36 results on '"Franco PS"'
Search Results
2. Copaifera spp. oleoresins control Trypanosoma cruzi infection in human trophoblast cells (BeWo) and placental explants.
- Author
-
Júnior JPL, Teixeira SC, de Souza G, Faria GV, Almeida MPO, Franco PS, Luz LC, Paschoalino M, Dos Santos NCL, de Oliveira RM, Martínez AFF, Rosini AM, Ambrosio MALV, Veneziani RCS, Bastos JK, Gomes AO, Alves RN, da Silva CV, Martins CHG, Ferro EAV, and Barbosa BF
- Subjects
- Humans, Female, Pregnancy, Reactive Oxygen Species metabolism, Cytokines metabolism, Cell Line, Trophoblasts parasitology, Trophoblasts drug effects, Trophoblasts metabolism, Trypanosoma cruzi drug effects, Plant Extracts pharmacology, Chagas Disease parasitology, Chagas Disease drug therapy, Placenta parasitology, Placenta drug effects, Placenta metabolism, Fabaceae chemistry
- Abstract
Congenital Chagas disease (CCD) is a worldwide neglected problem with significant treatment limitations. This study aimed to evaluate the potential of Copaifera spp. oleoresins (ORs) against Trypanosoma cruzi infection in trophoblast cells (BeWo lineage) and human chorionic villous explants (HCVE). The cytotoxicity of ORs was investigated using LDH and MTT assays. T. cruzi (Y strain) proliferation, invasion and reversibility were assessed in OR-treated BeWo cells, and proliferation was evaluated in OR-treated HCVE. The ultrastructure of T. cruzi trypomastigotes and amastigotes treated with ORs were analyzed by scanning and transmission electronic microscopy. ROS production in infected and treated BeWo cells and cytokines in BeWo and HCVE were measured. The ORs irreversibly decreased T. cruzi invasion, proliferation and release in BeWo cells by up to 70 %, 82 % and 80 %, respectively, and reduced parasite load in HCVE by up to 80 %. Significant structural changes in treated parasites were observed. ORs showed antioxidant capacity in BeWo cells, reducing ROS production induced by T. cruzi infection. Also, T. cruzi infection modulated the cytokine profile in both BeWo cells and HCVE; however, treatment with ORs upregulated cytokines decreased by T. cruzi infection in BeWo cells, while downregulated cytokines increased by the T. cruzi infection in HCVE. In conclusion, non-cytotoxic concentrations of Copaifera ORs demonstrated promising potential for controlling T. cruzi infection in models of the human maternal-fetal interface., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
3. Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.
- Author
-
Franco PS, Scussel ACMO, Silva RJ, Araújo TE, Gonzaga HT, Marcon CF, Brito-de-Sousa JP, Diniz ALD, Paschoini MC, Barbosa BF, Martins-Filho OA, Mineo JR, Ferro EAV, and Gomes AO
- Abstract
Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis., Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis., Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity., Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Priscila Silva Franco et al.)
- Published
- 2024
- Full Text
- View/download PDF
4. Polarisation of human macrophages towards an M1 subtype triggered by an atypical Brazilian strain of Toxoplasma gondii results in a reduction in parasite burden.
- Author
-
Guimaraes Gois PS, Franco PS, Cota Teixeira S, Guirelli PM, de Araujo TE, da Fonseca Batistao DW, de Oliveira FC, Licia Santos Ferreira G, de Oliveira Gomes A, Favoreto S, Mineo JR, de Freitas Barbosa B, and Ferro EAV
- Subjects
- Animals, Brazil epidemiology, Cytokines, Humans, Interleukin-6, Macrophages parasitology, Nitrites, Urea, Parasites, Toxoplasma, Toxoplasmosis
- Abstract
Toxoplasma gondii Nicolle et Manceaux, 1909, the etiologic agent of toxoplasmosis, was considered a clonal population with three distinct genetic lineages (I, II and III); however, sequence analysis of different strains has revealed distinct atypical genotypes. Macrophages are essential for immunity against toxoplasmosis and differential cell regulation may affect the course of the disease. In this context, our study aims to investigate the infection by TgChBrUD2, a highly virulent atypical Brazilian strain of T. gondii, on the activation and polarisation of human macrophages. Human macrophage-like cells obtained from THP-1 cells were infected with TgChBrUD2, RH or ME49 strains of T. gondii to evaluate the impact of parasite infection on macrophage polarisation. Our results indicate that the TgChBrUD2 and ME49 strains of T. gondii induced a classic activation of human macrophages, which was confirmed by the high rate of spindle-shaped macrophages, low amount of urea and increase in the levels of nitrite, as well as the down-regulation of M2-markers. In contrast, RH strain promoted an alternative activation of macrophages. The polarisation of human macrophages towards an M1 subtype mediated by TgChBrUD2 and ME49 strains resulted in a low parasite burden, with high levels of IL-6 and MIF. Finally, the M2 subtype triggered by the RH strain culminated in a lower intracellular proliferation index. We concluded that the atypical (TgChBrUD2) and clonal (ME49) strains are able to elicit an M1 subtype, which results in parasitism control, partially explained by the high levels of IL-6 and MIF produced during the infection by these genotypes. In contrast, the clonal (RH) strain promoted a macrophage polarisation towards an M2 subtype, marked by a high parasite burden, with a weak modulation of pro-inflammatory cytokines. Thus, atypical strains can present different mechanisms of pathogenicity and transmissibility compared to clonal strains, as well as they can use distinct strategies to evade the host's immune response and ensure their survival.
- Published
- 2022
- Full Text
- View/download PDF
5. Impact of Social Isolation on Physical Activity and Factors Associated With Sedentary Behavior in Older Adults During the COVID-19 Pandemic.
- Author
-
Mazo GZ, Fank F, Franco PS, Capanema BDSV, and Pereira FDS
- Subjects
- Aged, Cross-Sectional Studies, Exercise, Humans, SARS-CoV-2, Sedentary Behavior, Social Isolation, COVID-19, Pandemics
- Abstract
The objective was to analyze the impact of social isolation on moderate physical activity and factors associated with sedentary behavior of older adults during the COVID-19 pandemic. This was a cross-sectional study involving 111 older adults (aged 71.0 ± 6.87 years). The data were collected at two time points: in November 2019 and in June 2020. There was a decline in moderate physical activity when the minutes/week were compared before and during social isolation (p < .001). Sedentary behavior was associated with the condition of living alone. Older adults who lived alone were 3.29 times more likely to spend 4 hr or more in sedentary behavior than those who lived with a partner (95% confidence interval [1.01, 10.74]). Government agencies must establish PA-related health promotion strategies, especially in developing and low-income countries. Therefore, home exercises need to be encouraged to prevent the consequences of this pandemic period.
- Published
- 2022
- Full Text
- View/download PDF
6. BEWO trophoblast cells and Toxoplasma gondii infection modulate cell death mechanisms in THP-1 monocyte cells by interference in the expression of death receptor and intracellular proteins.
