Related Articles

Ustekinumab use in Crohn's disease: a Canadian tertiary care centre experience.

Scand J Gastroenterol. 2017 Dec;52(12):1354-1359

Authors: Greenup AJ, Rosenfeld G, Bressler B

Abstract
OBJECTIVES: Real world data regarding clinical response to ustekinumab in Crohn's disease is lacking. We report our experience of ustekinumab use using a novel subcutaneous (SC) induction strategy and aim to identify predictors of response.
MATERIALS AND METHODS: A retrospective, observational study of compassionate ustekinumab use in Crohn's disease was conducted with the use of a standard or high dose SC induction protocol. Symptomatic response was assessed after 3 months (short-term), and if remaining on therapy, within 3-12 months (medium-term) and at least 12 months (long-term). Endoscopic or radiologic response was assessed when available. Survival analysis of time to failure (cessation of ustekinumab) and multivariate logistic regression to identify predictors of response were performed.
RESULTS: Seventy-nine patients commenced ustekinumab, with six patients lost to follow-up and five asymptomatic at baseline. Symptomatic response was assessed in 68 patients; 56% (38) of patients had a short-term symptomatic response. Type of preceding anti-TNF response was the only significant predictor of short-term response, with primary non-response being a strong predictor. In the medium-term, symptomatic response occurred in 72% (30/42) of patients and endoscopic or radiologic response was achieved in 72% (26/36) of patients assessed. The median time to failure was 22 months. Maintenance dose escalation to 90 mg every 4 weeks was successful in three of 16 patients.
CONCLUSIONS: Fifty-six percent of patients had short-term symptomatic response, with a history of primary non-response to prior anti-TNF therapy being a predictor of response. Dose escalation had only modest benefit.

PMID: 28885058 [PubMed - indexed for MEDLINE]

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Optimizing Thiopurine Therapy in Inflammatory Bowel Disease Among 2 Real-life Intercept Cohorts: Effect of Allopurinol Comedication?

Inflamm Bowel Dis. 2017 Nov;23(11):2011-2017

Authors: Meijer B, Seinen ML, van Egmond R, Bouma G, Mulder CJJ, van Bodegraven AA, de Boer NKH

Abstract
BACKGROUND: Thiopurines (azathioprine and mercaptopurine) are frequently used immunosuppressive drugs to maintain remission in patients with inflammatory bowel disease. Half of the conventional thiopurine-derivative users have to discontinue treatment within 5 years, mainly because of intolerable adverse events. Over recent years, different strategies to optimize thiopurine treatment were suggested, yet, studies describing the clinical effectiveness of these strategies remain scarce. The aims of this study were to compare tolerability and sustained clinical benefit of conventional thiopurine derivatives therapy among two 5-year real-life intercept cohorts and to assess the clinical value of specifically allopurinol cotherapy.
METHODS: In this retrospective single-center cohort study, we analyzed data from patients in whom weight-based thiopurine monotherapy was initiated between 2005 and 2009 (cohort 1) or between 2010 and 2014 (cohort 2). The initiation of the second cohort was synchronic to the start of allopurinol-based optimization in our center. Optimization strategies were extracted from patient charts.
RESULTS: In total, 105 patients were included (60 in cohort 1, and 45 in cohort 2). Metabolite measurement was performed in 37% versus 84% of the patients (P < 0.001). Subsequent optimization strategies were applied in 33% versus 58% of the patients because of inadequate metabolite concentrations, intolerance, or ineffectiveness (P = 0.01). Allopurinol was coadministered to therapy in 18 patients (40%) in the second cohort. Therapy was switched to thioguanine in 11 versus 6 patients (P > 0.05). Overall, total duration was longer in the second cohort (10.8 versus 34.1 months, P < 0.001). The number of ongoing thiopurine users (20% versus 49%) and sustained clinical benefit (13% versus 38%) were higher in the second cohort (both P < 0.05). This was mainly because of a decrease in hepatotoxicity after optimization (P < 0.01).
CONCLUSIONS: Optimization of thiopurine therapy by the use of therapeutic drug monitoring with subsequent administration of allopurinol cotherapy successfully enhanced sustained clinical benefit and tolerability in patients with inflammatory bowel disease.

