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  1. Article ; Online: Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis.

    Costa Souza, Beatriz L S / Pinto, Eduardo F / Bezerra, Izabella P S / Gomes, Daniel C O / Martinez, Ana Maria B / Ré, Maria Inês / de Matos Guedes, Herbert L / Rossi-Bergmann, Bartira

    Vaccine: X

    2023  Volume 15, Page(s) 100403

    Abstract: Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate ...

    Abstract Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 μm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with
    Language English
    Publishing date 2023-11-03
    Publishing country England
    Document type Journal Article
    ISSN 2590-1362
    ISSN (online) 2590-1362
    DOI 10.1016/j.jvacx.2023.100403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Increased levels of cortisol are associated with the severity of experimental visceral leishmaniasis in a Leishmania (L.) infantum-hamster model.

    Barros-Gonçalves, Tayany de D / Saavedra, Andrea F / Silva-Couto, Luzinei da / Ribeiro-Romão, Raquel P / Bezerra-Paiva, Milla / Gomes-Silva, Adriano / Carvalho, Vinicius F / Da-Cruz, Alda Maria / Pinto, Eduardo F

    PLoS neglected tropical diseases

    2021  Volume 15, Issue 11, Page(s) e0009987

    Abstract: Background: Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden ... ...

    Abstract Background: Several infectious diseases are associated with hypothalamic-pituitary-adrenal (HPA) axis disorders by elevating circulating glucocorticoids (GCs), which are known to have an immunosuppressive potential. We conducted this study in golden hamsters, a suitable model for human visceral leishmaniasis (VL), to investigate the relationship of Leishmania (L.) infantum infection on cortisol production and VL severity.
    Methods: L. infantum-infected (n = 42) and uninfected hamsters (n = 30) were followed-up at 30, 120, and 180 days post-infection (dpi). Plasma cortisol was analyzed by radioimmunoassay and cytokines, inducible nitric oxide synthase (iNOS), and arginase by RT-qPCR.
    Results: All hamsters showed splenomegaly at 180 dpi. Increased parasite burden was associated with higher arginase expression and lower iNOS induction. Cortisol levels were elevated in infected animals in all-time points evaluated. Except for monocytes, all other leucocytes showed a strong negative correlation with cortisol, while transaminases were positively correlated. Immunological markers as interleukin (IL)-6, IL-1β, IL-10, and transforming growth-factor-β (TGF-β) were positively correlated to cortisol production, while interferon-γ (IFN-γ) presented a negative correlation. A network analysis showed cortisol as an important knot linking clinical status and immunological parameters.
    Conclusions: These results suggest that L. infantum increases the systemic levels of cortisol, which showed to be associated with hematological, biochemical, and immunological parameters associated to VL severity.
    MeSH term(s) Animals ; Cricetinae ; Glucocorticoids/blood ; Humans ; Hydrocortisone/blood ; Interleukins/blood ; Leishmania infantum/genetics ; Leishmania infantum/isolation & purification ; Leishmania infantum/physiology ; Leishmaniasis, Visceral/blood ; Leishmaniasis, Visceral/parasitology ; Leukocytes/immunology ; Male ; Mesocricetus ; Transforming Growth Factor beta/blood
    Chemical Substances Glucocorticoids ; Interleukins ; Transforming Growth Factor beta ; Hydrocortisone (WI4X0X7BPJ)
    Language English
    Publishing date 2021-11-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2727
    ISSN (online) 1935-2735
    ISSN 1935-2727
    DOI 10.1371/journal.pntd.0009987
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Structure-activity relationship of antileishmanials neolignan analogues.

    Aveniente, Mário / Pinto, Eduardo F / Santos, Lourivaldo S / Rossi-Bergmann, Bartira / Barata, Lauro E S

    Bioorganic & medicinal chemistry

    2007  Volume 15, Issue 23, Page(s) 7337–7343

    Abstract: Twenty-two synthetic analogues of neolignans comprising beta-ketoethers and beta-ketosulfides were obtained from condensation reactions among beta-bromoketones and phenols or thiophenols, respectively, in basic solutions, and assayed in vitro for ... ...

