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Ceska a Slovenska Oftalmologie :... 2017IgG-4 related disease (IgG4-RD) is a recently discovered systemic fibro-inflammatory disease which affects the ocular system. This pathology is not limited only to the...
IgG-4 related disease (IgG4-RD) is a recently discovered systemic fibro-inflammatory disease which affects the ocular system. This pathology is not limited only to the orbit, but may also frequently affect the anatomical structures of the eye, as well as other organs. Suspicion of IgG4-RD is based on careful clinical, radiological and immuno-histological examination with a finding of characteristic histopathological changes. Increased values of serum IgG4 need not necessarily be an unequivocal diagnostic criterion for the diagnosis of IgG4-RD. Only a careful histological and immunophenotyping examination together with a clinical finding provide a basis for distinguishing IgG4-RD from other inflammatory pathologies. Corticoids are applied in the treatment of this disease, but they do not exclude the possibility of relapses of clinical manifestations. Second choice pharmaceuticals are azathioprine, mycophenolate mofetil, and the effect of treating relapse of the disease with rituximab is significant.Key words: IgG4 related disease, eye, diagnosis, treatment.
Topics: Azathioprine; Eye Diseases; Humans; Immunoglobulin G; Mycophenolic Acid; Orbit
PubMed: 29394077
DOI: No ID Found -
Scientific Reports Feb 2019Disruption of mucosal structure and barrier function contribute to the pathogenesis of inflammatory bowel disease (IBD). Efficacy of therapy in IBD is based on...
Disruption of mucosal structure and barrier function contribute to the pathogenesis of inflammatory bowel disease (IBD). Efficacy of therapy in IBD is based on endoscopic mucosal healing, which occurs by a dynamic interplay of epithelial cell regeneration, migration and differentiation. Both mesalamine (5-ASA) and azathioprine (AZTP) promote this process through mechanisms not clearly understood. We examined molecular pathways implicated in epithelial barrier function that were altered by 5-ASA and AZTP. Paracellular permeability induced by inflammatory mediators was mitigated by both compounds through restoration of cellular anchoring complexes. 5-ASA and AZTP induced rearrangement and membranous localization of junctional proteins and modulated genes involved in tight junctions. Intestinal organoids from wildtype-mice treated with TNF-α and IL-10- deficient-mice displayed impaired epithelial barrier with loss of membranous E-cadherin and reduced Desmoglein-2 expression. These effects were counteracted by 5-ASA and AZTP. Unlike AZTP that exhibited antiproliferative effects, 5-ASA promoted wound healing in colon epithelial cells. Both affected cellular senescence, cell cycle distribution and restricted cells in G1 or S phase without inducing apoptosis. This study provides mechanistic evidence that molecular actions of 5-ASA and AZTP on intestinal epithelia are fundamental in the resolution of barrier dysfunction.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Colitis; Epithelial Cells; Inflammation; Inflammatory Bowel Diseases; Intestines; Mesalamine; Mice; Wound Healing
PubMed: 30809073
DOI: 10.1038/s41598-019-39401-0 -
British Medical Journal Dec 1966
Topics: Azathioprine; Chemical Phenomena; Chemistry; Humans
PubMed: 5957425
DOI: No ID Found -
BMC Gastroenterology Jul 2023Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse...
BACKGROUND
Thiopurines continue to play an important role in the treatment of inflammatory bowel disease (IBD). It is well known that thiopurines can cause several adverse reactions. Especially, hematopoietic toxicity may lead to severe agranulocytosis. In a previous prospective study, we investigated the relationship between inosine triphosphate pyrophosphatase (ITPA) c.94c > a polymorphism, 6-thioguanine nucleotide (6-TGN) concentration and toxicity.
METHODS
To clarify the cause of thiopurine toxicity, we analysed nucleoside disphosphate-linked moiety X-type motif 15 (NUDT15) gene polymorphisms, i.e., R139C, V18I, and V19_V19insGV, and measured 6-mercaptopurines and 6-methylmercaptopurines (6-MMP) using the archived blood samples collected from 49 IBD patients for our previous study.
