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Synthesis and biological evaluation of Amphotericin B formulations based on org...

Ferraz, Ricardo; Santarém, Nuno; Santos, Andreia F. M.; Jacinto, Manuel L.; Cordeiro-da-Silva, Anabela; Prudêncio, Cristina; Noronha, João Paulo

Nowadays, organic salts and ionic liquids (OSILs) containing active pharmaceutical ingredients (APIs) are being explored as drug delivery systems in modern therapies (OSILs-API). In that sense, this work is focused on the development of novel OSILs-API based on amphotericin B through an innovative procedure and the evaluation of the respective biological activity against Leishmania infantum. Several ammonium, m...


Pyrimido[5,4-d]pyrimidine-based compounds as a novel class of antitrypanosomal ...

Lopes, Andre; Santarem, Nuno; Cordeiro-da-Silva, Anabela; Carvalho, M. Alice

Sleeping sickness and leishmaniasis are neglected tropical diseases that threaten millions of people. The currently available therapies present several limitations, including high toxicity, lack of efficacy, and emerging drug resistance, prompting a search for novel therapeutic agents. In this work, we designed, synthesized, and in vitro evaluated the activity of new pyrimido[5,4-d]pyrimidines against Trypanoso...


Serological and Molecular Survey of Leishmania infantum in a Population of Iber...

Lima, Clara M.; Santarém, Nuno; Neves, Nuno Costa; Sarmento, Pedro; Carrapato, Carlos; de Sousa, Rita; Cardoso, Luís; Cordeiro-da-Silva, Anabela

Leishmania infantum, the sand fly-transmitted protozoan parasite responsible for leishmaniasis in humans, dogs, and cats, is endemic in the Iberian Peninsula. However, the impact of L. infantum infection on the conservation of the endangered Iberian lynx (Lynx pardinus) is unknown. Herein, we describe for the first time the occurrence of L. infantum infection among a population of reintroduced and wild-born L. ...


Evaluating the Role of Host AMPK in Leishmania Burden

Moreira, Diana Raquel Bento; Estaquier, Jérôme; Cordeiro-da-Silva, Anabela; Silvestre, Ricardo Jorge Leal

The study of host AMP-activated protein kinase (AMPK) activation during Leishmania infection imposes distinct types of techniques to measure protein expression and activation, as well as to quantify, at transcription and translational levels, its downstream targets. The investigation of host AMPK protein modulation during Leishmania infection should primarily be assessed during in vitro infections using as a ho...


Infection of hematopoietic stem cells by Leishmania infantum increases erythrop...

Carvalho-Gontijo, Raquel; Moreira, Diana Raquel; Resende, Mariana; Costa-Silva, Matheus Fernandes; Peruhype-Magalhães, Vanessa

Immunosuppression is a well-established risk factor for Visceral Leishmaniasis. Post-immunosuppression leishmaniasis is characterized by an increase of parasite burden, hematopoietic disorders and unusual clinical manifestations. Although there are many reports on bone marrow findings in VL, less is known about the relationship between parasite dynamics in this organ and the function of either hematopoietic ste...


AMPK in Pathogens

Mesquita, Inês Morais; Moreira, Diana; Marques, Belém Sampaio; Laforge, Mireille; Cordeiro-da-Silva, Anabela; Ludovico, Paula; Estaquier, Jérôme

During host–pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Amon...


Poly-N-acetyl glucosamine expression in Staphylococcus epidermidis biofilm cell...

Ferreirinha, Pedro; Pérez-Cabezas, Begoña; Correia, Alexandra; Miyazawa, Bruna; Carvalhais, Virgínia Maria Dinis; França, Ângela Maria Oliveira Sousa

Staphylococcus epidermidis is a biofilm - forming bacterium and a leading etiological agent of nosocomial infections. The ability to establish biofilms on indwelling medical devices is a key virulence factor for this bacterium. Still, the influence of poly - N - acetyl glucosamine (PNAG), the major component of the extracellular biofilm matrix, in the host immune response has been scarcely studied. Here, t h is...


Alginate coated chitosan nanoparticles are an effective subcutaneous adjuvant f...

Borges, Olga; Silva, Marta; Sousa, Adriano de; Borchard, Gerrit; Junginger, Hans E.; Cordeiro-da-Silva, Anabela

http://www.sciencedirect.com/science/article/B6W7N-4TFV6D6-1/2/da901d7d04c884f0b04f835c6e86c774


Immune response by nasal delivery of hepatitis B surface antigen and codelivery...

Borges, Olga; Cordeiro-da-Silva, Anabela; Tavares, Joana; Santarém, Nuno; Sousa, Adriano de; Borchard, Gerrit; Junginger, Hans E.

Alginate coated chitosan nanoparticles were previously developed with the aim of protecting the antigen, adsorbed on the surface of those chitosan nanoparticles, from enzymatic degradation at mucosal surfaces. In this work, this new delivery system was loaded with the recombinant hepatitis B surface antigen (HBsAg) and applied to mice by the intranasal route. Adjuvant effect of the delivery system was studied b...


Evaluation of the immune response following a short oral vaccination schedule w...

Borges, Olga; Tavares, Joana; Sousa, Adriano de; Borchard, Gerrit; Junginger, Hans E.; Cordeiro-da-Silva, Anabela

The purpose of this work was to assess the ability of recombinant hepatitis B vaccine, encapsulated in alginate-coated chitosan nanoparticles, to induce local and systemic immune responses following oral vaccination. The antigen was administered either alone or in combination with the immunopotentiator, synthetic oligodeoxynucleotide containing immunostimulatory CpG motif (CpG ODN) as adjuvant, and associated o...


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