Microbial Toxins in Dairy Products , chapter 9: Approaches to Assess the Risks/Modellingof Microbial Growth and Toxin Production

Chapter 9: Food-borne diseases, including those via dairy products, have been recognised as major threats to human health. The causes associated with dairy food-borne disease are the use of raw milk in the manufacture of dairy products, faulty processing conditions during the heat treatment of milk, post-processing contamination, failure in due diligence and an unhygienic water supply. Dairy food-borne diseases affecting human health are associated with certain strains of bacteria belonging to the genera of Clostridium, Bacillus, Escherichia, Staphylococcus and Listeria, which are capable of producing toxins, plus moulds that can produce mycotoxins such as aflatoxins, sterigmatocytin and ochratoxin. Microbial Toxins in Dairy Products reviews the latest scientific knowledge and developments for detecting and studying the presence of these toxins in dairy products, updating the analytical techniques required to examine bacterial and mould toxins and the potential for contamination of milk as it passes along the food chain, i.e. from 'farm-to-fork'. This comprehensive and accessible collection of techniques will help dairy processors, food scientists, technologists, researchers and students to further minimise the incidences of dairy food-borne illnesses in humans. The EU (2002) laid down the general principles and requirements of food law where it had changed the approach to food safety through the integrated control of the food chain, that is, the concept ‘from farm to table’, the precautionary principle, the responsibilities of food business operators, the traceability at all stage of food chain, and the introduction of ‘risk analysis’ (Codex Alimentarius Commission-FAO, 1999). The scope of a risk assessment is dependent on the risk management question and the reason for doing the assessment. The microbiological risk assessment would reveal, for example, either the sources of exposure to the pathogen or determine which pathogen(s) may be present in a specific and/or group of cheeses. This approach is largely a qualitative evaluation of the risk issue. in the process. If a hazard identification is orientated towards the food, then the focus will be on the use of available epidemiological and microbiological data to determine which pathogens could be associated with the products. In the dairy chain, contesting the hazard identification is linked to the microbiological quality of raw milk, the cheesemaking process including raw and/or pasteurization of the milk, maturation of the pressed curd, cross‐contamination, packaging, and handling at home

DEVELOPMENT OF BIOGENIC AMINES DURING THE RIPENING OF ITALIAN DRY SAUSAGES

The effect of modification of different chemical and microbiological parameters and the production of biogenic amines (histamine, cadaverine, putrescine, and tyramine) was examined during ripening of various types of typical Italian dry sausages (salami). Water activity decreased from 0.97 to 0.87, and pH reached the lowest value between the 13th and the 20th day of the ripening period, and then increased. Putrescine (up to 122.7 mg/kg) and tyramine (up to 105.9 mg/kg) mean levels showed dominance in comparison with cadaverine (up to 26.1 mg/kg) and histamine (up to 6.2 mg/kg) mean values in all sausage types. The highest putrescine and tyramine concentrations were observed in salami with the largest diameters. This comparative study suggests a good correlation between microbial behavior and amine evolution, particularly tyramine and putrescine, in dry sausage production

Blocking soluble TNFα sensitizes HER2-positive breast cancer to trastuzumab through MUC4 downregulation and subverts immunosuppression

Background The success of HER2-positive (HER2+) breast cancer treatment with trastuzumab, an antibody that targets HER2, relies on immune response. We demonstrated that TNFα induces mucin 4 (MUC4) expression, which shields the trastuzumab epitope on the HER2 molecule decreasing its therapeutic effect. Here, we used mouse models and samples from HER2+ breast cancer patients to unravel MUC4 participation in hindering trastuzumab effect by fostering immune evasion.Methods We used a dominant negative TNFα inhibitor (DN) selective for soluble TNFα (sTNFα) together with trastuzumab. Preclinical experiments were performed using two models of conditionally MUC4-silenced tumors to characterize the immune cell infiltration. A cohort of 91 patients treated with trastuzumab was used to correlate tumor MUC4 with tumor-infiltrating lymphocytes.Results In mice bearing de novo trastuzumab-resistant HER2+ breast tumors, neutralizing sTNFα with DN induced MUC4 downregulation. Using the conditionally MUC4-silenced tumor models, the antitumor effect of trastuzumab was reinstated and the addition of TNFα-blocking agents did not further decrease tumor burden. DN administration with trastuzumab modifies the immunosuppressive tumor milieu through M1-like phenotype macrophage polarization and NK cells degranulation. Depletion experiments revealed a cross-talk between macrophages and NK cells necessary for trastuzumab antitumor effect. In addition, tumor cells treated with DN are more susceptible to trastuzumab-dependent cellular phagocytosis. Finally, MUC4 expression in HER2+ breast cancer is associated with immune desert tumors.Conclusions These findings provide rationale to pursue sTNFα blockade combined with trastuzumab or trastuzumab drug conjugates for MUC4+ and HER2+ breast cancer patients to overcome trastuzumab resistance