cepted that free radicals play a role in carcinogenesis and that BPH should be considered a premalignant condition which may evolve into prostate cancer. High OS parameters and low antioxidant activity are more prominent in prostate cancer patients compared with BPH and controls. Conclusions: Further studies are needed to clarify the potential role of antioxidants in BPH also in view of preventing the progression to prostate cancer. IntroductionBenign prostatic hyperplasia (BPH) is a prevalent and chronic progressive disease that may be correctly defined as prostate gland enlargement secondary to hyperproliferation of stromal and glandular cells, with predominance of mesenchymal cells [1] . It is an extremely common disease of ageing men and carries a distressingly high morbidity because of its irritative and obstructive symptoms. The etiology and pathogenesis of BPH are not well understood [2] . Key WordsAntioxidants · Benign prostatic hyperplasia · Oxidative stress Abstract Background: Several parameters including inflammatory mediators, hormones, dietary factors, inflammatory genes, and oxidative stress (OS) have been considered to play a role in the development of benign prostatic hyperplasia (BPH). Prostate tissue damage and OS may lead to compensatory cellular proliferation with resulting hyperplastic growth. Methods: We searched MEDLINE for articles in English published up to March 2014 using the key words 'oxidative stress', 'antioxidants' and 'benign prostatic hyperplasia'. Results: Prostatic inflammation can cause the generation of free radicals. The extent of oxidative damage can be exacerbated by a decreased efficiency of antioxidant defense mechanisms. The balance between OS and the antioxidant component also has a role in developing prostate disease. Several works show the role of oxidant products and of depletion of antioxidant substances in BPH patients. It is ac-

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Its neuropathological hallmarks include deposition of beta amyloid (Aβ) fibrils in senile plaques. Numerous biochemical events, leading to Aβ neurotoxicity in AD, have been proposed and it seems that neuroinflammation plays a prominent role among these. Thus, since inflammatory processes and oxidative stress are considered to play an important role in neuroinflammatory disorders and in AD pathology, in the present work we decided to test a new composite, which is a formulation constituted of an anti-inflammatory compound such as palmitoylethanolamide (PEA) and the well recognized antioxidant flavonoid luteolin (Lut), subjected to an ultra-micronization process, here designated co-ultraPEALut. We investigated the effect of co-ultraPEALut in both an in vitro and ex vivo organotypic model of AD. For the in vitro model, we used human neuronal cells, obtained by differentiating SH-SY5Y neuroblastoma cells into sustainable neuronal morphology. These well differentiated cells express features specific to mature neurons, such as synaptic structures and functional axonal vesicle transport, making this new concept for in vitro differentiation valuable for many neuroscientific research areas, including AD. Differentiated SH-SY5Y cells were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 µM PEA) for 2 h. AD features were induced by Aβ₁₋₄₂ stimulation (1 µM). Twenty-four hours later cell vitality was evaluated by the colorimetric MTT assay, whereas the neuroinflammation underling AD was observed by Western blot analysis for IκBα degradation and nuclear factor-κB traslocation, as well as glial fibrillary acidic protein expression. For the organotypic model of AD, hippocampal slice cultures were prepared from mice at postnatal day 6 and after 21 days of culturing the slices were pre-treated with co-ultraPEALut (reference concentrations: 27, 2.7 and 0.27 µM PEA) for 2 h and then incubated with Aβ₁₋₄₂ (1 µg/ml) for 24 h. Pre-treatment with co-ultraPEALut significantly reduced inducible nitric oxide synthase and glial fibrillary acidic protein expression, restored neuronal nitric oxide synthase and brainderived neurotrophic factor and reduced the apoptosis. Taken together our results clearly showed that co-ultraPEALut is able to blunt Aβ-induced astrocyte activation and to exert a marked protective effect on glial cells. These findings suggest that the association of co-ultraPEALut may provide an effective strategy for AD.

