Intranasal Methylprednisolone Effectively Reduces Neuroinflammation in Mice With Experimental Autoimmune Encephalitis.

Relapsing-remitting multiple sclerosis, the most common form, is characterized by acute neuroinflammatory episodes. In addition to continuous disease-modifying therapy, these relapses require treatment to prevent lesion accumulation and progression of disability. Intravenous methylprednisolone (1-2 g for 3-5 days) is the standard treatment for relapses. However, this treatment is invasive, requires hospitalization, leads to substantial systemic exposure of glucocorticoids, and can only reach modest concentrations in the central nervous system (CNS). Intranasal delivery may represent an alternative to deliver relapse treatment directly to the CNS with higher concentrations and reducing side effects. Histopathological analysis revealed that intranasal administration of methylprednisolone to mice with experimental autoimmune encephalomyelitis (EAE) suppressed the neuroinflammatory peak, and reduced immune cell infiltration and demyelination in the CNS similarly to intravenous administration. Treatment also downregulated Iba1 and GFAP expression. A similar significant reduction of IL-1ß, IL-6, IL-17, IFN-γ, and TNF-α levels in the spinal cord was attained in both intranasal and intravenously treated mice. No damage in the nasal cavity was found after intranasal administration. This study demonstrates that intranasal delivery of methylprednisolone is as efficient as the intravenous route to treat neuroinflammation in EAE.

Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury.

Sepsis occurs when a systemic infection induces an uncontrolled inflammatory response that results in generalized organ dysfunction. The exacerbated peripheral inflammation can induce, in turn, neuroinflammation which may result in severe impairment of the central nervous system (CNS). Indeed, the ensuing blood-brain barrier disruption associated with sepsis promotes glial activation and starts a storm of proinflammatory cytokines in the CNS that leads to brain dysfunction in sepsis survivors. Endotoxic shock induced in mice by peripheral injection of lipopolysaccharides closely resembles the peripheral and central inflammation observed in sepsis. In this review, we provide an overview of the neuroinflammatory features in sepsis and of recent progress toward the development of new anti-neuroinflammatory therapies seeking to reduce mortality and morbidity in sepsis survivors.

The economic impact of H1N1 on Mexico's tourist and pork sectors.

By examining tourist arrivals and pork output and trade statistics, this analysis estimates the economic impact to the Mexican tourism and pork sectors because of the H1N1 influenza pandemic. It also assesses the role of the international response in the context of this economic impact. For tourism, losing almost a million overseas visitors translated into losses of around $US2.8bn, which extended over a five-month period, mostly because of the slow return of European travellers. For the pork industry, temporal decreases in output were observed in most of the country and related to H1N1 incidence (p = 0.048, r = 0.37). By the end of 2009, Mexico had a pork trade deficit of $US27m. The losses derived from this pandemic were clearly influenced by the risk perception created in tourist-supplying and pork trade partners. Results suggest that the wider economic implications of health-related emergencies can be significant and need to be considered in preparedness planning. For instance, more effective surveillance and data gathering would enable policy to target emergency funding to the sectors and regions hardest hit. These results also stress the importance of being familiar with trade networks so as to be able to anticipate the international response and respond accordingly.

Characterization of S3Pvac anti-cysticercosis vaccine components: implications for the development of an anti-cestodiasis vaccine.

BACKGROUND: Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms. CONCLUSIONS/SIGNIFICANCE: These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates.