PECAM-Independent Thioglycollate Peritonitis Is Associated With a Locus on Murine Chromosome 2

Background: Previous studies have demonstrated that knockout or inhibition of Platelet/Endothelial Cell Adhesion Molecule (PECAM, CD31) in a number of murine strains results in impaired inflammatory responses, but that no such phenotype is seen in the C57BL/6 (B6) murine background. Methodology/Principal Findings: We have undertaken a quantitative trait locus (QTL) mapping effort between FVB/n (FVB) and B6 mice deficient for PECAM to identify the gene or genes responsible for this unique feature of B6 mice. We have identified a locus on murine chromosome 2 at approximately 35.8 Mb that is strongly associated (LOD score = 9.0) with inflammatory responses in the absence of PECAM. Conclusions/Significance: These data potentiate further study of the diapedesis machinery, as well as potential identification of new components of this machinery. As such, this study is an important step to better understanding the processes of inflammation

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

Effect of selected milk protein preparations on growth and survival of Lactobacillus acidophilus as well as on rheological properties of fermented milk beverages

Białka serwatkowe są źródłem bioaktywnych peptydów i zawierają aminokwasy niezbędne do prawidłowego funkcjonowania organizmu. Preparaty białek mleka zastosowane do produkcji mlecznych napojów fermentowanych wpływały stymulująco na wzrost szczepu Lactobacillus acidophilus LA-5. Dodatek α-latktoalbuminy do mleka pełnego wpłynął na skrócenie czasu powstawania skrzepu kwasowego przy wykorzystaniu szczepu Lb. acidophilus LA-5. Po dwutygodniowym przechowywaniu w warunkach chłodniczych mlecznych napojów fermentowanych, uzyskanych z pełnego mleka w proszku, najwyższą liczbę komórek (4,1×107 jtk/ml) bakterii szczepu Lb. acidophilus LA-5 stwierdzono w produktach wzbogaconych WPC 65 – w ilości 1 %. Największą twardością (1,51 N) i wartością modułu zachowawczego G’ (5567 Pa) charakteryzowały się napoje otrzymane z 2-procentowym dodatkiem WPI. Wraz ze wzrostem stężenia α-la i WPI wzrastała twardość żeli kwasowych otrzymanych przy użyciu szczepu Lb. acidophilus LA-5. Mleczne napoje fermentowane otrzymywane z mleka odtłuszczonego charakteryzowały się wyższymi wartościami takich parametrów, jak twardość oraz moduł zachowawczy. Napoje z mleka odtłuszczonego wykazywały jednak większą synerezę w porównaniu z napojami z mleka pełnego. Wzrost dodatku preparatów białek mleka w napojach powodował stopniowe zmniejszanie ilości wydzielonej serwatki. Najniższą wartością synerezy (1,97 %) cechowały się napoje mleczne z 2-procentowym dodatkiem WPI. Oprócz poprawy właściwości fizykochemicznych mlecznych napojów fermentowanych, wzbogacenie preparatami białek mleka wpłynęło na zwiększenie walorów prozdrowotnych oraz nadało produktom cechy żywności funkcjonalnej.Whey proteins are a source of bioactive peptides and contain amino acids that are essential to the human body to properly function. Milk protein preparations used in the production of fermented milk beverages stimulated the growth of Lb. acidophilus LA-5 strain. A supplement of α-lactalbumin added to the whole milk caused the time of curd formation with the use of Lb. acidophilus LA-5 strain to be reduced. After a two week period of cold storage of the fermented milk beverages produced from the whole milk powder, the highest cell count (4.1x107 cfu/ml) of Lactobacillus acidophilus LA-5 strain was reported in the products enriched with WPC 65 added in an amount of 1 %. The beverages produced with a 2 % of WPI added were characterized by the highest values of hardness (1.51 N) and storage modulus G' (5567 Pa). Along with the increasing concentration of α-la and WPI, the hardness increased of the acid gels produced with the application of Lb. acidophilus LA-5 strains. The fermented milk beverages made from skimmed milk were characterized by higher values of the parameters such as hardness and storage modulus. However, the milk beverages from skimmed milk had higher levels of syneresis compared to beverages from the whole milk. The increase in the amount of milk protein preparations added to the beverages caused the amount of separated whey to gradually decrease. The milk beverages with 2 % of WPI added were characterized by the lowest value of syneresis (1.97 %). The enriching of fermented milk beverages with milk protein preparations improves physical and chemical properties of those beverages, influences the increase in their pro-health values, and gives those products the characteristics of functional beverages

An introduction to the biopsychosocial complexities of managing wound pain

Using the Manchester pain management model (PAIN), this review discusses the care of acute and chronic wounds, focussing on the particular skills required to manage pain associated with different types of wounds, and addressing the important area of dressing change. Acute and chronic wounds can be associated with either acute or chronic pain, making management of wound pain a significant challenge. Pain can be of either nociceptive or neuropathic origin, and the longer it has been present, the more likely that psychological, social or cultural determinants influence the reactions seen in the patient. Understanding the biopsychosocial and cultural elements of pain enables the practitioner to prepare, assess, intervene and normalise effectively, during all aspects of wound care management. Utilising individualised evidence-based practice is essential to ensure that high-quality care is delivered in this key area. © MA Healthcare Ltd, 2012