The variation of carnitine content in human blood cells during disease ? a study in bacterial infection and inflammatory bowel disease

1994 ◽  
Vol 153 (8) ◽  
pp. 565-568
Author(s):  
M. Demirkol ◽  
A. C. Sewell ◽  
H. B�hles
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bacterial Infection ◽  
Human Blood ◽  
Bowel Disease ◽  
Blood Cells ◽  
Human Blood Cells ◽  
Inflammatory Bowel

scholarly journals Carboxylesterase-1 assisted targeting of HDAC inhibitors to mononuclear myeloid cells in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Ahmed M I Elfiky ◽  
Mohammed Ghiboub ◽  
Andrew Y F Li Yim ◽  
Ishtu L Hageman ◽  
Jan Verhoeff ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Bowel Disease ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
Carboxylesterase 1 ◽  
T Cell Transfer

Abstract Background and Aims Histone deacetylase inhibitors (HDACi) exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif (ESM) technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 (CES1). This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease (IBD). Methods CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells and Crohn's disease (CD) colon mucosa by mass cytometry, quantitative PCR and immunofluorescence staining respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in DSS-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promotor. Results CES1 mRNA was highly expressed in human blood CD14 + monocytes, in vitro differentiated and LPS stimulated macrophages and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1 + cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1 high monocytes. In healthy donors peripheral blood, CES1 expression was significantly higher in CD14 ++CD16 - monocytes compared to CD14 +CD16 ++ monocytes. In CD inflamed colon, a higher number of mucosal CD68 + macrophages expressed CES1 compared to non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, whilst having limited potential in ameliorating DSS-induced colitis. Conclusions We demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

scholarly journals The Subpopulations of Circulating White Blood Cells in Inflammatory Bowel Disease

1976 ◽  
Vol 71 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Walter R. Thayer ◽  
Colette Charland ◽  
Cynthia E. Field
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Inflammatory Bowel

Azathioprine in the therapy of paediatric inflammatory bowel disease – part II: pharmacodynamics, pharmacokinetics, and the possibilities of measuring its metabolites in clinical practice

2021 ◽  
Vol 75 (6) ◽  
pp. 508-514
Author(s):  
Kristýna Pospíšilová ◽  
Jiří Bronský
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Blood Cells ◽  
Thiopurine Methyltransferase ◽  
Active Metabolites ◽  
Thioguanine Nucleotide ◽  
Inflammatory Bowel ◽  
Keywords Crohn's Disease ◽  
Hypoxanthine Guanine Phosphoribosyl Transferase

Summary Background: Thiopurines (predominantly azathioprine and mercaptopurine) are widely used in paediatrics to maintain remission in the treatment of inflammatory bowel disease. After its absorption from the gastrointestinal tract, azathioprine is converted into 6 mercaptopurine in approximately 90%. Several enzymes (such as thiopurine methyltransferase, xanthine oxidase and hypoxanthine-guanine phosphoribosyl transferase) participate in its further metabolism, producing non-active methylated metabolites (6 methylmercaptopurine) and thiouric acid and active 6-thioguanine nucleotide. The concentration of these metabolites can be measured in red blood cells. Aim: To map the benefits and possibilities of thiopurine metabolites measurements in patients suffering from inflammatory bowel disease. Conclusion: The measurement of active and non-active metabolites can help evaluate the bioavailability of those drugs, identify some causes of adverse effects and reveal non-adherence. Keywords Crohn’s disease, merkaptopurin, pediatrie, thiopuriny, ulcerative colitis

The Role of Bacterial Infection in the Pathogenesis of Inflammatory Bowel Disease

2004 ◽  
Vol 43 (7) ◽  
pp. 534-539 ◽  
Author(s):  
Toshifumi OHKUSA ◽  
Tetsuya NOMURA ◽  
Nobuhiro SATO
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bacterial Infection ◽  
Bowel Disease ◽  
Inflammatory Bowel
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