    Abstract Twenty-two synthetic analogues of neolignans comprising beta-ketoethers and beta-ketosulfides were obtained from condensation reactions among beta-bromoketones and phenols or thiophenols, respectively, in basic solutions, and assayed in vitro for activity against intracellular Leishmania amazonensis and Leishmania donovani amastigotes, the causative agents of cutaneous and visceral leishmaniasis. The highest selective activity was found for compounds with sulfur bridges, whereas beta-ketosulphoxides and beta-ketosulphones had significantly less growth inhibitory activity. Compounds 2-[(4-chlorophenyl)thio]propan-1-one and 1-(3,4-dimethoxy)-2-[(4-methylphenyl)thio]propan-1-one were the most potent, inhibiting the growth parasite species by over 90% at microgram/mL, but only compound 1-(3,4-dimethoxy)-2-[(4-methylphenyl)thio]propan-1-one was selectively toxic to the parasites.
    MeSH term(s) Animals ; Antiprotozoal Agents/chemistry ; Antiprotozoal Agents/pharmacology ; Antiprotozoal Agents/therapeutic use ; Cells, Cultured ; Disease Models, Animal ; Leishmania/drug effects ; Leishmaniasis/drug therapy ; Lignans/chemical synthesis ; Lignans/chemistry ; Lignans/pharmacology ; Macrophages, Peritoneal/drug effects ; Macrophages, Peritoneal/parasitology ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Parasitic Sensitivity Tests ; Species Specificity ; Stereoisomerism ; Structure-Activity Relationship
    Chemical Substances Antiprotozoal Agents ; Lignans
    Language English
    Publishing date 2007-12-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1161284-8
    ISSN 1464-3391 ; 0968-0896
    ISSN (online) 1464-3391
    ISSN 0968-0896
    DOI 10.1016/j.bmc.2007.08.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis.

    Pinheiro, Roberta O / Pinto, Eduardo F / Benedito, Alessandra B / Lopes, Ulisses G / Rossi-Bergmann, Bartira

    Anais da Academia Brasileira de Ciencias

    2004  Volume 76, Issue 3, Page(s) 519–527

    Abstract: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg) but not L. braziliensis promastigotes (LbAg) ... ...

    Abstract Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg) but not L. braziliensis promastigotes (LbAg) contains substances that suppress mitogenic and spontaneous proliferative responses of T cells. The suppressive substances in LaAg are thermoresistant (100 degrees C/1h) and partially dependent on protease activity. T cell anergy was not due to a decreased production of growth factors as it was not reverted by addition of exogenous IL-2, IL-4, IFN-gamma or IL-12. LaAg did not inhibit anti-CD3-induced T cell activation, suggesting that anergy was due to a defect in antigen presentation. It was also not due to cell necrosis, but was accompanied by expressive DNA fragmentation in lymph node cells, indicative of apoptosis. Although pre-incubation of macrophages with LaAg prevented their capacity to present antigens, this effect was not due to apoptosis of the former. These results suggest that the T cell anergy found in diffuse leishmaniasis may be the result of parasite antigen-driven apoptosis of those cells following defective antigen presentation.
    MeSH term(s) Animals ; Antigens, Protozoan/immunology ; Apoptosis/immunology ; Clonal Anergy/immunology ; Leishmania/immunology ; Leishmaniasis, Diffuse Cutaneous/immunology ; Leishmaniasis, Diffuse Cutaneous/parasitology ; Lymph Nodes/cytology ; Lymph Nodes/immunology ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes/immunology
    Chemical Substances Antigens, Protozoan
    Language English
    Publishing date 2004-08-23
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 2046885-4
    ISSN 1678-2690 ; 0001-3765
    ISSN (online) 1678-2690
    ISSN 0001-3765
    DOI 10.1590/s0001-37652004000300006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The T-cell anergy induced by Leishmania amazonensis antigens is related with defective antigen presentation and apoptosis

    Pinheiro Roberta O. / Pinto Eduardo F. / Benedito Alessandra B. / Lopes Ulisses G. / Rossi-Bergmann Bartira

    Anais da Academia Brasileira de Ciências, Vol 76, Iss 3, Pp 519-

    2004  Volume 527

    Abstract: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg) but not L. braziliensis promastigotes (LbAg) ... ...

    Abstract Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease associated with anergic immune responses. In this study we show that the crude antigen of Leishmania amazonensis (LaAg) but not L. braziliensis promastigotes (LbAg) contains substances that suppress mitogenic and spontaneous proliferative responses of T cells. The suppressive substances in LaAg are thermoresistant (100ºC/1h) and partially dependent on protease activity. T cell anergy was not due to a decreased production of growth factors as it was not reverted by addition of exogenous IL-2, IL-4, IFN-gamma or IL-12. LaAg did not inhibit anti-CD3-induced T cell activation, suggesting that anergy was due to a defect in antigen presentation. It was also not due to cell necrosis, but was accompanied by expressive DNA fragmentation in lymph node cells, indicative of apoptosis. Although pre-incubation of macrophages with LaAg prevented their capacity to present antigens, this effect was not due to apoptosis of the former. These results suggest that the T cell anergy found in diffuse leishmaniasis may be the result of parasite antigen-driven apoptosis of those cells following defective antigen presentation.
    Keywords Leishmania ; anergy ; apoptosis ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2004-01-01T00:00:00Z
    Publisher Academia Brasileira de Ciências
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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