Magnesium alloy stents are safe and are associated with less neointima formation; however, reduced neointima did not result in larger lumen.

BackgroundSurgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep.Methodology/Principal FindingsThe nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation.Conclusions/SignificanceThis study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

Streptococcus suis causes numerous diseases in pigs, most importantly, meningitis, arthritis, septicemia, and bronchopneumonia. One of the major problems in modern swine production is the lack of a vaccine protecting against more than one S. suis serotype. The objective of this study was to determine the protective efficacy of a serotype 2 murein-associated protein (MAP) fraction subunit vaccine in comparison to that of a bacterin against experimental challenge with serotype 2 (containing muramidase-released protein [MRP], extracellular factor, and suilysin [SLY]) and serotype 9 (containing MRP variant MRP* and SLY) strains. MAP was shown to include different surface-associated proteins, such as the MRP and surface antigen one (SAO) expressed by both pathotypes used for challenge. The results of this study demonstrated that the serotype 2 bacterin induced protective immunity against homologous challenge. In contrast, the protective efficacy of the MAP subunit vaccine was low, though MAP immunization resulted in high serum immunoglobulin G2 titers against MRP and SAO. Importantly, immunization with bacterin but not with MAP induced opsonizing antibody titers against the serotype 2 strain, and these antibody titers were found to correlate with protection. However, after absorption with a nonencapsulated isogenic mutant, the sera from bacterin-immunized piglets failed to facilitate neutrophil killing, indicating that antibodies directed against capsule may not have been essential for opsonophagocytosis. Furthermore, induction of opsonizing antibodies against serotype 9 was not detectable in the group receiving bacterin or in the group receiving the MAP vaccine. In agreement, protection against the heterologous serotype 9 strain was low in both groups. Thus, identification of an antigen protecting against these two important S. suis pathotypes remains an important goal of future studies.Streptococcus suis ranks among the five most important health challenges of pigs worldwide (11,12). It is associated with numerous diseases, such as meningitis, arthritis, serositis, and bronchopneumonia. S. suis isolates from diseased animals express a polysaccharide capsule which confers resistance to phagocytosis, as demonstrated for serotype 2 strains (21). Strains of various serotypes have been isolated from affected tissues. In Europe, serotype 2 and 9 strains are the most prevalent types isolated from infections. The 136-kDa muramidasereleased protein (MRP) and the 110-kDa extracellular factor (EF) are virulence-associated factors expressed only by virulent serotype 1 and 2 strains (22, 23). The majority of invasive serotype 9 isolates express a larger variant of MRP, termed MRP*, which shares high homology with the 136-kDa MRP protein of serotype 2 strains (20, 23).

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Actinobacillus pleuropneumoniae (A.pp) causes severe pneumonia associated with enormous economic loss in pigs. Peracute diseased pigs die in <24 h with pneumonia. Neutrophils are the prominent innate immune cell in this infection that massively infiltrate the infected lung. Here we show that neutrophils release neutrophil extracellular traps (NETs) as response to A.pp infection. Numerous NET-markers were identified in bronchoalveolar lavage fluid (BALF) of A.pp-infected piglets in vivo, however, most NET fibers are degraded. Importantly, A.pp is able to enhance its growth rate in the presence of NETs that have been degraded by nucleases efficiently. A.pp itself releases no nuclease, but we identified host nucleases as sources that degrade NETs after A.pp infection. Furthermore, the nucleases of co-infecting pathogens like Streptococcus suis increase growth of A.pp in presence of porcine NETs. Thus, A.pp is not only evading the antimicrobial activity of NETs, A.pp is rather additionally using parts of NETs as growth factor thereby taking advantage of host nucleases as DNase1 or nucleases of co-infecting bacteria, which degrade NETs. This effect can be diminished by inhibiting the bacterial adenosine synthase indicating that degraded NETs serve as a source for NAD, which is required by A.pp for its growth. A similar phenotype was found for the human pathogen Haemophilus (H.) influenzae and its growth in the presence of human neutrophils. H. influenzae benefits from host nucleases in the presence of neutrophils. These data shed light on the detrimental effects of NETs during host immune response against certain bacterial species that require and/or efficiently take advantage of degraded DNA material, which has been provided by host nuclease or nucleases of other co-infecting bacteria, as growth source.

