Health Risk Map of a Petrochemical Complex through GIS-Fuzzy Integration of Air Pollution Monitoring Data

From the mid-1990s, a network of surveillance and prevention of atmospheric contamination has been running to control the levels of airborne pollution in urban and industrial (petrochemical) areas of Tarragona (Catalonia, Spain). Airborne concentrations of SO₂, NO₂, O₃, H₂S, and CO, as well as PM_10, are routinely analyzed and used to establish the air quality. However, only single substances, rather than the global incidence of all contaminants as a whole, are taken into account. Moreover, specific data from the population are not considered. In the present study, a modified version of a previously developed fuzzy-based risk evaluation technique was developed. The method was fed with real monitoring data, instead of theoretical results from modeling. Hazard (air levels) and Exposure parameters (location sensitivity and population density) were used to create fuzzy sets and, subsequently, to generate a risk map. This tool was subsequently applied to the case-study of the petrochemical area of Tarragona by means of generating risk maps. The combination of geographic information system (GIS) and fuzzy logic tools proved to be successful as a help for stakeholders involved in the decision-making process.     

Involvement of ATP-sensitive potassium (K(ATP)) channels in the loss of beta-cell function induced by human islet amyloid polypeptide

Islet amyloid polypeptide (IAPP) is a major component of amyloid deposition in pancreatic islets of patients with type 2 diabetes. It is known that IAPP can inhibit glucose-stimulated insulin secretion; however, the mechanisms of action have not yet been established. In the present work, using a rat pancreatic beta-cell line, INS1E, we have created an in vitro model that stably expressed human IAPP gene (hIAPP cells). These cells showed intracellular oligomers and a strong alteration of glucose-stimulated insulin and IAPP secretion. Taking advantage of this model, we investigated the mechanism by which IAPP altered beta-cell secretory response and contributed to the development of type 2 diabetes. We have measured the intracellular Ca(2+) mobilization in response to different secretagogues as well as mitochondrial metabolism. The study of calcium signals in hIAPP cells demonstrated an absence of response to glucose and also to tolbutamide, indicating a defect in ATP-sensitive potassium (K(ATP)) channels. Interestingly, hIAPP showed a greater maximal respiratory capacity than control cells. These data were confirmed by an increased mitochondrial membrane potential in hIAPP cells under glucose stimulation, leading to an elevated reactive oxygen species level as compared with control cells. We concluded that the hIAPP overexpression inhibits insulin and IAPP secretion in response to glucose affecting the activity of K(ATP) channels and that the increased mitochondrial metabolism is a compensatory response to counteract the secretory defect of beta-cells.     

Impact of Virgin Olive Oil and Phenol-Enriched Virgin Olive Oils on the HDL Proteome in Hypercholesterolemic Subjects: A Double Blind,Randomized, Controlled,Cross-Over Clinical Trial (VOHF Study)

The effects of olive oil phenolic compounds (PCs) on HDL proteome, with respect to new aspects of cardioprotective properties, are still unknown. The aim of this study was to assess the impact on the HDL protein cargo of the intake of virgin olive oil (VOO) and two functional VOOs, enriched with their own PCs (FVOO) or complemented with thyme PCs (FVOOT), in hypercholesterolemic subjects. Eligible volunteers were recruited from the IMIM-Hospital del Mar Medical Research Institute (Spain) from April 2012 to September 2012. Thirty-three hypercholesterolemic participants (total cholesterol >200mg/dL; 19 men and 14 women; aged 35 to 80 years) were randomized in the double-blind, controlled, cross-over VOHF clinical trial. The subjects received for 3 weeks 25 mL/day of: VOO, FVOO, or FVOOT. Using a quantitative proteomics approach, 127 HDL-associated proteins were identified. Among these, 15 were commonly differently expressed after the three VOO interventions compared to baseline, with specific changes observed for each intervention. The 15 common proteins were mainly involved in the following pathways: LXR/RXR activation, acute phase response, and atherosclerosis. The three VOOs were well tolerated by all participants. Consumption of VOO, or phenol-enriched VOOs, has an impact on the HDL proteome in a cardioprotective mode by up-regulating proteins related to cholesterol homeostasis, protection against oxidation and blood coagulation while down-regulating proteins implicated in acute-phase response, lipid transport, and immune response. The common observed protein expression modifications after the three VOOs indicate a major matrix effect.

Trial Registration

International Standard Randomized Controlled Trials ISRCTN77500181.     

Structure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: Discovery of a quinazolinone chemotype

We describe the structure-based design of a novel lead chemotype that binds to thumb pocket 2 of HCV NS5B polymerase and inhibits cell-based gt1 subgenomic reporter replicons at sub-micromolar concentrations (EC₅₀ <200 nM). This new class of potent thumb pocket 2 inhibitors features a 1H-quinazolin-4-one scaffold derived from hybridization of a previously reported, low affinity thiazolone chemotype with our recently described anthranilic acid series. Guided by X-ray structural information, a key NS5B–ligand interaction involving the carboxylate group of anthranilic acid based inhibitors was replaced by a neutral two-point hydrogen bonding interaction between the quinazolinone scaffold and the protein backbone. The in vitro ADME and in vivo rat PK profile of representative analogs are also presented and provide areas for future optimization of this new class of HCV polymerase inhibitors.     

Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment

Background  

Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated to Alzheimer's disease (AD). The characterization of the clinical profile of AD patients might help to better understand disease evolution and to improve diagnosis and treatment. Thus, the aim of the present study is to describe the clinical profile of AD patients, and to correlate the presence of BPSD with the severity of the disease.     

Ultrastructure of Enteromyxum leei (Diamant, Lom, & Dyková, 1994) (Myxozoa), an enteric parasite infecting gilthead sea bream (Sparus aurata) and sharpsnout sea bream (Diplodus puntazzo).

The ultrastructure of the developmental stages of the myxozoan Enteromyxum leei parasitizing gilthead seabream (Sparus aurata) intestine and sharpsnout sea bream (Diplodus puntazzo) intestine and gallbladder are described. The earliest stage observed was a small dense trophozoite located among enterocytes. Proliferative stages, observed intercellularly in the epithelium of the intestine and gallbladder as well as in the lumen, possessed the typical cell-in-cell configuration throughout their development. Secondary cells were seen undergoing division within a common vacuolar membrane that also encompassed pairs of tertiary cells. Cytochemical studies showed that primary cells stored mainly lipids whereas secondary cells stored abundant beta-glycogen granules. Sporogonic development resembled that described for other disporous myxozoans. Within sporogonic stages, nonsporogonic secondary cells were observed accompanying two developing spores. Mature spores had a binucleated sporoplasm in which glycogen stores were abundant and no sporoplasmosomes were found. Our observations are discussed in relation to our knowledge on other myxozoans of the genus Enteromyxum.     

S-Nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner

Background  

Recent studies indicate that the G protein-coupled receptor (GPCR) signaling machinery can serve as a direct target of reactive oxygen species, including nitric oxide (NO) and S-nitrosothiols (RSNOs). To gain a broader view into the way that receptor-dependent G protein activation – an early step in signal transduction – might be affected by RSNOs, we have studied several receptors coupling to the G_i family of G proteins in their native cellular environment using the powerful functional approach of [³⁵S]GTPγS autoradiography with brain cryostat sections in combination with classical G protein activation assays.