Polyphenols as a partial replacement for vitamin E in nursery pig diets.

A total of 300 pigs (241 × 600; DNA, Columbus, NE; initially 6.0 ±â€…0.01 kg) were used in a 42-d trial to determine the effects of vitamin E levels and partially replacing vitamin E with a polyphenol (Cabanin CSD, R2 Argo, Denmark) on growth performance, complete blood count, serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and cytokine panel. Sixty pens of pigs were weighed and allotted to one of the five dietary treatments in a completely randomized design with 12 pens per treatment. A control treatment was formulated to provide 15 IU/kg of vitamin E equivalence from vitamin E. This control treatment was then used as a base for three replacement strategy diets to determine the effects of replacing an additional 60 IU/kg of vitamin E with polyphenol in diets containing a basal level of vitamin E requirement estimate (15 IU/kg). First, an additional 60 IU/kg of vitamin E was added for a total of 75 IU/kg of vitamin E equivalence. Second, 50% of the additional vitamin E (30 IU/kg) was replaced with the equivalency of polyphenol. Third, all 60 IU/kg of the additional vitamin E was replaced with the equivalency of polyphenol. To evaluate whether there are negative effects of feeding nursery pigs a high level of polyphenol, a fifth treatment was formulated to provide 575 IU/kg of vitamin E equivalence with 75 IU/kg from vitamin E and 500 IU/kg from polyphenol. Whole blood and serum samples were collected on days 10 and 42, and pig weights and feed disappearance were measured on days 10, 21, 31, 38, and 42. For growth performance, increasing vitamin E equivalence tended to improve (quadratic, P < 0.10) gain-to-feed ratio (G:F) from days 10 to 21, and tended to improve (linear, P < 0.10) G:F from days 21 to 42 and 0 to 42. There was a vitamin E equivalence × day interaction (P = 0.050) for serum SOD activity. Increasing vitamin E equivalence increased (linear, P < 0.05) serum SOD activity on day 42 but not on days 10 (P > 0.10). For serum cytokines, there was no evidence of differences (P > 0.10) between treatments and vitamin E equivalence. Moreover, there was no evidence of differences (P > 0.10) in all response variables between the three replacement strategies throughout the entire periods. In summary, increasing vitamin E equivalence tended to improve G:F, which may be related to the improved SOD activity. Furthermore, polyphenol can effectively replace vitamin E provided above the vitamin E requirement to provide similar benefits from increasing vitamin E equivalence.

Janus face of complement-driven neutrophil activation during sepsis.

During local and systemic inflammation, the complement system and neutrophil granulocytes are activated not only by pathogens, but also by released endogenous danger signals. It is recognized increasingly that complement-mediated neutrophil activation plays an ambivalent role in sepsis pathophysiology. According to the current definition, the onset of organ dysfunction is a hallmark of sepsis. The preceding organ damage can be caused by excessive complement activation and neutrophil actions against the host, resulting in bystander injury of healthy tissue. However, in contrast, persistent and overwhelming inflammation also leads to a reduction in neutrophil responsiveness as well as complement components and thus may render patients at enhanced risk of spreading infection. This review provides an overview on the molecular and cellular processes that link complement with the two-faced functional alterations of neutrophils in sepsis. Finally, we describe novel tools to modulate this interplay beneficially in order to improve outcome.

An observational study of the relationship between Capacity for Care as an animal shelter management model and cat health, adoption and death in three animal shelters.

Animal shelters struggle to function at their 'right size' in terms of physical, staffing and outcome capacity, especially with seasonal fluctuations in cat intake. To address this, a Capacity for Care (C4C) management model was devised to balance health and welfare requirements of all animals while maintaining or improving goals for positive outcomes, such as adoption or transfer. In this observational study of three shelters, applying the C4C management system gave each organization an optimal average daily shelter cat population target (to be achieved through proactive length of stay management) and helped each shelter to increase the size of their feline housing units. Pre- and post-C4C implementation data were evaluated to determine impact on average monthly isolation ward populations and cat outcomes such as adoptions and shelter deaths (euthanasia/died). Improved outcomes including increased adoption probability, decreased shelter death probability and fewer cats requiring infectious disease isolation were seen after C4C institution. Results suggest that implementation of this management model could help other shelters achieve similar results.

Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis.

