Mariana Strauss - Academia.edu (original) (raw)

Papers by Mariana Strauss

La enfermedad de Chagas es una infeccion hemohistoparasitaria, sistemica, cronica, transmitida po... more La enfermedad de Chagas es una infeccion hemohistoparasitaria, sistemica, cronica, transmitida por triatominos y causada por el parasito Trypanosoma cruzi ( T. cruz i). Es endemica en 21 paises de las Americas, donde debido a los movimientos migratorios el patron epidemiologico dejo de ser solo rural, considerandosela tambien una infeccion urbana. La evolucion clinica se caracteriza por la cronicidad. La cardiopatia chagasica cronica es un importante problema de Salud Publica que afecta a poblaciones en edad productiva. Objetivo: determinar la presencia del T. cruzi en sangre periferica de pacientes con Chagas cronico, y establecer si existe relacion con la sintomatologia clinica cardiaca. Se estudiaron 100 individuos con epidemiologia positiva para Chagas, mediante inspeccion clinica, electrocardiograma, ecocardiograma, serologia y Reaccion en cadena de la polimerasa (PCR) convencional especifica (utilizando los oligonucleotidos TCZ1 y TCZ2). Los datos se analizaron con ANAVA...

La cardiopatia dilatada es la manifestacion mas frecuente de la fase cronica de la enfermedad de ... more La cardiopatia dilatada es la manifestacion mas frecuente de la fase cronica de la enfermedad de Chagas, presentandose como un cuadro de insuficiencia cardiaca, arritmias ventriculares, bloqueos en el sistema de conduccion especifico, fenomenos embolicos y, a veces, muerte subita. Es posible que el sustrato arritmogenico se encuentre en las distintas zonas de fibrosis miocardicas de las diferentes cavidades cardiacas, mas frecuentemente en los ventriculos. El objetivo del presente trabajo fue evaluar, en pacientes chagasicos, el grado de fibrosis miocardica mediante resonancia magnetica nuclear cardiaca (RMN) 3D con secuencia especial y analisis de la misma con software para deteccion automatica de sustrato arritmogenico (fibrosis y canales de conduccion lenta), con el fin de determinar si este factor puede predecir la aparicion de eventos arritmogenicos. Se estudiaron 5 pacientes con serologia positiva para Enfermedad de Chagas (TIF, HAI y ELISA) a los cuales se les realizo examen ...

505 MEASUREMENT OF PRO-BRAIN NATRIURETIC PEPTIDE (PROBNP) FOR THE DETECTION OF SUBCLINICAL MYOCAR... more 505 MEASUREMENT OF PRO-BRAIN NATRIURETIC PEPTIDE (PROBNP) FOR THE DETECTION OF SUBCLINICAL MYOCARDIAL DAMAGE IN PATIENTS WITH CHAGAS DISEASE 1Buteler J, 1Mores M, 2Velazquez D, 3Rivolta S, 2Lo Presti MS, 2Strauss M, 2Miler N, 2Rivarola HW Persona que presenta: Buteler J, butelerjavier@yahoo.com.ar Abstract: Chagas disease (CHD) is divided into: ACUTE CHD: symptomatic or asymptomatic and CHRONIC CHD: with or without demonstrated pathology. About 30-40% of the infected individuals develop the chronic phase with demonstrated pathology. The heart disease is the most frequent and severe clinical manifestation. Efforts focusing on the chronic phase without demonstrated pathology are crucial to prevent the installation of heart alterations. This stage lasts from 10 to 20 years and is characterized by positive serology but normal chest x-ray and electrocardiography. Myocardial damage however cannot be verified by the usual methods of study at this stage. Pro-Brain Natriuretic Peptide (proBN...

Gene, Jan 27, 2018

Biliary atresia (BA) has complex genetic etiology, characterized by different levels of hepatic f... more Biliary atresia (BA) has complex genetic etiology, characterized by different levels of hepatic fibrosis after the Kasai procedure and immune responses to the bile duct. As an activator of the two most important inflammatory cells in Biliary atresia (T cells and NK cells), IL-18 is significantly increased in BA patients. This study aims to investigate the association of Interleukin 18(IL-18) with the susceptibility to BA. We examined the association of three polymorphisms (rs549908, rs187238 and rs1946518 in IL-18) and BA susceptibility in a Southern Chinese population composed of 506 cases and 1473 controls. SNP rs187238 and rs1946518 were identified as associated with BA. Interestingly, we also observed that the intragenic synergistic epistasis between SNPs rs187238 and rs1946518 boosting the risk to BA by logistic regression and Multifactor dimensionality reduction (MDR) analysis. This study provides for the first time a direct evidence to support IL-18 as a susceptibility gene f...

