The effects of dietary fibre type on satiety-related hormones and voluntary food intake in dogs

Depending on type and inclusion level, dietary fibre may increase and maintain satiety and postpone the onset of hunger. This 7-week study evaluated the effect of fibre fermentability on physiological satiety-related metabolites and voluntary food intake (VFI) in dogs. Sixteen healthy adult dogs were fed a low-fermentable fibre (LFF) diet containing 8·5 % cellulose or a high-fermentable fibre (HFF) diet containing 8·5 % sugarbeet pulp and 2 % inulin. Large intestinal fibre degradation was evaluated by apparent faecal digestibility of nutrients and faecal SCFA and NH3 concentrations. Postprandial blood samples were obtained to determine postprandial plasma glucose, insulin, total peptide tyrosine–tyrosine (PYY), total glucagon-like peptide-1 (GLP-1) and total ghrelin concentrations. At the end of the study, the dogs were given a single meal of a dry dog food to determine VFI. Dogs fed the HFF diet had a significantly higher large intestinal fibre degradation and production of SCFA compared with the dogs fed the LFF diet. The HFF-fed dogs tended (P = 0·058) to show a lower VFI at the end of the study. No treatment effects were found for postprandial plasma glucose, PYY, GLP-1 and ghrelin responses. The concentrations of these metabolites could not be related to the observed difference in VFI. The inclusion of fermentable fibre in canine diets may contribute to the prevention or mitigation of obesity through its effects on satiety. The underlying mechanisms require further investigatio

Drosophila Bruce Can Potently Suppress Rpr- and Grim-Dependent but Not Hid-Dependent Cell Death

Bruce is a large protein (530 kDa) that contains an N-terminal baculovirus IAP repeat (BIR) and a C-terminal ubiquitin conjugation domain (E2) 1, 2. BRUCE upregulation occurs in some cancers and contributes to the resistance of these cells to DNA-damaging chemotherapeutic drugs [2]. However, it is still unknown whether Bruce inhibits apoptosis directly or instead plays some other more indirect role in mediating chemoresistance, perhaps by promoting drug export, decreasing the efficacy of DNA damage-dependent cell death signaling, or by promoting DNA repair. Here, we demonstrate, using gain-of-function and deletion alleles, that Drosophila Bruce (dBruce) can potently inhibit cell death induced by the essential Drosophila cell death activators Reaper (Rpr) and Grim but not Head involution defective (Hid). The dBruce BIR domain is not sufficient for this activity, and the E2 domain is likely required. dBruce does not promote Rpr or Grim degradation directly, but its antiapoptotic actions do require that their N termini, required for interaction with DIAP1 BIR2, be intact. dBruce does not block the activity of the apical cell death caspase Dronc or the proapoptotic Bcl-2 family member Debcl/Drob-1/dBorg-1/Dbok. Together, these results argue that dBruce can regulate cell death at a novel point

Stress induced Salmonella Typhimurium re-excretion by pigs is associated with cortisol induced increased intracellular proliferation in porcine macrophages

Infections of pigs with Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) often result in the development of carriers that intermittently excrete Salmonella in very low numbers. During periods of stress, recrudescence of Salmonella may occur

Genomic innovations linked to infection strategies across emerging pathogenic chytrid fungi

We acknowledge the Broad Institute Sequencing Platform and Imperial College London for generating the DNA and RNA sequence described here. Financial support was provided by a UK Natural Environmental Research Council (NERC NE/K012509/1) grant to MCF, a Wellcome Trust Fellowship to RF, a Morris Animal Foundation grant to FP, and by the National Human Genome Research Institute grant number U54HG003067 to the Broad Institute. E.V. is supported by the Research Foundation Flanders (FWO grant 12E6616N).Peer reviewedPublisher PD

A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa

<p>Abstract</p> <p>Background</p> <p>Colistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) <it>Pseudomonas </it>spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking.</p> <p>Methods</p> <p>A retrospective study of 20 intensive care patients with a pneumonia associated with MDR <it>P. aeruginosa </it>receiving colistin sulphomethate sodium (Colistineb^®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate.</p> <p>Results</p> <p>Six patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the <it>Pseudomonas </it>spp. was eradicated from the follow-up cultures.</p> <p>All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally).</p> <p>Conclusions</p> <p>Aerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR <it>P. aeruginosa</it>.</p

