Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil.

INTRODUCTION: Clinical and epidemiological data on suspected congenital Zika syndrome (CZS) cases from southern Mato Grosso (MT) in Brazil during the Zika virus (ZIKV) outbreak in 2015-2016 were evaluated. METHODS: This is a descriptive case series study of newborns whose mothers were suspected cases of ZIKV infections during their pregnancies. The medical records of all the suspected CZS cases (mothers and newborns) treated by the specialized ambulatory service from June 2015 to August 2016 were analyzed. RESULTS: Twenty suspected CZS cases were included in these analyses. They were categorized into four groups based on the clinical and laboratory findings: confirmed cases (n=1), highly probable cases (n=13), moderately probable cases (n=5), and somewhat probable cases (n=1). The mothers tested negative for STORCH (syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) and other important congenital infections; however, specific ZIKV tests were not performed during the study period. Microcephaly was observed in the majority of these newborns, and all the patients showed altered cranial computed tomography image findings. Extracranial abnormalities such as arthrogryposis, and otological and ophthalmological manifestations were also observed. CONCLUSIONS: Although ZIKV was not confirmed to cause the congenital malformations, this study demonstrated that the clinical and epidemiological findings associated with a STORCH exclusion strengthened the CZS diagnosis. The suspected cases in MT occurred simultaneously with the first CZS cases reported in Brazil, suggesting ZIKV circulation in the study region during the same period.

Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil

Abstract INTRODUCTION: Clinical and epidemiological data on suspected congenital Zika syndrome (CZS) cases from southern Mato Grosso (MT) in Brazil during the Zika virus (ZIKV) outbreak in 2015-2016 were evaluated. METHODS: This is a descriptive case series study of newborns whose mothers were suspected cases of ZIKV infections during their pregnancies. The medical records of all the suspected CZS cases (mothers and newborns) treated by the specialized ambulatory service from June 2015 to August 2016 were analyzed. RESULTS: Twenty suspected CZS cases were included in these analyses. They were categorized into four groups based on the clinical and laboratory findings: confirmed cases (n=1), highly probable cases (n=13), moderately probable cases (n=5), and somewhat probable cases (n=1). The mothers tested negative for STORCH (syphilis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex) and other important congenital infections; however, specific ZIKV tests were not performed during the study period. Microcephaly was observed in the majority of these newborns, and all the patients showed altered cranial computed tomography image findings. Extracranial abnormalities such as arthrogryposis, and otological and ophthalmological manifestations were also observed. CONCLUSIONS: Although ZIKV was not confirmed to cause the congenital malformations, this study demonstrated that the clinical and epidemiological findings associated with a STORCH exclusion strengthened the CZS diagnosis. The suspected cases in MT occurred simultaneously with the first CZS cases reported in Brazil, suggesting ZIKV circulation in the study region during the same period.

First report of interruption of mast cell degranulation and endothelial cells activation by anti-inflammatory drugs controlling the acute response provoked by Pseudoplatystoma fasciatum fish venom.

This is the first report describing in mice the envenoming that possible to occur in humans provoked by Pseudoplatystomafasciatum and evaluated the different class of mediators involved in the inflammatory injury, identifying important targets for drugs intervention. First we demonstrate that P. fasciatum venom induces an acute inflammatory response characterized by the recruitment of immune cells into peripheral tissues choreographed by chemoattractants including lipid mediators (LTB4 and PGE2), cytokines (IL-1ß and TNF-α), and chemokines (KC and MCP-1). Intravital microscopy studies showed that only high dose (60 µg) of venom promoted hemodynamic changes inducing an abundant number of thrombi of varying sizes in venules leading to transient venular stasis with reduced blood flow. We found that serotonin, leukotrine and prostaglandin are involved in edematogenic and nociceptive responses, since a selective COX-2 inhibitor, a non-specific inhibitor for cytokines and COX-2, and a non-selective 5-HT receptor antagonist were able to reduce both symptoms. In conclusion, our data show that the main symptoms of acute inflammation as pain provoked by P. fasciatum fish venom could be well managed by available drugs as COX-2 inhibitors as well dexamethasone or non-selective 5-HT receptor antagonists.

Anti-inflammatory effect of Natterins, the major toxins from the Thalassophryne nattereri fish venom is dependent on TLR4/MyD88/PI3K signaling pathway.

Here we evaluated whether Natterins affect the leukocyte-endothelial cell interaction, hampering leukocyte mobilization and extravasation. Leukocyte-endothelial cell interactions were evaluated in venules of mouse cremaster muscle using intravital microscopy. We reported that low doses of Natterins interfere with the cell capturing, inhibiting the interaction of blood neutrophils with the post-capillary venules induced by the TLR4 agonist LPS, or the chemokine KC. Using endotoxemic mice challenged with LPS, we confirmed that Natterins reduce neutrophil accumulation in the peritoneum exudates. The rolling of leukocytes induced by KC or LPS was not impaired in Natterins-treated TLR2, MyD88 deficient or TLR4 mutant mice, indicating that TLR2- or TLR4-MyD88-mediated signals are required for the anti-inflammatory effect of Natterins. The inhibitory effect was not influenced by endogenous regulators of inflammation such as IL-10, corticosteroids, the HO-1 or the antagonist of the receptor of IL-1, nor by the disruption of their proteolytic activity. However, it was completely dependent on the activation of serine/threonine phosphatases and the PI3K signaling pathway, but independent on increased proteasome activity. This work started asking how the main toxins in the T nattereri venom contributes for the deficient influx of inflammatory leukocytes, which consequently drive to the delayed inflammatory reaction finalization in injured tissue; and finished demonstrating that Natterins can control the leukocyte-endothelial wall interactions in a mechanism dependent on negative signals derived from TLR2-TLR4/Myd88 signaling cascade. Interestingly, we confirmed that the antagonist effect of Natterins is mediated by the activation of serine/threonine phosphatases and by the key signaling PI3K molecule.