The predisposition of preterm neonates to invasive infection is, as yet, incompletely understood. Regulatory T cells (Tregs ) are potential candidates for the ontogenetic control of immune activation and tissue damage in preterm infants. It was the aim of our study to characterize lymphocyte subsets and in particular CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) Tregs in peripheral blood of well-phenotyped preterm infants (n = 117; 23 + 0 - 36 + 6 weeks of gestational age) in the first 3 days of life in comparison to term infants and adults. We demonstrated a negative correlation of Treg frequencies and gestational age. Tregs were increased in blood samples of preterm infants compared to term infants and adults. Notably, we found an increased Treg frequency in preterm infants with clinical early-onset sepsis while cause of preterm delivery, e.g. chorioamnionitis, did not affect Treg frequencies. Our data suggest that Tregs apparently play an important role in maintaining maternal-fetal tolerance, which turns into an increased sepsis risk after preterm delivery. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics.

Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol.

Neutrophils harbor a number of preformed effector proteins that allow for immediate antimicrobial functions without the need for time-consuming de novo synthesis. Evidence indicates that neutrophils also contain preformed cytokines, including interleukin (IL)-1ra, CXCL8 and CXCL2. In the search for additional preformed cytokines, a cytokine array analysis identified IL-16 and macrophage migration inhibitory factor (MIF) as preformed cytokines in lysates from human primary neutrophils. Both IL-16 and MIF are unconventional cytokines because they lack a signal sequence. Using confocal immunofluorescence microscopy as well as western blot analysis of subcellular fractions, IL-16 and MIF were found to be stored in the cytosol rather than in the granules of human neutrophils, which implies an unconventional secretion mechanism for both cytokines. IL-16 is synthesized and stored as a precursor (pre-IL-16). We present evidence that the processing of pre-IL-16 to the biologically active IL-16C is mediated by caspase-3 and occurs during both spontaneous and UV-induced apoptosis of human neutrophils. Although IL-16 processing occurs during apoptosis, IL-16C and MIF release was observed only during secondary necrosis of neutrophils. Screening a panel of microbial substances and proinflammatory cytokines did not identify a stimulus that induced the release of IL-16C and MIF independent of secondary necrosis. The data presented here suggest that IL-16 and MIF are neutrophil-derived inflammatory mediators released under conditions of insufficient clearance of apoptotic neutrophils, as typically occurs at sites of infection and autoimmunity.

C5a receptor signalling in dendritic cells controls the development of maladaptive Th2 and Th17 immunity in experimental allergic asthma.

The pathways underlying dendritic cell (DC) activation in allergic asthma are incompletely understood. Here we demonstrate that adoptive transfer of ovalbumin-pulsed wild-type (wt) but not of C5a receptor-deficient (C5aR⁻/⁻) bone marrow (BM)-derived DCs (BMDCs) induced mixed T helper type 2 (Th2)/Th17 maladaptive immunity, associated with severe airway hyperresponsiveness, mucus production, and mixed eosinophilic/neutrophilic inflammation. Mechanistically, antigen uptake, processing, and CD11b expression were reduced in C5aR⁻/⁻ BMDCs. Further, interleukin (IL)-1ß, -6, and -23 production were impaired resulting in reduced Th17 cell differentiation, associated with accelerated activated T-cell death in vitro and in vivo. Surprisingly, we found an increased frequency of CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ cells, expressing arginase and nitric oxide synthase in C5aR⁻/⁻ BM preparations. Intratracheal administration of ovalbumin-pulsed wt DCs and sorted CD11b(hi)CD11c(int)Gr1⁺F4/80⁺ C5aR⁻/⁻ cells reduced Th2 immune responses in vivo. Together, we uncover novel roles for C5aR in Th17 differentiation, T-cell survival, and differentiation of a DC-suppressor population controlling Th2 immunity in experimental allergic asthma.

Recruitment of the tumour suppressor protein p73 by Kaposi's Sarcoma Herpesvirus latent nuclear antigen contributes to the survival of primary effusion lymphoma cells.

