Sistema de Gestión del Conocimiento ANLIS MALBRÁN
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Cementoin-SLPI fusion protein binds to human monocytes and epithelial cells and shows higher biological activity than SLPI
Fil: Maffía, Paulo C. Universidad Nacional de Quilmes. Laboratorio de Microbiología Molecular; Argentina.Fil: Guerrieri, Diego. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología; Argentina.Fil: Villalonga, Ximena. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología; Argentina.Fil: Caro, Fiorella. Centro de Estudios Farmacológicos y Botánicos; Argentina.Fil: Gómez, Sonia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio Antimicrobianos. Departameno Bacteriología; Argentina.Fil: Tateosian, Nancy. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina.Fil: Bogado, Betiana P. Universidad Nacional de Quilmes. Laboratorio de Microbiología Molecular; Argentina.Fil: Sánchez, Mercedes L. Centro de Estudios Farmacológicos y Botánicos; Argentina.Fil: Ambrosi, Nella. Centro de Estudios Farmacológicos y Botánicos; Argentina.Fil: Chuluyan, H. Eduardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología, Parasitología e Inmunología; Argentina.Secretory Leukocyte Proteinase Inhibitor (SLPI) is an antiinflammatory peptide that blocks the activity of serine proteases, primarily the neutrophil elastase. In an attempt to direct the activity of SLPI on inflamed sites, a chimera consisting of the transglutaminase II substrate domain of trappin 2 (cementoin), and the mature SLPI protein was constructed. Cell attachment and biological activity were compared between SLPI and this chimera. By using whole cell ELISA, fluorescence microscopy and flow cytometry assays we observed that the cementoin-SLPI fusion protein (FP) but not SLPI attached to a human lung epithelial cell line and monocytes. A maximum attachment was achieved 15 min after FP was added to the cell cultures. In an elastase activity assay, we observed that FP retained its antiprotease activity and that at equimolar amount of proteins, FP was more efficient than SLPI in the inhibition. Both, FP and SLPI inhibits IL-2-induced lymphocyte proliferation, however, lower amounts of FP were required to achieve this inhibition. Furthermore, FP binds to mycobacteria and maintained the bactericidal activity observed for SLPI. Overall, these results show that this new chimera is able to attach to the cell surfaces retaining and improving some biological activities described for SLPI
Paracoccidioidomycosis: chronicle of a neglected disease
Fil: Canteros, Cristina Elena. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Micología. Servicio Micosis Profundas; Argentina.La paracoccidioidomicosis (PCM) es una micosis sistémica causada por especies del género Paracoccidioides. La PCM y su agente causal fueron descriptos por Adolfo Lutz en 1908 en Brasil. Desde entonces, un largo y arduo camino permitió descifrar, hasta el momento, apenas algunos de los aspectos biológicos, epidemiológicos y clínicos de la enfermedad y su agente1. La PCM es exclusiva de América Latina y los casos autóctonos se registran entre los paralelos 23° de latitud N (México) y 34.5° de latitud S (Argentina), en áreas de clima subtropical húmedo con ríos y bosque en galerías, asociadas a población rural2.
Los primeros estudios epidemiológicos de nivel nacional sobre frecuencia de PCM fueron realizados en 1985 y 1988 y en ambos, la PCM aparece como la micosis endémica más importante en el país3. A partir de 2001 y, en paralelo a la pandemia de sida, otras micosis como la histoplasmosis fueron superándola en frecuencia3. En 2004, en la primera encuesta nacional sobre micosis en la que participaron 79 laboratorios de la Red Nacional de Laboratorios de Micología y el Programa Nacional de Control de Calidad en Micología, la PCM fue la quinta micosis profunda con 110/23 600 casos de micosis4. En la segunda encuesta nacional realizada en 2008, sobre 109 laboratorios, la PCM ocupaba el sexto lugar entre las micosis profundas (86/23 904 casos de micosis) con una prevalencia de 0.2/100 000 habitantes5. El área endémica de Argentina comprende las provincias del Noreste (Chaco, Corrientes, Misiones y Formosa) donde se registra el 85% de los casos, y las provincias del Noroeste (Tucumán, Salta y Jujuy) de donde provienen los casos restantes6. En los últimos años se ha empezado a observar un aumento llamativo de la incidencia de PCM en nuestro país. En particular, en la provincia del Chaco, el número de casos ha aumentado cinco veces respecto de años anteriores, y la enfermedad está afectando con mayor frecuencia que antes a niños y jóvenes, produciendo cuadros graves de evolución aguda, progresiva y letal, de no mediar un diagnóstico temprano y un tratamiento oportuno7. Cabe recordar, sin embargo, que la forma infanto-juvenil sigue siendo predominante en los pacientes provenientes del Noroeste adonde representa el 26% de los casos diagnosticados6. Muchos casos de PCM son detectados en la Ciudad Autónoma de Buenos Aires, lejos del área endémica. Esto se debe a que los pacientes vivieron en un área endémica o la visitaron en algún momento de sus vidas y desarrollan formas crónicas cuando son adultos mayores y viven fuera del área endémica. Por ello, una minuciosa anamnesis es imprescindible para orientar el diagnóstico8.
