Effects of commercial organic acid blends on male broilers challenged with E. coli K88: Performance, microbiology, intestinal morphology, and immune response.

This study assessed the effects of 3 commercial organic acid (OA) preparations on growth performance, intestinal morphology, cecal microbiology, and immunity of Escherichia coli K88-challenged (ETEC) broiler chickens. One thousand one-day-old male broiler chickens were divided into 8 treatments of 5 replicate pens: Negative control (NC) birds received a basal diet (BD) and were not challenged with ETEC; positive control (PC) birds fed the BD and challenged with ETEC; BD + 0.2% (S1) or 0.4% (S2) of an OA mixture (Salkil) from one to 35 d; BD + 0.1, 0.075, and 0.05% (O1) of another OA mixture (Optimax) in the starter (one to 10 d), grower (11 to 24 d), and finisher (25 to 35 d) diets, respectively, or 0.1% (O2) from one to 35 d; BD + 0.07, 0.05, and 0.05% (P1) or 0.1, 0.07, and 0.05% (P2) of a further OA mixture (pHorce) in the starter, grower, and finisher diets, respectively. All groups (not NC) were challenged with one mL of ETEC (1 × 108 cfu/mL) at 7 d of age. The 3 OA mixtures are commercial formic and propionic acid preparations. Birds challenged with ETEC (PC) had reduced (P < 0.05) growth performance, ileal morphological parameters (not crypt depth, which was increased), cecal lactobacilli, and immune responses, and increased cecal E. coli compared with unchallenged, NC birds. The addition of OA to the diets of ETEC challenged birds (S1-P2) either numerically or significantly (P < 0.05) improved growth performance, ileal morphology and immune responses, increased cecal lactobacilli, and reduced cecal E. coli. For most OA additions, the assessed parameters were generally enhanced to equivalence to NC birds. The results suggest that dietary OA supplementation can enhance the growth performance, ileal morphology, cecal microbiota, and immunity of ETEC-challenged broilers to an extent that, under such circumstances, the formulations used in this study provided similar performance and assessed parameters as non-challenged birds.

Outcomes of isolated limb perfusion in the treatment of extremity soft tissue sarcoma: a systematic review.

BACKGROUND: Isolated limb perfusion (ILP) may provide a limb salvage option for locally advanced soft tissue sarcoma (STS) not amenable to local resection. METHODS: A systematic review was performed for studies reporting outcome of ILP for locally advanced STS performed after 1980 in patients aged ≥ 12 years old. The main endpoints were tumour response and limb salvage rates. Complication and recurrence rates were secondary endpoints. RESULTS: Eighteen studies were included, providing outcomes for 1030 patients. Tumour necrosis factor-alpha with melphalan was the commonest chemotherapy regime. When reported, 22% of cases achieved a complete tumour response (216/964, 15 studies) with an overall response rate of 72% (660/911, 15 studies). At median follow-up times ranging between 11 and 125 months, the limb salvage rate was 81% in patients who otherwise would have been subjected to amputation. However, 27% of patients suffered local recurrence and 40% suffered distant failure. ILP was associated with severe locoregional reactions in 4% (22/603) of patients. Amputation due to complications within 30 days was necessary in 1.2% of cases (7/586, nine studies). There was insufficient evidence to determine the effect of ILP on survival. CONCLUSION: ILP induces a high tumour response rate, leads to a high limb salvage rate but is associated with a high recurrence rate. It provides a limb salvage alternative to amputation when local control is necessary.

