Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1

Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8-diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-->113His (exon 3) and 139His-->139Arg (exon 4). We performed a case-control study among Northwestern Mediterranean Caucasians to investigate a possible association between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were analyzed in a group of lung cancer patients (n=176) and in a control group of healthy smokers (n=187). The results showed a significantly decreased risk for the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33-0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His, respectively, as the references. Thereafter, we analyzed the EPHX1 variants in combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1, and GSTP1) and we found a significant overepresentation of cancer patients with a combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1 (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of GSTP1 results in a Ile-->Val substitution, and the isoleucine GSTpi isoform has been found in vitro to be less active than the valine isoform towards the conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. Our results agree with these observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.     

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk

Objectives: The human GSTTP1 gene is polymorphic with an A G transition in exon 5 causing a replacement 105 IleVal in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility.Methods: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n=164) and in two control groups (healthy smokers, n=132; general population, n=200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin.Results and Conclusions: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67–2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.     

Emissions from residential combustion sector: how to build a high spatially resolved inventory

Usually, annual emission data from residential combustion sector are spatially disaggregated by population density to the sub-municipality spatial level. The aim of the present work is to define a methodological approach to develop/build a high-resolution emission inventory from residential combustion following a bottom–up approach. The conceptual model considers different approaches by fuel category (solid fuel–wood, gas and liquid fuels) according to distinct spatial coverage and type of activity data available for each category. For solid fuels, detailed activity data (per district), disaggregated according to the number and type of equipment, burned wood species and consumption rate, as well as specific emission factors (per wood species) were used. With regard to the gas and liquid fuels, the total national emission by fuel type using national consumption data and broader emission factors was disaggregated to the sub-municipality scale based only on the number of heating equipment. The choice of these disaggregation factors was influenced by both data availability and relevance. The results of the new disaggregated emission data have been compared with emission values resulting from the classical top–down approach using census/population data. The selected case study is Portugal. The results pointed out that major differences exist when comparing both approaches, namely regarding the spatial distribution/allocation of emissions. In the new approach, emissions are more redistributed over the territory, while in the old distribution, emissions are concentrated in the coastal urban areas (with hotspots in the main urban areas of Porto and Lisbon).     

Economic,Patient Preference,and Health-Related Quality of Life Considerations for Intranasal Corticosteroids in Allergic Rhinitis

Allergic rhinitis, as a medical condition, merits attention because of its prevalence in the population as well as the substantial economic impact of treating it. By virtue of their efficacy and low adverse effect profile, intranasal corticosteroids have gained recognition by healthcare providers as the first-line therapy for allergic rhinitis. For managed care decision makers, the use of intranasal corticosteroids as the gold standard of treatment in allergic rhinitis makes comparative economic and humanistic (patient preference or health-related quality of life [HR-QOL]) data between the various intranasal corticosteroids increasingly important for formulary decisions.Although the equal efficacy and safety of intranasal corticosteroid products in the treatment of allergic rhinitis is well documented, research that compares the different economic and humanistic aspects of intranasal corticosteroid products is limited and less conclusive. In this article, we review published studies reporting pharmacoeconomic and humanistic analyses of intranasal corticosteroids in the treatment of allergic rhinitis and make recommendations for managed care decision makers in the selection of intranasal corticosteroids for allergic rhinitis. Based on inclusion/exclusion criteria, 15 pharmacoeconomic and 19 patient preference/HR-QOL studies were selected and reviewed.The literature reviewed does not provide evidence of the superiority of a single intranasal corticosteroid product with respect to pharmacoeconomic, patient preference, or HR-QOL considerations. This finding is primarily owing to the lack of published head-to-head studies comparing pharmacoeconomic or humanistic outcomes between the different intranasal corticosteroids. Without further head-to-head studies on intranasal corticosteroids for the treatment of allergic rhinitis, cost minimization results may be the best decision strategy for managed care organizations (MCOs). Ideally, the results of cost-effectiveness or cost-utility studies comparing the different intranasal corticosteroids should guide the final formulary decision. In the absence of such studies, pharmacoeconomic and humanistic outcomes data from studies reported in the literature should be included into a pharmacoeconomic model, which considers the prevalence of allergic rhinitis in the MCOs to guide formulary inclusion decisions. Managed care decision makers will increasingly need to request this information from drug manufacturers if an informed, evidence-based decision is to be made.     

Anisakiasis as a cause of acute appendicitis and rheumatologic picture: the first case in medical literature

We report a case of acute abdomen due to appendicular lumen occlusion by anisakis larvae. This is the first case of human anisakiasis known in Spain, and the first case of acute appendicitis, in the medical World literature, produced by this nemathode. The association of myalgias and arthralgias stands out, being in this aspect the second case found the in medical litterature.     

Genetic Analysis of FAM46A in Spanish Families with Autosomal Recessive Retinitis Pigmentosa: Characterisation of Novel VNTRs

Retinitis pigmentosa (RP) is a group of retinal dystrophies characterised primarily by rod photoreceptor cell degeneration. Exhibiting great clinical and genetic heterogeneity, RP be inherited as an autosomal dominant (ad) and recessive (ar), X-linked (xl) and digenic disorder. RP25 , a locus for arRP, was mapped to chromosome 6p12.1-q14.1 where several retinal dystrophy loci are located. A gene expressed in the retina, FAM46A , mapped within the RP25 locus, and computational data revealed its involvement in retinal signalling pathways. Therefore, we chose to perform molecular evaluation of this gene as a good candidate in arRP families linked to the RP25 interval. A comprehensive bioinformatic and retinal tissue expression characterisation of FAM46A was performed, together with mutation screening of seven RP25 families.
Herein we present 4 novel sequence variants, of which one is a novel deletion within a low complexity region close to the initiation codon of FAM46A . Furthermore, we have characterised for the first time a coding tandem variation in the Caucasian population.
This study reports on bioinformatic and moleculardata for the FAM46A gene that may give a wider insight into the putative function of this gene and its pathologic relevance to RP25 and other retinal diseases mapping within the 6q chromosomal interval.     

Renal Transplantation in Second-Level Private Hospitals in the State of Mexico

Background

Kidney transplantation (KT) is the replacement therapy of choice in patients with end-stage renal disease (ESRD). Here we show a cohort of kidney transplant recipients from the period of May 1994 to May 2016 in 2 2nd-level private hospitals from the city of Toluca in the state of Mexico.