Ozone in Lombardy: Years 1998-1999

Photochemical pollutants, especially ozone, have reached very high levels in Lombardy in recent years, with peaks of up to 150 ppb in late spring and summer. Lombardy, lying on the Po Plain, supports a large number of cities and industries and these, along with heavy traffic, produce copious amounts of primary pollutants such as nitrogen oxides and numerous volatile organic compounds. Furthermore, the peculiar orography of this region fosters the stagnation of air masses on a basin-scale and the presence of diurnal breezes towards northern areas, along with the evolution of the Mixing Layer, spread the polluted air masses over a large territory. Numerous stations in Lombardy give the concentrations of ozone and of nitrogen oxides. In this paper, ozone measurements carried out at the plain area around Milan and at pre-alpine sites in the spring and summer 1998 and 1999 will be shown and discussed, focusing on the months of May and July. The study of temporal and spatial behaviour of ozone goes hand in hand with the analysis of the Boundary Layer’s evolution. A number of radon stations were operating in Milan and in other sites in Lombardy. Measurements of atmospheric concentrations of radon yield an index of atmospheric stability, of the formation of thermal inversion, of convective turbulence, and of the movement of air masses, and hence they are very relevant to the understanding of the conditions of atmospheric pollutants

Highly preferential association of NonF508del CF mutations with the M470 allele

AbstractBackgroundOn the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene.MethodsWe have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele.ResultsOut of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9× greater than VV subjects when F508del is excluded and 15.4× when F508del is included. In the Czech population a similar, although less pronounced, association is observed.ConclusionsBesides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit

A large-scale study of the random variability of a coding sequence: a study on the CFTR gene

Coding single nucleotide substitutions (cSNSs) have been studied on hundreds of genes using small samples (ngapproximate to100-150 genes). In the present investigation, a large random European population sample (average ngapproximate to1500) was studied for a single gene, the CFTR ( Cystic Fibrosis Transmembrane conductance Regulator). The nonsynonymous (NS) substitutions exhibited, in accordance with previous reports, a mean probability of being polymorphic (q>0.005), much lower than that of the synonymous ( S) substitutions, but they showed a similar rate of subpolymorphic (q<0.005) variability. This indicates that, in autosomal genes that may have harmful recessive alleles (nonduplicated genes with important functions), genetic drift overwhelms selection in the subpolymorphic range of variability, making disadvantageous alleles behave as neutral. These results imply that the majority of the subpolymorphic nonsynonymous alleles of these genes are selectively negative or even pathogenic

Selanylimidazopyridine Prevents Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Targeting Neurotrophins and Inflammatory/Oxidative Mediators

Inasmuch, as the major depressive disorder (MDD) has been characterized as a heterogeneous disease as the inflammatory processes, neurotrophic factors’ dysfunction and oxidative/nitrosative stress are believed to play a vital role in its establishment. Organoselenium compounds stand out due to their antioxidant, anti-inflammatory, neuroprotective, and antidepressant effects. In this sense, the present study investigated the effect of 3-((4-methoxyphenyl)selanyl)-2-phenylimidazo[1,2-a]pyridine (MPI; 20 and 50 mg/kg, intragastrically) pretreatment [30 min prior lipopolysaccharide (LPS) challenge (0.83 mg/kg)] on acute LPS induced depressive-like behavior, neuroinflammation, and oxidative stress. MPI was able to prevent the increased immobility time induced by LPS on the forced swimming test (FST), the increase in pro-inflammatory cytokines’ expression in the hippocampus (HC) of mice after LPS challenge via NFkB downregulation, and the increase of the reactive oxygen species generation and lipid peroxidation in the prefrontal cortex and HC of mice. It was observed that at the doses tested, MPI protected against reducing levels of BDNF in the cortex and HC of mice challenged with LPS. These observations suggest that the antidepressant-like effect of MPI depends on its capacity to modulate the inflammatory, antioxidant, and neurotrophic systems

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p