymond / Gryp, Tessa / Glorieux, Griet

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

2017 Volume 33, Issue 1, Page(s) 4–12

Abstract: Urea, a marker of uraemic retention in chronic kidney disease (CKD) and of adequacy of intradialytic solute removal, has traditionally been considered to be biologically inert. However, a number of recent experimental data suggest that urea is toxic at ... ...

Abstract	Urea, a marker of uraemic retention in chronic kidney disease (CKD) and of adequacy of intradialytic solute removal, has traditionally been considered to be biologically inert. However, a number of recent experimental data suggest that urea is toxic at concentrations representative for CKD. First of all, at least five studies indicate that urea itself induces molecular changes related to insulin resistance, free radical production, apoptosis and disruption of the protective intestinal barrier. Second, urea is at the origin of the generation of cyanate, ammonia and carbamylated compounds, which as such all have been linked to biological changes. Especially carbamylation has been held responsible for post-translational protein modifications that are involved in atherogenesis and other functional changes. In observational clinical studies, these carbamylated compounds were associated with cardiovascular and overall morbidity and mortality. These findings shed new light on the validity of Kt/Vurea as a marker of dialysis adequacy. Yet, also the views that the kinetics of urea are not representative of the kinetics of several other uraemic retention solutes, and that urea cannot be held responsible for all complex metabolic and clinical changes responsible for the uraemic syndrome, still remain valid. Future efforts to improve the outcome of patients with CKD might be directed at further improving removal of solutes implied in the uraemic syndrome, including but not restricted to urea, also taking into account the impact of the intestine and (residual) renal function on solute concentration.
MeSH term(s)	Biomarkers/metabolism ; Humans ; Kinetics ; Renal Dialysis ; Renal Insufficiency, Chronic/physiopathology ; Urea/metabolism ; Uremia/metabolism ; Uremia/pathology
Chemical Substances	Biomarkers ; Urea (8W8T17847W)
Language	English
Publishing date	2017-04-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	90594-x
ISSN	1460-2385 ; 0931-0509
ISSN (online)	1460-2385
ISSN	0931-0509
DOI	10.1093/ndt/gfx039
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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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Article ; Online: Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease.

Steenbeke, Mieke / Valkenburg, Sophie / Gryp, Tessa / Van Biesen, Wim / Delanghe, Joris R / Speeckaert, Marijn M / Glorieux, Griet

Toxins

2021 Volume 13, Issue 11

Abstract: Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, ... ...

Abstract	Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (
MeSH term(s)	Butyric Acid/metabolism ; Cohort Studies ; Dysbiosis/etiology ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Indoleacetic Acids/metabolism ; Renal Insufficiency, Chronic/microbiology ; Renal Insufficiency, Chronic/physiopathology ; Uremic Toxins/metabolism
Chemical Substances	Indoleacetic Acids ; Uremic Toxins ; Butyric Acid (107-92-6) ; indoleacetic acid (6U1S09C61L)
Language	English
Publishing date	2021-11-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins13110809
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: p-Cresyl Sulfate

Tessa Gryp / Raymond Vanholder / Mario Vaneechoutte / Griet Glorieux

Toxins, Vol 9, Iss 2, p

2017 Volume 52

Abstract	If chronic kidney disease (CKD) is associated with an impairment of kidney function, several uremic solutes are retained. Some of these exert toxic effects, which are called uremic toxins. p-Cresyl sulfate (pCS) is a prototype protein-bound uremic toxin to which many biological and biochemical (toxic) effects have been attributed. In addition, increased levels of pCS have been associated with worsening outcomes in CKD patients. pCS finds its origin in the intestine where gut bacteria metabolize aromatic amino acids, such as tyrosine and phenylalanine, leading to phenolic end products, of which pCS is one of the components. In this review we summarize the biological effects of pCS and its metabolic origin in the intestine. It appears that, according to in vitro studies, the intestinal bacteria generating phenolic compounds mainly belong to the families Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Eubacteriaceae, Fusobacteriaceae, Lachnospiraceae, Lactobacillaceae, Porphyromonadaceae, Staphylococcaceae, Ruminococcaceae, and Veillonellaceae. Since pCS remains difficult to remove by dialysis, the gut microbiota could be a future target to decrease pCS levels and its toxicity, even at earlier stages of CKD, aiming at slowing down the progression of the disease and decreasing the cardiovascular burden.
Keywords	p-cresyl sulfate ; intestinal microbiota ; chronic kidney disease ; Medicine ; R
Subject code	610
Language	English
Publishing date	2017-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of procedures for RNA-extraction from peripheral blood mononuclear cells.

Rodríguez, Antonio / Duyvejonck, Hans / Van Belleghem, Jonas D / Gryp, Tessa / Van Simaey, Leen / Vermeulen, Stefan / Van Mechelen, Els / Vaneechoutte, Mario

PloS one

2020 Volume 15, Issue 2, Page(s) e0229423

Abstract: RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Thus far, only a limited number of methodological studies have compared sample storage and RNA extraction ... ...

Abstract	RNA quality and quantity are important factors for ensuring the accuracy of gene expression analysis and other RNA-based downstream applications. Thus far, only a limited number of methodological studies have compared sample storage and RNA extraction procedures for human cells. We compared three commercially available RNA extraction kits, i.e., (NucliSENS) easyMAG, RNeasy (Mini Kit) and RiboPure (RNA Purification Kit-blood). In addition, additional conditions, such as storage medium and storage temperature of human peripheral blood mononuclear cells were evaluated, i.e., 4 °C for RNAlater or -80 °C for QIAzol and for the respective cognate lysis buffers; easyMAG, RNeasy or RiboPure. RNA was extracted from aliquots that had been stored for one day (Run 1) or 83 days (Run 2). After DNase treatment, quantity and quality of RNA were assessed by means of a NanoDrop spectrophotometer, 2100 Bioanalyzer and RT-qPCR for the ACTB reference gene. We observed that high-quality RNA can be obtained using RNeasy and RiboPure, regardless of the storage medium, whereas samples stored in RNAlater resulted in the least amount of RNA extracted. In addition, RiboPure combined with storage of samples in its cognate lysis buffer yielded twice as much RNA as all other procedures. These results were supported by RT-qPCR and by the reproducibility observed for two independent extraction runs.
MeSH term(s)	Actins/genetics ; Humans ; Leukocytes, Mononuclear/metabolism ; RNA/analysis ; RNA/genetics ; RNA/isolation & purification ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction/methods ; Real-Time Polymerase Chain Reaction/standards ; Reference Standards ; Reproducibility of Results ; Specimen Handling/methods
Chemical Substances	Actins ; Reagent Kits, Diagnostic ; RNA (63231-63-0)
Language	English
Publishing date	2020-02-21
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0229423
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

Mieke Steenbeke / Sophie Valkenburg / Tessa Gryp / Wim Van Biesen / Joris R. Delanghe / Marijn M. Speeckaert / Griet Glorieux

Toxins, Vol 13, Iss 809, p

2021 Volume 809

Abstract	Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD ( n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations ( r s = 0.212; p = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p -cresol correlate with its derived plasma UTs ( p -cresyl sulfate: r s = 0.342, p < 0.001; p -cresyl glucuronide: r s = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid ( r s = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR ( r s = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed.
Keywords	chronic kidney disease ; uremic toxins ; short-chain fatty acids (SCFAs) ; albumin symmetry factor ; fecal samples ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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