RESULTS
The ITPA c.94c > a polymorphism was detected in 19 patients (38.7%, all heterozygous). The R139C polymorphism was found in 10 patients (20.4%, 1 homozygous, 9 heterozygous), V18_V19insGV in 7 patients (14.3%, all heterozygous), and V18I in 2 patients (4.08%, all heterozygous). Although R139C was more strongly associated with leukopenia than c.94c > a, there were no significant correlations with 6-TGN and 6-MMP levels, as for c.94c > a. The leukopenia incidence rates for each gene polymorphism were 0% in those with all wild-type genes, 21.4% for c.94c > a only, 42.9% for NUDT15 polymorphism (s) only, and 80.0% for both polymorphisms.
CONCLUSIONS
All cases of leukopenia were associated with ITPA c.94c > a and/or polymorphism of NUDT15 and the risk of developing leukopenia was synergistically increased by ITPA and NUDT15 gene polymorphism. However, there was no association between the level of azathioprine metabolites and these polymorphisms.
Topics: Humans; Azathioprine; East Asian People; Inflammatory Bowel Diseases; Leukopenia; Mercaptopurine; Pyrophosphatases
PubMed: 37454061
DOI: 10.1186/s12876-023-02881-6 -
International Journal of Molecular... Apr 2022The effect of sodium thiosulfate (ST) on the photodegradation of azathioprine (AZA) was analyzed by UV-VIS spectroscopy, photoluminescence (PL), FTIR spectroscopy, Raman...
The effect of sodium thiosulfate (ST) on the photodegradation of azathioprine (AZA) was analyzed by UV-VIS spectroscopy, photoluminescence (PL), FTIR spectroscopy, Raman scattering, X-ray photoelectron (XPS) spectroscopy, thermogravimetry (TG) and mass spectrometry (MS). The PL studies highlighted that as the ST concentration increased from 25 wt.% to 75 wt.% in the AZA:ST mixture, the emission band of AZA gradual downshifted to 553, 542 and 530 nm. The photodegradation process of AZA:ST induced: (i) the emergence of a new band in the 320-400 nm range in the UV-VIS spectra of AZA and (ii) a change in the intensity ratio of the photoluminescence excitation (PLE) bands in the 280-335 and 335-430 nm spectral ranges. These changes suggest the emergence of new compounds during the photo-oxidation reaction of AZA with ST. The invoked photodegradation compounds were confirmed by studies of the Raman scattering, the FTIR spectroscopy and XPS spectroscopy through: (i) the downshift of the IR band of AZA from 1336 cm to 1331 cm, attributed to N-C-N deformation in the purine ring; (ii) the change in the intensity ratio of the Raman lines peaking at 1305 cm and 1330 cm from 3.45 to 4.57, as the weight of ST in the AZA:ST mixture mass increased; and (iii) the emergence of a new band in the XPS O1s spectrum peaking at 531 eV, which was associated with the C=O bond. Through correlated studies of TG-MS, the main key fragments of ST-reacted AZA are reported.
Topics: Azathioprine; Photolysis; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Thiosulfates
PubMed: 35409337
DOI: 10.3390/ijms23073975 -
Alimentary Pharmacology & Therapeutics Nov 2001The thioguanine derivative, azathioprine, is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and... (Review)
Review
The thioguanine derivative, azathioprine, is a prodrug of 6-mercaptopurine that is further metabolized by various enzymes present in the liver and gut. Azathioprine and 6-mercaptopurine have been used in the treatment of inflammatory bowel disease, i.e. ulcerative colitis and Crohn's disease, for more than 30 years. However, widespread use of azathioprine or 6-mercaptopurine in inflammatory bowel disease is of more recent origin, the primary reason being a long-standing debate on the efficacy of these agents in inflammatory bowel disease. Both drugs are slow acting, which is why clinical efficacy cannot be expected until several weeks or even months of treatment have elapsed. Consequently, azathioprine and 6-mercaptopurine have no place as monotherapy in the treatment of acute relapsing inflammatory bowel disease. Today, azathioprine and 6-mercaptopurine are the most commonly used immunomodulatory drugs in the treatment of inflammatory bowel disease. Their clinical effects are probably identical, although their exact mode of action is still unknown. The mode of action of azathioprine is thought to be multifactorial, including conversion to 6-mercaptopurine (which acts as a purine antimetabolite), possible blockade of thiol groups by alkylation, inhibition of several pathways in nucleic acid biosynthesis (preventing proliferation of cells involved in the determination and amplification of the immune response) and damage to DNA through the incorporation of thiopurine analogues. However, 6-thioguanine nucleotides may accumulate in toxic doses in myeloid precursor cells, resulting in life-threatening myelosuppression. Azathioprine and 6-mercaptopurine are further known to alter lymphocyte function, reduce the number of lamina propria plasma cells and affect natural killer cell function. The purpose of this comprehensive review is to suggest guidelines for the application of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease.