- Author
-
da Silva Castro A, Angeloni MB, de Freitas Barbosa B, de Miranda RL, Teixeira SC, Guirelli PM, de Oliveira FC, José da Silva R, Franco PS, Ribeiro M, Milian ICB, de Oliveira Gomes A, Ietta F, Júnior SF, Mineo TWP, Mineo JR, de Oliveira Simões Alves CM, and Ferro EAV
- Subjects
- Caspase 3 metabolism, Cell Death drug effects, Cell Line, Culture Media, Conditioned pharmacology, Down-Regulation drug effects, Fas Ligand Protein metabolism, Humans, MAP Kinase Signaling System drug effects, Macrophage Migration-Inhibitory Factors pharmacology, Monocytes drug effects, Monocytes metabolism, Phosphorylation drug effects, THP-1 Cells, Trophoblasts drug effects, Trophoblasts metabolism, fas Receptor metabolism, Intracellular Space metabolism, Monocytes parasitology, Monocytes pathology, Proteins metabolism, Receptors, Death Domain metabolism, Toxoplasmosis pathology, Trophoblasts parasitology
- Abstract
Crosstalk between trophoblast and monocytes is essential for gestational success, and it can be compromised in congenital toxoplasmosis. Cell death is one of the mechanisms involved in the maintenance of pregnancy, and this study aimed to evaluate the role of trophoblast in the modulation of monocyte cell death in the presence or absence of Toxoplasma gondii infection. THP-1 cells were stimulated with supernatants of BeWo cells and then infected or not with T. gondii. The supernatants were collected and analyzed for the secretion of human Fas ligand, and cells were used to determine cell death and apoptosis, cell death receptor, and intracellular proteins expression. Cell death and apoptosis index were higher in uninfected THP-1 cells stimulated with supernatants of BeWo cells; however, apoptosis index was reduced by T. gondii infection. Macrophage migration inhibitory factor (MIF) and transforming growth factor (TGF)-β1, secreted by BeWo cells, altered the cell death and apoptosis rates in THP-1 cells. In infected THP-1 cells, the expression of Fas/CD95 and secretion of FasL was significantly higher; however, caspase 3 and phosphorylated extracellular-signal-regulated kinase (ERK1/2) were downregulated. Results suggest that soluble factors secreted by BeWo cells induce cell death and apoptosis in THP-1 cells, and Fas/CD95 can be involved in this process. On the other hand, T. gondii interferes in the mechanism of cell death and inhibits THP-1 cell apoptosis, which can be associated with active caspase 3 and phosphorylated ERK1/2. In conclusion, our results showed that human BeWo trophoblast cells and T. gondii infection modulate cell death in human THP-1 monocyte cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
7. ERK1/2 phosphorylation and IL-6 production are involved in the differential susceptibility to Toxoplasma gondii infection in three types of human (cyto/ syncytio/ extravillous) trophoblast cells.
- Author
-
Oliveira FC, Silva RJ, Ribeiro M, Guirelli PM, Castro AS, Gomes AO, Franco PS, Teixeira SC, Mineo JR, Barbosa BF, and Ferro EAV
- Subjects
- Cell Differentiation, Cell Line, Tumor, Cell Proliferation, Disease Susceptibility, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Humans, Phosphorylation, Up-Regulation, Extracellular Signal-Regulated MAP Kinases metabolism, Giant Cells pathology, Interleukin-6 biosynthesis, Toxoplasmosis pathology, Trophoblasts parasitology, Trophoblasts pathology
- Abstract
During pregnancy, Toxoplasma gondii can triggers serious manifestations and potentially affect the fetal development. In this scenario, differences in susceptibility of trophoblast cells to T. gondii infection might be evaluated in order to establish new therapeutic approaches capable of interfering in the control of fetal infection by T. gondii. This study aimed to evaluate the susceptibility of cytotrophoblast, syncytiotrophoblast and extravillous trophoblast cells to T. gondii infection. Our data demonstrate that HTR-8/SVneo cells (extravillous trophoblast cells) present higher susceptibility to T. gondii infection when compared to syncytiotrophoblast and cytotrophoblast cells, whereas syncytiotrophoblast was the cell type more resistant to the parasite infection. Also, cytotrophoblast and syncytiotrophoblast cells produced significantly more IL-6 than HTR-8/SVneo cells. On the other hand, HTR-8/SVneo cells showed higher ERK1/2 phosphorylation than cytotrophoblast and syncytiotrophoblast cells. ERK1/2 inhibition reduced T. gondii infection and increased IL-6 production in HTR-8/SVneo cells. Thus, it is plausible to conclude that the greater susceptibility of HTR-8/SVneo cells to infection by T. gondii is related to a higher ERK1/2 phosphorylation and lower levels of IL-6 in these cells compared to other cells, suggesting that these mediators may be important to favor the parasite infection in this type of trophoblastic population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
8. Cyclooxygenase (COX)-2 modulates Toxoplasma gondii infection, immune response and lipid droplets formation in human trophoblast cells and villous explants.
- Author
-
de Souza G, Silva RJ, Milián ICB, Rosini AM, de Araújo TE, Teixeira SC, Oliveira MC, Franco PS, da Silva CV, Mineo JR, Silva NM, Ferro EAV, and Barbosa BF
- Subjects
- Cell Line, Cell Survival drug effects, Chorionic Villi immunology, Chorionic Villi metabolism, Cyclooxygenase 2 Inhibitors pharmacology, Extracellular Matrix Proteins metabolism, Host-Parasite Interactions, Humans, Interleukins metabolism, Macrophage Migration-Inhibitory Factors metabolism, Nitrites metabolism, Toxoplasma immunology, Transforming Growth Factor beta metabolism, Trophoblasts immunology, Trophoblasts metabolism, Chorionic Villi parasitology, Cyclooxygenase 2 metabolism, Lipid Droplets metabolism, Toxoplasma growth & development, Trophoblasts parasitology
- Abstract
Congenital toxoplasmosis is represented by the transplacental passage of Toxoplasma gondii from the mother to the fetus. Our studies demonstrated that T. gondii developed mechanisms to evade of the host immune response, such as cyclooxygenase (COX)-2 and prostaglandin E
2 (PGE2 ) induction, and these mediators can be produced/stored in lipid droplets (LDs). The aim of this study was to evaluate the role of COX-2 and LDs during T. gondii infection in human trophoblast cells and villous explants. Our data demonstrated that COX-2 inhibitors decreased T. gondii replication in trophoblast cells and villous. In BeWo cells, the COX-2 inhibitors induced an increase of pro-inflammatory cytokines (IL-6 and MIF), and a decrease in anti-inflammatory cytokines (IL-4 and IL-10). In HTR-8/SVneo cells, the COX-2 inhibitors induced an increase of IL-6 and nitrite and decreased IL-4 and TGF-β1. In villous explants, the COX-2 inhibitors increased MIF and decreased TNF-α and IL-10. Furthermore, T. gondii induced an increase in LDs in BeWo and HTR-8/SVneo, but COX-2 inhibitors reduced LDs in both cells type. We highlighted that COX-2 is a key factor to T. gondii proliferation in human trophoblast cells, since its inhibition induced a pro-inflammatory response capable of controlling parasitism and leading to a decrease in the availability of LDs, which are essentials for parasite growth.- Published
- 2021
- Full Text
- View/download PDF
9. Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.
- Author
-
Marcon CF, Ferreira PTM, Franco PS, Ribeiro M, Silva RJ, Sousa RAP, Oliveira CJF, Rodrigues Junior V, Gomes MLM, Lazo Chica JE, Mineo TWP, Mineo JR, Barbosa BF, Ferro EAV, and Gomes AO
- Subjects
- Animals, Female, Intramolecular Oxidoreductases genetics, Macrophage Migration-Inhibitory Factors genetics, Mice, Mice, Knockout, Pregnancy, Pregnancy Complications, Parasitic genetics, Toxoplasmosis genetics, Duodenum immunology, Ileum immunology, Intramolecular Oxidoreductases immunology, Macrophage Migration-Inhibitory Factors immunology, Pregnancy Complications, Parasitic immunology, Toxoplasma immunology, Toxoplasmosis immunology
- Abstract
Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF
-/- ) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
10. Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection" [Cytokine: X 2 (2020) 100034].