Kaposi's Sarcoma Herpesvirus (KSHV) is the causative agent of Kaposi's Sarcoma (KS) and two rare lymphoproliferative disorders, primary effusion lymphoma (PEL) and the plasmablastic variant of multicentric Castleman's disease (MCD). The KSHV latency-associated nuclear antigen-1 (LANA), required for the replication and maintenance of latent viral episomal DNA, is involved in the transcriptional regulation of viral and cellular genes and interacts with different cellular proteins, including the tumour suppressor p53. Here, we report that LANA also recruits the p53-related nuclear transcription factor p73, which influences cellular processes like DNA damage response, cell cycle progression and apoptosis. Both the full-length isoform TAp73α, as well as its dominant negative regulator ΔNp73α, interact with LANA. LANA affects TAp73α stability and sub-nuclear localisation, as well as TAp73α-mediated transcriptional activation of target genes. We observed that the small-molecule inhibitor Nutlin-3, which disrupts the interaction of p53 and p73 with MDM2, induces apoptotic cell death in p53 wild-type, as well as p53-mutant PEL cell lines, suggesting a possible involvement of p73. The small-molecule RETRA, which activates p73 in the context of mutant p53, leads to the induction of apoptosis in p53-mutant PEL cell lines. RNAi-mediated knockdown of p73 confirmed that these effects depend on the presence of the p73 protein. Furthermore, both Nutlin-3 and RETRA disrupt the LANA-p73 interaction in different PEL cell lines. These results suggest that LANA modulates p73 function and that the LANA-p73 interaction may represent a therapeutic target to interfere with the survival of latently KSHV-infected cells.

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004.

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries.

[Acute pancreatitis - association with a Campylobacter coli-infection]. / Campylobacter coli-assoziierte akute Pankreatitis.

A 37-year-old male presented with intermittent abdominal pain and 9 kg weight loss within 3 weeks. Gastroscopy showed no pathological findings, coloscopy showed a colitis limited to the left flexure. Histology revealed a sustained infectious enterocolitis. A culture of the patient's stool was positive for CAMPYLOBACTER COLI. Because of the recurrent abdominal discomfort and weight loss the patient was admitted to the hospital. Ultrasound and multislice spiral computed tomography showed an acute oedematous pancreatitis. No other causes for the pancreatitis were found, the only remaining possibility was a CAMPYLOBACTER COLI-associated pancreatitis. Under symptomatic therapy the patient recovered definitively. An administration of antibiotics was not necessary.

[Motor potentials following spinal and transcranial stimulation: normal values for recording without voluntary pre-innervation]. / Motorische Potentiale nach spinaler und transkranieller Stimulation: Normalwerte für die Ableitung ohne willkürliche Vorinnervation.

The transcranial motor stimulation with a special, short discharging stimulator can assess the conduction of central motor pathways. Voluntary preinnervation of certain muscles leads to amplitude augmentation and allows reduction of the stimulus intensity. Preinnervation is impossible, if comatose patients are studied or if the method is used for intraoperative monitoring. We examined the spinal and transcranial stimulated motor responses of the muscle opponens pollicis without preinnervation in 18 healthy volunteers. The latencies after hemispheric stimulation showed an increase of latency of more than 2.5 ms compared with normative data from the literature which is significant on the .05-level. The central conduction time was prolonged also. The latencies of the spinal stimulated muscle potentials are comparable under both conditions. It is concluded that for intraoperative monitoring or the assessment of motor function in comatose patients one has to relay on normative values achieved without preinnervation.

[The influence of umbilical cord structure on the course of pregnancy and parturition (author's transl)]. / Zum Einfluss der Nabelschnurstruktur auf Schwangerschafts- und Geburtsverlauf.

A series of 549 not selected placentas and umbilical cords were examined to show the influence of the different development of the umbilical cord structure on the umbilical cord perfusion and the course of parturition. For this purpose the quantity of Wharton's jelly, the spiraling of the umbilical vessels as well as the length of the cord are defined. At the same time anatomical pecularities and complications like umbilical cord torsions and true knots are considered. To judge the decisive condition of the newborn and with that the course of parturition, the pH-value of umbilical artery blood is determined. The analysis results that umbilical cords with much Wharton's jelly and with spiraling vessels are converted into an association with extremely better value than those with little jelly and less spiraling vessels. Short and rich jellied umbilical cords show a significantly lower incidence of loops around the fetal body. A similar trend can be demonstrated for umbilical cords with strong spiraling arteries. Rare phenomena like velamentous insertion, haematomas, edemas and true knots of the cords etc. proved to have no influence on the course of parturition in our relatively small examination series.