The efficacy of a homologous vaccination in preventing infection of suckling piglets with Salmonella (S.) Typhimurium was evaluated after an immunization of pregnant sows using an inactivated herd-specific S. Typhimurium vaccine. Twenty-five pregnant sows were vaccinated three times antepartum. The efficiency of this vaccine regime was assessed by comparison with a control group of 37 sows and their suckling piglets, which were daily treated with enrofloxacin from day 14 antepartum until the day of weaning. From the first day of life until day 142 post-partum, faecal samples of the piglets were collected and analysed for Salmonella shedding. In parallel, systemic antibody responses were monitored using a whole cell-based isotype-specific enzyme-linked immunosorbent assay (ELISA). The bacteriological investigation showed marked effects of vaccination. Salmonella Typhimurium could not be detected in any of the faecal samples of the piglets from the vaccinated sows. In contrast, the piglets of the group with long-time antibiotic treatment shed salmonellae rating to 47.4% of the animals. Furthermore, the offspring from vaccinated sows showed significantly decreased antibody activities of immunoglobulin (Ig)A and IgG. These bacteriological and serological results indicate a significantly lower Salmonella prevalence in piglets of the vaccinated group. As this study shows, the presented strategy of vaccination of pregnant sows with an inactivated Salmonella vaccine seems to be a suitable measure in decreasing Salmonella prevalence in offspring of infected sows.

Streptococcus suis is an important porcine pathogen causing meningitis and other invasive diseases in piglets of different ages. Application of S. suis serotype 2 bacterins to specific-pathogen-free (SPF) weaning piglets has been demonstrated to protect against the homologous serotype. However, autogenous S. suis bacterins are also applied to sows and suckling piglets in the field. Therefore, comparative evaluation of different bacterin immunization regimes, including sow vaccination, was performed in this study. The main objectives were to determine the immunogenicity of an S. suis bacterin in sows prepartum and its influence on active immunization of piglets. Experimental infection of 6-and 8-week-old weaning piglets was performed to elucidate protective efficacies. Humoral immune responses were investigated by an enzyme-linked immunosorbent assay (ELISA) measuring muramidase-released protein (MRP)-specific IgG titers and by opsonophagocytosis assays. Bacterin application elicited high MRP-specific IgG titers in the serum and colostrum of sows, as well as opsonizing antibodies. Piglets from vaccinated sows had significantly higher MRP-specific titers than respective piglets from nonvaccinated sows until 6 weeks postpartum. Vaccination of suckling piglets did not result in high MRP-specific titers nor in induction of opsonizing antibodies. Furthermore, neither vaccination of suckling nor of weaning piglets from immunized sows was associated with a prominent active immune response and protection at 8 weeks postpartum. However, protection was observed in respective 6-week-old weaning piglets, most likely because of protective maternal immunity. In conclusion, this study provides the first results suggesting protective passive maternal immunity for S. suis serotype 2 after bacterin vaccination of sows and a strong inhibitory effect on active immunization of suckling and weaning piglets, leading to highly susceptible growers.Streptococcus suis causes various pathologies, such as meningitis, arthritis, serositis, bronchopneumonia, and endocarditis (11). Furthermore, S. suis serotype 2 is also an important zoonotic agent (9). S. suis is characterized by a high diversity, and different serotypes might be involved in invasive diseases in pigs (6,24). However, most of the experimental studies have been performed with serotype 2. Based on comparative evaluation of virulence of wild-type strains in intranasal infection experiments, serotype 2 isolates expressing the 136-kDa muramidase-released protein (MRP) and the 110-kDa extracellular factor (EF) are regarded as more virulent than serotype 2 strains which lack these factors or express MRP and a large variant of EF called EF* (22,23). On the other hand, MRP ϩ

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