La enfermedad de Chagas, causada por el Trypanosoma cruzi , afecta entre 10 y 18 millones de per... more La enfermedad de Chagas, causada por el Trypanosoma cruzi , afecta entre 10 y 18 millones de personas en America. Los farmacos para su tratamiento son nifurtimox y benznidazol (Bz) los cuales son moderadamente toxicos. Esta toxicidad podria deberse a la dosis acumulativa y a los protocolos de largo tratamiento. El objetivo del presente estudio es valorar, mediante parasitemia y enzimas hepaticas (para evaluar dano hepatico por el farmaco utilizado) terapias basadas en la utilizacion de dosis reducidas de Bz y administradas en forma intermitente en ratones en fase aguda de la enfermedad de Chagas experimental. Utilizamos ratones Albino suizos adultos (30 ± 3 g) inoculados intraperitonealmente con 1000 tripomastigotes de cepa Tulahuen. Los ratones infectados fueron divididos en los siguientes grupos, cada uno con 7 animales: I: Sin tratamiento. II: Bz, 100 mg/kg/dia en 40 dosis consecutivas. III: Bz, 50 mg/kg/dia en 40 dosis consecutivas. IV: Bz, 50 mg/kg/dia en 16 dosis, un...

Scientific Reports, 2020

Genetic factors and the immunologic response have been suggested to determine the susceptibility ... more Genetic factors and the immunologic response have been suggested to determine the susceptibility against the infection and the outcome of Chagas disease. In the present study, we analysed three IL17A genetic variants (rs4711998, rs8193036 and rs2275913) regarding the predisposition to Trypanosoma cruzi infection and the development of chronic Chagas cardiomyopathy (CCC) in different Latin American populations. A total of 2,967 individuals from Colombia, Argentina, Bolivia and Brazil, were included in this study. The individuals were classified as seronegative and seropositive for T. cruzi antigens, and this last group were divided into asymptomatic and CCC. For T. cruzi infection susceptibility, the IL17A rs2275913*A showed a significant association in a fixed-effect meta-analysis after a Bonferroni correction (P = 0.016, OR = 1.21, 95%CI = 1.06–1.41). No evidence of association was detected when comparing CCC vs. asymptomatic patients. However, when CCC were compared with seronegat...

Experimental and Molecular Pathology, 2016

Clomipramine (CLO), a tricyclic antidepressant drug, has been used for the treatment of mice infe... more Clomipramine (CLO), a tricyclic antidepressant drug, has been used for the treatment of mice infected with Trypanosoma cruzi. In this work we evaluated the effectiveness of CLO treatment upon T. cruzi-infected mice in the chronic phase of the experimental infection using Quantitative polymerase chain reaction (qPCR) and recombinant ELISA. Sixty Swiss albino mice were inoculated with 50 trypomastigote forms of T. cruzi (Tulahuen strain). CLO treatment consisted of 5 mg/kg/day during 60 days by intraperitoneal injection, beginning on day 90 post infection (p.i) when the mice presented electrocardiographic (ECG) alterations compatible with the chronic phase of the disease. The evolution of experimental infection and the treatment efficacy were studied through survival, electrocardiography, serology using a mixture and individual (1, 2, 13, 30, 36 and SAPA) recombinant proteins from epimastigotes and trypomastigotes of T. cruzi; and qPCR on days 180 and 270 p.i. CLO treatment in the chronic phase decreased the parasite load, reduced the levels of antibodies against antigen 13 throughout 270 days p.i and reversed the ECG abnormalities in the treated animals, from 100% of the mice with alterations at the beginning of the treatment to only 20% of the mice with alterations by day 270 p.i. This study shows that qPCR and the use of recombinant antigens are more sensitive to evaluate the effectiveness of the treatment and proves that clomipramine may be considered as a new chemotherapy for the chronic phase of the disease.

International Journal of Medical Microbiology, 2016

Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rew... more Drug repositioning, i.e. use of existing medicals to treat a different illness, is especially rewarding for neglected tropical diseases (NTD), since in this field the pharmaceutical industry is rather reluctant to spend vast investments for drug development. NTDs afflict primarily poor populations in under-developed countries, which minimizes financial profit. Here we investigated the trypanocidal effect of clomipramine, a commercial antipsychotic drug, on Trypanosoma brucei. The data showed that this drug killed the parasite with an IC50 of about 5μM. Analysis of the involved cell death mechanism revealed furthermore an initial autophagic stress response and finally the induction of apoptosis. The latter was substantiated by a set of respective markers such as phosphatidylserine exposition, DNA degradation, loss of the inner mitochondrial membrane potential and characteristic morphological changes. Clomipramine was described as a trypanothione inhibitor, but as judged from our results it also showed DNA binding capacities and induced substantial morphological changes. We thus consider it likely that the drug induces a multifold adverse interaction with the parasite&amp;amp;amp;amp;amp;amp;amp;#39;s physiology and induces stress in a way that trypanosomes cannot cope with.

