1,721,199 research outputs found

    Role of the B1 Bradykinin Receptor and gC1qR/p33 in Angioedema

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    Patients affected by angioedema (AE) are subject to asymmetric, nonerythematous, nonpruritic, localized, transient, episodic swelling of deeper layers or submucosal tissues of the skin, oropharyngolaryngeal tissue, and/or gastrointestinal wall. The nonapeptide bradykinin (BK) may be largely responsible for the vascular permeability seen in most AE. During AE attacks, activation of the serine proteases leads to the release of BK. Enzymes expressed on the endothelial cell membrane can metabolize BK, producing the agonist of the B1R, which can then be upregulated by proinflammatory stimuli, suggesting that the blockade of B1R and B2R, or gC1q/p33, may provide novel therapeutic targets

    Use of chitin and its derivatives obtained from sustainable sources as an alternative to the use of chemical additives in the food production

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    Winemaking is a complex process in which the management of microbiological control plays a crucial role in determining the quality of the final product. Traditionally, the addition of sulphur dioxide (SO2) has been the main method for ensuring the microbiological stabilisation of wine, due to its broad spectrum of action against unwanted microorganisms and its ability to prevent oxidative phenomena. However, in recent years, interest toward tools as alternatives to SO2 has grown significantly due to concerns over its negative health effects on consumers and its potential organoleptic impact on wine. Scientific research has focused its efforts on finding alternative methods to reduce or eliminate the use of SO2, while maintaining the microbiological stability of the wine. Among the potential solutions, the use of chitosan, derived from sustainable sources such as insects, could represent a promising innovation. This type of chitosan not only might assure the microbiological stabilization of the wine, but, as a consequence of its source, has also a reduced environmental impact, meeting the needs of an increasingly sustainability-conscious wine industry. This Industrial PhD thesis sets out to explore chemical methods for the microbiological control of winemaking, analysing both traditional and more innovative treatments, with a focus on chitosan derived from alternative sources, such as insects. Through a critical review of the available evidence, the efficacy, limitations and effects of these alternatives on wine quality are discussed, offering an integrated view of future prospects for more sustainable winemaking. This project was financed by the Basilicata Region (Italy), the activities were carried out in collaboration with the industrial partner of the project ‘Cantina di Venosa’ located in Venosa (Potenza, Italy), University Institute of Vine and Wine Jules Guyot - University of Burgundy, Dijon (France) and the Department of Biosciences, Biotechnology and Environment - University of Bari ‘Aldo Moro’ (Italy). The activities were carried out following a scale-up approach, which allowed the transition from laboratory experiments to industrial-scale studies. The preliminary study of the literature was essential in order to plan the research activities to follow during the project. Indeed, Chapter 1 provides an overview of the chemical methods used for microbiological control in winemaking. The traditional use of sulphur dioxide (SO2) as the main antimicrobial agent to prevent microbial spoilage and maintain wine quality is emphasised. However, the growing interest in alternatives to SO2 is also discussed, as it may have negative health effects. Alternative chemical compounds, such as sorbic acid, dimethyl dicarbonate (DMDC), lysozyme and chitosan are examined, focusing on the latter and alternative, sustainable sources for its supply, such as insects. It is concluded that although these treatments are effective, there is still no single compound that can completely replace SO2. A combination of methods might be the best solution to reduce the sulphite content in wine. The first laboratory activities, reported in Chapter 2, involved the selection and study of several non-Saccharomyces yeast strains, potentially present during wine fermentation, with a focus on their resistance to commercial and insect-based chitosan. The strains were tested under controlled conditions to determine the resistance level to chitosan, in comparison to SO2 tolerance. This characteristic was assayed by using different approaches, which were the test on liquid and agarized media, added with different concentrations of antimicrobials, and the influence of SO2 and chitosan addition during laboratory-scale fermentations, using different combinations of the antimicrobials. These activities showed that many non-Saccharomyces yeast strains have medium/high resistance to chitosan; good results were obtained by the combined use of chitosan and low SO2 levels (20 mg/L) during inoculated fermentations with Saccharomyces cerevisiae. This approach might be a promising tool for production of low-sulphite wines. Another research step was addressed to evaluate the antimicrobial activity of chitosan against Brettanomyces bruxellensis, a yeast known to cause sensory defects in wines. Furthermore, the use of fungal chitosan is the current approved application for the control of these wine-contaminating yeasts during barrel aging. The study reported in Chapter 3 was conducted in a synthetic medium, and the effectiveness of three types of chitosan (from crustacean, insect and fungi) was compared. It was shown that chitosan from crustaceans and chitosan from insects significantly reduced the microbial population, showing greater efficacy than the fungal chitosan permitted in oenology. The evaluation of the effect of different chitosan types by using the flow cytometry technique on B. bruxellensis cells, in comparison to S. cerevisiae, confirmed the effectiveness of this compound only against Brettanomyces yeasts. Furthermore, insect-based chitosan showed better antimicrobial activity compared to the fungal chitosan currently permitted in oenology. Finally, after confirming the effectiveness of chitosan at laboratory scale, the scale-up approach included experiments at higher volumes to test the effectiveness under conditions closer to real production. Chapter 4 reports the results obtained by transferring the lab-scale tests to real vinification conditions. These activities concerned the artificial contamination with a B. bruxellensis strain of wine produced by the ‘Cantina di Venosa’ cellar and added with the different types of chitosan tested in the previous studies. The scale-up approach adopted in this study allowed to test the effectiveness of chitosan as a natural antimicrobial in winemaking and wine ageing. The results suggest that chitosan, especially those obtained from sustainable sources such as insects, could be a promising alternative to SO2 for both the production of low-sulphite wines and the protection of wine from contaminating yeasts during storage and ageing

    Endothelial cells are a target of both complement and kinin system.

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    The endothelium is a continuous physical barrier that regulates coagulation and selective passage of soluble molecules and circulating cells through the vessel wall into the tissue. Endothelial cells may contact components of the complement, the kinin and the coagulation systems and their functional activity can be influenced by these interactions. Therefore, complement activation products can induce pro-inflammatory and pro-coagulant responses by endothelial cells. Moreover complement can regulate the release of kinins on the endothelial cell surface influencing the vascular leakage. The aim of this review is to discuss the complex interplay that can be established among the endothelium, the complement proteins or its activation products, and the kinin system

    Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases.

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    Abstract The endothelial layer represents a continuous physical barrier that controls coagulation and allows selective passage of soluble molecules and circulating cells across the vessel wall into the tissue. The functional activity of the endothelial cells may be influenced by their interaction with components of the complement system. In this review we shall discuss the complex interplay that can be established between the endothelium and complement proteins or activation products. Endothelial cells may also secrete several complement components which contribute to the circulating pool. This process can be regulated by cytokines and other pro-inflammatory stimuli. In addition, complement activation products stimulate endothelial cells to acquire a pro-inflammatory and pro-coagulant status. Expression of regulatory molecules on the cell surface provides protection against an undesired attack by complement activation products. Unrestricted complement activation under pathological conditions may lead to structural and functional changes of the endothelium resulting in vascular disease
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