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Paratuberculosis is an infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is an intracellular pathogen with a possible zoonotic potential since it has been successfully isolated from the intestine and blood of Crohn’s disease patients.Since no cure is available, after the detection of the disease, animal culling is the sole applicable containment strategy. However, the difficult detection of the disease in its subclinical form, facilitates its spread raising the need for the development of effective diagnosis and vaccination strategies. The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. These proteins were chosen according to a previously published immunoproteomics approach. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The retrieved peptide sequences were analyzed for their specificity and cross-reactivity. The final aim is to employ the discovered peptides sequences as a filtered library useful for early-stage diagnosis and/or to be used in novel multi-subunit or recombinant vaccine formulations.

Mycobacterium avium subsp. paratuberculosis (MAP) is the cause of a chronic enteritis of ruminants (bovine paratuberculosis (PTB)-Johne's disease) that is associated with enormous worldwide economic losses for the animal production. Diagnosis is based on observation of clinical signs, the detection of antibodies in milk or serum, or evaluation of bacterial culture from feces. The limit of these methods is that they are not able to detect the disease in the subclinical stage and are applicable only when the disease is already advanced. For this reason, the main purpose of this study is to use the MAP proteome to detect novel immunoreactive proteins that may be helpful for PTB diagnoses. 2DE and 2D immunoblotting of MAP proteins were performed using sera of control cattle and PTB-infected cattle in order to highlight the specific immunoreactive proteins. Among the assigned identifiers to immunoreactive spots it was found that most of them correspond to surface-located proteins while three of them have never been described before as antigens. The identification of these proteins improves scientific knowledge that could be useful for PTB diagnoses. The sequence of the identified protein can be used for the synthesis of immunoreactive peptides that could be screened for their immunoreaction against bovine sera infected with MAP. All MS data have been deposited in the ProteomeXchange consortium with identifier PXD001159 and DOI 10.6019/PXD001159.

Il contributo esamina l'e-pubblic procurement nella normativa europea e italiana all'interno del processo di dicitalizzazione dell'amministrazione. L'esigenza di semplificazione e modernizzazione il settore degli appalti pubblici, unitamente alla necessità di giungere ad una gestione efficiente ed organica degli stessi, spingono ad adottare strategie di implementazione dell'uso delle tecnologie informatiche e telematiche negli acquisti della pubblica amministrazione, sia a livello nazionale, sia a livello europeo. E' opinione dominante che l'elettric pubblic procuremente costituisce uno strumento in grado di garantire il rispetto dei principi generali di massima trasparenza, concorrenza, economicità e rapidità nello svolgimento delle gare d'appalto. Tuttavia, l'instaurazione di un rapporto in via telematica tra amministrazione appaltante e concorrenti, comporta complessi problemi di natura informatica e telematica che spesso costituiscono un ostacolo alla realizzazione in via concreta dei principi citati. Il contributo evidenzia il contenuto di siffatti aspetti.

Background: Non-alcoholic fatty liver disease, one of the most prevalent liver disorders in Western countries, is characterized by hepatic accumulation of triglycerides. Bile acids have long been known to affect triglyceride homeostasis through a not completely understood mechanism. Aim: To analyse the effects of two different manipulations of bile acid circulation on non-alcoholic fatty liver disease. Methods: Two animal models of non-alcoholic fatty liver disease were developed by either feeding rats with a choline deficient or with a high fat diet. After 4 weeks, rats were randomized to undergo either bile duct ligation, sham operation or cholic acid administration. Results: During cholestasis there was an increased CYP7A1 expression, the rate limiting enzyme in bile acid synthesis, and a reduction of hepatic concentration of oxysterols, ligands of the liver X receptors. Target genes of the liver X receptors, involved in fatty acid and triglyceride synthesis, were down-regulated in association with decreased hepatic triglyceride content and improvement of fatty liver. Administration of cholic acid, ligand of farnesoid X receptor, also had a beneficial effect on fatty liver in rats on choline deficient diet. Conclusion: These results indicate that pharmacological approaches increasing the expression of CYP7A1 or stimulating farnesoid X receptor pathway could represent a promising treatment for non-alcoholic fatty liver disease. © 2012 Editrice Gastroenterologica Italiana S.r.l

Background/aim: Hepatic bile acid synthesis is the main mechanism whereby the organism can degrade cholesterol. Plasma levels of 7 -hydroxy-4-cholesten-3-one have been reported to reflect bile acid synthesis and the expression or activity of the limiting enzyme of the main biosynthetic pathway, cholesterol 7 -hydroxylase. Aim of this study was to correlate the levels of this metabolite with the rates of cholesterol 7 -hydroxylation in vivo, a direct measurement of bile acid synthesis, in hyperlipidemic patients. Design: Concentrations of 7 -hydroxy-4-cholesten-3-one were assayed by gas¿liquid chromatography: mass spectrometry in plasma samples obtained in 18 patients with primary hyperlipoproteinemia who previously underwent determination of cholesterol 7 - hydroxylation rates in vivo by tritium release analysis. Both determinations were performed in basal conditions and after treatment with hypolipidemic drugs (the fibric acid derivatives gemfibrozil and bezafibrate, cholestyramine alone or associated with simvastatin). Results: Changes in plasma 7 -hydroxy-4-cholesten-3-one profile closely reflected in vivo cholesterol 7 -hydroxylation rates during treatment with fibrates, cholestyramine and cholestyramine plus simvastatin. When plotting determinations from all studies (n = 40), a very strict correlation was disclosed between plasma 7 -hydroxy-4-cholesten-3-one and cholesterol 7 -hydroxylation rates (r = 0.81, P < 0.001). Conclusions: Plasma 7 -hydroxy-4-cholesten-3-one closely mirrors measurements of cholesterol 7 -hydroxylation rates in vivo in hyperlipidemic subjects and therefore stands as a reliable marker of global bile acid synthesis. In view of the correlation observed, these data may help to interpret changes of plasma levels of this metabolite in terms of cholesterol balance quantification. © 2008 Elsevier Inc. All rights reserved.