HEAT SHOCK PROTEINS AND AUTOIMMUNE SYSTEM ACTIVATION IN IBD: ARTICULAR MANIFESTATIONS AND THE EPIDEMIOLOGICAL FREQUENCY IN ORTHPEDICS

clinical evidence suggest that arthritis is one of the complications of inflammatori bowel disease (IBD) of which the etiological causes are still not completely understood. Among the possible explanations the most probable theory is poor regulation of the intestinal immune system, which causes a cross-like immune reactivity against the resident micro flora. Arthritis is these subjects involves different joints and is asymmetric, with greater involvement of the large joints of the lower limbs. Joints may also be involved with the spinal forms of sacroileitis and ankilosing spondylitis. This clinical evidence explains the existence of Lesnioski-Crohn's disease, a variant of IBD in which patients have bone joint problems that may also be the primary manifestations of the disease

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

Observation of Collider Muon Neutrinos with the SND@LHC Experiment

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at √ s = 13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb − 1 . The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2 < η < 8.4 , inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν μ interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν μ signal

CHRONIC INFLAMMATORY BOWEL DISEASES IN PATIENTS WITH ORTHOPEDIC MANIFESTATION. COMPARISON WITH THE DATA REPORTED IN INTERNATIONAL LITERATURE

In Inflammatory Bowel Disease (IBD) the suspected etiological cause is a dysregulation of the intestinal immune system, in which it is possible to determine a cross-like immune reactivity against the resident microbiota; this mechanism explains the exsistence of Lesnioski-Chron's disease, a variant of IBD in which patients manifest osteoarticular problems that may also be the primary manifestation of the disease. The aim of this study was to compare some cases encountered by our research group at the University of Palermo with others reported in international literature on osteoarticular manifestations in IDB

BENEFICIAL EFFECT OF PROBIOTICS ADMINISTRATION IN INFLAMMATORY BOWEL DISEASE AND RELATED SPONDYLOARTHROPATHY: A PROSPECTIVE STUDY

Therapeutic treatment for inflammatory bowel disease (IBD) may follow different approaches, systemic as well as local, especially when the target is the osteoarticular apparatus. Although some clinical trials have suggested benefits from probiotics administration in IBD, there is still a great deal of controversy on their use. the aim of this study was to further investigate the effects of probiotics in patients with IBD and related spondyloarthropathy. Fifty-nine patients affected by IBD with extra-intestinal involvement where evaluated from 2006 to 2010. Twenty-eight patients received administration of a standard therapy with mesalazine and 31 where treated with the same therapy plus probiotic supplement. Comparative analysis performed between the 2 groups showed a better clinical response and a reduction of occasional corticosteroids administration in patients receiving probiotic administration. Conclusions: this prospective study supports the beneficial effects of probiotic administration in improving the clinical response to standard therapy and in reducing the need for corticosteroids use. Large randomized trials would provide reliable and conclusive results in this field

Genotypic and environmental effects on wheat technological and nutritional quality

International audienceTechnological (processing performance and end-product) and nutritional quality of wheat is in principle determined by a number of compounds within the wheat grain, including proteins, polysaccharides, lipids, minerals, heavy metals, vitamins and phytochemicals, effecting these characters. The genotype and environment is of similar importance for the determination of the content and composition of these compounds. Furthermore, the interaction between genotypes and the cultivation environment may play a significant role. Many studies have evaluated whether the genotype or the environment plays the major role in determining the content of the mentioned compounds. An overall conclusion of these studies is that except for compounds encoded by single major genes, importance of certain factors mainly depend on how wide environments and how diverse cultivars are within these comparative studies. Comparing environments all over, e.g. across Latin America, ends up with a high significance of the environment while large studies including genotypes of wide genetic background result in a significant role for the genotype. In addition, for some technological properties and components, genotype has a higher effect (e.g. grain hardness and gluten proteins), while environment influences stronger on others (e.g. protein and mineral content).Content and concentration of proteins, but also to some extent of starch, some non-starch polysaccharides and lipids, are essential in determining the technological quality of a wheat flour. For nutritional quality of the flour, the majority of the compounds are together the important determinant. Thus an increased understanding of environmental effects is essential. As to how the environment is influencing the content of the compounds, there are some differences. The protein content and composition is strongly affected by environmental factors influencing nitrogen availability and cultivar development time. However, these two factors are impacted by a range of environmental (temperature, precipitation, humidity/sun hours, etc.) and agronomic (soil properties, crop management practices such as seeding density, nitrogen fertilizer application timing and amount, etc.) components. Thus, to understand the interplay between the various environmental and agronomic factors impacting the technological quality of a wheat flour, modeling is a useful tool. Several other compounds, including minerals and heavy metals, are to a higher extent determined by site specific variation, resulting in similar rankings of entries across locations, although the total content is varying among years. The bioactive compounds and vitamins are a part of the defense mechanisms of plants and thus there is a variation in these compounds depending on prevailing biotic and abiotic stresses (heat, drought, excess rainfall, nutrition, diseases and pests). Thus, even for nutritional quality of wheat, incorporating all compounds of relevance in the evaluation would benefit from modeling tools