- Author
-
Marcon CF, Ferreira PTM, Franco PS, Ribeiro M, Silva RJ, Sousa RAP, Oliveira CJF, Rodrigues Junior V, Gomes MLM, Chica JEL, Mineo TWP, Mineo JR, Barbosa BF, Ferro EAV, and Gomes AO
- Abstract
[This corrects the article DOI: 10.1016/j.cytox.2020.100034.]., (© 2020 The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
11. WITHDRAWN: Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.
- Author
-
Marcon CF, Ferreira PTM, Franco PS, Ribeiro M, Silva RJ, Sousa RAP, Oliveira CJF, Junior VR, Gomes MLM, Chica JEL, Mineo TWP, Mineo JR, Barbosa BF, Ferro EAV, and Gomes AO
- Published
- 2020
- Full Text
- View/download PDF
12. Experimental models of maternal-fetal interface and their potential use for nanotechnology applications.
- Author
-
de Araújo TE, Milián ICB, de Souza G, da Silva RJ, Rosini AM, Guirelli PM, Franco PS, Barbosa BF, Ferro EAV, and da Costa IN
- Abstract
During pregnancy, the placenta regulates the transfer of oxygen, nutrients, and residual products between the maternal and fetal bloodstreams and is a key determinant of fetal exposure to xenobiotics from the mother. To study the disposition of substances through the placenta, various experimental models are used, especially the perfused placenta, placental villi explants, and cell lineage models. In this context, nanotechnology, an area of study that is on the rise, enables the creation of particles on nanometric scales capable of releasing drugs aimed at specific tissues. An important reason for furthering the studies on transplacental transfer is to explore the potential of nanoparticles (NPs), in new delivery strategies for drugs that are specifically aimed at the mother, the placenta, or the fetus and that involve less toxicity. Due to the fact that the placental barrier is essential for the interaction between the maternal and fetal organisms as well as the possibility of NPs being used in the treatment of various pathologies, the aim of this review is to present the main experimental models used in studying the maternal-fetal interaction and the action of NPs in the placental environment., (© 2019 International Federation for Cell Biology.)
- Published
- 2020
- Full Text
- View/download PDF
13. Cyclooxygenase (COX)-2 Inhibitors Reduce Toxoplasma gondii Infection and Upregulate the Pro-inflammatory Immune Response in Calomys callosus Rodents and Human Monocyte Cell Line.
- Author
-
Pereira ACA, Silva RJ, Franco PS, de Oliveira Gomes A, Souza G, Milian ICB, Ribeiro M, Rosini AM, Guirelli PM, Ramos ELP, Mineo TWP, Mineo JR, Silva NM, Ferro EAV, and Barbosa BF
- Abstract
Toxoplasma gondii is able to infect a wide range of vertebrates, including humans. Studies show that cyclooxygenase-2 (COX-2) is a modulator of immune response in multiple types of infection, such as Trypanosoma cruzi . However, the role of COX-2 during T. gondii infection is still unclear. The aim of this study was to investigate the role of COX-2 during infection by moderately or highly virulent strains of T. gondii in Calomys callosus rodents and human THP-1 cells. C. callosus were infected with 50 cysts of T. gondii (ME49), treated with COX-2 inhibitors (meloxicam or celecoxib) and evaluated to check body weight and morbidity. After 40 days, brain and serum were collected for detection of T. gondii by real-time PCR and immunohistochemistry or cytokines by CBA. Furthermore, peritoneal macrophages or THP-1 cells, infected with RH strain or uninfected, were treated with meloxicam or celecoxib to evaluate the parasite proliferation by colorimetric assay and cytokine production by ELISA. Finally, in order to verify the role of prostaglandin E
2 in COX-2 mechanism, THP-1 cells were infected, treated with meloxicam or celecoxib plus PGE2 , and analyzed to parasite proliferation and cytokine production. The data showed that body weight and morbidity of the animals changed after infection by T. gondii , under both treatments. Immunohistochemistry and real-time PCR showed a reduction of T. gondii in brains of animals treated with both COX-2 inhibitors. Additionally, it was observed that both COX-2 inhibitors controlled the T. gondii proliferation in peritoneal macrophages and THP-1 cells, and the treatment with PGE2 restored the parasite growth in THP-1 cells blocked to COX-2. In the serum of Calomys , upregulation of pro-inflammatory cytokines was detected, while the supernatants of peritoneal macrophages and THP-1 cells demonstrated significant production of TNF and nitrite, or TNF, nitrite and MIF, respectively, under both COX-2 inhibitors. Finally, PGE2 treatment in THP-1 cells triggered downmodulation of pro-inflammatory mediators and upregulation of IL-8 and IL-10. Thus, COX-2 is an immune mediator involved in the susceptibility to T. gondii regardless of strain or cell types, since inhibition of this enzyme induced control of infection by upregulating important pro-inflammatory mediators against Toxoplasma .- Published
- 2019
- Full Text
- View/download PDF
14. Brazilian strains of Toxoplasma gondii are controlled by azithromycin and modulate cytokine production in human placental explants.
- Author
-
Franco PS, Gois PSG, de Araújo TE, da Silva RJ, de Freitas Barbosa B, de Oliveira Gomes A, Ietta F, Dos Santos LA, Dos Santos MC, Mineo JR, and Ferro EAV
- Subjects
- Brazil, Female, Humans, Pregnancy, Pregnancy Trimester, Third, Azithromycin pharmacology, Coccidiostats pharmacology, Cytokines metabolism, Placenta parasitology, Toxoplasma drug effects
- Abstract
Background: Toxoplasma gondii is a protozoan parasite that causes congenital toxoplasmosis by transplacental transmission. Parasite strains are genetically diverse and disease severity is related to the genotype. In Uberlândia city, Brazil, two virulent strains were isolated: TgChBrUD1 and TgChBrUD2. Congenital toxoplasmosis is more prevalent in South America compared to Europe, and more often associated with severe symptoms, usually as a result of infection with atypical strains., Methods: Considering that T. gondii has shown high genetic diversity in Brazil, the effectiveness of traditional treatment may not be the same, as more virulent strains of atypical genotypes may predominate. Thus, the aim of this study were to evaluate the Brazilian strain infection rate in human villous explants and the azithromycin efficacy with regard to the control of these strains compared to traditional therapy. Villi were infected with RH, ME49, TgChBrUD1 or TgChBrUD2 strains and treated with azithromycin, spiramycin or a combination of pyrimethamine plus sulfadiazine. The villous viability was analyzed by LDH assay and morphological analysis. Parasite proliferation, as well as production of cytokines was analyzed by qPCR and ELISA, respectively. Statistical analysis was performed using the GraphPad Prism 5.0., Results: The treatments were not toxic and TgChBrUD1 infected villi showed a higher parasite burden compared with others strains. Treatments significantly reduced the intracellular proliferation of T. gondii, regardless of the strain. TgChBrUD1-infected villi produced a larger amount of MIF, IL-6 and TGF-β1 compared with other infected villi. Azithromycin treatment increased MIF production by RH- or TgChBrUD2-infected villi, but in ME49- or TgChBrUD1-infected villi, the MIF production was not altered by treatment. On the other hand, azithromycin treatment induced lower IL-6 production by ME49- or TgChBrUD1-infected villi., Conclusions: Azithromycin treatment was effective against T. gondii Brazilian strains compared with conventional treatment. Also, the TgChBrUD1 strain replicated more in villi and modulated important cytokines involved in parasite control, showing that different strains use different strategies to evade the host immune response and ensure their survival.
- Published
- 2019
- Full Text
- View/download PDF
15. Within and between-days repeatability and variability of plantar pressure measurement during walking in children, adults and older adults.
