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Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase-containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis.
This article was published in the following journal.
Name: Inflammatory bowel diseases
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Hypoxia inducible factor (HIF) is identified to be a promising target to mediate the response to hypoxia. Its stability and activation are negatively controlled by prolyl hydroxylase 2 (PHD2). Thus, P...
The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of disease states including anemia. One PHD inhibitor is approved for use in the...
Erythropoietin (EPO) production in the kidney is regulated by the oxygen-sensing transcription factor HIF-1α, which is degraded under normoxic conditions by HIF-prolyl hydroxylase (HIF-PHD). Inhibiti...
Previous studies have suggested that the functions of prolyl hydroxylase 3 (PHD3) in tumor growth, apoptosis and angiogenesis are essentially dependent on hypoxia-inducible factor (HIF)-1α signaling....
Patients with the chronic bowel disease pouchitis is disabled by bloody diarrhoea and abdominal pain often followed by fever. Pouchitis is an inflammation in a pouch, a reservoir formed by...
A Phase III, multi-centre, double-blind randomised controlled trial in subjects with chronic antibiotic refractory pouchitis. Subjects will undertake a
To evaluate the efficacy and safety of ustekinumab in the treatment of chronic antibiotic refractory and relapsing pouchitis.
This is a randomized double-blind placebo controlled trial involving a single centre (McMaster University) recruiting patients from Hamilton, ON and the surrounding regions, to evaluate wh...
The aim of our study is to investigate the efficacy and safety of fecal transplantation in the treatment of antibiotic dependent chronic pouchitis. This is a double-blinded randomized plac...
Compounds that inhibit the action of HYDROXYLASES that act on PROLINE to form HYDROXYPROLINE.
A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.
A group of inherited disorders of the ADRENAL GLANDS, caused by enzyme defects in the synthesis of cortisol (HYDROCORTISONE) and/or ALDOSTERONE leading to accumulation of precursors for ANDROGENS. Depending on the hormone imbalance, congenital adrenal hyperplasia can be classified as salt-wasting, hypertensive, virilizing, or feminizing. The most common defect is in STEROID 21-HYDROXYLASE. Other defects occur in STEROID 11-BETA-HYDROXYLASE; STEROID 17-ALPHA-HYDROXYLASE; or 3-beta-hydroxysteroid dehydrogenase (3-HYDROXYSTEROID DEHYDROGENASES).
A steroid hydroxylase that functions in CHOLESTEROL homeostasis in the brain. It converts cholesterol into 24S-hydroxycholesterol, which is transported over the BLOOD-BRAIN BARRIER more rapidly than unmetabolized cholesterol.
Acute INFLAMMATION in the INTESTINAL MUCOSA of the continent ileal reservoir (or pouch) in patients who have undergone ILEOSTOMY and restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...