Toxicity of nanoparticles.

Nowadays more than thousands of different nanoparticles are known, though no well-defined guidelines to evaluate their potential toxicity and to control their exposure are fully provided. The way of entry of nanoparticles together with their specificities such as chemistry, chemical composition, size, shape or morphology, surface charge and area can influence their biological activities and effects. A specific property may give rise to either a safe particle or to a dangerous one. The small size allows nanoparticles to enter the body by crossing several barriers, to pass into the blood stream and lymphatic system from where they can reach organs and tissues and strictly interact with biological structures, thus damaging their normal functions in different ways. This review provides a summary of what is known on the toxicology related to the specificity of nanoparticles, both as technological tools or ambient pollutants. The aim is to highlight their potential hazard and to provide a balanced update on all the important questions and directions that should be focused in the near future.

Interaction of Cu(II) and Ni(II) with Ypk9 protein fragment via NMR studies.

P1D2E3K4H5E6L7 (PK9-H), a fragment of Ypk9, the yeast homologue of the human Park9 protein, was studied for its coordination abilities towards Ni(II) and Cu(II) ions through mono- and bi-dimensional NMR techniques. Both proteins are involved in the transportation of metal ions, including manganese and nickel, from the cytosol to the lysosomal lumen. Ypk9 showed manganese detoxification role, preventing a Mn-induced Parkinsonism (PD) besides mutations in Park9, linked to a juvenile form of the disease. Here, we tested PK9-H with Cu(II) and Ni(II) ions, the former because it is an essential element ubiquitous in the human body, so its trafficking should be strictly regulated and one cannot exclude that Ypk9 may play a role in it, and the latter because, besides being a toxic element for many organisms and involved in different pathologies and inflammation states, it seems that the protein confers protection against it. NMR experiments showed that both cations can bind PK9-H in an effective way, leading to complexes whose coordination mode depends on the pH of the solution. NMR data have been used to build a model for the structure of the major Cu(II) and Ni(II) complexes. Structural changes in the conformation of the peptide with organized side chain orientation promoted by nickel coordination were detected.

More than 20 years of registration of type 1 diabetes in Sardinian children: temporal variations of incidence with age, period of diagnosis, and year of birth.

We analyzed Sardinian registry data to assess time trends in incidence rates (IRs) of type 1 diabetes during the period 1989-2009 (2,371 case subjects 0-14 years of age). Poisson regression models were used to estimate the effects of sex, age, period of diagnosis, and birth cohorts. IR was 44.8 cases/100,000 person-years (95% CI 43.1-46.7). The annual increase was 2.12% (1.45-2.80; test for linear trend, P < 0.001). For boys, the increasing trend was evident up to 5 years of age and for girls up to 8 years of age. Compared with the 1989-1994 birth cohort, the relative risk increased from 0.78 (0.61-1.10) in 1974-1979 to 1.62 (1.18-2.23) in 2004-2009. The increase over period was less striking, with a tendency to regress in more recent years. The best-fitting model for boys included age and a linear time trend, and for girls age and nonlinear effects of calendar period and birth cohort. In conclusion, incidence increased over time, and the increase tended to level off in more recent years by calendar period but not by birth cohort, with some evidence of a stronger increase among girls than boys. Should the increase be attributable to the effects of some perinatal environmental factor, this would mean that such a factor has started affecting females before males.