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Poultry biodiversity represents a key factor to improve poultry resilience and promote sustainable and low input farming systems. The EU and member states promote protection of livestock biodiversity and the development of alternative farming through funding projects such as “Local Chicken Breeds in Alternative Production Chain: Welfare, Quality and Sustainability” (funded by the Italian Ministry of Research and University). The aim of the present research was to identify among five different poultry genotypes Bionda Piemontese (BP), Robusta Maculata (RM), RM x Sasso (RMxS), BP x Sasso (BPxS) and a commercial hybrid (Ross 308) the best suitable breed in terms of productivity and welfare for alternative housing system. A total of 300 (60 x genotype), 21 days old male birds were randomly allotted in two housing systems: 1) standard intensive farming (controlled environment, 33 kg/m2 and standard diet) and 2) free-range (“natural” environmental conditions, 21 kg/m2, access to outdoor area and low-input diet). Slaughtering was performed at 81 days of age. During the trial, the productive performance and behaviour of the animals were evaluated. The housing system, the genotype and their interaction significantly affected many of the studied variables, showing broiler not the ideal genotype for extensive farming system, which is more suited for low/medium performance strains.

The slaughter performance and meat quality of two native Italian chicken breeds

The aim of this study was to evaluate how different rearing systems (intensive or semi-extensive) and sexual hormones could affect stress parameters and the development of stress-related intramural coronary arteriosclerosis in Lidia bulls (n = 18) and Piemontese oxen (n = 17). At slaughter, hearts were sampled and submitted to histological investigations in order to evaluate coronary arteriosclerosis. Blood and hair samples were also collected to measure d-ROMS and 20β-dihydrocortisol levels, respectively. No significant differences were recorded for serum levels of d-ROMS between Piemontese oxen and Lidia bulls. On the contrary, Lidia bulls presented higher levels of hair 20β-dihydrocortisol compared to Piemontese oxen (p = .007). Arteriosclerosis was recorded in both the groups. In Lidia bulls, mild to moderate coronary arteriosclerosis was recorded in all the evaluated regions of the heart (right and left papillary muscle; interventricular septum; right and left ventricle free wall; right and left atrium). In Piemontese oxen, mild to severe coronary arteriosclerosis was observed, especially in the left papillary muscle. These results suggest that both cattle breed experienced stress during their rearing cycle. Further studies are needed to clarify the role of housing system and sexual hormones in the development of these subclinical vascular pathology.Highlights Rearing systems can affect animal welfare. Coronary arteriosclerosis, d-ROMS and hair 20β-dihydrocortisol levels can be affected by stress. Lidia bulls and Piemontese oxen experienced different levels of stress during their rearing cycle.

Aims: Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. Methods: a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid&reg, ), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. Results: Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid&reg, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid&reg, loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. Conclusions: In these preliminary studies, Intralipid&reg, proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.

The present study aims to evaluate beef cattle welfare with an integrated approach as housing conditions and management practices change and to investigate the relationship between the adopted parameters and their applicability. A total of 15 Piemontese breed bulls reared in a tied stall housing system and 15 Piemontese, 15 Blonde d’Aquitaine and 15 cross-breed from Ireland reared in group-pen were considered. A welfare protocol including a checklist and the ‘RIBECA’ scoring system was prepared for the assessment of animal-based measures and resource-based measures. Blood parameters and hair 20β-dihydrocortisol were also analysed. The animal-based score was not significantly different among the farms, while the total welfare score was ‘poor’ for the animals in the tied stall system, ‘fair’ for Piemontese cattle in the in pen and Irish cross-breed, and ‘very good’ for the Blonde d’Aquitaine cattle. Irish cross-breed were the most fearful, with the blood findings also suggesting that these animals showed the worst adaptation, whereas Blonde d’Aquitaine cattle were well adapted. Furthermore, 20β-dihydrocortisol was lower (p

The blood brain barrier is a functional barrier allowing the entry into the brain of only essential nutrients, excluding other molecules. Its structure, although essential to keep the harmful entities out, is also a major roadblock for pharmacological treatment of brain diseases. Several alternative invasive drug delivery approaches, such as transcranial drug delivery and disruption of blood brain barrier have been explored, with limited success and several challenges. Intranasal delivery is a non-invasive methodology, which bypasses the systemic circulation, and, through the intra- and extra- neuronal pathways, provides direct brain drug delivery. Colloidal drug delivery systems, particularly lipidic nanoparticles offer several unique advantages for this goal.This review focuses on key brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, and provide a detailed overview of the current lipid nanoparticle based treatment options explored thus far. The review also delves into basic preparation, challenges and evaluation methods of lipid drug delivery systems.Brain diseases present complex pathophysiology, in addition to the practically inaccessible brain tissues, hence according to the authors, a two-pronged approach utilizing new target discovery coupled with new drug delivery systems such as lipid carriers must be adopted.

Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We found that highly sensitive MPM lines display lower proteasome activity than more bortezomib-resistant clones, suggesting that reduced proteasomal capacity might contribute to the intrinsic susceptibility of mesothelioma cells to proteasome inhibitors-induced apoptosis. Moreover, MPM equipped with fewer active proteasomes accumulated polyubiquitinated proteins, at the expense of free ubiquitin, a condition known as proteasome stress, which lowers the cellular apoptotic threshold and sensitizes mesothelioma cells to bortezomib-induced toxicity as shown herein. Taken together, our data suggest that an unfavorable load-versus-capacity balance represents a critical determinant of primary apoptotic sensitivity to bortezomib in MPM.