- Author
-
Franco PS, Moro CF, Figueiredo MM, Azevedo RR, Ceccon FG, and Carpes FP
- Subjects
- Adult, Age Factors, Aged, Analysis of Variance, Biomechanical Phenomena, Child, Female, Forefoot, Human physiology, Humans, Male, Manometry methods, Reproducibility of Results, Time Factors, Foot physiology, Gait physiology, Pressure, Walking physiology
- Abstract
Background: Previous studies discussed the repeatability and variability in plantar pressure measurement, but a few considered different age groups. Here we determine within and between-days repeatability and variability of plantar pressure measurement during gait in participants from different age groups., Method: Plantar pressure was recorded in children, young adults and older adults walking at preferred speed in four non-consecutive days within one week. Data from 10 steps from each foot in each day were analyzed considering the different regions of the foot. Mean and peak plantar pressure and data variability were compared between the steps, foot regions and days., Results: To describe mean and peak pressure during gait in children and adults a single measurement can be enough, but elderly will requires more attention especially concerning peak values. Variability in mean pressure did not differ between age groups, but peak pressure variability differed across foot regions and age groups., Conclusion: One single observation can be used to describe plantar pressure during gait in children and adults. When the interest concerns older people, it might be pertinent to consider more than one day of assessment, especially when looking at peak pressure.
- Published
- 2018
- Full Text
- View/download PDF
16. Macrophage Migration Inhibitory Factor (MIF) Prevents Maternal Death, but Contributes to Poor Fetal Outcome During Congenital Toxoplasmosis.
- Author
-
Gomes AO, Barbosa BF, Franco PS, Ribeiro M, Silva RJ, Gois PSG, Almeida KC, Angeloni MB, Castro AS, Guirelli PM, Cândido JV, Chica JEL, Silva NM, Mineo TWP, Mineo JR, and Ferro EAV
- Abstract
Migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important roles in physiology, pathology, immunology and parasitology, including the control of infection by protozoa parasites such as Toxoplasma gondii . As the MIF function in congenital toxoplasmosis is not fully elucidated yet, the present study brings new insights for T. gondii infection in the absence of MIF based on pregnant C57BL/6MIF
-/- mouse models. Pregnant C57BL/6MIF-/- and C57BL/6WT mice were infected with 05 cysts of T. gondii (ME49 strain) on the first day of pregnancy (dop) and were euthanized at 8 dop. Non-pregnant and non-infected females were used as control. Our results demonstrated that MIF-/- mice have more accentuated change in body weight and succumbed to infection first than their WT counterparts. Otherwise, pregnancy outcome was less destructive in MIF-/- mice compared to WT ones, and the former had an increase in the mast cell recruitment and IDO expression and consequently presented less inflammatory cytokine production. Also, MIF receptor (CD74) was upregulated in MIF-/- mice, indicating that a compensatory mechanism may be required in this model of study. The global absence of MIF was associated with attenuation of pathology in congenital toxoplasmosis, but resulted in female death probably because of uncontrolled infection. Altogether, ours results demonstrated that part of the immune response that protects a pregnant female from T. gondii infection, favors fetal damage.- Published
- 2018
- Full Text
- View/download PDF
17. Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms.
- Author
-
Damasceno A, Amaral JMSDS, Barreira AA, Becker J, Callegaro D, Campanholo KR, Damasceno LA, Diniz DS, Fragoso YD, Franco PS, Finkelsztejn A, Jorge FMH, Lana-Peixoto MA, Matta APDC, Mendonça ACR, Noal J, Paes RA, Papais-Alvarenga RM, Pereira AG, Spedo CT, and Damasceno BP
- Subjects
- Adolescent, Adult, Age Factors, Aged, Brazil, Cognitive Dysfunction diagnosis, Cognitive Dysfunction physiopathology, Educational Status, Female, Humans, Male, Middle Aged, Multiple Sclerosis physiopathology, Reference Standards, Reference Values, Regression Analysis, Reproducibility of Results, Sex Factors, Statistics, Nonparametric, Young Adult, Cognition physiology, Neuropsychological Tests standards
- Abstract
Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.
- Published
- 2018
- Full Text
- View/download PDF
18. Azithromycin treatment is able to control the infection by two genotypes of Toxoplasma gondii in human trophoblast BeWo cells.
- Author
-
Ribeiro M, Franco PS, Lopes-Maria JB, Angeloni MB, Barbosa BF, Gomes AO, Castro AS, Silva RJD, Oliveira FC, Milian ICB, Martins-Filho OA, Ietta F, Mineo JR, and Ferro EAV
- Subjects
- Cell Line, Tumor, Cytokines metabolism, Drug Combinations, Genotype, Humans, Interleukin-12 metabolism, Pyrimethamine pharmacology, Spiramycin pharmacology, Sulfadiazine pharmacology, Toxoplasma classification, Toxoplasma genetics, Toxoplasma immunology, Trophoblasts drug effects, Antiprotozoal Agents pharmacology, Azithromycin pharmacology, Toxoplasma drug effects, Trophoblasts parasitology
- Abstract
Trophoblast infection by Toxoplasma gondii plays a pivotal role in the vertical transmission of toxoplasmosis. Here, we investigate whether the antibiotic therapy with azithromycin, spiramycin and sulfadiazine/pyrimethamine are effective to control trophoblast infection by two Brazilian T. gondii genotypes, TgChBrUD1 or TgChBrUD2. Two antibiotic protocols were evaluated, as follow: i) pre-treatment of T. gondii-tachyzoites with selected antibiotics prior trophoblast infection and ii) post-treatment of infected trophoblasts. The infection index/replication and the impact of the antibiotic therapy on the cytokine milieu were characterized. It was observed that TgChBrUD2 infection induced lower infection index/replication as compared to TgChBrUD1. Regardless the therapeutic protocol, azithromycin was more effective to control the trophoblast infection with both genotypes when compared to conventional antibiotics. Azithromycin induced higher IL-12 production in TgChBrUD1-infected cells that may synergize the anti-parasitic effect. In contrast, the effectiveness of azithromycin to control the TgChBrUD2-infection was not associated with the IL-12 production. BeWo-trophoblasts display distinct susceptibility to T. gondii genotypes and the azithromycin treatment showed to be more effective than conventional antibiotics to control the T. gondii infection/replication regardless the parasite genotype., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
19. Enrofloxacin and Toltrazuril Are Able to Reduce Toxoplasma gondii Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy.
- Author
-
da Silva RJ, Gomes AO, Franco PS, Pereira AS, Milian ICB, Ribeiro M, Fiorenzani P, Dos Santos MC, Mineo JR, da Silva NM, Ferro EAV, and de Freitas Barbosa B
- Subjects
- Cell Line, Cell Survival drug effects, Cytokines metabolism, Enrofloxacin, Female, Humans, Organ Culture Techniques, Parasite Load, Pregnancy, Toxoplasma cytology, Antiprotozoal Agents metabolism, Fluoroquinolones metabolism, Placenta parasitology, Toxoplasma drug effects, Toxoplasma growth & development, Triazines metabolism, Trophoblasts parasitology
- Abstract
Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line) and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain), whereas villous samples were only infected by the 2F1 clone. Then, infected cells and villous were treated with all antibiotics and the T. gondii intracellular proliferation as well as the cytokine production were analyzed. Finally, we evaluated the direct effect of enrofloxacin and toltrazuril in tachyzoites to verify possible changes in parasite structure. Enrofloxacin and toltrazuril did not decrease the viability of cells and villous in lower concentrations. Both drugs were able to significantly reduce the parasite intracellular proliferation in BeWo cells and villous explants when compared to untreated conditions. Regardless of the T. gondii strain, BeWo cells infected and treated with enrofloxacin or toltrazuril induced high levels of IL-6 and MIF. In villous explants, enrofloxacin induced high MIF production. Finally, the drugs increased the number of unviable parasites and triggered damage to tachyzoite structure. Taken together, it can be concluded that enrofloxacin and toltrazuril are able to control T. gondii infection in BeWo cells and villous explants, probably by a direct action on the host cells and parasites, which leads to modifications of cytokine release and tachyzoite structure.
