The nervous system of flatworms is quite simple although there is increasing evidence indicating ... more The nervous system of flatworms is quite simple although there is increasing evidence indicating that it is chemically complex. Studies of the nervous system in these animals have only been performed in the larval stage or in the adult worms, which are easy to obtain in nature, while the description of the nervous system in developing stages of these organisms is missing. Mesocestoides corti is a parasitic platyhelminth whose larvae can be induced in vitro to develop to adult, sexually mature worms, opening the possibility of studying the nervous system of a flatworm in different stages of development. Here, we describe the presence, activity, location, and molecular forms of acetylcholinesterase (AChE) in different stages of development of M. corti, from the larvae to adult forms of this endoparasite, obtained in in vitro cultures after induction of the larval stage with trypsin. Our results point to AChE as a molecular marker of the nervous system in platyhelminthes. The change in...
... Radical Generation by 1,1'-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bi... more ... Radical Generation by 1,1'-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds Benjamín Aguilera-Venegas1 , Claudio Olea-Azar 1,*, Vicente J. Arán2 , Juan DiegoMaya 3 , Ulrike Kemmerling 4, Hernán Speisky5, Fernando Mendizábal6 ...
The congenital transmission of Trypanosoma cruzi (T. cruzi) is responsible for one-third of new C... more The congenital transmission of Trypanosoma cruzi (T. cruzi) is responsible for one-third of new Chagas disease cases each year. During congenital transmission, the parasite breaks down the placental barrier formed by the trophoblast, basal laminae and villous stroma. The observation that only 5% of infected mothers transmit the parasite to the fetus implies that the placenta may impair parasite transmission. The trophoblast undergoes continuous epithelial turnover, which is considered part of innate immunity. Therefore, we propose that T. cruzi induces differentiation in the trophoblast as part of a local antiparasitic mechanism of the placenta. We analyzed β-human chorionic gonadotropin (β-hCG) and syncytin protein expression in HPCVE and BeWo cells using immunofluorescence and western blotting. Additionally, β-hCG secretion into the culture medium was measured by ELISA. We assessed the differentiation of trophoblastic cells in BeWo cells using the two-color fusion assay and by determining desmoplakin re-distribution. T. cruzi trypomastigotes induce β-hCG secretion and protein expression as well as syncytin protein expression in HPCVE and BeWo cells. Additionally, the parasite induces the trophoblast fusion of BeWo cells. T. cruzi induces differentiation of the trophoblast, which may contribute to increase the trophoblast turnover. The turnover could be a component of local antiparasitic mechanisms in the human placenta.
Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma c... more Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier. In the present study we analyzed the participation of matrix metalloproteases (MMPs) in the extracellular matrix (ECM) remodeling during T. cruzi ex vivo infection of human placental chorionic villi explants. Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10⁵ or 10⁶ T. cruzi trypomastigotes (Y strain) with or without the MMPs inhibitor doxycycline. Effective infection was tested measuring parasite DNA by real time PCR (qPCR). MMP-2 and MMP-9 expression were determined by western blotting and immunohistochemistry and their activities were measured by zymography. The effect of MMPs on ECM structure was analyzed histochemically. T. cruzi induces the expression and activity of MMP-2 and MMP-9 in chorionic villi. Inhibition of the MMPs prevents the tissue damage induced by T. cruzi and partially decreases the ex vivo infection of the chorionic villi. MMPs are partially responsible for the ECM changes observed in human chorionic villi during T. cruzi infection and participate in tissue invasion. On the other hand, MMPs may be part of a local placental antiparasitic mechanism.
Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas disease, an endemic ... more Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas disease, an endemic and neglected pathology in Latin America. It presents a life cycle that involves a hematophagous insect and man as well as domestic and wild mammals. The parasitic infection is not eliminated by the immune system of mammals; thus, the vertebrate host serves as a parasite reservoir. Additionally, chronic processes leading to dysfunction of the cardiac and digestive systems are observed. To establish a chronic infection some parasites should resist the oxidative damage to its DNA exerted by oxygen and nitrogen free radicals (ROS/RNS) generated in host cells. Till date there are no reports directly showing oxidative DNA damage and repair in T. cruzi. We establish that ROS/RNS generate nuclear and kinetoplastid DNA damage in T. cruzi that may be partially repaired by the parasite. Furthermore, we determined that both oxidative agents diminish T. cruzi cell viability. This effect is significantly augmented in parasites subsequently incubated with methoxyamine, a DNA base excision repair (BER) pathway inhibitor, strongly suggesting that the maintenance of T. cruzi viability is a consequence of DNA repair mechanisms.
Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-t... more Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC 50 values in the micromolar range against two different strains of ...
Chagas’ disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one ... more Chagas’ disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. In spite that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce.The placental tissue undergoes apoptosis throughout gestation, as part of its normal turnover. On the other
Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics w... more Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop.
Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting... more Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting the human population. Tumor pathogenesis implies a multistep process in which cells acquire features that enable them to become tumorigenic and ultimately malignant. The process of OSCC carcinogenesis can be reproduced in animal models, the OSCC induction with 4-nitroquinoline-1-oxide (4NQO) in mice is a widely used tool for studying tumor pathogenesis. Objective. The aim of the present study was to determine the progressive changes in basal lamina and connective tissue remodeling during 4NQO-induced OSCC carcinogenesis. Material and Methods. Samples were classified according to “International Histological Classification of tumors” in mild, moderate, and severe dysplasia and invasive carcinoma. Five samples of each pathologic entity and control healthy tongues were used. Immunohistochemical analysis of collagen IV as well as histochemical analysis of glycosylated molecules (PAS) and collagen I (Picro Sirius red) were performed. Results. During experimental-induced carcinogenesis by 4NQO a progressive basal lamina destruction and collagen I disorganization in adjacent connective tissue can be observed. Conclusion. Our results confirm previous studies that show alterations in extracellular matrix (ECM) in malignant lesions, validating the experimental carcinogenesis induced by 4NQO
The nervous system of flatworms is quite simple although there is increasing evidence indicating ... more The nervous system of flatworms is quite simple although there is increasing evidence indicating that it is chemically complex. Studies of the nervous system in these animals have only been performed in the larval stage or in the adult worms, which are easy to obtain in nature, while the description of the nervous system in developing stages of these organisms is missing. Mesocestoides corti is a parasitic platyhelminth whose larvae can be induced in vitro to develop to adult, sexually mature worms, opening the possibility of studying the nervous system of a flatworm in different stages of development. Here, we describe the presence, activity, location, and molecular forms of acetylcholinesterase (AChE) in different stages of development of M. corti, from the larvae to adult forms of this endoparasite, obtained in in vitro cultures after induction of the larval stage with trypsin. Our results point to AChE as a molecular marker of the nervous system in platyhelminthes. The change in...
... Radical Generation by 1,1'-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bi... more ... Radical Generation by 1,1'-Hydrocarbylenebisindazoles and Its Evaluation as Potential Bio-Active Compounds Benjamín Aguilera-Venegas1 , Claudio Olea-Azar 1,*, Vicente J. Arán2 , Juan DiegoMaya 3 , Ulrike Kemmerling 4, Hernán Speisky5, Fernando Mendizábal6 ...
The congenital transmission of Trypanosoma cruzi (T. cruzi) is responsible for one-third of new C... more The congenital transmission of Trypanosoma cruzi (T. cruzi) is responsible for one-third of new Chagas disease cases each year. During congenital transmission, the parasite breaks down the placental barrier formed by the trophoblast, basal laminae and villous stroma. The observation that only 5% of infected mothers transmit the parasite to the fetus implies that the placenta may impair parasite transmission. The trophoblast undergoes continuous epithelial turnover, which is considered part of innate immunity. Therefore, we propose that T. cruzi induces differentiation in the trophoblast as part of a local antiparasitic mechanism of the placenta. We analyzed β-human chorionic gonadotropin (β-hCG) and syncytin protein expression in HPCVE and BeWo cells using immunofluorescence and western blotting. Additionally, β-hCG secretion into the culture medium was measured by ELISA. We assessed the differentiation of trophoblastic cells in BeWo cells using the two-color fusion assay and by determining desmoplakin re-distribution. T. cruzi trypomastigotes induce β-hCG secretion and protein expression as well as syncytin protein expression in HPCVE and BeWo cells. Additionally, the parasite induces the trophoblast fusion of BeWo cells. T. cruzi induces differentiation of the trophoblast, which may contribute to increase the trophoblast turnover. The turnover could be a component of local antiparasitic mechanisms in the human placenta.
Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma c... more Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier. In the present study we analyzed the participation of matrix metalloproteases (MMPs) in the extracellular matrix (ECM) remodeling during T. cruzi ex vivo infection of human placental chorionic villi explants. Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10⁵ or 10⁶ T. cruzi trypomastigotes (Y strain) with or without the MMPs inhibitor doxycycline. Effective infection was tested measuring parasite DNA by real time PCR (qPCR). MMP-2 and MMP-9 expression were determined by western blotting and immunohistochemistry and their activities were measured by zymography. The effect of MMPs on ECM structure was analyzed histochemically. T. cruzi induces the expression and activity of MMP-2 and MMP-9 in chorionic villi. Inhibition of the MMPs prevents the tissue damage induced by T. cruzi and partially decreases the ex vivo infection of the chorionic villi. MMPs are partially responsible for the ECM changes observed in human chorionic villi during T. cruzi infection and participate in tissue invasion. On the other hand, MMPs may be part of a local placental antiparasitic mechanism.
Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas disease, an endemic ... more Trypanosoma cruzi, a parasitic protozoan, is the etiological agent of Chagas disease, an endemic and neglected pathology in Latin America. It presents a life cycle that involves a hematophagous insect and man as well as domestic and wild mammals. The parasitic infection is not eliminated by the immune system of mammals; thus, the vertebrate host serves as a parasite reservoir. Additionally, chronic processes leading to dysfunction of the cardiac and digestive systems are observed. To establish a chronic infection some parasites should resist the oxidative damage to its DNA exerted by oxygen and nitrogen free radicals (ROS/RNS) generated in host cells. Till date there are no reports directly showing oxidative DNA damage and repair in T. cruzi. We establish that ROS/RNS generate nuclear and kinetoplastid DNA damage in T. cruzi that may be partially repaired by the parasite. Furthermore, we determined that both oxidative agents diminish T. cruzi cell viability. This effect is significantly augmented in parasites subsequently incubated with methoxyamine, a DNA base excision repair (BER) pathway inhibitor, strongly suggesting that the maintenance of T. cruzi viability is a consequence of DNA repair mechanisms.
Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-t... more Eight new platinum(II) complexes with 3-(5-nitrofuryl)acroleine thiosemicarbazones showing anti-trypanosomal activity were synthesized, characterized and in vitro evaluated. Most of the complexes showed IC 50 values in the micromolar range against two different strains of ...
Chagas’ disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one ... more Chagas’ disease, produced by the haemoflagellated protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. In spite that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce.The placental tissue undergoes apoptosis throughout gestation, as part of its normal turnover. On the other
Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics w... more Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop.
Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting... more Introduction. Oral squamous cell carcinoma (OSCC) is one of the ten most common cancers affecting the human population. Tumor pathogenesis implies a multistep process in which cells acquire features that enable them to become tumorigenic and ultimately malignant. The process of OSCC carcinogenesis can be reproduced in animal models, the OSCC induction with 4-nitroquinoline-1-oxide (4NQO) in mice is a widely used tool for studying tumor pathogenesis. Objective. The aim of the present study was to determine the progressive changes in basal lamina and connective tissue remodeling during 4NQO-induced OSCC carcinogenesis. Material and Methods. Samples were classified according to “International Histological Classification of tumors” in mild, moderate, and severe dysplasia and invasive carcinoma. Five samples of each pathologic entity and control healthy tongues were used. Immunohistochemical analysis of collagen IV as well as histochemical analysis of glycosylated molecules (PAS) and collagen I (Picro Sirius red) were performed. Results. During experimental-induced carcinogenesis by 4NQO a progressive basal lamina destruction and collagen I disorganization in adjacent connective tissue can be observed. Conclusion. Our results confirm previous studies that show alterations in extracellular matrix (ECM) in malignant lesions, validating the experimental carcinogenesis induced by 4NQO
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