- Biologics Monitoring: Incongruity between Recommendations and Clinician Monitoring Trends. [Journal Article]
- JDJ Dermatolog Treat 2018 May 24; :1-9
- CONCLUSIONS: Patient comorbidities might confound some of our findings, as these laboratory tests may have been ordered for a comorbidity rather than for biologics side effect monitoring.There are inconsistencies between current monitoring practices and guidelines. Clarifying biologics monitoring recommendations in psoriasis patients may reduce healthcare costs and provider workload.
- Recent advances in personalizing rheumatoid arthritis therapy and management. [Journal Article]
- PMPer Med 2009; 6(2):159-170
- Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterized by synovial inflammation in diarthrodial joints. There are significant interindividual variations in the degree o...
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder characterized by synovial inflammation in diarthrodial joints. There are significant interindividual variations in the degree of inflammation, disease course and the rate of joint progression in patients with RA. A number of clinical, serological, environmental and genetic severity factors have been identified in patients with RA and can be used to help guide treatment. Therapeutic options for RA have significantly expanded in the last decade and now include both synthetic disease-modifying antirheumatic drugs as well as biologic disease-modifying antirheumatic drugs. Owing to the variety of new drugs, their cost and incomplete information on side effects, markers of treatment response are needed. The study of treatment-specific genetic and protein biomarkers of response and toxicity in RA has produced exciting, yet inconsistent, results. Large scale genetic and proteome studies, which can now be performed at a relatively low cost, will likely broaden the scope and significance of biomarker studies in RA. Integration of these results into clinical practice will vastly improve our ability to provide safe and effective therapy to individuals with RA.
- Malignancy in a retrospective cohort of 17 patients with Dermatomyositis or Polymyositis in southern Tunisia. [Journal Article]
- RJRom J Intern Med 2018 May 21
- CONCLUSIONS: There are no specific clinical or biological features in paraneoplastic DM. In our series, breast neoplasm represented the first cancer associated with DM. Cancers of nasopharynx, colon and urinary tract had the second position.
- A Pharmacokinetic and Pharmacogenetic Analysis of Osteosarcoma Patients Treated With High-Dose Methotrexate: Data From the OS2006/Sarcoma-09 Trial. [Journal Article]
- JCJ Clin Pharmacol 2018 May 23
- Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (...
Growing evidence suggests that polymorphisms of genes coding for transporters or enzymes may partially explain the large between subject variability reported for methotrexate (MTX) pharmacokinetics (PK). This prospective study aimed to develop a population PK-pharmacogenetic model to evaluate the part of between-subject variability due to single-nucleotide polymorphisms (SNPs) in transporters and enzyme genes implicated in MTX distribution and elimination. MTX concentrations and 54 SNPs (located in ABCB1, ABCC1, ABCC2, ABCC3, ABCC4, ABCG2, SLC19A1, SLCO1B1, and UGT1A1 genes) were analyzed in patients treated with MTX included in the OS2006/sarcoma-09 trial (a multicenter, open-label, phase III trial, ClinicalTrials.gov. Identifier: NCT00470223). PK data were analyzed using the nonlinear mixed-effect modeling software program Monolix. The influence of each SNP was evaluated using a stepwise procedure under additive, recessive, or dominant genetic model. The likelihood ratio test was used to test the effect of each SNP on PK parameters. Overall, 187 patients with 7898 MTX blood concentrations were included in the PK-pharmacogenetic analysis. A 2-compartment model adequately described the data. Although high-dose MTX dosing recommendations in pediatric patients are currently based on body surface area, body weight was more predictive of clearance between-subject variability than body surface area. The most significant polymorphism associated with MTX clearance was rs13120400 (on the ABCG2 gene) under the recessive genetic model (P < .0001). GG genotype carriers for rs13120400 appeared to have a moderate decrease in MTX exposure compared to AA or GA carriers.
- Brain Activity Associated With Attention Deficits Following Chemotherapy for Childhood Acute Lymphoblastic Leukemia. [Journal Article]
- JNCIJ Natl Cancer Inst 2018 May 21
- CONCLUSIONS: Brain activation during attention and executive function tasks was associated with serum methotrexate exposure and age at diagnosis. These findings provide evidence for compromised and compensatory changes in regional brain function that may help clarify the neural substrates of cognitive deficits in acute lymphoblastic leukemia survivors.