Full and partial peroxisome proliferation-activated receptor-γ agonists, but not δ agonist, rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor that has been shown to have anti-inflammatory and matrix metalloproteinase (MMP) inhibitor properties. PPARγ agonists have been shown to have neuroprotective effects in various neurodegeneration models where inflammation is implicated, including models of Parkinson's disease. However, no studies have looked at the effects of partial PPARγ agonists. EXPERIMENTAL APPROACH: The neuroprotective effects of the PPARγ full agonist, pioglitazone (20 mg/kg), partial PPARγ agonist GW855266X (15 mg/kg) and PPAR-δ full agonist GW610742X (10 mg/kg) were investigated in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease when administered prior to or post 6-OHDA lesioning. The integrity of the nigrostriatal system was assessed by assessing the numbers dopaminergic neurons in the substantia nigra (SN) and by assessing striatal dopamine content. The degree of microglia activation in the SN was also immunohistochemistry assessed utilizing the marker OX-6 for activated microglia and CD-68 a marker for phagocytic microglia. Additionally we performed immunocytochemistry for MMP3 in the SN. Finally, we investigated whether a period of drug withdrawal for a further 7 days affected the neuroprotection produced by the PPARγ agonists. KEY RESULTS: Both pioglitazone and GW855266X protected against 6-OHDA induced loss of dopaminergic neurons in the substantia nigra and depletion of striatal dopamine when administered orally twice daily for either 1) 7 day prior to and 7 days post lesioning or 2) for 7 days starting 2 days post lesioning when neurons will be severely traumatized. 6-OHDA lesioning was associated with an increase in microglia activation and in numbers of MMP-3 immunoreactive cells which was attenuated by pioglitazone and GW855266X. Neuroprotective effects were not replicated using the PPARδ agonist GW610742X. Subsequent withdrawal of both pioglitazone and GW855266X, for a further 7 days negated any neuroprotective effect suggesting that long-term administration may be required to attenuate the inflammatory response. CONCLUSIONS AND IMPLICATIONS: For the first time a partial PPAR-γ agonist has been shown to be neuroprotectory when administered post lesioning in a parkinsonian model. Effects may be via the inhibition of microglial and MMP activation and support further research.

Effect of rearing environment and dietary zinc oxide on the response of group-housed weaned pigs to enterotoxigenic Escherichia coli O149 challenge.

A 2 × 2 factorial experiment was conducted to determine the effects of rearing environment (indoor (In) v. outdoor (Out)) and dietary zinc oxide (ZnO) supplementation (0 (-Zn) v. 3100 (+Zn) mg/kg feed) on the response of weaned pigs to a challenge infection with enterotoxigenic Escherichia coli (ETEC). Pigs from the two rearing environments were weaned onto trial diets at 4 weeks of age, moved into conventional accommodation and infected 3 days later with 109 CFU ETEC per os. Faecal ETEC shedding was determined before and after challenge. After 7 days of ETEC infection, all pigs were euthanized for gut lactic acid bacteria (LAB)-to-coliform ratio, pH and small intestine morphological measurements. Both ZnO and outdoor rearing reduced ETEC excretion, and these effects were additive. Outdoor rearing increased small intestine and colon tissue weight. ZnO increased villus height and goblet cell number in the upper small intestine, LAB-to-coliform ratio (through reduced coliforms) in the lower small intestine and proximal colon, and improved growth performance. There were interactive effects of rearing environment and ZnO supplementation on upper small intestine villus height and daily gain, as outdoor rearing conferred advantages on these variables only with ZnO dietary supplementation. Daily gains were 233, 174, 277 and 347 (s.e.m. 27.2) g/day for the In - Zn, Out - Zn, In + Zn and Out + Zn, respectively. These results suggest different, but complementary mechanisms of intestinal health and performance in outdoor-reared pigs and those offered ZnO supplemented diets. The results indicate that the benefits of ZnO to the weaned pig extend beyond suppression of ETEC and appear mediated through altered development of the small intestine mucosa.

Effects of zinc oxide and Enterococcus faecium SF68 dietary supplementation on the performance, intestinal microbiota and immune status of weaned piglets.

