Effect of dietary seaweed (Ascophyllum nodosum) supplementation on milk mineral concentrations, transfer efficiency, and hematological parameters in lactating Holstein cows.

This study investigated the effect of feeding seaweed (Ascophyllum nodosum) to dairy cows on milk mineral concentrations, feed-to-milk mineral transfer efficiencies, and hematological parameters. Lactating Holstein cows (n = 46) were allocated to 1 of 2 diets (n = 23 each): (1) control (CON; without seaweed) and (2) seaweed (SWD; replacing 330 g/d of dried corn meal in CON with 330 g/d dried A. nodosum). All cows were fed the CON diet for 4 wk before the experiment (adaptation period), and animals were then fed the experimental diets for 9 wk. Samples included sequential 3-wk composite feed samples, a composite milk sample on the last day of each week, and a blood sample at the end of the study. Data were statistically analyzed using a linear mixed effects model with diet, week, and their interaction as fixed factors; cow (nested within diet) as a random factor; and data collected on the last day of the adaptation period as covariates. Feeding SWD increased milk concentrations of Mg (+6.6 mg/kg), P (+56 mg/kg), and I (+1,720 µg/kg). It also reduced transfer efficiency of Ca, Mg, P, K, Mn, and Zn, and increased transfer efficiency of Mo. Feeding SWD marginally reduced milk protein concentrations, whereas there was no effect of SWD feeding on cows' hematological parameters. Feeding A. nodosum increased milk I concentrations, which can be beneficial when feed I concentration is limited or in demographics or populations with increased risk of I deficiency (e.g., female adolescents, pregnant women, nursing mothers). However, care should also be taken when feeding SWD to dairy cows because, in the present study, milk I concentrations were particularly high and could result in I intakes that pose a health risk for children consuming milk.

Clinical assessment and management of severe acute pancreatitis: a multi-disciplinary approach in the XXI century.

Acute pancreatitis (AP) is the most common gastrointestinal disorder requiring hospitalization, with a high rate of morbidity and mortality. Severe AP is characterized by the presence of persistent organ failure involving single or multiple organs. Clinical evolution, laboratory and radiological assessment are necessary to evaluate the prognosis and inform the management of AP. The onset of severe AP may be classified in two principal phases. The early phase, during the first week, is characterized by the activation of the auto-inflammatory cascade, gut dysbiosis, bacterial translocation, and the down-regulation of immune responses. The late phase is characterized by the development of local and systemic complications. Several old paradigms have been amended in the management of AP patients, such as the indication of nutrition, the use of antibiotic therapy, pain control strategies, and even the use of surgery. Real world evidence has shown that in the majority of cases a step-up approach is most effective. In this review, we discuss the clinical assessment and improvements to the management of patients with severe AP in a high volume center where a multi-disciplinary approach is performed.

The Importance of Complying with Vaccination Protocols in Developed Countries: "Anti-Vax" Hysteria and the Spread of Severe Preventable Diseases.

BACKGROUND: Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinations in developed countries. Outbreaks of vaccine-preventable diseases (e.g. measles) have occurred in Europe and North America, causing also some causalities. OBJECTIVES: In this review, data on safety and efficacy of vaccines are discussed, showing that the benefits of vaccines far outweigh the risks and that it is important to comply with vaccination protocols, to avoid spreading of severe, preventable diseases. METHODS: Those opposed to vaccinations suggest that scientific literature supporting vaccines is influenced by pharmaceutical companies. In this review, studies on influenza produced by independent scientists and those authored by those who received some kind of benefit from the industry are discussed separately. All the chosen papers were selected through a MEDLINE research. RESULTS: Vaccination rates are decreasing, even though they are effective public health tools. Influenza, for example, is responsible for 250,000-500,000 deaths each year, according to the WHO. Yet, campaigns to extend influenza vaccine to all elderly subjects report little success, because of the vaccine scare and because not all patients develop immunity following vaccination. CONCLUSIONS: This review proves that vaccine hysteria is detrimental because: 1) it causes an increased morbidity and mortality from preventable diseases; 2) it jeopardizes research for new vaccines; 3) patients are reluctant to accept any form of immune-therapy, commonly referred to as "vaccination".

Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders.

Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders.

The involvement of IgH enhancer HS1.2 in the pathogenesis of Crohn's disease: how the immune system can influence a multifactorial disease.

OBJECTIVE: To study the 3' immunoglobulin heavy-chain regulatory region (3'RR) enhancer complex, active in class switching recombination and in B-cells, in Crohn's disease. PATIENTS AND METHODS: A total of 167 patients [79 females (47.3%) and 88 males (52.7%)] affected by Crohn's disease were enrolled in the study. As a control, we included 64 healthy subjects, age and sex matched, from the same geographical area. Blood tests were performed on all subjects to determine their antibody levels and to detect the presence of any possible infections. We conducted a selective PCR, which amplified the hs1.2-A region. The nested second PCR to amplify the polymorphic core of the enhancer was performed. RESULTS: No differences between cases and controls were observed with respect to sex distribution (43.8% females among controls and 49.5% among cases), age, tTG IgA, RF, serum or secretory IgA, IgG1, IgG2 and IgG3. No correlation was found between both seric and secretory immunoglobulins levels, with except of statistically significant differences between cases and controls with respect to IgA and IgG ASCA positivity (p<0.001), serum IgG4 (p<0.001) and IgD (p=0.001). CONCLUSIONS: We have demonstrated that in Crohn's disease, the HS1,2 immunoglobulins enhancer is not implicated in the disease pathogenesis. Moreover, we have found that IgG4 levels are lower in Crohn's disease patients than in controls; these data may be related to an impairment of number and function of Tregs, further linked to the presence of tissue inflammation. Crohn's disease is a complex multifactorial disease. The pathogenesis of Crohn's disease is incompletely understood although it is clear that the disease involves multiple interacting agents.

Central and Mucosal Immunities are Modified by Non Adsorbable Antibiotic Treatment in Uncomplicated Diverticular Disease.

We review our experience on Rifaximin in uncomplicated diverticular disease. Our data show that a 2 week treatment induces modifications in the immune system: local mucosal lymphocytes with TLR-4 were increased. In the peripheral blood CD103 cells, which increased before treatment, returned to normal values after Rifaximin.

The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop.

Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.

Strategies to overcome obstacles to successful immunotherapy of melanoma.

The immunogenicity of malignant melanomas has been recognized by the observed recruitment of tumor-specific cytotoxic T-cells (CTL), leading to the identification of several melanoma associated antigen (MAA). However, numerous strategies to treat melanoma with immunotherapy have resulted in only partial success. In this editorial, we discuss recent data related to the ability of tumors to elude immune responses. We therefore discuss different strategies to induce a clinically effective immune response. These approaches include 1) immunostimulation: including peptide/protein based vaccines, dendritic cell vaccines, and adoptive cell transfer; and 2) overcoming immunosuppression, including targeting of checkpoint molecules such as CTLA-4, circumventing the activity of Tregs, and assuring antigen expression by tumor cells (thwarting antigen silencing). Finally, we discuss recent advances in gene therapy, including adoptive therapy with engineered T cell receptors (TCRs). These issues lead to the conclusion that successful immunotherapy in malignant melanoma requires a combination of strategies aimed at both inducing immunostimulation and blocking immunosuppression.

Effects of mutations in potential phosphorylation sites on transcytosis of FcRn.

The neonatal Fc receptor, FcRn, transports immunoglobulin G (IgG) across intestinal epithelial cells of suckling rats and mice from the lumenal surface to the serosal surface. In cell culture models FcRn transports IgG bidirectionally, but there are differences in the mechanisms of transport in the two directions. We investigated the effects of mutations in the cytoplasmic domain of FcRn on apical to basolateral and basolateral to apical transport of Fc across rat inner medullary collecting duct (IMCD) cells. Basolateral to apical transport did not depend upon determinants in the cytoplasmic domain. In contrast, an essentially tailless FcRn was markedly impaired in apical to basolateral transport. Using truncation and substitution mutants, we identified serine-313 and serine-319 as phosphorylation sites in the cytoplasmic domain of FcRn expressed in Rat1 fibroblasts. Mutations at Ser-319 did not affect transcytosis across IMCD cells. FcRn-S313A was impaired in apical to basolateral transcytosis to the same extent as tailless FcRn, whereas FcRn-S313D transported at wild-type levels. FcRn-S313A recycled more Fc to the apical medium than the wild-type receptor, suggesting that Ser-313 is required to allow FcRn to be diverted from an apical recycling pathway to a transcytotic pathway.