- Acute kidney injury, agranulocytosis, drug-induced liver injury, and posterior reversible encephalopathy syndrome caused by high-dose methotrexate-possible role of low activity ABC and SLC drug transporters. [Letter]
- EJEur J Clin Pharmacol 2018 May 22
- An Update on Drug-induced Oral Reactions. [Journal Article]
- JPJ Pharm Pharm Sci 2018; 21(1):171-183
- Adverse drug reactions (ADRs) are one of the major culprits in the development of oral lesions, which can be misdiagnosed with underlying diseases. The goal of this study is to summarize and update t...
Adverse drug reactions (ADRs) are one of the major culprits in the development of oral lesions, which can be misdiagnosed with underlying diseases. The goal of this study is to summarize and update the current knowledge about drug-induced oral reactions. Electronic searches were performed in Scopus, Google Scholar, Cochrane and PubMed databases, for articles published between January 2008 and August 2017. Two authors screened the titles and abstracts for eligibility. Finally, 56 studies included in this review. There was no systematic homogeneity in the included studies; thereby no meta-analysis was performed. The most frequent oral ADR was xerostomia,andthe most reported cause was antihypertensive medications. Cardiovascular drugs were the most reported culprit agents for induction of oral ulcerative and vesiculo-bullous lesions, followed by methotrexate. Nonsteroidal anti-inflammatory drugs (NSAIDs) and β-blockers were found the most common responsible drugs for induction of oral lichen planus. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
- Further insight into the markers of methotrexate resistance in childhood acute lymphoblastic leukemia patients. [Journal Article]
- PMPer Med 2008; 5(4):325-329
- Expression, purification, and inhibition profile of dihydrofolate reductase from the filarial nematode Wuchereria bancrofti. [Journal Article]
- PlosPLoS One 2018; 13(5):e0197173
- Filariasis is a tropical disease caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. Known inhibitors of dihydrofolate reductase (DHFR) have been previously shown to kill Brugia...
Filariasis is a tropical disease caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. Known inhibitors of dihydrofolate reductase (DHFR) have been previously shown to kill Brugia malayi nematodes and to inhibit Brugia malayi DHFR (BmDHFR) at nanomolar concentrations. These data suggest that BmDHFR is a potential target for the treatment of filariasis. Here, protocols for cloning, expression and purification of Wuchereria bancrofti DHFR (WbDHFR) were developed. The Uniprot entry J9F199-1 predicts a 172 amino acid protein for WbDHFR but alignment of this sequence to the previously described BmDHFR shows that this WbDHFR sequence lacks a crucial, conserved 13 amino acid loop. The presence of the loop in WbDHFR is supported by a noncanonical splicing event and the loop sequence was therefore included in the gene design. Subsequently, the KM for dihydrofolate (3.7 ± 2 μM), kcat (7.4 ± 0.6 s-1), and pH dependence of activity were determined. IC50 values of methotrexate, trimethoprim, pyrimethamine, raltitrexed, aminopterin, (-)-epicatechin gallate, (-)-epicatechin, and vitexin were measured for WbDHFR and BmDHFR. Methotrexate and structurally related aminopterin were found to be effective inhibitors of WbDHFR, with an KI of 1.2 ± 0.2 nM and 2.1 ± 0.5 nM, respectively, suggesting that repurposing of known antifolate compound may be an effective strategy to treating filariasis. Most compounds showed similar inhibition profiles toward both enzymes, suggesting that the two enzymes have important similarities in their active site environments and can be targeted with the same compound, once a successful inhibitor is identified.
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- Association of different immunosuppressive medications with periodontal condition in patients with rheumatoid arthritis - results from a cross-sectional study. [Journal Article]
- JPJ Periodontol 2018 May 22
- CONCLUSIONS: RA medication is associated with periodontal inflammation, without differences in periodontal disease severity. Thereby, combination of MTX + TNF-α shows an increased potential to periodontal inflammation. Additionally, several differences in prevalence of selected bacteria were detected. This article is protected by copyright. All rights reserved.