The anti-inflammatory action of Bothrops jararaca snake antithrombin on acute inflammation induced by carrageenan in mice.

OBJECTIVE AND DESIGN: Antithrombin is known as the most important natural coagulation inhibitor and has been shown to have anti-inflammatory properties. The present study aimed to investigate the effects of Bothrops jararaca antithrombin on acute inflammation induced by carrageenan in mice. METHODS: We evaluated the anti-inflammatory activity of antithrombin on models of paw edema formation, cell migration and leukocyte-endothelium interaction in mice (Swiss; n = 5). Acute inflammation was induced by the administration of carrageenan (15 mg kg⁻¹). RESULTS: Treatment with B. jararaca antithrombin (1 mg kg⁻¹) 1 h before or after carrageenan administration significantly inhibited paw edema formation, reduced cell influx to the peritoneal cavity due to reduction in the migration of polymorphonuclear cells, and attenuated leukocyte rolling in the microcirculation of the cremaster muscle.The effects of antithrombin on vascular and cellular events of inflammation were completely abolished by treatment with the cyclo-oxygenase inhibitor indomethacin (4 mg kg⁻¹), suggesting the involvement of prostacyclin in the mechanism of inflammation inhibition by B. jararaca antithrombin. CONCLUSION: This work showed for the first time the anti-inflammatory properties of B. jararaca antithrombin on vascular and cellular events of inflammation. These findings suggest that antithrombin is effective in preventing paw edema formation, cell migration and leukocyte rolling induced by carrageenan in mice.

Role of interplay between IL-4 and IFN-γ in the in regulating M1 macrophage polarization induced by Nattectin.

Recently our group described that Nattectin, a C-type lectin of the venom of Thalassophryne nattereri shows a potent pro-inflammatory capacity. Here, we demonstrated that Nattectin is able to induce M1 macrophage marker iNOS, and up-regulate the expression of MHC class II, CD80, CD86 and CD40 molecules. The increase in MHC class II and CD49a integrin expression with MMP-9 production and endocytic capacity depend on lectin function of Nattectin. Moreover, the polarization of peritoneal and bone marrow-derived macrophages induced by Nattectin to M1 profile is dependent on Th1 cytokines (IL-12 and IFN-γ), and negatively regulated by Th2 cytokines (IL-4, IL-10 and IL-13). Also we reveal that IL-4 play a dual role in this polarization: a regular action of IL-4 was seen in the negative regulation of the CD40 expression, but an unexpected positive regulation was seen in the expression of CCR7 and MHC class II. Finally, our in vivo studies showed that the influx of neutrophils and small peritoneal macrophage--F4/80(low)MHCII(hi) induced by Nattectin is totally dependent on IL-4 and IFN-γ cytokines. Furthermore, the induction of IL-6 release is negatively regulated by IL-4 and positively regulated by IL-12 and IFN-γ. Together, the results allowed us to expand the knowledge about the regulation of macrophage activation, as well as confirmed the ability of Nattectin, a fish C-type lectin, as an important immunomodulatory agent.

Analysis in vivo of antitumor activity, cytotoxicity and Interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride.

Several metallic compounds recognized as potent antitumor agents, have been developed and tested in vivo and in vitro. In this work, we evaluated the toxic, therapeutic, and cytotoxic properties of the cis-dichloro-tetra-amine-ruthenium(III) chloride. Transplanted animals with Sarcoma 180 cells were treated with ruthenium(III) complex and injected i.p., at different time intervals. After the 15th day, tumoral postimplant, the animals were sacrificed and their lungs, kidneys, liver, and tumors were removed and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses. Interaction between the ruthenium complex and the DNA was also investigated. Besides being cytotoxic for the S180 cells, the metallic compound induced tumoral volume reduction and increased survival time of the animals treated. Serum levels of LDH, creatinine, and bilirubin increased, but no serious irreversible histopathological alterations were observed in the analyzed tissues. The compound did not cause anemia, but reduced the number of leukocytes in the treated animals. The absence of viable S180 cells, necrotic cells, and the presence of granulation tissue were observed in tumor tissue of treated animals. The Ru(III) complex, in the presence of the reduction agent, caused plasmid DNA to fragment. These results suggest that cis-RuCl(2)(NH(3))(4)Cl compound is a potent antitumoral drug in vitro and in vivo, which seems to involve binding to DNA molecule.