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G Lungarella

Publications and source records attributed to G Lungarella.

85 records · Page 5Linked to original sources
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Lung injury and degradation of extracellular matrix components by Aspergillus fumigatus serine proteinase.

Aspergillus fumigatus produces a variety of extracellular proteinases that are believed to be virulence factors towards Aspergillus-related lung disease. Among Aspergillus proteinases, the serine proteinase is thought to play a major virulent role because of its widespread production. Nevertheless, evidence of direct pulmonary injury caused by the A. fumigatus serine proteinase is still lacking. The purpose of our work was: (1) to provide evidence for a pivotal role of A. fumigatus serine proteinase in producing lung injury in an animal model, and (2) to investigate the broadness of the substrate specificity of the proteinase towards extracellular matrix components. To achieve this aim, the proteinase from an A. fumigatus strain isolated from human airways was purified by a four-step procedure, including cation exchange and hydrophobic interaction. High-performance capillary electrophoresis, SDS-PAGE, determination of K(m) towards synthetic substrates, and inhibitory studies were used to further characterize the A. fumigatus serine proteinase. With reference to extracellular matrix components, the A. fumigatus serine proteinase was shown to degrade human lung elastin at a higher rate than an equimolar amount of human neutrophil elastase. Human lung collagen, type I and type III collagens, as well as fibronectin, were quickly digested by the A. fumigatus serine proteinase. Finally, mice intratracheally injected with the proteinase showed a significant degree of lower respiratory tract destruction. We conclude that the A. fumigatus serine proteinase is capable per se of hydrolyzing the major structural barriers of the lung.

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Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice.

Bleomycin (BLM) induction of lung fibrosis in mice is an established model to study the mechanism of pulmonary fibrosis. Cytokine secretion has been implicated as a fundamental component of the lung fibrotic process observed in response to BLM. Among the cytokines implicated in lung fibrosis, Tumor necrosis factor (TNF) alpha has been considered to play a fundamental role. In the present study, we characterized the cellular sources of TNF during BLM-induced lung injury and examined the importance of TNF receptors in this process. To characterize the expression of TNF, we utilized two strains of mice, one sensitive (C57BL/6) and one resistant (BALB/c) to BLM-induced lung injury. Mice received BLM (120 mg/kg total) or saline, as control, by multiple subcutaneous injections. BLM induced the development of inflammation in subpleural areas only in the lungs of BLM-sensitive mice. These subpleural areas were characterized by infiltration of CD68-positive macrophages and increased collagen deposition. BLM enhanced the expression of TNF mRNA in BLM-sensitive, but not in BLM-resistant, mice. In situ hybridization studies localized the expression of TNF in the areas of BLM-induced inflammation in 6% and 27% of macrophages at 14 and 21 days post BLM treatment. In addition to TNF, BLM exposure resulted in the upregulated expression of transforming growth factor (TGF)-beta 1, but not interleukin (IL)-1, mRNA in the lungs of both murine strains at 14 and 21 days. This upregulated expression of TGF-beta 1 mRNA was greater in the lungs of BLM-sensitive mice. In separate experiments, double TNF receptor knockout mice were exposed to BLM. These animals demonstrated an increased expression of TNF, but not TGF-beta 1, mRNA in response to BLM and did not exhibit histologic evidence of lung injury following BLM exposure. In summary, the upregulation of TNF mRNA in macrophages correlated with the appearance of inflammation following BLM exposure and was limited to the BLM-sensitive strain. Furthermore, in addition to the release of the TNF ligand, it appears that the presence of TNF receptors is necessary for the development of BLM-induced lung injury, and signaling through these receptors may contribute to the regulation of the TGF-beta 1 mRNA expression observed in response to bleomycin. These results provide further support for a role of macrophages and TNF in the induction of lung inflammation.

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PubMedDate not supplied

Ultrastructural abnormalities in respiratory cilia and sperm tails in a patient with Kartagener's syndrome.

Ultrastructural abnormalities of spermatozoa and respiratory cilia have been reported in a male patient with Kartagener's syndrome and infertility. In this patient both respiratory cilia and sperm tails showed defects in radial spokes and dynein arms. Such defects are heretofore undescribed in the same subject with immotile cilia syndrome. Absence of both inner and outer dynein arms and absence of the inner dynein arms only were detected in spermatozoa and in respiratory tract cilia, respectively. Moreover, total absence of axoneme was seen in several sperm tails from this patient. The possibility that the features described are of genetic origin is discussed.