- Published
- 2017
- Full Text
- View/download PDF
20. Plantar pressure asymmetry and risk of stress injuries in the foot of young soccer players.
- Author
-
Azevedo RR, da Rocha ES, Franco PS, and Carpes FP
- Subjects
- Adolescent, Biomechanical Phenomena, Case-Control Studies, Humans, Posture, Pressure, Risk Factors, Shoes, Athletic Injuries physiopathology, Foot Injuries etiology, Foot Injuries physiopathology, Fractures, Stress etiology, Fractures, Stress physiopathology, Soccer injuries
- Abstract
Background: Asymmetries in the magnitude of plantar pressure are considered a risk factor for stress fracture of the fifth metatarsal in soccer athletes., Objective: To investigate the presence of plantar pressure asymmetries among young soccer athletes., Design: Observational., Setting: Laboratory., Participants: Thirty young adolescents divided into a soccer player group (n = 15) or a matched control group (n = 15)., Main Outcome Measures: Mean plantar pressure was determined for seven different regions of the foot. Data were compared between the preferred and non-preferred foot, and between the groups, during barefoot standing on a pressure mat system., Results: Higher pressure was found in the hallux, 5th metatarsal and medial rearfoot of the non-preferred foot in the young soccer players. These asymmetries were not observed in the control group. Magnitudes of plantar pressure did not differ between the groups., Conclusion: Young soccer players present asymmetries in plantar pressure in the hallux, 5th metatarsal and medial rearfoot, with higher pressure observed in the non-preferred foot., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
21. Effects of Religious Priming Concepts on Prosocial Behavior Towards Ingroup and Outgroup.
- Author
-
Batara JB, Franco PS, Quiachon MA, and Sembrero DR
- Abstract
Several studies show that there is a connection between religion and prosociality (e.g., Saroglou, 2013). To investigate whether there is a causal relationship between these two variables, a growing number of scholars employed priming religious concepts and measure its influence on prosocial behavior (e.g., Pichon, Boccato, & Saroglou, 2007). In the recent development of religious priming, Ritter and Preston (2013) argued that different primes (agent prime, spiritual/abstract prime, and institutional prime) may also have varying influence on prosocial behavior specifically helping an ingroup or an outgroup target. With this in mind, a 2 (social categorization of the target of help) by 3 (agent prime, institutional prime, spiritual prime) experiment was conducted to directly investigate this hypothesis. Results suggest that priming religious concepts especially the spiritual prime can increase prosocial behaviors. However, no significant effect was found on the social categorization which implies that Filipino participants elicit prosocial behavior regardless of the social categorization (be it ingroup or outgroup) of the target of help. The present study's findings contribute to further the literature on religious priming and its influence on prosocial behavior., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2016
- Full Text
- View/download PDF
22. Phenotypic and genotypic characterization of two Toxoplasma gondii isolates in free-range chickens from Uberlândia, Brazil.
- Author
-
Lopes CS, Franco PS, Silva NM, Silva DA, Ferro EA, Pena HF, Soares RM, Gennari SM, and Mineo JR
- Subjects
- Agglutination Tests, Animals, Antibodies, Protozoan blood, Biological Assay, Brain parasitology, Brazil epidemiology, Cross-Sectional Studies, DNA, Protozoan genetics, Genotype, Heart parasitology, Mice, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Seroepidemiologic Studies, Serum immunology, Toxoplasma genetics, Toxoplasma physiology, Virulence, Chickens parasitology, Toxoplasma classification, Toxoplasma isolation & purification, Toxoplasmosis, Animal epidemiology, Toxoplasmosis, Animal parasitology
- Abstract
The aim of this study was to determine the seroprevalence of Toxoplasma gondii infection in free-range chickens from Uberlândia, Minas Gerais state, Brazil, and characterize the genotypic and phenotypic features of two isolates of this parasite, considering the importance of these hosts in the epidemiology of toxoplasmosis. Serum samples from 108 free-range chickens were obtained from ten different districts, and submitted to the modified agglutination test (MAT) for the presence of anti-T. gondii antibodies, and brain and heart tissue samples from infected chickens were processed for mouse bioassay. An overall seroprevalence of 71·3% was found and antibody titres ranged from 16 to 4096. After confirmation of seropositivity by mouse bioassay, the determination of the T. gondii genotypes of two isolates was performed by PCR-RFLP, using primers for the following markers: SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, new SAG2, Apico and CS3. These T. gondii isolates, designated TgChBrUD1and TgChBrUD2, were obtained from heart samples of free-range chickens. The TgChBrUD1 isolate belonged to ToxoDB PCR-RFLP genotype 11 and the TgChBrUD2 isolate belonged to ToxoDB PCR-RFLP genotype 6. Both isolates demonstrated high virulence in a rodent model, with the TgChBrUD1 isolate able to induce brain cysts, in accord with its pattern of multiplication rates in human fibroblast culture. Taken together, these results reveal high prevalence of T. gondii infection in free-range chickens throughout Uberlândia, indicating an important degree of oocyst environmental contamination and the existence of considerable risk for T. gondii transmission to humans by consumption of free-range chicken as a food source.
- Published
- 2016
- Full Text
- View/download PDF
23. Trophoblast-macrophage crosstalk on human extravillous under Toxoplasma gondii infection.
- Author
-
Guirelli PM, Angeloni MB, Barbosa BF, Gomes AO, Castro AS, Franco PS, Silva RJ, Oliveira JG, Martins-Filho OA, Mineo JR, Ietta F, and Ferro EA
- Subjects
- Apoptosis, Cell Line, Culture Media, Conditioned, Fas Ligand Protein metabolism, Humans, fas Receptor metabolism, Cytokines metabolism, Macrophages metabolism, Receptor Cross-Talk, Toxoplasmosis metabolism, Trophoblasts physiology
- Abstract
Introduction: The interaction between human extravillous trophoblasts and macrophages has an important role in implantation and placentation. However, any dysfunction in this communication system is associated with pregnancy pitfalls, and a Toxoplasma gondii infection can be a potential problem in this crosstalk. Therefore, the aim of this study was to assess the influence of infected macrophages on cytokine production and the incidence of apoptosis in T. gondii-infected extravillous trophoblast cells., Methods: HTR-8/SVneo cells were treated with supernatant from macrophages infected or not by T. gondii (conditioned medium) in order to analyze apoptosis and cytokine production in comparison to uninfected control conditions., Results: The IL-6 secretion by HTR-8/SVneo cells increased synergistically by treatment with conditioned medium and T. gondii infection. The apoptosis index of HTR-8/SVneo cells was also upregulated by treatment with conditioned medium and infection. In addition, a low expression of Fas/CD95 and a high soluble FasL release were observed during infection, although no significant change was observed in the proliferation of T. gondii., Discussion: The parasite modulates the high apoptosis index in HTR-8/SVneo cells in order to favor its establishment inside its host cells. On the other hand, the conditioned medium from uninfected macrophages restores the apoptosis rates, although the effect of the infection seems to be stronger. In conclusion, our results showed that T. gondii infection in human extravillous trophoblasts is able to modulate the trophoblast-macrophage crosstalk., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
24. Variability and repeatability analysis of plantar pressure during gait in older people.
- Author
-
Franco PS, Silva CB, Rocha ES, and Carpes FP
- Subjects
- Aged, Biomechanical Phenomena, Cross-Sectional Studies, Female, Gait, Humans, Male, Pressure, Reproducibility of Results, Foot physiology, Walking physiology
- Abstract
Introduction: Repeatability and variability of the plantar pressure during walking are important components in the clinical assessment of the elderly. However, there is a lack of information on the uniformity of plantar pressure patterns in the elderly., Objective: To analyze the repeatability and variability in plantar pressure considering mean, peak and asymmetries during aged gait., Methods: Plantar pressure was monitored in four different days for ten elderly subjects (5 female), with mean±standard-deviation age of 73±6 years, walking barefoot at preferred speed. Data were compared between steps for each day and between different days., Results: Mean and peak plantar pressure values were similar between the different days of evaluation. Asymmetry indexes were similar between the different days evaluated., Conclusion: Plantar pressure presented a consistent pattern in the elderly. However, the asymmetry indexes observed suggest that the elderly are exposed to repetitive asymmetric loading during locomotion. Such result requires further investigation, especially concerning the role of these asymmetries for development of articular injuries., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
25. Calomys callosus chronically infected by Toxoplasma gondii clonal type II strain and reinfected by Brazilian strains is not able to prevent vertical transmission.
