Impact of Deep-seated Gravitational Slope Deformation on urban areas and large infrastructures in the Italian Western Alps.

Deep-seated Gravitational Slope Deformations (DsGSDs) are huge ground-deformation slow evolving phenomena, highly widespread in alpine territory. Their long-lasting evolution, with continuous deformation rate, may represents a natural hazard, able to endanger various anthropic structures and infrastructures. Until today, the development of technical and regulatory tools, aimed to effectively manage the interactions between DsGSDs and anthropic elements, has been generally lightly considered in risk management and land use planning. The definition of the type and severity of impacts on the anthropic elements, becomes increasingly important in terms of urban planning and risk management, and deserve an update in the current adopted procedures. Focusing on the Western Italian Alps, we implemented an interdisciplinary analysis, based on multi-source data, by means of geoinformatics, remote sensing and archive consultation approaches. Intersecting DsGSDs available information with the urbanized territory in a Geographic Information System environment, we obtained, despite the high data heterogeneity, an overall framework of the existing interactions. Specifically, we defined the interactions between these large phenomena and buildings, roads and rail networks, and linear infrastructures, as penstocks, waterworks or dams, also highlighing the state of activity of the inventoried phenomena. Moreover, we analysed the degree of the DsGSD impacts on the anthropic elements, detecting and classifying all the documented damages within the Italian Western Alps territory. The obtained results highlight the need for an innovative approach in DsGSDs risk assessment, both in terms of the definition of their behavior over time and of their impacts on the anthropic elements, for a more effective land use planning and a proper handling of these phenomena in the legislation framework.

A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.

In many parkinsonian syndromes, neuromelanin (NM)-containing dopaminergic neurons of the substantia nigra (SN) are selectively targeted by the noxius pathogens. Studies of the constitutional and functional features of human NM allow the formulation of a logical hypothesis on its role in parkinsonian syndromes. In the early stages, NM synthesis and iron-chelating properties may act as a powerful protective mechanism, delaying symptom appearance and/or slowing disease progression. Once these systems have been exhausted, the pathogenic mechanisms affecting cytoplasmic organelles other than NM destroy NM-harboring neurons, with consequent pouring out of NM granules. These in turn activate microglia, causing release of nitric oxide, interleukin-6 and tumor necrosis factor-alpha, thus becoming an important determinant of disease aggravation. Neuromelanin appears to be a suitable target for devising chemical agents that might modify the course of these diseases.

Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability.

In this study a comparative analysis of iron molecules during aging was performed in locus coeruleus (LC) and substantia nigra (SN), known targets of Parkinson's Disease (PD) and related disorders. LC and SN neurons, especially the SN pars compacta, degenerate in PD and other forms of parkinsonism. Iron and its major molecular forms, such as ferritin and neuromelanin (NM), were measured in LC and SN of normal subjects at various ages. Iron levels were lower, H-ferritin/iron ratio was higher and the iron content in NM was lower in LC than in SN. Iron deposits were abundant in SN tissue, very scarse in LC tissue and completely absent in pigmented neurons of both SN and LC. In both regions H- and L-ferritins were present only in glia. This suggests that in LC neurons iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM. Ferritins accomplish the same buffering function in glial cells.

Amyloid beta and neuromelanin--toxic or protective molecules? The cellular context makes the difference.

Alzheimer's disease (AD) and Parkinson's disease (PD) share several pathological mechanisms. The parallels between amyloid beta (Abeta) in AD and alpha-synuclein in PD have been discussed in several reports. However, studies of the last few years show that Abeta also shares several important characteristics with neuromelanin (NM), whose role in PD is emerging. First, both molecules accumulate with aging, the greatest risk factor for AD and PD. Second, in spite of their different structures, Abeta and NM have similar characteristics that could also lead to neuroprotection. Metals are required to catalyze their formation and they can bind large amounts of these metals, generating stable complexes and thus playing a protective role against metal toxicity. Moreover, they may be able to remove toxic species such as oligopeptides and excess cytosolic dopamine. Third, both Abeta and NM have been implicated in parallel aspects of the neuronal death that underlies AD and PD, respectively. For example, both molecules can activate microglia, inducing release of toxic factors such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). A careful analysis of these parallel effects of Abeta and NM, including their seemingly paradoxical ability to participate in both cell death and protection, may lead to an improved understanding of the roles of these molecules in neurodegeneration and also provide insights into possible parallels in the pathological mechanisms underlying AD and PD.

