153 research outputs found

    Limited Trafficking of a Neurotropic Virus Through Inefficient Retrograde Axonal Transport and the Type I Interferon Response

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    Poliovirus is an enteric virus that rarely invades the human central nervous system (CNS). To identify barriers limiting poliovirus spread from the periphery to CNS, we monitored trafficking of 10 marked viruses. After oral inoculation of susceptible mice, poliovirus was present in peripheral neurons, including vagus and sciatic nerves. To model viral trafficking in peripheral neurons, we intramuscularly injected mice with poliovirus, which follows a muscle–sciatic nerve–spinal cord–brain route. Only 20% of the poliovirus population successfully moved from muscle to brain, and three barriers limiting viral trafficking were identified. First, using light-sensitive viruses, we found limited viral replication in peripheral neurons. Second, retrograde axonal transport of poliovirus in peripheral neurons was inefficient; however, the efficiency was increased upon muscle damage, which also increased the transport efficiency of a non-viral neural tracer, wheat germ agglutinin. Third, using susceptible interferon (IFN) α/β receptor knockout mice, we demonstrated that the IFN response limited viral movement from the periphery to the brain. Surprisingly, the retrograde axonal transport barrier was equivalent in strength to the IFN barrier. Illustrating the importance of barriers created by the IFN response and inefficient axonal transport, IFN α/β receptor knockout mice with muscle damage permitted 80% of the viral population to access the brain, and succumbed to disease three times faster than mice with intact barriers. These results suggest that multiple separate barriers limit poliovirus trafficking from peripheral neurons to the CNS, possibly explaining the rare incidence of paralytic poliomyelitis. This study identifies inefficient axonal transport as a substantial barrier to poliovirus trafficking in peripheral neurons, which may limit CNS access for other viruses

    B-type natriuretic peptide (BNP) in patients undergoing mitral valve surgery

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    BACKGROUND AND AIM: Plasma B-type natriuretic peptide (BNP) level may be increased in patients with valvular disease. Recent studies have suggested that in patients undergoing aortic valve replacement, an increased preoperative BNP is associated with a worse operative outcome. Little is known about the perioperative value of BNP in patients undergoing mitral valve (MV) surgery. We measured the preoperative and postoperative BNP levels in this population and analyzed the impact of the increased BNP level on surgical outcome. METHODS: From March 2004 to February 2005, 42 patients (mean age 64 +/- 12 years, 18 [42%] male) were enrolled in a prospective study. All patients underwent surgery for severe mitral regurgitation. The mean ejection fraction was 49 +/- 13%, and 26 (62%) patients presented with atrial fibrillation (AF). RESULTS: The median preoperative and postoperative BNP levels were 108 (9.7 to 995) and 357 (143 to 904) pg/mL, respectively (p = 0.002). Heart failure (p = 0.03), atrial fibrillation (AF) (p = 0.01), and ejection fraction (p = 0.01) were associated with an increased preoperative BNP level. In a multivariate analysis, the only independent predictor of the increased BNP level was AF (p = 0.01). In a univariate analysis, the preoperative BNP level was a significant predictor for inotropic support (p < 0.001), ventilation time (p = 0.003), intensive care unit (ICU; p = 0.01), and hospital length of stay (p = 0.02). In the multivariate analysis, BNP was not a predictor of these variables. CONCLUSIONS: Preoperative plasma BNP level presents with a high individual variability in patients with MV regurgitation. AF was the only independent predictor of an increased preoperative BNP level. The preoperative BNP level was not a predictor of surgical outcome. Further studies are required to confirm these findings and evaluate the potential role of this marker for patient selection
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