Cadmium (Cd) is an environmental contaminant, highly toxic to humans. This biologically non-essential element accumulates in the body, especially in the kidney, liver, lung and brain and can induce several toxic effects, depending on the concentration and the exposure time. Cd has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows higher concentrations in brain tissues of AD patients than in healthy people, its implication in the formation of neurofibrillary tangles and in the aggregation process of amyloid beta peptides (AβPs). AβPs seem to have toxic properties, particularly in their aggregated state; insoluble AβP forms, such as small and large aggregates, protofibrils and fibrils, appear to be implicated in the pathogenesis of AD. In our study, we have evaluated the effect of Cd, at different concentrations, both on the AβP1-42 ion channel incorporated in a planar lipid membrane made up of phosphatidylcholine containing 30 % cholesterol and on the secondary structure of AβP1-42 in aqueous environment. Cadmium is able to interact with the AβP1-42 peptide by acting on the channel incorporated into the membrane as well as on the peptide in solution, both decreasing AβP1-42 channel frequency and in solution forming large and amorphous aggregates prone to precipitate. These experimental observations suggesting a toxic role for Cd strengthen the hypothesis that Cd may interact directly with AβPs and may be a risk factor in AD.

Mercury (Hg) and lead (Pb) are known to be toxic non-radioactive elements, with a well-described neurotoxicology.Much evidence supports the implication of metals as potential risk cofactors in Alzheimer's disease (AD). Although the action mechanism of the two metals remains unclear, Hg and Pb toxicity in AD could depend on their ability to favour misfolding and aggregation of amyloid beta proteins (As) that seem to have toxic properties, particularly in their aggregated state. In our study, we evaluated the effect of Hg and Pb both on the Aβ42 ion channel incorporated in a planar lipid membrane made up of phosphatidylcholine containing 30% cholesterol and on the secondary structure of Aβ42 in aqueous environment. The effects of Hg and Pb on the A42 peptide, observed on the channel incorporated into the membrane as well as on the peptide in solution, both decreasing A42 channel frequency and in solution forming large and amorphous aggregates that are prone to precipitate, are dependent on metal concentration. These experimental data suggest that Hg and Pb interact directly with As, strengthening the hypothesis that the two metals may be a risk factor in AD.

Amyloid beta peptide (AβP) is a natural peptide, normally released into the cerebrospinal fluid (CSF), that plays a key role in Alzheimer's disease. The conversion of the peptide from a native soluble form to a non-native and often insoluble form, such as small and large aggregates, protofibrils and fibrils of AβP appears to be implicated in the pathogenesis of AD. Although the molecular mechanisms of AβP neurotoxicity are not fully understood, a large body of data suggests that the primary target of amyloid peptides is the cell membrane of neurons, that may modulate the structural and functional conversion of AβP into assemblies involved in pathological processes. In our study, we provide a systematic investigation of AβP1-42's ability to incorporate and form channel-like events in membranes of different lipid composition and focus on cholesterol and its oxidation products. We propose that cholesterol and its oxidation products can be considered neuroprotective factors because a) by favouring AβP1-42 insertion into membranes, the fibrillation/clearance balance shifts toward clearance; b) by shifting channel selectivity toward anions, the membrane potential is moved far from the threshold of membrane excitability, thus decreasing the influx of calcium into the cell.

BackgroundAccording to international guidelines, HPV DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more severe lesions. The aim of this study was to assess whether REALQUALITY RQ-HPV Screen, a new assay based on real time PCR that targets the E6-E7 region of 14 high-risk human papillomaviruses, meets the criteria for primary cervical cancer screening.MethodsAs required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with that of a clinically validated reference test (Hybrid Capture 2, HC2). The reproducibility of the device was assessed as well. The clinical samples used to test the hypothesis of non-inferiority and to asses reproducibility comprised 910 and 536 cervical specimens respectively. All specimens were originating from a population-based screening cohort.ResultsThe study demonstrates that both the clinical sensitivity and specificity of REALQUALITY RQ-HPV Screen are non-inferior to those of HC2. In addition, an adequate intra- and inter-laboratory reproducibility has been reached by the test.ConclusionsREALQUALITY RQ-HPV Screen fulfils all the requirements of the international guidelines and can be considered clinically validated for primary cervical cancer screening purposes.

Amyloid beta-peptide (Abeta) is a natural peptide of about 39-42 amino acids, which can aggregate and accumulate into senile plaques, one of the main pathological features in Alzheimer's disease (AD). There is extensive evidence that neurodegenerative pathologies, such as AD, are associated with protein misfolding and environmental factors, such as heavy metals, that are known to pollute the environment and can be taken up by the organism in food. They can accumulate within organs and tissues, with sometimes dramatic effects. There is increasing evidence that heavy metals can interact with amyloid beta peptides, contributing to the neurodegenerative events of AD. We investigated the effects of Cd++, an environmental contaminant on AbetaP1-42 aggregation, incorporation and channel formation into planar lipid membranes made up of phosphatidylcholine: cholesterol (70:30, w/w). Our results suggest that Cd++ interferes both with channels already incorporated into membranes and with peptides in solution. These findings provide important clues to the effect of this environmental contaminant on AbetaP1-42 that similarly to other metal ions, such as copper, zinc, aluminium and iron, can lead to abnormal interactions with proteins, contributing to cell damage