Effects of Helicobacter suis γ-glutamyl transpeptidase on lymphocytes: modulation by glutamine and glutathione supplementation and outer membrane vesicles as a putative delivery route of the enzyme

Helicobacter (H.) suis colonizes the stomach of the majority of pigs as well as a minority of humans worldwide. Infection causes chronic inflammation in the stomach of the host, however without an effective clearance of the bacteria. Currently, no information is available about possible mechanisms H. suis utilizes to interfere with the host immune response. This study describes the effect on various lymphocytes of the γ-glutamyl transpeptidase (GGT) from H. suis. Compared to whole cell lysate from wild-type H. suis, lysate from a H. suis ggt mutant strain showed a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed H. suis GGT resulted in an impaired proliferation, and cell death was shown to be involved. A similar but more pronounced inhibitory effect was also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with known GGT substrates was able to modulate the observed effects. Glutamine restored normal proliferation of the cells, whereas supplementation with reduced glutathione strengthened the H. suis GGT-mediated inhibition of proliferation. H. suis GGT treatment abolished secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-γ. Finally, H. suis outer membrane vesicles (OMV) were identified as a possible delivery route of H. suis GGT to lymphocytes residing in the deeper mucosal layers. Thus far, this study is the first to report that the effects on lymphocytes of this enzyme, not only important for H. suis metabolism but also for that of other Helicobacter species, depend on the degradation of two specific substrates: glutamine and reduced glutatione. This will provide new insights into the pathogenic mechanisms of H. suis infection in particular and infection with gastric helicobacters in general

Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium

The transcytosis of antigens across the gut epithelium by microfold cells (M cells) is important for the induction of efficient immune responses to some mucosal antigens in Peyer’s patches. Recently, substantial progress has been made in our understanding of the factors that influence the development and function of M cells. This review highlights these important advances, with particular emphasis on: the host genes which control the functional maturation of M cells; how this knowledge has led to the rapid advance in our understanding of M-cell biology in the steady-state and during aging; molecules expressed on M cells which appear to be used as “immunosurveillance” receptors to sample pathogenic microorganisms in the gut; how certain pathogens appear to exploit M cells to infect the host; and finally how this knowledge has been used to specifically target antigens to M cells to attempt to improve the efficacy of mucosal vaccines

Multinational development and validation of an early prediction model for delirium in ICU patients

Rationale Delirium incidence in intensive care unit (ICU) patients is high and associated with poor outcome. Identification of high-risk patients may facilitate its prevention. Purpose To develop and validate a model based on data available at ICU admission to predict delirium development during a patient’s complete ICU stay and to determine the predictive value of this model in relation to the time of delirium development. Methods Prospective cohort study in 13 ICUs from seven countries. Multiple logistic regression analysis was used to develop the early prediction (E-PRE-DELIRIC) model on data of the first two-thirds and validated on data of the last one-third of the patients from every participating ICU. Results In total, 2914 patients were included. Delirium incidence was 23.6 %. The E-PRE-DELIRIC model consists of nine predictors assessed at ICU admission: age, history of cognitive impairment, history of alcohol abuse, blood urea nitrogen, admission category, urgent admission, mean arterial blood pressure, use of corticosteroids, and respiratory failure. The area under the receiver operating characteristic curve (AUROC) was 0.76 [95 % confidence interval (CI) 0.73–0.77] in the development dataset and 0.75 (95 % CI 0.71–0.79) in the validation dataset. The model was well calibrated. AUROC increased from 0.70 (95 % CI 0.67–0.74), for delirium that developed 6 days. Conclusion Patients’ delirium risk for the complete ICU length of stay can be predicted at admission using the E-PRE-DELIRIC model, allowing early preventive interventions aimed to reduce incidence and severity of ICU delirium