This study was designed to determine the contribution of the central nervous system (CNS) to the effects of glucagon-like peptide-1-(7-36) amide (tGLP-1) on arterial blood pressure and heart rate in rats. Accordingly, intracerebroventricular administration of the peptide produced an increase in cardiovascular parameters, which was blocked by previous administration of exendin-(9-39) through the same route, but not when it was intravenously injected. Intravenous administration of tGLP-1 produced a significant increase in arterial blood pressure and heart rate, which was blocked by the previous intracerebroventricular or intravenous administration of exendin-(9-39). Bilateral vagotomy blocked the stimulating effect of intracerebroventricular tGLP-1 administration on arterial blood pressure and heart rate. Also, bilateral vagotomy prevented the blocking effect of intracerebroventricular but not of intravenous exendin-(9-39) on cardiovascular parameters after intravenous administration of tGLP-1. These findings suggest that the action of tGLP-1 on cardiovascular parameters is under a dual control generated in the CNS and in peripheral structures and that the neural information emerging in the brain is transmitted to the periphery through the vagus nerve.

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To evaluate the clinical, laboratory, and immune characteristics of Zika virus (ZIKV)-associated encephalitis in pediatric patients after the epidemic in Huila, southern Colombia. Methods: A pediatric neuro-surveillance hospital study was conducted in a referral health center in southern Colombia, from October 2016 to October 2017. Cases of encephalitis were confirmed by nucleic acid amplification tests and serological methods in cerebrospinal fluid (CSF), plasma, and/or urine. Levels of six cytokines were evaluated by flow cytometry. Patients underwent daily clinical and laboratory follow-up. Results: Twenty children with probable encephalitis were included for further studies and 16 of them were confirmed. Four cases of bacterial meningoencephalitis (Streptococcus pneumoniae, group B Streptococcus, Staphylococcus epidermidis, and Escherichia coli) and 12 cases of viral encephalitis were identified, six of them associated with ZIKV infection. Other viral encephalitis cases were caused by herpes viruses (n = 3), enterovirus (n = 2), and dengue virus type 2 (DENV-2; n = 1) infections. ZIKVassociated encephalitis symptoms subsided faster than those of patients with encephalitis caused by other agents. CSF analysis revealed lymphocytic pleocytosis. Compared to healthy controls, children with ZIKV-associated encephalitis presented modest plasma interleukin (IL)-10 but not IL-2, IL-4, IL-6, interferon gamma (IFN-g), or tumor necrosis factor alpha (TNF-α). Cytokine expression was differentially regulated, as dramatically elevated IL-6, IL-10, and IFN-g levels were observed in CSF but not in paired plasma samples in one of the patients with ZIKV detectable in CSF. Conclusions: This study provides evidence that ZIKV is responsible for pediatric encephalitis in endemic areas, and the local presence of the virus may induce cephalic but not systemic expression of cytokines.

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We read with interest the article by Ben-Tal and coworkers 1 who reported that concentrations of prothrombin, Factor (F) VII, F IX, FX, and fibrinogen remained stable in plasma that had been twice-frozen and stored at -80 ∞ C. These data support their conclusion that this component can be used safely for transfusion as a source of vitamin K-dependent clotting factors and fibrinogen, but do not provide information on the use of this component for replacing protein C, protein S, or antithrombin III. We performed the following study to provide data on the stability of these proteins in twice-frozen fresh frozen plasma (FFP).Ten units of FFP were prepared from whole blood collected in citrate phosphate dextrose (Macopharma, Mouvaux, France). The units were thawed and 5-mL aliquots were removed by sterile technique (first thaw, Time 0). Concentrations of protein C, protein S, and antithrombin III were measured using a coagulation analyzer (IL Futura, Instrumentation Laboratory, Warrington, UK). The thawed units were stored at 4 ∞ C for 24 hours, and another sample was obtained (first thaw, Time 24). The units were refrozen at -80 ∞ C for 1 week, and a third sample was obtained immediately after thawing (second thaw, Time 0) and a fourth sample 24 hours later (second thaw, Time 24).The results of factor measurements (Table 1) show that although there are individual variations in the plasma concentrations of protein C, protein S, and fibrinogen among normal blood donors, these proteins remain stable after two thaws and storage at 4 ∞ C for two 24-hour periods. We believe that these findings complement those of Ben-Tal and colleagues, indicating that twice-frozen and thawed plasma is suitable not only for replacing vitamin K-dependent coagulation factors, but also for replacing protein C, protein S, and antithrombin. Also, using twicefrozen and thawed plasma may significantly reduce wastage of thawed and unused FFP. Muttuswamy Sivakumaran, MSc, FRCP, FRCPath, PhD

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Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers’ cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals to L. panamensis lysate antigens. We conclude that, in silico analysis allowed for the identification of natural Leishmania epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.

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