Topics: Azathioprine; Clinical Trials as Topic; DNA Damage; Female; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Killer Cells, Natural; Lactation; Lymphocytes; Male; Mercaptopurine; Neoplasms; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Risk Factors
PubMed: 11683683
DOI: 10.1046/j.1365-2036.2001.01102.x -
World Journal of Gastroenterology Sep 2008Inflammatory bowel disease (IBD) includes two entities, Crohn's disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical... (Review)
Review
Inflammatory bowel disease (IBD) includes two entities, Crohn's disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient's quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependent disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn's disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunosuppressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn's disease and ulcerative colitis, and (3) demonstration that early immunosuppression has a very positive impact on pediatric, recently diagnosed Crohn's disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn's disease patients (AZTEC study).
Topics: Azathioprine; Colectomy; Colitis, Ulcerative; Crohn Disease; Disease Progression; Drug Administration Schedule; Humans; Immunosuppressive Agents
PubMed: 18810768
DOI: 10.3748/wjg.14.5512 -
World Journal of Gastroenterology Dec 2016The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical... (Review)
Review
The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.
Topics: Azathioprine; Colitis, Ulcerative; Crohn Disease; Drug Therapy, Combination; Gastrointestinal Agents; History, 20th Century; History, 21st Century; Humans; Immunosuppressive Agents; Infliximab; Maintenance Chemotherapy; Mercaptopurine; Remission Induction; Tumor Necrosis Factor-alpha
PubMed: 28028358
DOI: 10.3748/wjg.v22.i46.10103 -
Digestive Diseases (Basel, Switzerland) 2012For more than a decade, methotrexate has been known to be an effective therapeutic agent in the treatment of steroid-dependent active Crohn's disease. However,... (Review)
Review
For more than a decade, methotrexate has been known to be an effective therapeutic agent in the treatment of steroid-dependent active Crohn's disease. However, international data on medication utilization suggest that this drug is rarely used in clinical practice for an indication of Crohn's disease. This review investigates the potential reasons for the underuse of methotrexate in patients with inflammatory bowel diseases.
Topics: Azathioprine; Colitis, Ulcerative; Crohn Disease; Humans; Methotrexate; Patient Preference; Treatment Outcome
PubMed: 23295701
DOI: 10.1159/000342735 -
Digestive and Liver Disease : Official... 2000The treatment of Crohn's disease and ulcerative colitis has evolved and has improved the quality of life of patients afflicted with these disorders. Immune modulators... (Review)
Review
The treatment of Crohn's disease and ulcerative colitis has evolved and has improved the quality of life of patients afflicted with these disorders. Immune modulators such as azathioprine and 6-mercaptopurine are an important class of medications used for the treatment of patients with inflammatory bowel disease. Controlled studies have demonstrated their efficacy in both induction and maintenance of remission in Crohn's disease, and similarly, for the induction and maintenance of remission in patients with ulcerative colitis. These agents have had an increasing importance in the management of steroid-resistant, steroid-dependent diseases, and fistulizing Crohn's disease. The primary limitations to these agents have been their slow onset of action and their side effect profile. Despite these limitations, these agents have demonstrated efficacy and have become paramount to the management of patients with these incurable potentially disabling disorders. The precise role of azathioprine/6-mercaptopurine, their limitations and their safety are reviewed in this paper.
Topics: Azathioprine; Clinical Trials as Topic; Drug Interactions; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Mercaptopurine; Neoplasms; Risk Factors
PubMed: 11057928
DOI: 10.1016/s1590-8658(00)80010-9