Search

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder due to three frequent mtDNA mutations affecting complex I and leading to retinal ganglion cells degeneration and optic atrophy. Penetrance is incomplete, even when the mtDNA mutation is homoplasmic. The modifying role of nuclear genes is assumed to play a role in expressing the pathology. Biochemical investigations in LHON established that bioenergetic inefficiency is combined with increased production of reactive oxygen species. In this study we explored the possible role of the antioxidant machinery as modifier for the expression of LHON. We screened functional polymorphisms in the manganese and copper/ zinc superoxide dismutases (MnSOD, Cu/ZnSOD), in the glutathione peroxidase (GPx) and in the catalase (CAT). We first investigated a large LHON Brazilian/Italian pedigree, comparing affected individuals (n = 26) with unaffected mutation carriers (n = 41). The only significant association (p = 0.036) was found with the MnSOD Ala9Val variant, for which the Ala/Val genotype was most frequent in the affected subjects (65.4%), whereas the Val/Val genotype was most frequent in the carrier individuals (55.3%). Furthermore, we collected 111 Italian LHON unrelated probands and we found that the Ala9Val variant distribution overlapped that found in the Brazilian affected individuals, being significantly different from an equivalent control group of Italians matched for age and sex (p = 0.05). We conclude that only the MnSOD variant seems to modulate the risk of becoming affected. Contrary to the prediction the protective allele is Val, which affects the targeting sequence for mitochondrial import inducing a partial stalling of MnSOD transport, thus lowering the final amount of active enzyme in the matrix. We propose that high MnSOD activity in mitochondria of LHON subjects, which overproduce superoxide, may become deleterious if downstream GPx fails to buffer the excess H2O2.

Vascular and bronchial endocasts represent a useful instrument to study the ramification pattern of these structures. Casts have been made from different materials, such as waxes in ancient times and, more recently, silicon-like compounds or resins (see e.g. Mercox) to study the finest details. These techniques are valuable for small specimens, whereas they are inadequate for very large organs, where technical difficulties require the development of specific instrumentation. In this study we present a new simple injection technique, based on expanded polyurethane, which allows preparing vascular and bronchial trees for macroscopic and microscopic studies. The new injection technique is very easy to carry out, since the propulsion is provided by compressed air, and it does not require special instrumentation. To this aim, endocasts of the entire tracheal-bronchial tree and casts of vascular kidney from different animals were prepared. The specimens have a very low weight, show the finest ramifications, and are very stable and resistant to mechanical stress. To examine microscopically the details of the casts, specimens from the kidney cast were also analyzed by scanning electron microscopy, revealing good preservation of microcirculatory structures, functional sphincters and endothelial cell impressions. Therefore, the technique may be useful for macroscopic studies of large specimens, retaining sufficiently fine details.

This study was performed to study the microvascular changes that occur during the first 12 hours after traumatic brain injury (TBI) using the corrosion casting technique.The authors performed a qualitative and quantitative morphological study of the changes in cerebral vessels at acute (3 hours) and subacute (12 hours) stages after experimental TBI. They used a model of controlled cortical impact (CCI) injury induced by a recently developed electromagnetic device (impactor), focusing their observations mainly on the microvascular alterations responsible for the formation and maintenance of tissue edema and consequent brain swelling during the first hours after TBI. They used corrosion casting, scanning electron microscopy (SEM), light microscopy, and transmission electron microscopy (TEM) to obtain a morphological qualitative map with both 2D and 3D details.Scanning electron microscopy analysis of vascular casts documented in 3 dimensions the typical injuries occurring after a TBI: subdural, subarachnoid, and intraparenchymal hemorrhages, along with alterations of the morphological characteristics and architecture of both medium-sized and capillary vessels, including ectasia of pial vessels, sphincter constrictions at the origin of the perforating vessels, focal swelling of perforating vessels, widening of intercellular junctions, and some indirect evidence of structural impairment of endothelial cells. All of these vascular alterations were confirmed in 2D analyses using light microscopy and TEM.The corrosion casting-SEM technique applied to a CCI experimental model proved to be a reliable method for studying the pathophysiology of the vascular alterations occurring at acute and subacute stages after CCI injury. It was also possible to obtain topographical localization of the vascular and cellular events that usually lead to hyperemia, edema, and brain swelling. Moreover, by applying informatic software to anatomical images it was possible to perform quantification and statistical analysis of the observed events.

The present work shows the results of the investigation conducted on the coarse ware from two important archaeological sites in the city of Cagliari (Sardinia, Italy), respectively the S. Eulalia Church underground and Vico III Lanusei. The excavations, carried out during the 90s, discovered a great quantity of coarse ware shards regarding coarse ceramic pastes. The study of these materials was particularly interesting and suggested to advance further investigations on a particular group of fire ware artefacts which belong to the Pantellerian Ware, according to a first formal macroscopical analysis. This work reports the results of an archaeological and archaeometrical investigation on these artefacts, carried out to verify the reliability of this first attribution, comparing there characteristics with the other productions discovered in Pantelleria and in northern Sardinia (particularly in Porto Torres area). In this we verified if the finds from Cagliari area were related to the Pantellerian Ware production, giving further information on the shapes exported in southern Sardinia.