Thioguanine Therapy in Inflammatory Bowel Diseases. A Practical Guide

Crouwel, Femke; Simsek, Melek; Mulder, Chris J.; Buiter, Hans J C; Boer, Nanne K de

doi:10.15403/jgld-2765

Cited by 14 publications

(16 citation statements)

References 76 publications

(113 reference statements)

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“…6‐thioguanine, the third therapeutic formulation, bypasses the pathways mentioned above and can restore therapeutic efficacy in patients with ineffective metabolism. 5 …”

Section: Thiopurine Metabolismmentioning

confidence: 99%

“…Thioguanine is used in a dose of 20 mg/day (0.2–0.3 mg/kg/day). 5 Once a feared complication of 6‐TG use, nodular regenerative hyperplasia is not associated with the lower dose used for IBD. Regarding efficacy, in a systematic review, TG treatment after AZA/6‐MP failure showed clinical improvement in 65% of patients.…”

Section: Genetic Polymorphisms Impacting Thiopurine Metabolismmentioning

confidence: 99%

“…Hypoxanthine‐guanine phosphoribosyl‐transferase (HPRT) enzyme, through a series of enzymatic reactions, converts 6‐MP into active 6‐thioguanine nucleotides (6‐TGN) metabolites (6‐thioguanine triphopshate: 6‐TGTP and deoxy‐6‐thioguanine triphopshate: d′6‐TGTP), which are responsible for efficacy and myelosuppression. 6‐thioguanine, the third therapeutic formulation, bypasses the pathways mentioned above and can restore therapeutic efficacy in patients with ineffective metabolism 5 …”

Section: Thiopurine Metabolismmentioning

confidence: 99%

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Personalized medicine to implementation science: Thiopurines set for the leap

2022

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“…6‐thioguanine, the third therapeutic formulation, bypasses the pathways mentioned above and can restore therapeutic efficacy in patients with ineffective metabolism. 5 …”

Section: Thiopurine Metabolismmentioning

confidence: 99%

Section: Genetic Polymorphisms Impacting Thiopurine Metabolismmentioning

confidence: 99%

Section: Thiopurine Metabolismmentioning

confidence: 99%

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Personalized medicine to implementation science: Thiopurines set for the leap

2022

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“…Additionally, two nucleoside analogs, namely gemcitabine and 6-thioguanine, have a weak HDP-inducing activity as well. Both compounds work mainly by incorporating into DNA and RNA as fraudulent bases to cause termination of cellular synthesis of DNA/RNA and have been approved for treatment of cancers and inflammatory bowel diseases [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Identification of Epigenetic Compounds to Enhance Chicken Host Defense Peptide Gene Expression

2022

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Enhancing the synthesis of endogenous host defense peptides (HDPs) has emerged as a novel antibiotic-free approach to infectious disease control and prevention. A number of epigenetic compounds have been identified as HDP inducers and several have proved beneficial in antimicrobial therapy. However, species-specific regulation of HDP synthesis is evident. In attempt to identify epigenetic compounds with potent HDP-inducing activity for poultry-specific application, we developed a stable luciferase reporter cell line, known as HTC/AvBD10-luc, following our earlier construction of HTC/AvBD9-luc. HTC/AvBD10-luc was developed through permanent integration of a chicken macrophage cell line, HTC, with a lentiviral luciferase reporter vector driven by a 4-Kb AvBD10 gene promoter. Using a high throughput screening assay based on the two stable cell lines, we identified 33 hits, mostly being histone deacetylase (HDAC) inhibitors, from a library of 148 epigenetic compounds. Among them, entinostat and its structural analog, tucidinostat, were particularly effective in promoting multiple HDP gene expression in chicken macrophages and jejunal explants. Desirably, neither compounds triggered an inflammatory response. Moreover, oral gavage of entinostat significantly enhanced HDP gene expression in the chicken intestinal tract. Collectively, the high throughput assay proves to be effective in identifying HDP inducers, and both entinostat and tucidinostat could be potentially useful as alternatives to antibiotics to enhance intestinal immunity and disease resistance.

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“…Other out of fashion drugs such as purine can still be used. 45 Psychological alterations are managed by neuromodulators. Beside these drugs, surgical therapy can be considered in special cases.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Management of Inflammatory Bowel Disease: a Century of Expert Opinions in Cecil Textbook of Medicine

Manu

Rogozea

Dumitraşcu

2022

American Journal of Therapeutics

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Background: Advances in drug therapy for inflammatory bowel disease (IBD) [Crohn disease and ulcerative colitis (UC)] have contributed to a decrease in the severity of these chronic and disabling conditions.Study Question: What are the milestones of the changes in the expert approach to the pharmacological management of IBD in the past century?Study Design: To determine the changes in the experts' approach to the management of regional ileitis and UC, as presented in a widely used textbook in the United States. Data Sources: The chapters presenting the management of IBD in the 26 editions of Cecil Textbook of Medicine published from 1927 through 2020. Results: No specific interventions existed from 1927 through 1942. The pharmacological management of IBD has had 3 slightly overlapping eras starting in 1943. During the first period (1943)(1944)(1945)(1946)(1947)(1948)(1949)(1950)(1951), the medical management relied on antibiotics, primarily sulfonamides and chloramphenicol. In the second , experts recommended the use of adrenocorticotropic hormone or corticosteroids and 5-aminosalicylate. In the third era, which commenced in 1979 and is continuing to date, the pharmacological interventions have been expanded and refined to include 5 main drug classes, 5-aminosalicylates (sulfasalazine, mesalamine, and olsalazine), corticosteroids (prednisone and budesonide), immunomodulators (azathioprine, 6mercaptopurine, cyclosporine, and tofacitinib), biologics (infliximab adalimumab certolizumab pegol, and natalizumab), and antibiotics (metronidazole and ciprofloxacin). A consensus exists that the monoclonal antibodies again tumor necrosis factor alpha are cost-effective for induction and maintenance of clinical remission in both UC (golimumab) and Crohn disease (certolizumab pegol). The newer agents ustekinumab (a monoclonal antibody to the interleukin p40 subunit) and vedolizumab (a monoclonal antibody to the homing receptor integrin complex) have also performed well. Conclusions:The pharmacological management of IBD has been the focus of intense research and development in the past 60 years. The pillars of drug treatment have been 5-aminosalicylates and corticosteroids. Recent pharmacological innovations (immunomodulators and biologicals) constitute an encouraging paradigm shift in the treatment of UC and Crohn disease.

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Thioguanine Therapy in Inflammatory Bowel Diseases. A Practical Guide

Cited by 14 publications

References 76 publications

Personalized medicine to implementation science: Thiopurines set for the leap

Personalized medicine to implementation science: Thiopurines set for the leap

High-Throughput Identification of Epigenetic Compounds to Enhance Chicken Host Defense Peptide Gene Expression

Pharmacological Management of Inflammatory Bowel Disease: a Century of Expert Opinions in Cecil Textbook of Medicine

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