Implications of oxidative stress and placental structural alterations in Trypanosoma cruzi infection in vitro and ex vivo

2pHuman placenta participates in the control of Chagas congenital infection, which could be due by nitric oxide synthase (NOS) and peroxinitrites which are deleterious for Trypanosoma cruzi and placental tissue. We proposed to analyze the detachment of STB and its relation to oxidative stress and congenital transmission. Two experimental designs: In vitro: Placental villi explants co-cultured with and without T. cruzi. Ex vivo: placentas from chagasic mothers with (CT) and without (NC) congenital transmission. It was analyzed eNOS, Nitrotyrosine (NT) and detachment of STB. Detachment of STB was increased and induced by Tc and H2O2 in vitro, however it was not significantly higher in ex vivo placentas. These changes were associated to modifications in the expression of eNOS and NT both in vitro and ex vivo. The balance between deleterious effect on T. cruzi, and structural placental alterations produced by nitrosative stress, could participate in the infection of placenta by the parasitehttp://www.placentajournal.org/articleFil: Araya, Ornella. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Triquell, María Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Días Luján, Cintia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Mezzano, Luciana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Piegari, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Fretes, Ricardo Emilio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular. Cátedra de Biología Celular, Histología y Embriología; Argentina.Patologí

La infección materna por T. cruzi produce alteraciones en la proliferación del citotrofoblasto placentario

La primera estructura placentaria en contacto con la sangre materna es el sinciciotrofoblasto y su indemnidad es fundamental para el desarrollo fetal. Es mantenido a través de la proliferación y fusión del citotrofoblasto (CTB)subyacente, proceso esencial para el desarrollo normal del embarazo. El trofoblasto es una de las vías descriptas para la infección placentaria por el T cruzi. Objetivo: Analizar proliferación del CTB, en placentas humanas chagásicas y normales.Fil: Moran, Joana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Moran, Joana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Mezzano, Luciana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Mezzano, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Triquell, María Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Triquel, María Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Díaz Luján, Cintia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Díaz Luján, Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Moreira, María José. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Moreira, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Hardisson, David. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Departamento de Anatomía Patológica.Fil: Fretes, Ricardo Emilio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Instituto de Biología Celular, Histología y Embriología; Argentina.Fil: Fretes, Ricardo Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Parasitologí

Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.This work has received support from the Fundación Alicia Koplowitz to realize the epigenetic wide association study and to the clinical assessment to the children. This work has also received public support from the Consejería de Salud y Familias para la financiación de la investigación, desarrollo e innovación (i + d + i) biomédica y en ciencias de la salud en Andalucía (CSyF 2021 - FEDER). Grant Grant number PECOVID- 0195-2020. Convocatoria financiada con Fondo Europeo de Desarrollo Regional (FEDER) al 80% dentro del Programa Operativo de Andalucía FEDER 2014-2020. Andalucía se mueve con Europa. NG-T received payment under Rio Hortega contract CM20-00015 with the Carlos III Health Institute.Peer reviewe

Effect of Arsenite on Nitrosative Stress in Human Breast Cancer Cells and Its Modulation by Flavonoids

Arsenic (As) is used in the treatment of leukemia and breast cancer due to its oxidative cytotoxic action. However, it is also toxic to normal cells. One proposed anticancer mechanism induced by As might be nitrosative stress (NS). It is believed that antioxidant flavonoids in combination with As might reduce its toxic action on normal cells without interfering with its antitumor action. In the present study, we evaluated the antineoplastic potential of As on breast human cancer lines MCF-7 and ZR-75-1 treated with redox-modulating flavonoids, such as quercetin (Q) and silymarin (S). Even though both cell lines differed about their oxidative responsiveness, their viability was decreased by NS induction through γ-glutamyltranspeptidase inhibition. Arsenic triggered NS in both MCF-7 and ZR-75-1 cultures, with the formers more sensitive without recovering their pre-treatment capacity. ZR-75-1 cells maintained their antioxidant status, whereas MCF-7 ones treated with S, As, and As + Q did not. Silymarin did not interfere with the described As bioactivity. NS was an anticancer mechanism exerted by As depending on the redox cellular response that could be differentially modified by dietary antioxidants. Hence, it is worthwhile to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy, especially when using As.Fil: Soria, Elio Andres. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Bongiovanni, Guillermina Azucena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Patagonia Norte. Instituto de Investigación y Desarrollo en Ingeniería de Procesos, Biotecnología y Energías Alternativas; Argentina. Universidad Nacional del Comahue; ArgentinaFil: Díaz Luján, Cintia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; ArgentinaFil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentin

Effect of Arsenic on Nitrosative Stress in Human Breast Cancer Cells and its Modulation by Flavonoids

Arsenic (As) is used in the treatment of leukaemia and breast cancer due to its strong oxidative cytotoxic action. However, it is also cytotoxic to normal cells. One proposed anticancer mechanism induced by As might be nitrosative stress (NS). Hence, it is believed that use of antioxidants such as flavonoids in combination with As might reduce its toxic action on normal cells without interfering with its antitumor action. In the present study, we evaluated the antineoplastic potential of As on breast human cancer lines MCF-7 and ZR- 75-1 treated with redox-modulating flavonoids, such as quercetin (Q) and silymarin (S). It was noted that, even though both cell lines differed in their oxidative responsiveness, their viability was decreased by NS induction through -glutamyltranspeptidase inhibition. Arsenic triggered NS in both MCF-7 and ZR-75-1 cultures, with the formers being more sensitive without recovering their pre-treatment capacity. ZR-75-1 cells maintained their antioxidant status, whereas MCF-7 ones treated with S, As and As+Q did not. Silymarin did not interfere with the described As bioactivity. In summary, NS appears as an important anticancer mechanism exerted by As depending on the redox cellular response that could be differentially modified by dietary antioxidants. Hence, it is worthwhile to consider the use of dietary antioxidants as adjuvant in cancer chemotherapy, especially when using As.Fil: Soria, Elio Andres. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Bongiovanni, Guillermina Azucena. Universidad Nacional del Comahue; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz, Luján Cintia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Eynard, Aldo Renato. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin

Efecto de la suplementación con L-Arginina en las alteraciones del desarrollo fetal en un modelo de enfermedad de Chagas congénito en ratones

3 p.A nutritional protein deficit would induce modifications in fetal development, parasitemia and congenital Chagas transmission, while arginine suministration would improve this situation. Female mice (C3H strain) were fed with hypoproteic (H), and normoproteic (N) diets during a month, some of them were provided also with 0.1% of arginine (Arg). They were infected with Trypanosoma cruzi trypomastigotes and were sacrificed at 14th day of gestation. It was evaluated maternal parasitemia, uterine horns infection, embryos and absorptions quantity; embryos and placentae size, and horns uterine weight. In serum arginine, urea and nitrites was measured. Infection reduces the fetal size independently of diet (HTC=1,092±0,74 mm; NTC=4,81±1,02mm) with respect to the controls (N=7,56±0,42 mm; H=2,72±0,86) (HTC p<0,05; NTC p=0,015). The H diet emphasizes infection effects, affecting fetal development and maternal parasitemia. (HTC=725.000±567.890p; NTC=87.500±88.987p) (p<0.05). Arginine supplementation of low-protein diet had a more marked effect. To decrease significantly from the maternal parasitemia (HTCarg = 300.000 ± 282.842p) (p <0.05) and infection of the uterus (HTCarg=70% PCR+; NTCarg=100% PCR+), plus an increase in the size of the fetuses (HTCarg = 5,75 ± 0,5 mm) (p <0,05) with a tendency to decrease resorption, which were associated with significative increased levels (p<0,05) of nitrite (HTC= 12,66 3,2uM; HTCarg= 26,068,03uM) in maternal serum. Usually, the pregnant women affected with Chagas disease are exposed to unfavorable socio-economic conditions, with deficient diets that would affect fetal development, and would be associated with congenital Chagas transmission. The Arginine supplementation, that was employed in others pregnancy pathologies, would improve fetal development in chagasic pregnancies in the acute phase of infection, possible due to an increment of Nitric Oxide production.http://www.revista2.fcm.unc.edu.ar/jornadas.pdfFil: Diaz Luján, Cintia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaFil: Piegari, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaFil: Glocker, Mónica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaFil: Triquell, María Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaFil: Mezzano, Luciana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaFil: Fretes, Ricardo. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Biología Celular, Histología y Embriología; ArgentinaPatologí