- Author
-
Franco PS, da Silva NM, de Freitas Barbosa B, de Oliveira Gomes A, Ietta F, Shwab EK, Su C, Mineo JR, and Ferro EA
- Abstract
Considering that Toxoplasma gondii has shown high genetic diversity in Brazil, the aim of this study was to determine whether Calomys callosus chronically infected by the ME-49 strain might be susceptible to reinfection by these Brazilian strains, including vertical transmission of the parasite. Survival curves were analyzed in non-pregnant females chronically infected with ME-49 and reinfected with the TgChBrUD1 or TgChBrUD2 strain, and vertical transmission was analyzed after reinfection of pregnant females with these same strains. On the 19th day of pregnancy (dop), placentas, uteri, fetuses, liver, spleen, and lung were processed for detection of the parasite. Blood samples were collected for humoral and cellular immune response analyses. All non-pregnant females survived after reinfection and no changes were observed in body weight and morbidity scores. In pregnant females, parasites were detected in the placentas of ME-49 chronically infected females and reinfected females, but were only detected in the fetuses of reinfected females. TgChBrUD2 reinfected females showed more impaired pregnancy outcomes, presenting higher numbers of animals with fetal loss and a higher resorption rate, in parallel with higher levels of pro-inflammatory cytokines and IgG2a subclass antibodies. Vertical transmission resulting from chronic infection of immunocompetent C. callosus is considered a rare event, being attributed instead to either reactivation or reinfection. That is, the pregnancy may be responsible for reactivation of the latent infection or the reinfection may promote T. gondii vertical transmission. Our results clearly demonstrate that, during pregnancy, protection against T. gondii can be breached after reinfection with parasites belonging to different genotypes, particularly when non-clonal strains are involved in this process and in this case the reinfection promoted vertical transmission of both type II and Brazilian T. gondii strains.
- Published
- 2015
- Full Text
- View/download PDF
26. IL10, TGF beta1, and IFN gamma modulate intracellular signaling pathways and cytokine production to control Toxoplasma gondii infection in BeWo trophoblast cells.
- Author
-
Barbosa BF, Lopes-Maria JB, Gomes AO, Angeloni MB, Castro AS, Franco PS, Fermino ML, Roque-Barreira MC, Ietta F, Martins-Filho OA, Silva DA, Mineo JR, and Ferro EA
- Subjects
- Cell Line, Tumor, Choriocarcinoma pathology, Disease Susceptibility, Female, Humans, In Vitro Techniques, Interleukin-16 metabolism, Phosphorylation, Pregnancy, STAT1 Transcription Factor metabolism, STAT3 Transcription Factor metabolism, Signal Transduction physiology, Smad2 Protein metabolism, Toxoplasma isolation & purification, Toxoplasmosis metabolism, Toxoplasmosis pathology, Trophoblasts metabolism, Tumor Necrosis Factor-alpha metabolism, Uterine Neoplasms pathology, Cytokines metabolism, Interferon-gamma pharmacology, Interleukin-10 pharmacology, Signal Transduction drug effects, Toxoplasmosis prevention & control, Transforming Growth Factor beta1 pharmacology, Trophoblasts drug effects, Trophoblasts parasitology
- Abstract
Considering that interleukin 10 (IL10), transforming growth factor beta1 (TGFB1), and interferon gamma (IFNG) are involved in the susceptibility of BeWo trophoblast cells to Toxoplasma gondii infection, the aim of the present study was to investigate the effector mechanisms triggered by these cytokines in the control of T. gondii in BeWo cells. For this purpose, infected/uninfected BeWo cells were treated with IL10, TGFB1 (50 ng/ml), and IFNG (20 or 100 ng/ml) in order to verify the phosphorylation of signal transducers and activators of transcription 1 (STAT1), STAT3, and Smad2, parasite intracellular proliferation, as well as the Th1/Th2/IL17A cytokine production. The treatment of BeWo cells with IL10 and TGFB1 favored T. gondii proliferation, and these findings were associated with STAT3 and Smad2 phosphorylation, respectively (P < 0.05). Also, these cytokine treatments were able to down-modulate TNF alpha (TNFA) and IL6 production (P < 0.05). Low concentration of IFNG was unable to control T. gondii infection but was able to trigger STAT1 phosphorylation and up-regulate IL6 and IL17A production; whereas a high concentration of IFNG was unable to activate STAT1 but down-modulated IL6 and TNFA and increased T. gondii proliferation (P < 0.05). IL10, TGFB1, and IFNG regulate a differential T. gondii proliferation in BeWo cells because they distinctly trigger intracellular signaling pathways and cytokine production, especially IL6 and TNFA. Our data open new windows to understand the mechanisms triggered by IL10, TGFB1, and IFNG at the maternal-fetal interface in the presence of T. gondii, contributing to recognizing the importance of these effector mechanisms involved in the vertical transmission of this parasite., (© 2015 by the Society for the Study of Reproduction, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
27. Experimental infection of Calomys callosus with atypical strains of Toxoplasma gondii shows gender differences in severity of infection.
- Author
-
Franco PS, Ribeiro M, Lopes-Maria JB, Costa LF, Silva DA, de Freitas Barbosa B, de Oliveira Gomes A, Mineo JR, and Ferro EA
- Subjects
- Animals, Body Weight, Brain parasitology, Brazil, Disease Susceptibility, Female, Liver parasitology, Male, Rodent Diseases mortality, Rodent Diseases transmission, Sex Factors, Spleen parasitology, Survival Analysis, Toxoplasmosis, Animal mortality, Toxoplasmosis, Animal transmission, Rodent Diseases parasitology, Sigmodontinae parasitology, Toxoplasma genetics, Toxoplasmosis, Animal parasitology
- Abstract
There is a significant genetic diversity of Toxoplasma gondii in Brazil. Two parasite isolates were recently obtained from chickens in Uberlândia, Minas Gerais state, Brazil, namely, TgChBrUD1 and TgChBrUD2. In this study, we investigated Calomys callosus susceptibility to these atypical T. gondii strains. Male and female animals were intraperitoneally infected with tachyzoites and monitored to evaluate body weight change, morbidity, and mortality. Immunohistochemical assay and qPCR were performed to determine the parasitism in liver, spleen, and brain. Our data showed that TgChBrUD2-infected males died earlier than TgChBrUD1-infected males and 100% of mortality was observed after 10 and 12 days of infection, respectively. Also, TgChBrUD1-infected females died earlier than TgChBrUD1-infected males and 100% of mortality was observed after 9 and 12 days of infection, respectively. Both strains were able to induce a decrease in body weight of males, but only the TgChBrUD1 strain induced an increase in body weight of females. TgChBrUD2-infected females had significantly higher parasite load in both liver and spleen in comparison to TgChBrUD1-infected females, but no significant difference was found between genders or strains when males were infected. There was higher parasitism in the liver than the brain from both males and females infected with either strain. In conclusion, C. callosus specimens are susceptible to both T. gondii atypical strains with differences between males and females in severity of infection. These findings open new prospects for understanding different aspects of T. gondii infection, including reinfection and vertical transmission with these atypical strains when utilizing this experimental model.
