ZIKV replication is differential in explants and cells of human placental which is suppressed by HSV-2 coinfection.

During the Zika fever outbreak in Brazil in 2015-2016, only some babies from infected mothers had teratogenic effects, suggesting that cofactors may influence congenital transmission. We investigated the ZIKV infection profile in explants and isolated cells from full-term human placenta to infection with the Brazilian Zika virus strain (ZIKVBR) and the effect of coinfection with the Brazilian Human alphaherpesvirus 2 strain (HSV-2BR) on ZIKV replication. We found that the ZIKVBR infect the explants of amniotic and chorionic membranes, as well as chorionic villi core, but not the trophoblasts layer. It was also observed that ZIKV replication was higher in amniotic cells than chorionic and trophoblasts cells. Upon coinfection, the replication of ZIKVBR was reduced according to exposed HSV-2BR load in trophoblasts cells and the levels of TNF-α and IL-6 cytokines were also reduced. These findings suggest that the placental cell types and HSV-2BR coinfection may impact on ZIKV replication.

Inducible nitric oxide synthase/CD95L-dependent suppression of pulmonary and bone marrow eosinophilia by diethylcarbamazine.

RATIONALE: The mechanism of action of diethylcarbamazine (DEC), an antifilarial drug effective against tropical pulmonary eosinophilia, remains controversial. DEC effects on microfilariae depend on inducible NO synthase (iNOS). In eosinophilic pulmonary inflammation, its therapeutic mechanism has not been established. We previously described the rapid up-regulation of bone marrow eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway allergen challenge, and further evidenced the down-regulation of eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms. OBJECTIVES: We investigated whether: (1) DEC can prevent the effects of airway challenge of sensitized mice on lungs and bone marrow, and (2) its effectiveness depends on iNOS/CD95L. METHODS: OVA-sensitized BALB/c mice were intranasally challenged for 3 consecutive days, with DEC administered over a 12-, 3-, or 2-day period, ending at the day of the last challenge. We evaluated: (1) airway resistance, cytokine (IFN-gamma, IL-4, IL-5, and eotaxin) production, and pulmonary eosinophil accumulation; and (2) bone marrow eosinophil numbers in vivo and eosinophil differentiation ex vivo. MEASUREMENTS AND MAIN RESULTS: DEC effectively prevented the effects of subsequent challenges on: (1) airway resistance, Th1/Th2 cytokine production, and pulmonary eosinophil accumulation; and (2) eosinophilopoiesis in vivo and ex vivo. Recovery from unprotected challenges included full responses to DEC during renewed challenges. DEC directly suppressed IL-5-dependent eosinophilopoiesis in naive bone marrow. DEC was ineffective in CD95L-deficient gld mice and in mice lacking iNOS activity because of gene targeting or pharmacological blockade. CONCLUSIONS: DEC has a strong impact on pulmonary eosinophilic inflammation in allergic mice, as well as on the underlying hemopoietic response, suppressing the eosinophil lineage by an iNOS/CD95L-dependent mechanism.

Hydralazine reduces myocardial tissue damage in rats submitted to chronic inhibition of systemic nitric oxide synthesis during 4, 14 and 28 days

The aim of the present work was to develop a qualitative chronopathological study concerning abnormalities in myocardium, due to nitric oxide (NO) blockage. We used 60 Wistar normotensive young male rats from several breeds. Groups of rats were submitted to L-Name (L) via oral administration dissolved in water (750mg/l) during days 4, 14 and 28. Other groups were submitted concomitantly to L-Name and hydralazine hydrocloride (L + H) (120mg/l). On days 4 and 14 (L group) we have found myocardial abnormalities and lesions while in L + H we could not identify abnormalities. Considering L group on day 28, the myocardium presented characteristic fibrosis (reactive and reparative), vascular damage with increasing wall thickness due mainly to proliferation of the arterial smooth muscle cell. Total obliteration of vessels was noted only in this period. We also observed reactive fibrosis between muscle cells of the vascular wall and proliferation of cells in the intimal layer. In L + H (day 28), similar vascular abnormalities described for L group (less frequent and less apparent) were also observed. In L + H we did not identify total vascular obstructions. In L + H, infarct areas were not observed. Control groups did not present any abnormalities. Our results support the idea that, at least in some cases, hypertrophy vascular abnormalities and myocardial lesions in arterial hypertension can occur because of the reduction in organic nitric oxide production. Our results also suggested that these morbid processes can be postponed by the use of hydralazine which, however, does not avoid abnormalities after long-term experimental blockage of NO