Effect of unsaturated fatty acid supplementation on performance and milk fatty acid profile in dairy cows fed a high fibre diet.

The influence of unsaturated fatty acid (UFA) supplement on productive performance, physiochemical properties and fatty acid (FA) profile of milk, was investigated in lactating dairy cows fed with high fibre diets. According to a cross-over design, twelve cows were assigned to two experimental settings characterized by different FA profiles. Cows received a high fibre diet (~42% NDF on DM basis) supplemented with soybean based mixtures with these FA compositions: 92.0% of saturated FA (SFA), 2.8% of monounsaturated FA (MUFA) and 5.2% of polyunsaturated FA (PUFA) in the control diet (C-diet); 19.1% of SFA, 20.9% of MUFA and 60.0% of PUFA in the experimental diet (E-diet). The E-diet did not affect dry matter intake nor milk yield. Milk composition and coagulation traits resulted similar between treatments, except for the lactose level, which was lower in the E-diet (5.0 vs 4.8%; P<0.05) and the freezing point (-0.546 vs -0.535 °C; P<0.05). As respects the milk FA profile, the E-diet significantly increased the percentage of UFA because of their greater amount in the ration; however the "transfer" of UFA in milk was limited by the high level of FA biohydrogenation (BH) at the ruminal level. UFA showed low values of carry over in milk (67.5 vs 39.7%; P<0.001) due to the saturation process; on the contrary SFA had a threefold increment (124 vs 323%; P<0.001), mostly due to a peak in the production of stearic acid. In this study, the percentage of CLA in milk (0.50 vs 0.62%; P<0.05) was quite low for both diets, if compared with other studies, and this was probably due to a low vaccenic acid supply at duodenal level

Lecithin: a by-product of biodiesel production and a source of choline for dairy cows

The aim of the present study was to compare the effects of soy lecithins (L), a by-product of the biodiesel production process, and choline chloride microencapsulated with hydrogenated vegetable oils (C) on dry matter intake, milk yield, milk quality traits, milk choline and haematological profile of dairy cows. A total of 12 mid-lactating Holstein Friesian cows were assigned to one of two experimental groups and fed according to cross-over design (2 diets x 2 periods). Diets were isoenergetic, isofibrous and isonitrogenous and had the same content of choline. Dry matter intake was not affected by the diet, but L led to lower milk choline (P<0.05) and to a significantly higher milk yield (P<0.05), although the 3.5% fat-corrected milk (FCM) did not change owing to the higher content of fat in the milk of the C-diet group (P<0.01). The remaining milk components were unaffected by the supplements, except for the milk urea, which was lower in the L-diet group (P<0.01), reflecting a more effective use of degradable proteins by the micro-organisms present in the rumen. With regard to the haematological profile, L led to lower urea (P<0.001) and to higher values of glucose (P<0.01) and non-esterified fatty acids (NEFA)/Cholesterol ratio (P< 0.05), but all of the values fell within the physiological range of lactating dairy cows. Results indicated that soy lecithins can be used as an available and cost-effective source of choline in mid-lactating dairy cows

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Versatility of gene therapy vectors through viruses.

Abstract: Several viruses have been engineered for gene therapy applications, and the specific properties of each viral vector have been exploited to target a variety of inherited and acquired diseases. Preclinical and clinical studies demonstrated that viral vectors are highly versatile tools capable of efficient transfer of foreign genetic information into almost all cell types and tissues. Gene therapy applications depend on vector characteristics, such as host range, cell- or tissue-specific targeting, genome integration, efficiency and duration of transgene expression, packaging capacity, and suitability for scale-up production. This review discusses the advances in the development of viral vectors, with particular emphasis on how knowledge of virus biology has been exploited to design a variety of vectors with improved safety characteristics and efficiency, potentially suitable for a large number of gene therapy applications

Trend overtime of total haemoglobin, iron metabolism and trace minerals in veal calves fed high amounts of two different solid feeds

Fifty Polish Friesian veal calves were administrated high amounts of two different solid feeds (maize grain and a mix diet containing 10% of straw and 8% of soy) in addition to the traditional milk replacer diet. Compared to the mix diet, maize grain had a lower content of iron, copper and zinc and a minor fibre level. Effects of the two diets on calves&rsquo; blood haemoglobin, iron, iron metabolism parameters, copper and zinc concentrations were studied. Haemoglobin concentration resulted higher at the end of the fattening for calves fed the mix diet, as expected. Values remained, however, within ranges that allowed acceptable carcass paleness. Haematic iron, unsaturated iron binding capacity (UIBC) and total iron binding capacity (TIBC) levels were not significantly different between the two solid feeds. Lower copper and zinc blood concentrations resulted for calves fed the mix diet were likely due to the feed fibre interfering with the bioavailability of the two minerals, according to what happens for iron

Combined suicide/cytokine gene therapy of hepatocellular carcinoma

Abstract 7th Annual Meeting of the American-Society-of-Gene-Therap

Loss of growth hormone secretagogue receptor 1a and overexpression of type 1b receptor transcripts in human adrenocortical tumors

Abstract OBJECTIVE AND METHODS: Quantitative analysis of mRNA expression of ghrelin and its receptors GHS-R1a and -R1b in a large series of normal and neoplastic human adrenocortical tissues. Evaluation of the effects of ghrelin on GHS-R expression and proliferation of human adrenocortical carcinoma (ACC) cell lines. RESULTS: Ghrelin and GHS-R transcripts are expressed in normal adrenal cortex, with GHS-R1b mRNA levels being 5- to 10-fold higher than GHS-R1amRNA. A significant increase in ghrelin expression was observed in adrenocortical adenomas, but not in carcinomas. GHS-R1a was undetectable in about 60% of both benign and malignant tumor samples, except for cortisol-producing adenomas, which showed increased receptor expression. At variance, GHS-R1b was overexpressed in both benign and malignant adrenocortical tumors. In vitro studies in human ACC cell lines demonstrated that GHS-R1a is downregulated and GHS-R1bmRNA expression is upregulated by ghrelin, while inhibiting cell proliferation. CONCLUSION: Downregulation ofGHS-R1a in adrenal tumors and the presence of high levels of GHS-R1b transcripts in adrenocortical tissue suggest a role for these receptors in adrenal function and growth. In this regard, ghrelin inhibits cell proliferation and modulates GHS-R expression in ACC cells in vitro