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PubMedDate not supplied

[Biocompatibility and physico-mechanical properties of the new Venezia root canal sealer. In vivo and in vitro test according international standards].

At the moment, in most countries, there are laws in force which impose to the manufacturers well regulated testing in order to investigate and guarantee an acceptable biocompatibility of medical devices before their commercialization. Many international laboratories are committed to the definition of investigation methodologies and to the evaluation of biocompatibility in order to obtain research standards, capable to provide reproducible and comparable objective quantitative data. In every country, technical committees were put together for a standardization of methodological procedures, followed by European and international technical boards which proposed and codified methodologies and investigation approaches. UNI-EN-ISO laws contain all the results and constitute a reference point for any consideration on or evaluation of the biocompatibility of a medical device. Based on these laws, we evaluated the biocompatibility and determined the physical-mechanical characteristics of the new Venezia (Cabon S.p.A.) endodontic ZOE sealer. The Subcutaneous Implant Technique according Safavi et al. (in vivo test, ISO 10993: 1-6 Biological evaluation of medical and dental materials and devices) and Autian test of Emolysis on Rabbit Erythrocytes (in vitro test) allowed us to evaluate a good biocompatibility of the new product. Furthermore, its Setting and Working time, its radiopacity, Solubility and its Flow value completely satisfy the requirements of international standards (ISO/DIS 6876 Dental root Canal Sealing Materials). We can finally deduce that Venezia fulfil the ideal functional properties of an endodontic cements.

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PubMedDate not supplied

Genetically modified animals as models of pulmonary disease.

Improvements in biological research and the development of new techniques for human health protection require animal experimentation of various species. In particular, animal models are always necessary to test new therapies for the treatment of various human diseases. The latest advances in molecular biology involving genetic modification are aimed at developing new animal models of human diseases that are not present in spontaneous murine broods or obtainable with other experimental manipulations. Transgenic techniques and, in particular, the possibility to directly modify specific genetic information in the experimental animal have led to the acquisition of important knowledge on the physiologic functions of many proteins and their function in the course of various diseases. The advent of new transgenic animals is opening up new and interesting frontiers, full of hope and opportunity, for the research into pulmonary diseases. New advances in cystic fibrosis, emphysema, and pulmonary fibrosis have been made through the study of a large number of proteins implicated in the complex of acute and chronic inflammatory processes of lung parenchyma, which are responsible for permanent changes in organ structure and function. Recent studies carried out on murine inbred strains have yielded significant new data on the multifactor origin of pulmonary disease, because of their correlation with the major histocompatibility complex (H2 in mice) or through the different genetic map of the strains. Today it is possible to outweigh or potentiate the function and expression of some genes, obtaining a deficit or abundance, respectively, of specific proteins. These techniques have permitted and will continue to permit the development of new models of human disease, leading to further therapeutic advances as a consequence.

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PubMedDate not supplied

In vitro and in vivo effects of chloramine T on rat serum elastase inhibitor.

Recent studies have shown that oxidizing agents may block the elastase inhibitory activity of alpha 1-antiproteinase in humans and some animal species. It has been postulated that this protein plays a critical role in modulating the activity of the neutral proteinase, i.e. elastase, in the lung; its inactivation has been implicated in the destruction of lung tissue seen in emphysema. In this work, we have studied the inactivation in vitro of rat serum elastase inhibitor by chloramine T (CT) and whether the in vivo use of the same oxidizing agent in the development of a functional model of alpha 1-antiproteinase deficiency in the rat is feasible. Although serum alpha 1-antiproteinase is readily inactivated in vitro by CT, it was observed, in vivo, that serum elastase inhibitory capacity was reduced to about 28-35% of initial levels 1-3 h after CT injection, and returned to control values within 9 h. Therefore, the in vivo study demonstrated that in the rat a functional model of alpha 1-antiproteinase deficiency cannot be achieved by inactivation of the protein molecule with CT. The relatively short half-life (1.45 h) of the serum elastase inhibitor found in normal rats is consistent with a rapid synthesis of the protein molecule, which might contribute to the fast recovery of the elastase inhibitory capacity observed in experimental animals after CT administration.

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