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Parkinson's disease (PD) is a disorder resulted by degeneration of dopaminergic neurons. To counteract the neuroinflammation and oxidative stress of PD, we decided to test a new composite constituted by palmitoylethanolamide (PEA) and luteolin (Lut), in a mass ratio of 10:1, respectively (co-ultraPEALut). In this study the neuroprotective property of the new compound was investigated. For the in vivo model of PD, mice received four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Starting 24 h after the first administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we treated animals with co-ultraPEALut daily until 7 days. On day 8, brains were processed for Western blotting and immunohistochemical analysis. Treatment with co-ultraPEALut reduced the specific markers of PD (tyrosine hydroxylase immunopositive), and the increased levels of activated astrocytes and pro-inflammatory cytokines as well as inducible nitric oxide synthase. Further, the possible association of autophagy with the beneficial effects of coultraPEALut. Western blot analysis and immunofluorescence staining showed that co-ultraPEALut administration increased autophagy process. These data were confirmed by an in vitro model, using SH-SY5Y neuroblastoma cells. Western blot analysis showed that co-ultraPEALut pre-treatment maintained high Beclin-1 and p62 expression, while continued to inhibit the p70S6K expression. Altogether, these results put forward that treatment with co-ultraPEALut is able to modulate both the neuroinflammatory process and the autophagic pathway involved in PD, actions which may underlie its neuroprotective effect.

Background Tranexamic acid is a synthetic lysine derivate that exerts its antifibrinolytic effect by reversible blocking lysine binding sites on plasminogen preventing fibrin degradation. It is widely used for haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Aim The aim of our work was to review the literature regarding the best evidence on tranexamic adverse reactions and to describe them according to the apparatus involved. Methods The literature was searched for publications on tranexamic acid adverse reactions, adverse events, using MEDLINE, Scopus, Embase, Web of Science and Google Scholar. Results In the light of the results, seems to be clear that tranexamic acid causes several adverse reactions involving different apparatus. Hypersensitivity reactions, cerebrovascular infarction, myocardial infarction and pulmonary embolism seem to be the more common tranexamic acid adverse reactions. Conclusion Despite the wide use of tranexamic acid the number of cases reported for type of reaction is relatively low, thus causing a not easy understanding of mechanisms underlying the adverse reaction. Therefore, it would be appropriate to conduct epidemiological studies on a large scale in order to better understand risk factors favoring tranexamic acid adverse reactions and encourage pharmacovigilance in medical practice.

The miRNAs seem to influence regulatory mechanisms of inflammation in both inducing and contrasting acute and chronic skin inflammation. They also seem to be useful instruments in identifying and staging diseases such as dermatitis and other inflammatory skin diseases. Also, the potential application of miRNAs in genetic therapies demonstrated its efficacy on animal models.

Quercetin is a major constituent of various dietary products, which is increasingly being investigated as a therapeutic option in the oncological field. It has attracted extensive interest due to its ability of interacting with different molecular targets and evoking a broad spectrum of chemopreventive and anticancer activities. In this review, we have tried to present and critically discuss its potential against an extensive range of cancers including lung, ovarian, prostate, breast, colorectal, bladder cancers. We also highlighted studies that combined quercetin with standard anticancer drugs and delivered it via novel techniques and included a detailed description of its proposed mechanism(s) of action, and pharmacokinetic and safety profile. KeywordsQuercetin, cancer, bioavailability, mechanisms of action, in vivo and in vitro studies Funding Nothing to declare.

Vibrio anguillarum is the etiological agent of a fatal hemorrhagic disease known as vibriosis that affects a wide range of fish species, causing severe economic losses. Several investigations have been carried out to elucidate the virulence mechanisms of this pathogen and to develop rapid detection techniques and effective disease-prevention strategies. The aim of our study was to evaluate the most effective way to induce mild enteritis in a fish model, in order to allow further applications. The experiments were carried out using 2 methods of administration of V. anguillarum serotype O1 to adult zebrafish Danio rerio: via intraperitoneal injection and via ingestion of infected Artemia nauplii. The results showed that the intraperitoneal administration often caused massive fish death due to severe systemic involvement. In our experiments, the effect of intraperitoneal infection was evident 48 h post infection, with cumulative mortality within 7 d post infection with severe histopathological changes in kidney hematopoietic tissue and in the intestine. In contrast, oral infection via Artemia did not show systemic involvement and only a moderate degree of inflammatory influx of the mucosa, a partial recovery at 12 d post infection, and no mortality. For these reasons, oral infection with live food appears to be the most effective method to induce mild enteritis with a local inflammatory response.