- Published
- 2014
- Full Text
- View/download PDF
28. Differential apoptosis in BeWo cells after infection with highly (RH) or moderately (ME49) virulent strains of Toxoplasma gondii is related to the cytokine profile secreted, the death receptor Fas expression and phosphorylated ERK1/2 expression.
- Author
-
Angeloni MB, Guirelli PM, Franco PS, Barbosa BF, Gomes AO, Castro AS, Silva NM, Martins-Filho OA, Mineo TW, Silva DA, Mineo JR, and Ferro EA
- Subjects
- Cell Line, Cytokines genetics, Female, Humans, Mitogen-Activated Protein Kinase 1 biosynthesis, Mitogen-Activated Protein Kinase 3 biosynthesis, Phosphorylation, Placenta immunology, Placenta metabolism, Placentation, Pregnancy, Pregnancy Complications, Parasitic immunology, Pregnancy Complications, Parasitic metabolism, Pregnancy Complications, Parasitic parasitology, Pregnancy Complications, Parasitic pathology, Protein Processing, Post-Translational, Recombinant Proteins metabolism, Species Specificity, Toxoplasma immunology, Toxoplasmosis immunology, Toxoplasmosis metabolism, Toxoplasmosis parasitology, Toxoplasmosis pathology, Trophoblasts immunology, Trophoblasts metabolism, Trophoblasts parasitology, Up-Regulation, Virulence, fas Receptor biosynthesis, Apoptosis, Cytokines metabolism, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Placenta parasitology, Toxoplasma pathogenicity, fas Receptor metabolism
- Abstract
Introduction: Alterations of apoptosis are commonly associated with pregnancy complications and abortion. Modulation of apoptosis is a relevant feature of Toxoplasma gondii infection and it is related to parasite strain types. The aim of the present study was to evaluate the possible factors that are involved in the differential apoptosis of BeWo cells infected with distinct T. gondii strain types., Methods: Human trophoblastic cells (BeWo cell line) were infected with RH or ME49 strains, the cytokine production was measured and the phosphorylation of anti-apoptotic ERK1/2 protein was analyzed. Also, cells were treated with different cytokines, infected with RH or ME49 strain, and analyzed for apoptosis index and Fas/CD95 death receptor expression., Results: ME49-infected BeWo cells exhibited a predominantly pro-inflammatory cytokine profile, whereas cells infected with RH strain had a higher production of anti-inflammatory cytokines. Also, the incidence of apoptosis was higher in ME49-infected cells, which have been treated with pro-inflammatory cytokines compared to cells infected with RH and treated with anti-inflammatory cytokines. Moreover, Fas/CD95 expression was higher in cells infected with either ME49 or RH strain and treated with pro-inflammatory cytokines compared to anti-inflammatory cytokine treatment. The phosphorylation of ERK1/2 protein increased after 24 h of infection only with the RH strain., Conclusion: These results suggest that opposing mechanisms of interference in apoptosis of BeWo cells after infection with RH or ME49 strains of T. gondii can be associated with the differential cytokine profile secreted, the Fas/CD95 expression and the phosphorylated ERK1/2 expression., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
29. Trophoblast cells are able to regulate monocyte activity to control Toxoplasma gondii infection.
- Author
-
Castro AS, Alves CM, Angeloni MB, Gomes AO, Barbosa BF, Franco PS, Silva DA, Martins-Filho OA, Mineo JR, Mineo TW, and Ferro EA
- Subjects
- Cell Line, Tumor, Choriocarcinoma immunology, Choriocarcinoma metabolism, Choriocarcinoma parasitology, Cytokines metabolism, Female, Humans, Monocytes immunology, Monocytes parasitology, Toxoplasma growth & development, Toxoplasmosis immunology, Toxoplasmosis parasitology, Trophoblasts immunology, Trophoblasts parasitology, Culture Media, Conditioned pharmacology, Host-Parasite Interactions, Monocytes drug effects, Toxoplasma metabolism, Toxoplasmosis metabolism, Trophoblasts metabolism
- Abstract
Introduction: Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Trophoblast cells constitute an important maternal-fetal barrier, with monocytes concentrating around them. Thus, interactions between trophoblasts and monocytes are important for maintaining a successful pregnancy, especially in cases of infection. This study aimed to evaluate the role of trophoblast cells (BeWo line) on monocyte (THP-1 line) activity in the presence or absence of T. gondii infection., Methods: THP-1 cells were stimulated with supernatants of BeWo cells, previously infected or not with T. gondii, and then infected with parasites. The supernatant of both cells were collected and analyzed for cytokine production and T. gondii proliferation in THP-1 cells was determined., Results: The results showed that after infection, the pattern of cytokines secreted by THP-1 and BeWo cells was characterized as a pro-inflammatory profile. Furthermore, supernatant of BeWo cells infected or not, was able to change the cytokine profile secreted by infected THP-1 cells, and this supernatant became THP-1 cells more able to control T. gondii proliferation than those that had not been stimulated., Discussion: This effect was associated with secretion of interleukin (IL)-6 by the THP-1 cells and soluble factors secreted by BeWo cells, such as IL-6 and MIF., Conclusion: Together, these results suggest that trophoblast cells are able to modulate monocyte activity, resulting in the control of T. gondii infection and subsequent maintenance of pregnancy., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
30. Azithromycin and spiramycin induce anti-inflammatory response in human trophoblastic (BeWo) cells infected by Toxoplasma gondii but are able to control infection.
- Author
-
Franco PS, Gomes AO, Barbosa BF, Angeloni MB, Silva NM, Teixeira-Carvalho A, Martins-Filho OA, Silva DA, Mineo JR, and Ferro EA
- Subjects
- Animals, Anti-Inflammatory Agents pharmacology, Cell Line, Cell Survival drug effects, Female, Humans, Inflammation prevention & control, Mice, Pregnancy, Toxoplasmosis immunology, Toxoplasmosis prevention & control, Trophoblasts immunology, Trophoblasts pathology, Azithromycin pharmacology, Spiramycin pharmacology, Toxoplasma drug effects, Toxoplasma immunology, Toxoplasmosis pathology, Trophoblasts drug effects
- Abstract
Toxoplasma gondii is an important pathogen which may cause fetal infection if primary infection. Our previous studies have used human choriocarcinoma trophoblastic cells (BeWo cell line) as experimental model of T. gondii infection involving placental microenvironment. This study aimed to examine the effects of azithromycin and spiramycin against T. gondii infection in BeWo cells. Cells were treated with different concentrations of the macrolide antibiotics and analyzed first for cell viability using thiazolyl blue tetrazole (MTT) assay. As cell viability was significantly decreased with drug concentrations higher than 400 μg/mL, the concentration range used in further experiments was from 50 to 400 μg/mL. The number of infected cells and intracellular replication of T. gondii decreased after treatment with each drug. The infection induced up-regulation of the macrophage migration inhibitory factor (MIF), which was also enhanced in infected cells after treatment with azithromycin, but not with spiramycin. Analysis of the cytokine profile showed increase TNF-α, IL-10 and IL-4 production, but decreased IFN-γ levels, were detected in infected cells and treated with each drug. In conclusion, treatment of human trophoblastic BeWo cells with with azithromycin or spiramycin is able to control the infection and replication of T. gondii. In addition, treatment with these macrolides, especially with azityromycin induces an anti-inflammatory response and high MIF production, which can be important for the establishment and maintenance of a viable pregnancy during T. gondii infection., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
31. Effect of macrophage migration inhibitory factor (MIF) in human placental explants infected with Toxoplasma gondii depends on gestational age.