Peripheral nerve function is significantly affected by ageing. During ageing process, multiple changes occur on tissue cells and extracellular matrix. The aim of this work was to study the ageing-associated changes of peripheral nerves in adult and old regularly slaughtered cattle compared with young calves, and correlate them to the features reported in humans and laboratory animals. Samples of axial dorsal metacarpal nerves from 44 cows were collected immediately after slaughtering. Each nerve was dissected and divided into two fragments: one used for morphological evaluation (n = 43) and the other one for biochemical analysis (n = 31). Axonal degeneration, demyelination, thickness of perineurium and endoneurium and increase of mast cells were the most important features detected. The mean amount of glycosaminoglycan quantitative content recorded in the samples increased with the age. Axonal degeneration, demyelination and thickness of endoneurium were positively and significantly correlated with biochemistry. The presence of changes affecting the different elements of the peripheral nerves, similar to that reported in humans and in laboratory species, the easy availability of the nerve tissue in this species, the considerable size of the samples and the life conditions more similar to humans than to laboratory animals, allows the authors to consider cattle as a potential good model for the comparative study of spontaneous ageing nerve lesions.

The aim of this paper was to determine the food quality and safety of two Mediterranean sea cucumbers species, Holothuria tubulosa (HT) and Holothuria polii (HP) collected in the Italian Southern Adriatic Sea. Three hundred samples were collected in the spring of the 2008 and some of them were analyzed for their proximate composition, fatty acid composition, amino acid composition and heavy metals content. Proximate composition was similar in both species: HT: dry matter 16.19%; crude protein 44.58%; ash 46.43 %; HP: dry matter 22.03%; crude protein 36.99%; ash 48.22%. Lipid content resulted very low in both species and an interesting content of polyunsaturated fatty acids (PUFA) was found. Among PUFA, eicosapentaenoic acid (EPA) and eicosatrienoic acid were present in high percentages in both species. Considering the total amino acids composition, glutamic acid, glycine and aspartic acid were the most abundant amino acids. In terms of food safety, the heavy metals concentrations in the analyzed species were under the maximum limits for the Italian legislation. These results confirmed that the HT and HP could be considered as a suitable seafood for human consumption.

Aims In circulating lymphocytes of NIDDM patients pyruvate dehydrogenase (PDH), the major determinant in glucose consumption through oxidative pathways, is poorly active. The aim of this study is to examine whether sulphonylurea drug treatment revives PDH activity in circulating lymphocytes from NIDDM patients. Methods Twenty normal-weight individuals with NIDDM were enrolled in this study. They had maintained their glycaemic levels close to normal by means of a restricted diet that had no longer been successful in the proceeding 2 months. The treatment protocol consisted in 160 mg gliclazide daily for 5 weeks. Twenty healthy subjects, matched for age, body mass index and gender, were enrolled as a control group. Patients, before and after treatment, as well as controls were tested for PDH activity in their circulating lymphocytes. Nine other untreated patients and nine healthy subjects, with the above mentioned characteristics, were recruited for the assay of PDH activity in their circulating lymphocytes before and after exposure, in vitro, to gliclazide, to insulin, and to gliclazide and insulin in combination. Results In gliclazide-treated NIDDM patients, PDH activity in circulating lymphocytes recovered. In vitro, in circulating lymphocytes of untreated patients and controls insulin at 5 μU ml−1 was ineffective and highly effective, respectively, in raising enzyme activity; gliclazide at 10 ng ml−1 was ineffective on PDH in both groups, but in combination with insulin at 5 μU ml−1 in both groups PDH was as active as in cells of controls exposed to insulin only. In cells of controls, gliclazide alone at 25–50 ng ml−1 caused enzyme activation, whereas above 50 ng ml−1 it caused inhibition; in cells of patients below 50 ng ml−1 it had no effects, but at 50 ng ml−1 and above raised enzyme activity to the basal level of controls. Conclusions This study suggests that free gliclazide concentrations determine recovery of PDH activity in circulating lymphocytes of treated patients through drug-mediated enhanced insulin control over PDH or through the drug alone.

Poorly structured domains in proteins enhance their susceptibility to proteasomal degradation. To learn whether the presence of such a domain near either end of a protein determines its direction of entry into the proteasome, directional translocation was enforced on several proteasome substrates. Using archaeal PAN-20S complexes, mammalian 26S proteasomes, and cultured cells, we identified proteins that are degraded exclusively from either the C or N terminus and some showing no directional preference. This property results from interactions of the substrate's termini with the regulatory ATPase and could be predicted based on the calculated relative stabilities of the N and C termini. Surprisingly, the direction of entry into the proteasome affected markedly the spectrum of peptides released and consequently influenced the efficiency of MHC class I presentation. Thus, easily unfolded termini are translocated first, and the direction of translocation influences the peptides generated and presented to the immune system.

Protein gene product 9.5 (PGP9.5) is a cytosolic protein that is highly expressed in vertebrate neurons, which is now included in the ubiquitin C-terminal hydrolase subclass (UCH) on the basis of primary-structure homology and hydrolytic activity on the synthetic substrate ubiquitin ethyl ester (UbOEt). Some UCHs show affinity for immobilized ubiquitin, a property exploited to purify them. In this study we show that this property can also be applied to PGP9.5, since a protein has been purified to homogeneity from bovine retina by affinity chromatography on a ubiquitin–Sepharose column that can be identified with: (a) PGP9.5 with respect to molecular mass, primary structure and immunological reactivity; (b) the known UCHs with respect to some catalytic properties, such as hydrolytic activity on UbOEt, (which also characterizes PGP9.5), Km value and reactivity with cysteine and histidine-specific reagents. However, it differs with respect to other properties, e.g. inhibition by UbOEt and a wider pH range of activity.