Papers by Juan Antonio Posadas Macedo
Odontología Sanmarquina, 2018
Objetivo: Determinar el efecto antibacteriano del extracto de Stevia rebaudiana (S. rebaudiana) f... more Objetivo: Determinar el efecto antibacteriano del extracto de Stevia rebaudiana (S. rebaudiana) frente a Streptococcus sanguinis (S. sanguinis) y Actinomyces viscosus (A. viscosus). Métodos: Se desarrolló la prueba de sensibilidad en placa de agar con discos, para lo cual se cultivaron las cepas de S. sanguinis y A. viscosus en placas de agar tripticasa soya (TSA) y agar sangre respectivamente, incubando a 37 °C por 48 horas a S. sanguinis y por 7 días en condiciones de anaerobiosis a A. viscosus. Las cepas bacterianas fueron estandarizadas a una escala de 0,5 de Mc Farland, y tomando inóculos de 100 μL fueron sembradas en diez placas de agar sangre y TSA, luego sobre cada placa se colocaron los discos de papel secante de 6 mm de diámetro de forma equidistante, cargados con 10 μL de las diferentes concentraciones del extracto, para luego ser incubados. Resultados: Las concentraciones de 15, 30, 50, 60 y 120 mg/ml presentaron un halo de inhibición promedio de 6,8±0,258; 8,2±1,15; 8,2...
Parasites & Vectors, 2016
Background: Reactive oxygen species (ROS) protect the host against a large number of pathogenic m... more Background: Reactive oxygen species (ROS) protect the host against a large number of pathogenic microorganisms. ROS have different effects on parasites of the genus Leishmania: some parasites are susceptible to their action, while others seem to be resistant. The role of ROS in L. amazonensis infection in vivo has not been addressed to date. Methods: In this study, C57BL/6 wild-type mice (WT) and mice genetically deficient in ROS production by phagocytes (gp91 phox−/−) were infected with metacyclic promastigotes of L. amazonensis to address the effect of ROS in parasite control. Inflammatory cytokines, parasite loads and myeloperoxidase (MPO) activity were evaluated. In parallel, in vitro infection of peritoneal macrophages was assessed to determine parasite killing, cytokine, NO and ROS production. Results: In vitro results show induction of ROS production by infected peritoneal macrophages, but no effect in parasite killing. Also, ROS do not seem to be important to parasite killing in vivo, but they control lesion sizes at early stages of infection. IFN-γ, TNF-α and IL-10 production did not differ among mouse strains. Myeloperoxidase assay showed augmented neutrophils influx 6 h and 72 h post-infection in gp91 phox−/− mice, indicating a larger inflammatory response in gp91 phox−/− even at early time points. At later time points, neutrophil numbers in lesions correlated with lesion size: larger lesions in gp91 phox−/− at earlier times of infection corresponded to larger neutrophil infiltrates, while larger lesions in WT mice at the later points of infection also displayed larger numbers of neutrophils. Conclusion: ROS do not seem to be important in L. amazonensis killing, but they regulate the inflammatory response probably by controlling neutrophils numbers in lesions.
PLoS Neglected Tropical Diseases, 2012
NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infec... more NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91 phox2/2 or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-c and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with N NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi.
Molecular and Biochemical Parasitology, 2013
Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synt... more Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-containing phospholipids, such as phosphatidylcholine (PC). According to published data, Trypanosoma brucei parasites are unable to take up choline from the environment but instead use lysophosphatidylcholine as precursor for choline lipid synthesis. We now show that T. brucei procyclic forms in culture readily incorporate [ 3 H]-labeled choline into PC, indicating that trypanosomes express a transporter for choline at the plasma membrane. Characterization of the transport system in T. brucei procyclic and bloodstream forms shows that uptake of choline is independent of sodium and potassium ions and occurs with a K m in the low micromolar range. In addition, we demonstrate that choline uptake can be blocked by the known choline transport inhibitor, hemicholinium-3, and by synthetic choline analogs that have been established as anti-malarials. Together, our results show that T. brucei parasites express an uptake system for choline and that exogenous choline is used for PC synthesis.
Journal of parasitology research, 2012
Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmani... more Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO(-)) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive T(h)-cell immune response.
IDS Bulletin, 2010
In this article, we present an emergent capacity development approach that we are developing thro... more In this article, we present an emergent capacity development approach that we are developing through participatory action research in Peru and Ecuador, which we call 'systemic theories of change' (STOC), for organisational capacity development. We argue that capacity development should be understood as systemic learning. The STOC approach promotes reflection about how we as individuals, organisations, and broader social groups and societal configurations, understand how change occurs. This makes it possible to build improved strategic and methodological clarity about how we might continually develop the capacities to contribute more effectively to emergent, social change in highly complex environments.
Rev. méd. …, 1990
Resumo: Como una contribución a la construcción del campo de la medicina general, se presentan al... more Resumo: Como una contribución a la construcción del campo de la medicina general, se presentan algunos datos referidos a la epidemiología clínica de las anemias y la morbilidad crónica en pacientes con 75 años y mayores no agudamente enfermos. El trabajo abarcó ...
congreso.gob.pe
... Francisco Eguiguren, Sinesio López, Nicolas Lynch, Romeo Grompone, Carlos Franco, Luis Nunes,... more ... Francisco Eguiguren, Sinesio López, Nicolas Lynch, Romeo Grompone, Carlos Franco, Luis Nunes, Pepi Patrón, Santiago Pedraglio, Alvaro Rojas Samanez ... Acción Popular Luis Enrique Gálvez (Secretario General) Javier Diaz Orihuela (Vicepresidente) ... Nidia Puelles (Asesora ...
Acta Tropica, 2008
Experimental models of infection with Leishmania spp. have provided knowledge of several immunolo... more Experimental models of infection with Leishmania spp. have provided knowledge of several immunological events involved in the resistance mechanism used by the host to restrain parasite growth. It is well accepted that concomitant immunity exists, and there is some evidence that it would play a major role in long-lasting acquired resistance to infection. In this paper, the resistance to Leishmania amazonensis infection in C57BL/6 mice infected with Leishmania major was investigated. C57BL/6 mice, which spontaneously heal lesions caused by infection with L. major, were infected with L. amazonensis at different times before and after L. major. We demonstrated that C57BL/6 mice previously infected with L. major restrain pathogenic responses induced by L. amazonensis infection and decrease parasite burdens by one order of magnitude. Coinfected mice showed production of IFN-␥ in lesions similar to mice infected solely with L. major, but higher TNF-␣ and nitric oxide synthase (iNOS) mRNA expression was observed. Surprisingly, the restrained pathogenic response was not related to IL-10 production, as evidenced by lower levels of both mRNA, protein expression in lesions from co-infected mice and in co-infections in IL-10 −/− mice. Examination of the inflammatory infiltrate at the site of infection showed a reduced number of monocytes and lymphocytes in L. amazonensis lesions. Additionally, differential production of the CCL3/MIP-1␣ and CCL5/RANTES was observed. We suggest that the control of lesion progression caused by L. amazonensis in C57BL/6 mice pre-infected with L. major is related to the induction of a down-regulatory environment at the site of infection with L. amazonensis.
PLOS Pathogens, 2015
Elucidating the mechanism of action of trypanocidal compounds is an important step in the develop... more Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knockout parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug action or targeting.
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Papers by Juan Antonio Posadas Macedo