The Dilemma of Influenza Vaccine Recommendations when Applied to the Tropics: The Brazilian Case Examined Under Alternative Scenarios

Since 1999 the World Health Organization issues annually an additional influenza vaccine composition recommendation. This initiative aimed to extend to the Southern Hemisphere (SH) the benefits—previously enjoyed only by the Northern Hemisphere (NH)—of a vaccine recommendation issued as close as possible to the moment just before the onset of the influenza epidemic season. A short time between the issue of the recommendation and vaccine delivery is needed to maximize the chances of correct matching between putative circulating strains and one of the three strains present in the vaccine composition. Here we compare the effectiveness of the SH influenza vaccination adopted in Brazil with hypothetical alternative scenarios defined by different timings of vaccine delivery and/or composition. Scores were based on the temporal overlap between vaccine-induced protection and circulating strains. Viral data were obtained between 1999 and 2007 from constant surveillance and strain characterization in two Brazilian cities: Belém, located at the Equatorial region, and São Paulo, at the limit between the tropical and subtropical regions. Our results show that, among currently feasible options, the best strategy for Brazil would be to adopt the NH composition and timing, as in such case protection would increase from 30% to 65% (p<.01) if past data can be used as a prediction of the future. The influenza season starts in Brazil (and in the equator virtually ends) well before the SH winter, making the current delivery of the SH vaccination in April too late to be effective. Since Brazil encompasses a large area of the Southern Hemisphere, our results point to the possibility of these conclusions being similarly valid for other tropical regions

Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis

BACKGROUND: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals. METHODOLOGY/PRINCIPAL FINDINGS: On a murine model of endotoxemia induced by lipopolysaccharide (LPS), we found that the median effective dose (ED50) of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

<p>Abstract</p> <p>Background</p> <p>Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of <it>M. fasciculata </it>geopropolis against oral pathogens, its effects on <it>S. mutans </it>biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on <it>S. mutans </it>and its immunotoxicological potential.</p> <p>Methods</p> <p>Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs.</p> <p>Results</p> <p>Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for <it>S. mutans </it>and <it>C. albicans</it>, but presented no activity against <it>L</it>. <it>acidophilus</it>. The MBCs for HAE-2 and HAE-3 against <it>S. mutans </it>were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on <it>S. mutans </it>biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected.</p> <p>Conclusions</p> <p>In summary, geopropolis produced by <it>M. fasciculata </it>can exert antimicrobial action against <it>S. mutans </it>and <it>C. albicans</it>, with significant inhibitory activity against <it>S. mutans </it>biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the highest antimicrobial activity. In addition, a geopropolis-based gel is not toxic in an animal model and displays anti-inflammatory effect.</p

A novel antimicrobial lectin from Eugenia malaccensis that stimulates cutaneous healing in mice model

Objective The present work reports the purification and partial characterization of an antibacterial lectin (EmaL) obtained from Eugenia malaccensis seeds as well as the evaluation of its effect in the daily topical treatment of repairing process of cutaneous wounds in mice. Materials and methods The cutaneous wound was produced by the incision of the skin and use of lectin in the treatment of mice cutaneous wounds was evaluated. Surgical wounds were treated daily with a topical administration of EmaL and parameters such as edema, hyperemia, scab, granulation and scar tissues as well as contraction of wounds were analyzed. Results A novel lectin, with a molecular mass of 14 kDa, was isolated from E. malaccensis using affinity chromatography. The lectin (EmaL) agglutinated glutaraldehyde-treated rabbit and human erythrocytes; the lectin-induced rabbit erythrocyte agglutination was inhibited by glucose, casein, ovalbumin and fetuin. Also, Emal was very effective in the inhibition of bacterial growth, with the best inhibition results obtained for Staphylococcus aureus. Inflammatory signals such as edema and hyperemia were statistically less intense when EmaL was applied compared to the control. The histopathological analysis showed that the treated injured tissue presented reepithelialization (complete or partial) and areas of transition more evidenced than those of the control group, especially due to well organized pattern of collagen fibers presented in the granulation fibrous tissue. Conclusion Presented results are a preliminary indication of the pharmacological interest in using EmaL as antimicrobial agent and in the repairing process of cutaneous wounds.This paper was financially supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), FACEPE and CAPES, Brazil. The authors are deeply grateful for the technical assistance of Maria Barbosa Reis da Silva and João Antonio Virgínio and Alfa/VALNATURA Project.info:eu-repo/semantics/publishedVersio