Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
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PMID:Measurement of Human Cytochrome P450 Enzyme Induction Based on Mesalazine and Mosapride Citrate Treatments Using a Luminescent Assay. 2633 90

Infection with Clostridium difficile (C. difficile) causes a severe colitis with high recurrence. Treatment of C. difficile infection (CDI) is based on antibiotics in spite of the increase of resistance. To interrupt the vicious cycles such as new antibiotics treatment and appearance of resistance strains, photodynamic therapy (PDT) might be a possible alternative therapy for CDI. Tetracycline (TC) has been used as a broad spectrum antibiotic with low risk of CDI and a photosensitizer (PS) in PDT. In vitro PDT against C. difficile was conducted using UVA and TC as a PS before in vivo study. To enhance the photodynamic antibacterial activity of TC, we applied chitosan as a boostering agent. Bactericidal effects after PDT, were measured by counting viable cells, DNA damage and membrane integrity. At 1mg/mL of TC, chitosan treatment combined with PDT, increased the bactericidal effect by >10,000-fold of the effect of PDT alone. Membrane damage and cellular DNA damage demonstrated by EMA-qPCR were also greater in the group treated with PDT+chitosan than in that treated PDT alone. The present study showed that PDT using a combination of TC and chitosan is an effective method for killing C. difficile.
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PMID:In vitro augmented photodynamic bactericidal activity of tetracycline and chitosan against Clostridium difficile KCTC5009 in the planktonic cultures. 2638 40

Background. Food protein-induced proctitis/proctocolitis (FPIP) is the most common noninfectious colitis in children in the first year of life. Along with the overall clinical symptoms, diarrhoea and rectal bleeding are the main manifestations of the disease. There is no routine noninvasive test that would be specific for this type of colitis. The aim of our study was to find a noninvasive laboratory test or tests that may be helpful in differential diagnosis of food protein-induced proctitis/proctocolitis. Methods. ANA, ANCA, ASCA, a-EMA, a-tTg, specific IgE, total IgE, IgG, IgA, IgM, and concentration of serum calprotectin were measured in a group of 25 patients with colitis and 18 children with other diagnoses. Results. Atypical-pANCA antibodies of IgG isotype were detected in the sera of 24 patients by the method of indirect immunofluorescence, and 5 patients showed also the positivity of IgA isotype. In control samples these autoantibodies were not detected. Other autoantibodies were not demonstrated in either patient or control group. Conclusions. Of the parameters tested in noninfectious colitis, atypical-pANCA on ethanol-fixed granulocytes appears to be a suitable serological marker of food protein-induced proctitis/proctocolitis and suggests a possible involvement of an autoimmune mechanisms in the pathogenesis of this disease.
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PMID:High Prevalence of Neutrophil Cytoplasmic Autoantibodies in Infants with Food Protein-Induced Proctitis/Proctocolitis: Autoimmunity Involvement? 2648 55

The emergence of biosimilars is generally considered as an opportunity to guarantee accessibility to affordable treatments and to enhance financial sustainability of national health systems. Since 2017, five biosimilars of adalimumab were approved by the European Medicines Agency [EMA] for use in inflammatory bowel disease: ABP 510, SB5, GP2017, FKB327, and MSB11022. In this position statement, the available efficacy and safety data of the different adalimumab biosimilars in immune-mediated inflammatory diseases are summarised. Furthermore, the Belgian IBD research group [BIRD] formulates statements concerning the use of adalimumab biosimilars in inflammatory bowel disease.
J Crohns Colitis 2020 Jun 19
PMID:Belgian IBD Research Group [BIRD] Position Statement 2019 on the Use of Adalimumab Biosimilars in Inflammatory Bowel Diseases. 3187 91