Esta revisión presenta los conocimientos actuales sobre la PCM, con énfasis en información reciente sobre agentes causales, epidemiología y diagnóstico, con el propósito de contribuir a revertir su condición de enfermedad ignorada.
(EN) Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease is produced by thermodimorphic fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of members of this genus is the soil, where they produce infectious conidia. Little is known, however, about their specific ecologic niche(s), and this knowledge gap hampers the design of measures to control the infection. Rural male workers are the group most at risk of developing PCM. Infection occurs by inhalation of aerosolized conidia and may either be asymptomatic or cause mild respiratory symptoms. In turn, this primary infection may be self-limited or progress to severe pulmonary or disseminated disease. The disease has two clinical presentations: (i) acute or subacute (juvenile), frequent in children, adolescents and people with immunodeficiencies; and (ii) chronic progressive, in adults. Active lesions often resolve into fibrotic scars which can cause dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although efficient tools are available for diagnosis and treatment, the nonspecific nature of PCM clinical manifestations frequently delay the diagnosis. In addition, the poor adherence to long antifungal treatments allows the advance of the disease and the development of extensive fibrosis compromising severely and permanently respiratory and adrenal functions, thus altering the patient"s quality of life and even causing his/her death
Distribution of influenza virus types by age using case-based global surveillance data from twenty-nine countries, 1999-2014
Influenza disease burden varies by age and this has important public health implications. We compared the proportional distribution of different influenza virus types within age strata using surveillance data from twenty-nine countries during 1999-2014 (N=358,796 influenza cases)
Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
Fil: Garavaglia, Patricia A ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Rubio, María Fernanda. Laboratorio de Biología Molecular y Apoptosis,Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET),Universidad de Buenos Aires,Ciudad de Buenos Aires (1427); Argentina.Fil: Laverrière, Marc. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.Fil: Tasso, Laura Mónica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Cannata, Joaquín J B. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.Fil: García, Gabriela Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Several ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation
Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical isolates
Fil: Quebrada Palacio, Luz P. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina.Fil: Gonzalez, Mariela N. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Investigación y Docencia; Argentina.Fil: Hernandez-Vasquez, Yolanda. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Investigación y Docencia; Argentina.Fil: Perrone, Alina E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología. Departamento de Investigación y Docencia; Argentina.Fil: Parodi-Talice, Adriana. Universidad de la República. Facultad de Ciencias. Sección Genética. Instituto Pasteur de Montevideo. Unidad de Biología Molecular Montevideo; Uruguay.Fil: Bua, Jacqueline. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina.Fil: Postan, Miriam. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET); Argentina.Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause Chagas disease. It has been long suspected that the clinical outcome of the disease and response to therapeutic agents are, at least in part, related to the genetic characteristics of the parasite. Herein, we sought to validate the significance of the genotype of T. cruzi isolates recovered from patients with different clinical forms of Chagas disease living in Argentina on their biological behaviour and susceptibility to drugs. Genotype identification of the newly established isolates confirmed the reported predominance of TcV, with a minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked dissimilar responses to benznidazole, nifurtimox, pentamidine and dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to benznidazole in epimastigote assays were further tested for the expression of anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and overexpression of mitochondrial superoxide dismutase and tryparedoxin- 1, compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays on intracellular amastigotes and trypomastigotes reproduced the higher susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in epimastigotes assays. However, the susceptibility/resistance profile of amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin varied markedly with respect to that of epimastigotes. C3H/He mice infected with AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate during the acute phase of infection compared to mice infected with BOL-FC10A trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was efficient to reduce patent parasitemia induced by either isolate. Nevertheless, qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level of intra-type diversity which may represent an important obstacle for the testing of chemotherapeutic agents
Prevalence of Burkholderia cepacia complex species in cystic fibrosis patients in Argentina during the period 2011-2015
Burkholderia cepacia (B. cepacia) complex is composed of 20 phylogenetically closely related bacterial species. Some species have emerged as opportunistic pathogens in immunocompromised patients and are responsible for nosocomial outbreaks. The B. cepacia complex is a recognized respiratory pathogen in patients with cystic fibrosis. Burkholderia cenocepacia and Burkholderia multivorans (B. multivorans) are the most prevalent species in the world, according to the literature. However, research groups in Argentina have described a particular local epidemiology, with prevalence of Burkholderia contaminans (B. contaminans)
Rodent-borne viruses survey in rural settlers from Central Brazil