Effects of the L-arginine supplementation in the fetal development alterations in a congenital chagas disease mouse model

1 p.A nutritional protein deficit would induce modifications in fetal development, parasitemia and congenital Chagas transmission, while arginine intake would improve this situation. Female mice (C3H strain) were feeded with hypoproteic (H), and normoproteic (N) diets during a month, some of them were provided also with 0.1% of arginine (Arg). They were infected with Trypanosoma cruzi trypomastigotes and were sacrificed at 14th day of gestation. It was evaluated maternal parasitemia, embryos and absorptions quantity; embryos and placentae size, and uterine horns weight. The H diet increased infection effects, affecting fetal development and maternal parasitemia. Arg improved protective effects, with fetal size increment, reduced embryo absorptions and maternal parasitemia. The high incidence of pregnant women affected with Chagas disease are related to deficient diets that would affect fetal development, and would be associated with susceptibility to congenital transmission. The Arg supplementation improve fetal development in the acute phase of Chagas infection, possible due to the nourishment increment including sources for nitric oxide productionhttp://www.placentajournal.org/articleFil: Díaz Luján, Cintia. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Piegari, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Glocker, Mónica. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Triquell, María Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Mezzano, Luciana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Fretes, Ricardo Emilio. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Cátedra de Biología Celular, Histología y Embriología; Argentina.Fil: Fretes, Ricardo Emilio. Universidad Nacional de La Rioja. Histología y Embriología. Instituto de Investigaciones en Ciencias de la Salud Humana; Argentina

Congenital transmission of protozoa: placental infection by Trypanosoma Cruzi

Artículo de publicación IS

NLRP3 Inflammasome and Caspase-1/11 Pathway Orchestrate Different Outcomes in the Host Protection Against Trypanosoma cruzi Acute Infection

Infection with protozoan parasite Trypanosoma cruzi results in activation of nucleotide-binding domain and leucine-rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Considering that inflammasome activation and IL-1β induction by macrophages are key players for an appropriate T cell response, we investigated the relevance of NLR pyrin domain-containing 3 (NLRP3) and caspase-1/11 to elucidate their roles in the induction of different T cell phenotypes and the relationship with parasite load and hepatic inflammation during T. cruzi-Tulahuen strain acute infection. We demonstrated that infected nlrp3−/− and C57BL/6 wild type (WT) mice exhibited similar parasitemia and survival, although the parasite load was higher in the livers of nlrp3−/− mice than in those of WT mice. Increased levels of transaminases and pro-inflammatory cytokines were found in the plasma of WT and nlrp3−/− mice indicating that NLRP3 is dispensable to control the parasitemia but it is required for a better clearance of parasites in the liver. Importantly, we have found that NLRP3 and caspase-1/11-deficient mice differentially modulate T helper (Th1, Th2, and Th17) and cytotoxic T lymphocyte phenotypes. Strikingly, caspase-1/11−/− mice showed the most dramatic reduction in the number of IFN-γ- and IL-17-producing CD4+ and CD8+ T cells associated with higher parasitemia and lower survival. Additionally, caspase-1/11−/− mice demonstrated significantly reduced liver inflammation with the lowest alanine aminotransferase (ALT) levels but the highest hepatic parasitic load. These results unequivocally demonstrate that caspase-1/11 pathway plays an important role in the induction of liver adaptive immunity against this parasite infection as well as in hepatic inflammation