Neuromelanin inhibits enzymatic activity of 26S proteasome in human dopaminergic SH-SY5Y cells.

Recently, impairment of the ubiquitin-proteasome system is suggested to be responsible for the neuronal death in ageing and Parkinson's disease. The specific degeneration of dopamine neurons containing neuromelanin (NM) suggests that NM itself may be involved in the cellular dysfunction and death, even though the direct link has never been reported. We examined the effects of NM isolated from the human substantia nigra on the proteasome activity in human dopaminergic SH-SY5Y cells. NM reduced the activities of 26S proteasome, as shown in situ using a green fluorescent protein homologue targeted to 26S proteasome and also in vitro using ubiquitinated lysozyme as a substrate. However, NM did not affect 20S proteasome activity in vitro. NM reduced the amount of PA700 regulatory subunit of 26S proteasome, but did not affect that of alpha- and beta-subunits of 20S proteasome. These results suggest that NM may inhibit the ubiquitin-26S proteasome system, and determine the selective vulnerability of dopamine neurons in ageing and related disorders.

The neuromelanin of human substantia nigra: structure, synthesis and molecular behaviour.

The pigmented neurons of the substantia nigra (SN) are typically lost in Parkinson's disease: however the possible relationship between neuronal vulnerability and the presence of neuromelanin (NM) has not been elucidated. Early histological studies revealed the presence of increasing amounts of NM in the SN with aging in higher mammals, showed that NM granules are surrounded by membrane, and comparatively evaluated the pigmentation of SN in different animal species. Histochemical studies showed the association of NM with lipofuscins. However, systematic investigations of NM structure, synthesis and molecular interactions have been undertaken only during the last decade. In these latter studies, NM was identified as a genuine melanin with a strong chelating ability for iron and affinity for compounds such as lipids, pesticides, and MPP+. The affinity of NM for a variety of inorganic and organic toxins is consistent with a postulated protective function for NM. Moreover, the neuronal accumulation of NM during aging, and the link between its synthesis and high cytosolic concentration of catechols suggests a protective role. However, its putative neuroprotective effects could be quenched in conditions of toxin overload.

[Care of skin infections in patients in peritoneal dialysis]. / Indagine descrittiva sulla cura dell'emergenza cutanea nel paziente in dialisi peritoneale.

The incidence of exit-site infections among peritoneal home-dialysis patients was quantified following for 1 year all home dialysis patients of 23 dialysis centres. The exit site conditions were observed and classified according to Twardowsky. When an infection occurred data on its treatment were collected. 393 patients were observed. The infection occurred in 40 patients (10.1%). 82.2% of patients wear a Tenckoff catheter, 3% do not protect the exit site with any kind of dressing. The strategies adopted by different centres vary for the choice of antiseptics, the suggested frequency of changes dressing and the routine use of nasal swabs. Due to the limited number of patients with infection no association was found between tunnel direction or frequency of dressing changes and infections occurrence. Discussion on controversial aspects and the definition of common guidelines for instance for frequency of dressing changes, use of antiseptics is warranted.

[Biologic dosage: its use in high irradiation]. / Dosimetria biologica: l'impiego nelle irradiazioni elevate.

It is impossible, in high-dose irradiation, using only one physical dosimeter, to get any valid information to quantify biological damage to subjects, even if it's possible to measure skin-dose with great accuracy. Radiosensibility changes from one subject to another, thus it's necessary to consider some specific biological parameters to evaluate physical conditions of treated patients. Hematological, genetic and chemical tests are valid means to determine the internally distributed dose and to choose the most appropriate therapeutic "protocol".