The objective of this study was to determine the effects of zinc oxide (ZnO) and the probiotic Enterococcus faecium SF68 (Cylactin) dietary supplementation on the performance, intestinal microbiota and immune parameters of the weaned piglet reared under commercial conditions. The diets were devoid of antibiotic growth promoters (AGP). Two hundred and eight crossbred piglets were allocated to a 2 x 2 factorial experiment involving two levels of zinc oxide supplementation (0 or 3100 mg ZnO/kg feed), and two levels of E. faecium SF68 supplementation (0 or 1.4 x 10(9)CFU/kg feed (Cylactin ME10)). The diets were offered ad libitum for 20 days post-weaning. Piglet performance was assessed by calculating average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) on a pen basis. In addition, components of the distal ileal digesta, tissue-associated and mesenteric lymph node (MLN) bacterial populations were enumerated and serum immunoglobulin G (IgG) and intestinal immunoglobulin A (IgA) concentrations were determined on days 6 and 20 post-weaning. Regression analysis was used to determine the relationship between the bacterial populations at the different sites. Supplementation of the post-weaning diet with either ZnO or E. faecium SF68 did not affect piglet performance. E. faecium SF68 did not affect gastrointestinal bacterial populations but did tend to reduce serum IgG (P<0.1) on day 20. Zinc oxide reduced anaerobic (P<0.05) and tended to decrease lactic acid (P<0.1) bacterial translocation to the MLN, and tended to increase intestinal IgA concentration (P<0.1) on day 20. Generally, luminal bacterial populations were found to be poor predictors of tissue-associated or MLN populations. ZnO and E. faecium SF68 dietary supplementation were ineffective under these trial conditions. Further investigations into the possible immunomodulator role of dietary ZnO are warranted.

The polysialyltransferase ST8Sia II/STX: posttranslational processing and role of autopolysialylation in the polysialylation of neural cell adhesion molecule.

The presence of alpha2,8-linked polysialic acid on the neural cell adhesion molecule (NCAM) is known to modulate cell interactions during development and oncogenesis. Two enzymes, the alpha2,8-polysialyltransferases ST8Sia IV()/PST and ST8Sia II()/STX are responsible for the polysialylation of NCAM. We previously reported that both ST8Sia IV/PST and ST8Sia II/STX enzymes are themselves modified by alpha2,8-linked polysialic acid chains, a process called autopolysialylation. In the case of ST8Sia IV/PST, autopolysialylation is not required for enzymatic activity. However, whether the autopolysialylation of ST8Sia II/STX is required for its ability to polysialylate NCAM is unknown. To understand how autopolysialylation impacts ST8Sia II/STX enzymatic activity, we employed a mutagenesis approach. We found that ST8Sia II/STX is modified by six Asn-linked oligosaccharides and that polysialic acid is distributed among the oligosaccharides modifying Asn 89, 219, and 234. Coexpression of a nonautopolysialylated ST8Sia II/STX mutant with NCAM demonstrated that autopolysialylation is not required for ST8Sia II/STX polysialyltransferase activity. In addition, catalytically active, nonautopolysialylated ST8Sia II/STX does not polysialylate any endogenous COS-1 cell proteins, highlighting the protein specificity of polysialylation. Furthermore, immunoblot analysis of NCAM polysialylation by autopolysialylated and nonautopolysialylated ST8Sia II/STX suggests that the NCAM is polysialylated to a higher degree by autopolysialylated ST8Sia II/STX. Therefore, we conclude that autopolysialylation of ST8Sia II/STX, like that of ST8Sia IV/PST, is not required for, but does enhance, NCAM polysialylation.

Morbidity of Hurricane Elena.

On Sept 2, 1985, Hurricane Elena struck the Gulf Coast of Mississippi. We conducted a retrospective review of Emergency Department logs for a one-week period before and a two-week period after the storm to determine what additional support would be needed to manage such a disaster. There was a significant increase in the number of patients treated for psychiatric problems and trauma. These findings are similar to the results obtained in a study at the same hospital after Hurricane Frederic in 1979.