PMID: 28617756 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/06/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Notice NOT-CA-18-077 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-18-831 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications from the scientific community to support outstanding research in the area of epitranscriptomics, i.e., the chemical modifications of RNA. Evidence is accumulating that RNA modifications regulate the function of both coding and noncoding RNAs, suggesting that these modifications are involved in both development, and in health and disease. Yet the extent and types of these RNA modifications as well as their roles in particular biological processes remain either poorly understood or not known. The goal of the FOA is to promote research into the role of RNA chemical modifications in the initiation and progression of various developmental processes and disease states and conditions relevant to the scientific mission of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Funding Opportunity PAR-18-830 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications from the scientific community to support outstanding research in the area of epitranscriptomics, i.e., the chemical modifications of RNA. Evidence is accumulating that RNA modifications regulate the function of both coding and noncoding RNAs, suggesting that these modifications are involved in both development, and in health and disease. Yet the extent and types of these RNA modifications as well as their roles in particular biological processes remain either poorly understood or not known. The goal of the FOA is to promote research into the role of RNA chemical modifications in the initiation and progression of various developmental processes and disease states and conditions relevant to the scientific mission of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), and the National Eye Institute (NEI).

Notice NOT-OD-18-192 from the NIH Guide for Grants and Contracts

Notice NOT-OD-18-191 from the NIH Guide for Grants and Contracts

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Notice NOT-NS-18-072 from the NIH Guide for Grants and Contracts

Funding Opportunity RFA-AI-18-023 from the NIH Guide for Grants and Contracts. This initiative will support research to determine the roles and interactions of immune cells at the maternal-fetal interface throughout pregnancy, including mechanisms of responses to vaccination and infection that protect the fetus and that may influence fetal immune system development.

Notice NOT-AI-18-040 from the NIH Guide for Grants and Contracts

Notice NOT-NS-18-058 from the NIH Guide for Grants and Contracts

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Notice NOT-NS-18-069 from the NIH Guide for Grants and Contracts

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/06/14

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Uridine 5'-diphospho-glucronosyltrasferase: Its role in pharmacogenomics and human disease.

Exp Ther Med. 2018 Jul;16(1):3-11

Authors: Sanchez-Dominguez CN, Gallardo-Blanco HL, Salinas-Santander MA, Ortiz-Lopez R

Abstract
Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes. In the last five years, the study of the genetic variants of the UGTs at a molecular level has become important due to its association with several diseases and the ability to predict adverse events due to drug metabolism. In the present review, the structure and the prominent genetic variants of the UGT1A subfamily and their metabolic and clinical implications are described.

PMID: 29896223 [PubMed]

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Genetic Determinants Associated With in Vivo Survival of Burkholderia cenocepacia in the Caenorhabditis elegans Model.

Front Microbiol. 2018;9:1118

Authors: Wong YC, Abd El Ghany M, Ghazzali RNM, Yap SJ, Hoh CC, Pain A, Nathan S

Abstract
A Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.

PMID: 29896180 [PubMed]

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Therapeutic potentials of superoxide dismutase.

Int J Health Sci (Qassim). 2018 May-Jun;12(3):88-93

Authors: Younus H

Abstract
Superoxide dismutases (SODs) constitute a very important antioxidant defense against oxidative stress in the body. The enzyme acts as a good therapeutic agent against reactive oxygen species-mediated diseases. The present review describes the therapeutic effects of SOD in various physiological and pathological conditions such as cancer, inflammatory diseases, cystic fibrosis, ischemia, aging, rheumatoid arthritis, neurodegenerative diseases, and diabetes. However, the enzyme has certain limitations in clinical applications. Therefore, SOD conjugates and mimetics have been developed to increase its therapeutic efficiency. Here, an overview is provided of some in vivo therapeutic effects observed with SOD.

PMID: 29896077 [PubMed]