Provenance-Centered Dataset of Drug-Drug Interactions

Over the years several studies have demonstrated the ability to identify potential drug-drug interactions via data mining from the literature (MEDLINE), electronic health records, public databases (Drugbank), etc. While each one of these approaches is properly statistically validated, they do not take into consideration the overlap between them as one of their decision making variables. In this paper we present LInked Drug-Drug Interactions (LIDDI), a public nanopublication-based RDF dataset with trusty URIs that encompasses some of the most cited prediction methods and sources to provide researchers a resource for leveraging the work of others into their prediction methods. As one of the main issues to overcome the usage of external resources is their mappings between drug names and identifiers used, we also provide the set of mappings we curated to be able to compare the multiple sources we aggregate in our dataset.Comment: In Proceedings of the 14th International Semantic Web Conference (ISWC) 201

Polymorphic variants of SCN1A and EPHX1 influence plasma carbamazepine concentration, metabolism and pharmacoresistance in a population of Kosovar Albanian epileptic patients

Aim The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. Materials & Methods Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. Results The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71±0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76±0.16 vs 0.94±0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; PG showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13±0.08 to 0.26±0.17, pT SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657±285 vs 489±231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84±4.37 vs 7.41±3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. Conclusions The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy

A Functional NQO1 609C>T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

Background: The functional polymorphism (rs1800566) in the NQO1 gene, a 609C.T substitution, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results. Methodology/Principal Findings: We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C.T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C.T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95 % CI = 1.01 – 1.19, P heterogeneity = 0.27, I 2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, Pheterogeneity = 0.14; I 2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies. Conclusions: This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyse

Dentinal dysplasia type I: two cases in one family

Dentinal dysplasia type 1 is a rare herediatary disease which is attributed to an automosal dominant trait. It&apos;s incidence is about 1: 100.000. Both dentition are affected with, although the involved teeth have a normal size, shape and consistency, and they are occasionally amber. The most common clinical feature, due to their extreme mobility, is malalignement and malpositioning of teeth. Such a mobility is resulted from abnormal development of root structure. In radiographs, the roots are sharp, biunt, and conic which can be absent in both dentition. Sometimes, multiple periapical radioiucences, without any carious lesion, are observed. There is no treatment for this anomaly and retaining teeth, as long as possible, is the main goal. In this article two cases dentinal dysplasia type 1 observed in one family, are reported

‍Prevalence and Comparison of DMFT in 15 Year Old Male High School Students of Yazd City, 2002-2009

Introduction: The purpose of this cross- sectional study was to evaluate the prevalence of dental caries in 15 year old high school students of Yazd. Methods: A total of 295 boy students with mean age of 15 years± 6 month in 2002 and 180 boy students in 2009 were selected randomly and after necessary examination, the obtained data was recorded and evaluated. Results: The over all mean DMFT was 4.8± 3.13 and 11.5% of the subjects(34 cases) were caries free. 4.4% of the population had DMFT> 10 and 6.92% of DMFT was due to extracted teeth. Meanwhile, 77.5% of the DMFT was due to decayed teeth. Also, the percentage of teeth with fillings was 15.53%. Of the total, 93.08% had all the teeth present in their mouth that is a little higher than the 2000 WHO criteria which is 85%. Conclusion: Preventive and therapeutic dentistry services in Yazd city are far from the standard levels and therefore the results of this study could be utilized for systematic planning of preventive and therapeutic affairs

Cold deformation and heat treatment influence on the microstructures and corrosion behavior of AISI 304 stainless steel

In the present study AISI 304 stainless steel with different degrees of cold deformation and annealing parameters were investigated. Microstructural evolutions by optical micrography and scanning electron microscopy showed relatively fully austenitic ultrafine-grained structure obtained after annealing at 700°C for 80 min. The volume fraction of α'-martensite increased with increasing compressive deformation rate and maximum volume fraction of α'-martensite was attained in the samples subjected 0·65% strain. The potentiodynamic polarization results in 3% NaCl indicated that the corrosion current density increased with cold deformation, while after annealing, it reduced from 2·86 to 2·29 μA cm-2, showing an enhancement of corrosion resistance. The immersion test showed that the austenitic ultrafine-grained structure exhibits moderate and more uniform pitting corrosion attack compared to the coarser grain in NaCl solution

The Anticonvulsant Triheptanoin Shows Anaplerotic Activity in the Pilocarpine Model of Temporal Lobe Epilepsy in Mice

This journal suppl. entitled: Special Issue: 30th International Epilepsy Congress, Montreal, Canada, 23-27 June 2013Late Breaking Abstracts: LBP1090PURPOSE: High frequency action potentials are mediated by voltage-gated sodium channels, composed of one large a subunit and two small β subunits, encoded mainly by SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B genes in the CNS. Since mutations of these can cause certain genetic epilepsy syndromes, we investigated whether polymorphisms in these genes may affect epilepsy risk in general. METHOD: Epilepsy patients and control subjects from Hong Kong and Kuala Lumpur were matched in age, sex and ethnicity. Epilepsy was broadly classified based on ILAE criteria. Blood was withdrawn for DNA extraction. Using Haploview, we tagged the five genes with 43 polymorphisms: 27 in Hong Kong, 28 in Malaysia, and 12 in both locations. Polymorphisms were genotyped by Sequenom Mass Array. RESULTS: The study included 1529 epilepsy patients (mean+/-SD age: 35 +/- 16 years) and 1935 control subjects (34 +/- 16 years) from four ethnic groups or locations: Malay, Indian, and Chinese, all from Malaysia, and Chinese from Hong Kong (the latter comprising 54% of patients and 44% of controls). Of patients, 19% were idiopathic, 42% symptomatic, and 40% cryptogenic. The strongest association with epilepsy was rs3812718, or SCN1A IVS5N+5G>A, odds ratio (OR) = 0.85 for allele G (p = 0.0009) and 0.73 for genotypes GG vs. AA (p = 0.003). The association was consistent across ethnicities. Allele G is known to affect splicing and to speed recovery from inactivation. Since SCN1A is preferentially expressed in inhibitory neurons, G may decrease epilepsy risk. SCN1A rs10188577 displayed OR = 1.20 for allele C (p = 0.003); SCN2A rs12467383 had OR = 1.16 for allele A (p = 0.01), and displayed LD with rs2082366 (r2 = 0.67), whose genotypes tended toward association with SCN2A brain expression (p = 0.10). SCN1A rs2298771 was associated with epilepsy in Indians (OR = 0.56, p = 0.005). SCN2B rs602594 was associated with idiopathic epilepsy (OR = 0.62, p = 0.002). CONCLUSION: Common genetic variants in neuronal sodium channel genes are associated with the risk of epilepsy.link_to_OA_fulltex