Parasitology International, 2016

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' d... more The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against T. cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss Albino mice were infected with T. cruzi and treated daily with 10 mg/kg/day ICTX (i.p.). Infected mice and injected with either saline or the vehicle DMSO were used as controls. Animal´s survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5 th week after infection. It was observed that the administration of ICTX increased survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5 th week post-infection, the presence of amastigotes nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

Acta Tropica, 2015

Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiaz... more Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T. cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80mg/kg/day, for 3 days starting 1h after infection (acute phase), or TDZ 80mg/kg/day for 12 days starting 180 days post infection (d.p.i.) (chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical abnormalities, and modified the natural evolution of the experimental infection. These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potential chemotherapeutic agent for Chagas disease treatment is also revised.

Archives of Medical Research, 2014

Parasitology International, 2013

Alternative strategies are being designed to identify candidates among drugs already available on... more Alternative strategies are being designed to identify candidates among drugs already available on the market 28 that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates 29 the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimen-30 tal Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. 31 Infected mice were treated with CLO 5 mg/kg/day and BZN 50 and 100 mg/kg/day, each separately or togeth-32 er. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopatho-33 logical studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly 34 (P b 0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of 35 mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The 36 lower dose of BZN (50 mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of 37 BZN (100 mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO 38 presented lesser side effects than the treatment with BZN.

Parasitology, 2013

SUMMARYChagas infection is a major endemic disease affecting Latin American countries. The persis... more SUMMARYChagas infection is a major endemic disease affecting Latin American countries. The persistence of Trypanosoma cruzi generates a chronic inflammatory reactivity that induces an immune response directed to the host's tissues. The effectiveness of the treatment in the chronic phase is still unsatisfactory due, amongst other reasons, to the collateral effects of the drugs used. We investigated the effect of clomipramine, a tricyclic antidepressant that, when used as a treatment of T. cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive and vital enzyme of T. cruzi. Clomipramine improved survival (P<0·05) by diminishing the parasite intensity as demonstrated by PCR studies in the heart and skeletal muscle, and significantly prevented the evolution to fibrosis of the inflammatory infiltrates. Clomipramine could be a good candidate for the treatment of chronic Chagas disease.

Acta Tropica, 2014

We evaluated the presence and distribution of two Trypanosoma cruzi natural isolates in blood, he... more We evaluated the presence and distribution of two Trypanosoma cruzi natural isolates in blood, heart, skeletal muscle, liver, and spleen tissues in the acute phase of the experimental infection (35 days postinfection) in order to determine if the populations present in blood were different to those found in the tissues of the same host. Thirty mice were infected with 50 forms of each isolate or with a combination of them. Presence and molecular characterization of the parasites in the host tissues were determined by specific PCR. Cardiac and skeletal muscle alterations were analyzed by histological studies. T. cruzi variability in the host tissues was analyzed through RFLP studies. Both isolates used consisted of a mixture of two T. cruzi lineages. Specific PCRs were positive for most of the samples from the 3 groups analyzed. Cardiac and skeletal muscle sections from the groups infected with one isolate presented mild to moderate inflammatory infiltrates; the group infected with both isolates showed severe inflammatory infiltrates and the presence of amastigote nests in both tissues. Different parasite populations were found in circulation and in the tissues from the same host. These results are important for patients with high probability of mixed infections in endemic areas and contribute to the knowledge of parasite/host interactions.

Resumen: Introducción: la actividad mitocondrial es esencial para el músculo cardíaco y esqueléti... more Resumen: Introducción: la actividad mitocondrial es esencial para el músculo cardíaco y esquelético. La relación entre la disfunción mitocondrial y diferentes condiciones cardiovasculares ha sido bien descrita. El tratamiento farmacológico de la insuficiencia cardíaca implica diferentes medicamentos como: inhibidores de la enzima convertidora de la angiotensina, bloqueadores B-adrenérgicos, glucósidos digitálicos y diuréticos. Los beneficios clínicos del tratamiento son claros, sin embargo, el papel de estos fármacos en el metabolismo mitocondrial no está bien establecido. Objetivo del estudio: Analizar las características estructurales y funcionales de las mitocondrias del músculo cardíaco y esquelético en ratones tratados con fármacos habitualmente utilizados para la insuficiencia cardíaca y compararlo con un grupo control. Métodos: Veinticinco ratones albinos divididos en cinco grupos fueron tratados con la medicación para insuficiencia cardíaca durante 30 días (grupo I a IV). Tr...

Areté, 2016

University students produce thesis for obtaining graduate degree. This production helps to visual... more University students produce thesis for obtaining graduate degree. This production helps to visualize aspects of reality in which a profession is involved. The aim of thisstudy was to describe the production of thesis by year, the type of relationship between the director and the area of the topics approached in the career degree at the School of Speech, Language and Hearing Sciences, Faculty of Medical Sciences, Universidad Nacional de Cordoba (UNC), Argentina, from 1993 to 2014. Four hundred sixty-one theses were analyzed with a descriptive studyThe results showed a higher participation of external director’s professors than directors professors from the School of Speech, Language and Hearing Sciences in the first eleven years, while in the following eleven years this distribution is reversed. In relation to topics area it was observed in both the first eleven years and the following eleven years, a predominance of audiology area. The level of association was statistically signific...