- Author
-
de Oliveira Gomes A, de Oliveira Silva DA, Silva NM, de Freitas Barbosa B, Franco PS, Angeloni MB, Fermino ML, Roque-Barreira MC, Bechi N, Paulesu LR, Dos Santos MC, Mineo JR, and Ferro EA
- Subjects
- Antigens, Differentiation, B-Lymphocyte genetics, Antigens, Differentiation, B-Lymphocyte metabolism, Female, Gene Expression Regulation, Histocompatibility Antigens Class II genetics, Histocompatibility Antigens Class II metabolism, Humans, Intramolecular Oxidoreductases biosynthesis, Intramolecular Oxidoreductases pharmacology, Macrophage Migration-Inhibitory Factors biosynthesis, Macrophage Migration-Inhibitory Factors pharmacology, Models, Biological, Nitrites metabolism, Placenta drug effects, Placenta pathology, Pregnancy, Pregnancy Trimester, First drug effects, Pregnancy Trimester, Third drug effects, Toxoplasma cytology, Toxoplasma drug effects, Toxoplasmosis pathology, Toxoplasmosis prevention & control, Gestational Age, Intramolecular Oxidoreductases metabolism, Macrophage Migration-Inhibitory Factors metabolism, Placenta metabolism, Placenta parasitology, Toxoplasma physiology, Toxoplasmosis parasitology
- Abstract
Because macrophage migration inhibitory factor (MIF) is a key cytokine in pregnancy and has a role in inflammatory response and pathogen defense, the objective of the present study was to investigate the effects of MIF in first- and third-trimester human placental explants infected with Toxoplasma gondii. Explants were treated with recombinant MIF, IL-12, interferon-γ, transforming growth factor-β1, or IL-10, followed by infection with T. gondii RH strain tachyzoites. Supernatants of cultured explants were assessed for MIF production. Explants were processed for morphologic analysis, immunohistochemistry, and real-time PCR analysis. Comparison of infected and stimulated explants versus noninfected control explants demonstrated a significant increase in MIF release in first-trimester but not third-trimester explants. Tissue parasitism was higher in third- than in first-trimester explants. Moreover, T. gondii DNA content was lower in first-trimester explants treated with MIF compared with untreated explants. However, in third-trimester explants, MIF stimulus decreased T. gondii DNA content only at the highest concentration of the cytokine. In addition, high expression of MIF receptor was observed in first-trimester placental explants, whereas MIF receptor expression was low in third-trimester explants. In conclusion, MIF was up-regulated and demonstrated to be important for control of T. gondii infection in first-trimester explants, whereas lack of MIF up-regulation in third-trimester placentas may be involved in higher susceptibility to infection at this gestational age., (Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
32. Evaluation of vertical transmission of Toxoplasma gondii in Calomys callosus model after reinfection with heterologous and virulent strain.
- Author
-
Franco PS, Silva DA, Costa IN, Gomes AO, Silva AL, Pena JD, Mineo JR, and Ferro EA
- Subjects
- Animals, DNA, Protozoan analysis, Female, Mice, Pregnancy, Sigmodontinae, Toxoplasma genetics, Toxoplasma immunology, Toxoplasmosis, Animal congenital, Toxoplasmosis, Animal immunology, Infectious Disease Transmission, Vertical prevention & control, Toxoplasma pathogenicity, Toxoplasmosis, Animal transmission
- Abstract
Toxoplasma gondii is an obligate intracellular protozoan parasite that causes a variety of clinical syndromes, but the infection is severe in immunocompromised individuals and during pregnancy due to the possibility of transplacental transmission of the parasite causing congenital toxoplasmosis. Vertical transmission of the parasite usually occurs when females are primarily infected during pregnancy. Calomys callosus is resistant to T. gondii ME49 strain, which presents a moderate virulence and congenital disease occurs only during the acute phase of infection. The aim of this study was to determine whether vertical transmission occurs when females of C. callosus chronically infected with ME49 strain of T. gondii are reinfected with a highly virulent strain (RH, type I). Females were infected with cysts of the ME49 strain. On the 1st day of pregnancy, animals were reinfected with tachyzoites of the RH strain. In the 19th day of pregnancy, placentas and embryos were processed for morphological analysis, immunohistochemistry and for detection of the parasite by PCR and mouse bioassay. Morphological and immunohistochemical analyses revealed the presence of parasites only in placental tissues. Mouse bioassay results showed seroconversion only in mice that were inoculated with placental tissues. Also, T. gondii DNA was detected only in placental samples. Congenital toxoplasmosis does not occur in C. callosus females chronically infected with the moderately virulent ME49 strain of T. gondii and reinfected with the highly virulent RH strain, thus indicating that primary T. gondii infection before pregnancy leads to an effective long-term immunity preventing transplacental transmission to the fetus., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
33. [Possible serotonergic syndrome caused by combination of tramadol and sertraline in an elderly woman].
- Author
-
Sauget D, Franco PS, Amaniou M, Mazere J, and Dantoine T
- Subjects
- Aged, Aged, 80 and over, Analgesics, Opioid therapeutic use, Antidepressive Agents therapeutic use, Drug Interactions, Female, Humans, Sertraline therapeutic use, Tramadol therapeutic use, Analgesics, Opioid adverse effects, Antidepressive Agents adverse effects, Serotonin Syndrome etiology, Sertraline adverse effects, Tramadol adverse effects
- Published
- 2002
34. [Chondromyxoid fibroma of the thoracic spine: a case report and review of the literature].
- Author
-
Leal Filho MB, Pereira Neto A, Pereira LC, Franco PS, Suzuki K, De Mello PA, Burnett JC, and Veloso MG
- Subjects
- Adult, Chondroblastoma surgery, Female, Follow-Up Studies, Humans, Laminectomy, Spinal Cord Neoplasms surgery, Chondroblastoma complications, Spinal Cord Compression etiology, Spinal Cord Neoplasms complications
- Abstract
A case of chondromyxoid fibroma (CMF) arising from the 5th right costovertebral junction and spreading into spinal canal causing spinal cord compression is presented. A myelotomography revealed a complete block at T5 level. The patient underwent a decompressive laminectomy with removal of an epidural tumor. This specimen was sent for pathological examination and interpreted as a CMF. The patient had a neurological improvement, post operative MRI revealed a spinal cord free of compression, and we decided on the follow up of the case. Two years later there was recurrence of the tumor. A posterolateral access by costotransversectomy was made and the lesion was resected. The patient had a neurological improvement which persists on the follow up (two years, at present). Clinical, radiologic and histologic findings, surgical management and recurrence are discussed. The pertinent literature is reviewed.
- Published
- 1995
35. Response to thyrotropin-releasing hormone compared with thyroid suppression tests in euthyroid Graves' disease.
- Author
-
Franco PS, Hershman JM, Haigler ED Jr, and Pittman JA Jr
- Subjects
- Adult, Female, Humans, Iodine metabolism, Iodine Radioisotopes, Male, Middle Aged, Thyroid Function Tests, Thyroid Gland metabolism, Thyroiditis, Autoimmune physiopathology, Triiodothyronine, Graves Disease physiopathology, Thyroid Gland drug effects, Thyrotropin metabolism, Thyrotropin-Releasing Hormone
- Published
- 1973
- Full Text
- View/download PDF
36. Treatment of acromegaly by stereotaxic cryohypophysectomy.
- Author
-
Franco PS, Hershman JM, and Galbraith JG
- Subjects
- Abducens Nerve, Adrenocorticotropic Hormone blood, Adult, Aged, Biopsy, Needle, Cerebrospinal Fluid Rhinorrhea etiology, Diabetes Insipidus etiology, Female, Gonadotropins, Pituitary urine, Growth Hormone blood, Humans, Male, Meningitis etiology, Middle Aged, Paralysis etiology, Radiography, Radioimmunoassay, Skull diagnostic imaging, Thyrotropin blood, Acromegaly surgery, Adenoma, Acidophil surgery, Adenoma, Chromophobe surgery, Cryosurgery, Hypophysectomy adverse effects, Pituitary Neoplasms surgery, Stereotaxic Techniques
- Published
- 1973
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.