Fil: Fernandes, Jorlan. Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ; Brasil.Fil: Oliveira, Renata Carvalho de. Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ; Brasil.Fil: Coelho, Thayssa Alves. Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ; Brasil.Fil: Martins, Regina Maria Bringel. Universidade Federal de Goiás, Instituto de Patologia Tropical e Saúde Pública, Goiânia, GO; Brasil.Fil: Caetano, Karlla Antonieta Amorim. Universidade Federal de Goiás, Faculdade de Enfermagem, Goiânia, GO; Brasil.Fil: Horta, Marco Aurélio Pereira. Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Rio de Janeiro, RJ; Brasil.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.Fil: Carneiro, Megmar Aparecida Dos Santos. Universidade Federal de Goiás, Instituto de Patologia Tropical e Saúde Pública, Goiânia, GO; Brasil.Fil: Teles, Sheila A. Universidade Federal de Goiás, Faculdade de Enfermagem, Goiânia, GO; Brasil.Fil: Lemos, Elba Regina Sampaio de. Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Hantaviroses e Rickettsioses, Rio de Janeiro, RJ; Brasil.Anthropogenic environmental changes arising from settlement and agriculture include deforestation and replacement of natural vegetation by crops providing opportunities for pathogen spillover from animals to humans. This study aimed to investigate the prevalence of rodent-borne virus infections in seven rural settlements from Midwestern Brazil. Of the 466 individuals tested 12 (2.57%) were reactive for orthohantavirus and 3 (0.64%) for mammarenavirus. These rural settlers lived under unfavorable infrastructure, socioeconomic disadvantages, and unsanitary conditions, representing a risk for rodent-borne infections. Development of public policies towards the improvement of health, sanitation and awareness of rodent-borne diseases in improvised camps and settlements is imperative, in order to reduce morbidity and mortality caused by these diseases
Presence of Lutzomyia longipalpis and Nyssomyia whitmani in Entre Rios, Argentina
Fil: Santini, María Soledad. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Manteca Acosta, Mariana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Medicina Tropical (INMeT), Puerto Iguazú, Misiones; Argentina.Fil: Utgés, Maria Eugenia. ANLIS Dr.C.G.Malbrán. Centro Nacional de Diagnóstico e Investigación en Endemo-Epidemias; Argentina.Fil: Aldaz, Maria Esther. Hospital Delicia Concepción Masvernat. Dirección de Epidemiologia. Programa Provincial de Zoonosis y Vectores, Entre Ríos; Argentina.Fil: Salomón, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires; Argentina.The objective of this study was to evaluate the presence of Lutzomyia longipalpis in the Argentine city of Concordia, in the province of Entre Rios, without record of this species despite previous samplings, but with canine cases of visceral leishmaniasis and Lu. longipalpis reports both, from Northern Argentine localities and from the city of Salto, Uruguay, located just across the river and the international border. This study confirms the presence of Lu. longipalpis and Nyssomyia whitmani, related to the risk of visceral and tegumentary leishmaniasis, respectively, in Concordia-Entre Rios. The presence of Lu. longipalpis confirms the ongoing dispersal along the Uruguay river basin. The presence of these species in the study area alerts about the risk of transmission of Leishmania spp
Some Limitations for Early Diagnosis of Congenital Chagas Infection by PCR
Fil: Volta, Bibiana Julieta. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Perrone, Alina E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Rivero, Rocio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Scollo, Karenina . ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bustos, Patricia L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Bua, Jacqueline. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Trypanosoma cruzi, the causing agent of Chagas disease, can be transmitted to the offspring of infected pregnant women, thus being an epidemiologically important way of parasite transmission in humans. In addition, the migration of infected women from endemic areas to nonendemic countries may export this parasite infection. The diagnosis of congenital Chagas disease relies on the detection of the parasite because maternal antibodies are passively transferred to infants during pregnancy. The diagnosis of congenital infection can also be confirmed by detection of infant-specific anti-T cruzi antibodies at 10 months after delivery. Because early detection of T cruzi infection in newborns allows an efficient trypanocidal treatment and cure, more sensitive molecular techniques such as DNA amplification are being used for a prompt parasitological diagnosis of children born to seropositive mothers. In this report, we describe a diagnosis case of a child congenitally infected with T cruzi who tested negative for parasite detection both by microscopic observation and DNA amplification at 20 days and 6 months after delivery. However, at 7 months of age, a hemoculture was made from the infant's blood, and the infective parasite was finally isolated and classified as T cruzi discrete typing unit I. In a retrospective study, real-time polymerase chain reaction also allowed detecting the parasite but failed to detect any parasite load in earlier control samples. This case report stresses that even when molecular techniques are negative, a long-term follow-up is necessary for the diagnosis of infants congenitally infected with T cruzi
Prevalence of Burkholderia cepacia complex species in cystic fibrosis patients in Argentina during the period 2011-2015
Burkholderia cepacia (B. cepacia) complex is composed of 20 phylogenetically closely related bacterial species. Some species have emerged as opportunistic pathogens in immunocompromised patients and are responsible for nosocomial outbreaks. The B. cepacia complex is a recognized respiratory pathogen in patients with cystic fibrosis. Burkholderia cenocepacia and Burkholderia multivorans (B. multivorans) are the most prevalent species in the world, according to the literature. However, research groups in Argentina have described a particular local epidemiology, with prevalence of Burkholderia contaminans (B. contaminans)